DR. KRISTA ZANETTI: Welcome to the second day of the NIH Workshop on
Multigenerational Nutritional Influences on Health and Disease. I’m Dr. Krista Zanetti,
one of the scientific leads for the workshop, along with Dr. Ashley Vargas. We had a day filled
with exciting and informative presentations yesterday on the foundational concepts
within the field and individual-level aspects of multigenerational influences on nutrition. Today,
we will continue with more exciting presentations that focus on family- and society-level aspects
of multigenerational influences on nutrition. These aspects are equally as important as the
individual aspects. And today, we have the opportunity to learn more about those. Again,
today, to reach the goals identifying the next steps needed for research in multigenerational
nutritional effects, we need each of you to click on the Zoom Q&A and ask the critical questions
that will push the discussion towards the most important research gaps and opportunities.
I will now introduce the keynote speaker and be your moderator for this presentation.
Dr. Mary Barker from the University of South Hampton will be our keynote speaker and will
present on the family- and societal-level aspects of multigenerational influences on
nutrition. During the presentation, virtual participants, please share your questions in
the Q&A box. And I want to thank Dr. Montessa Mitchell in the NIH Office of the Director,
who will assist with prioritizing questions during this discussion.
DR. MARY BARKER: Thank you. Good morning, everybody. Thank you, Krista. Thank you,
everybody. Thank you, Ashley. Thank you for the invitation. I was very flattered to receive the
invitation, though a little bit baffled and did actually have to check with Krista and Ashley
that it really was me that they wanted to come and speak. But yes, apparently it was, so here I am.
So, the other thing I wanted to say before I start was how wonderful my father, David Barker,
would have thought yesterday’s meeting was. He would have loved the science and the biology that
you were all speaking about. He’d have been blown away by the fact that 10 years after his death,
his legacy is still being explored in a room full of really exciting scientists and a room full of
excited people. So, thank you for that. And I thank Usha for the kind words she said about
my father yesterday. So, today, I…I’m going to do something that’s…is a little bit different
from what Usha did. Usha did the most phenomenal review yesterday of a whole field of amazing and
groundbreaking epidemiological and other work. I’m not going to do that.
I’m going to do something a bit more prosaic. I’m going to tell you, really, what I think
about the way people experience nutrition, and the way they experience diet, and the impact
that those experiences have, and the context in which they eat food and experience nutrition,
how that impacts their own health and the health of multiple generations and across generations.
So, the first thing, really, to understand, which may sound obvious, but actually,
it pays us to sometimes stop and think, is that not everybody finds nutrition quite as important
or exciting as we do. This is a rather lovely quote—and a rather sad quote, in some ways—from
a young woman that we spoke to in a study we did some years ago, who was very young. She was 16.
She was just…she was pregnant. She had nowhere to live, so she was living in a mother and baby unit,
which is set up in the U.K. that we have for very young pregnant women. And when we were
speaking to her, it was about the context of nutrition and diet and looking after herself.
And an early question in these conversations was, “What’s important to you during this pregnancy?”
And you can see that basically…her basic needs were the most important thing. And yes, nutrition
is a basic need, but unless she has somewhere safe to live, a…a job, she has an ability to
actually learn and progress herself, and she’s able to look after that baby, then actually
nutrition comes a very poor one, two, three, four, five, six, seven after all those other things.
And that’s worth bearing in mind, because I think the rest of my talk, really, I want to set…I
want to set nutrition within that kind of context of what really bothers and preoccupies people for
an awful lot of their lives. So, this model, the…socioecological model has been used for
many years. And I’m sure many of you recognize it. It was introduced by Whitehead and Dahlgren
in the…in the early ’90s, and it really puts health in a…in this lovely rainbow context. And
we call it the rainbow model for short. So, for health [inaudible] nutrition…so, at the center of
the diagram, there are…there is the individual and all the individual-level impacts on…on
people. So, all the constitutional stuff, their age, their sex, as it says there; their gender;
and also things to do…how they respond generally. Their psychology, if you like. So,
individual-level lifestyle factors then operate on that individual; things like…things like, I guess,
your…your choices that you make about things that you like to do, things that you don’t like to do.
And then there’s your social/community networks over the top of that; you know, who you respond
to and who you work with and where you live. And then there is the kind of…the broader green level
of the rainbow, which really describes much more about your environment and the way you live and
work and the conditions that you live within. And then outside of that, the blue-purple level is the
sort of general policy, cultural, sociological context of your…of you. So, if we think about
all these levels and the way that they interact with one another and the way they interact with
what people then choose or don’t choose—we all have to eat—then we can see that the actual…the
behavior of putting a certain food item in your mouth is a hugely constrained one. It’s
not a free choice very often, and it depends on so, so many other things. So, the choices
that mothers make for themselves and the choices that mothers make for their children, I believe
the point of my talk today is to explain or to make us think a bit more about the constraints
on those choices and why women and families and young people end up doing the things they do.
So, many years ago in Southampton, we started something called the Southampton Women’s Survey.
And it was a study of 12,500 women in Southampton. It was a preconception study…Sonia. And we
recruited 12,500 women and produced…who produced very kindly for us about 3,000 pregnancies.
Part of what we did with the…the baseline group, if you like, of 12,500 women was
some very interesting work. And the…the graph shows you that what we found very predictive
of their quality of diet was their educational qualifications, their educational attainment.
This is…not earth-shattering news. I mean, this is quite an old slide now. You can see the data are
quite old. But it never fails to amaze me. So…so, you’ve got highest educational qualification
across the bottom. And in the U.K. terms, these are…like…so, no educational qualifications; GCSE
is what we do at the age of 16; A-levels are what we do at 18; and HND and Degree are beyond 18.
So, you can see that the proportion of women who have the poorest quality diet by our standards
as part of the study were much, much more likely to fall in the No Education group.
But the striking thing about this, as I said, is that this response is graded. So, for every
each individual increase…for every individual increase in level of educational attainment,
there are fewer women who fall in the poorest-quality diet group, which is very
interesting because very little is taught in the U.K. schools about food. This is not nutrition
education we’re talking about. This is education generally. And somebody—and I can’t remember now
who it was who mentioned it yesterday—talked about education—I think it was Usha, actually—talked
about education as being protective of women’s quality of diet and children’s quality of diet.
And this graph, this particular analysis, triggered my colleagues and I to go in and have
a think about why education might be protective, what was it about education, given that these
women were not learning about…you know, the longer they were in school was not telling
them more about how to cook and eat. It was just education per se. So, we embarked on a series of
studies, some of which were qualitative, so we interviewed and we ran focus groups, and
some of which were quantitative—we did surveys, we collected data on a one-to-one basis from lots and
lots of women and all over Southampton. And what we found was that there were four key things that
seemed to identify amongst women of lower educational attainment why they might not be
eating so well. So, the four blue squares—kind of rounded squares—in the middle of this diagram are
the four factors which we found in surveys to…to independently predict women’s quality of diet.
So, whether they had social support…and these are very different in women of
higher educational attainment. These were not features of women of higher
educational attainment’s diet. It did not predict in the same way. These were
predictive of a diet for these women of low educational attainment. Very particular.
So, we found that social support was very important for eating well. So…so if women
lacked social support, it was much harder for them to…to eat well. And that’s within the family and
with outside the family. And I’m not going to read the quotes because you can see them, but
they are illustrative of what we mean by lacking social support. They found it really difficult
to prioritize food over competing priorities, the priorities that I just suggested just now.
The women who doesn’t…really didn’t like cooking would be using the microwave. It just wasn’t head
space for her, if you like, to take on cooking. This thing called lower sense of self-efficacy
and sense of control over life is really about a woman’s individual belief that she
has the…the capacity to overcome problems. And this was really, really important. Her sense of
personal agency in her life was really important and predictive in her quality of diet, as well.
I love that, “My husband tells me what to cook and I cook it.” My husband rolls his eyes every time I
show him this slide. It couldn’t be more different in our house, as you can probably imagine.
And then the last of these four is that actually this kind of fundamental belief
that maybe eating well wasn’t that…wasn’t really that important. And I never know quite what to
say about this particular factor because…because people’s instinctual response is to say, “Well,
we [inaudible]. Obviously, it’s important. You know, we all think it’s terribly important. It’s
very important.” But, again, I think this is relative to the other things that are happening
in…in women’s lives, particularly in…in this context, and I think we have to think about
why they might not push healthy if actually keeping your children safe and stopping your
husband being violent is…comes kind of first. Right? So, this was the…to…to put this in
context of the socioecological model, this was the kind of…the first two levels, if you like. This
was the individual and the…I can’t even remember which color it is now. I should now, shouldn’t I,
but I…I can’t remember. This was the kind of individual lifestyle and some of the social
factors. So, going slightly broader outside those factors into the next layer of the socioecological
model, we also found that women spoke a lot about the socioeconomic and community factors that they
had to deal with and the way these impacted their diet. And of course, unsurprisingly,
money and food insecurity was a major factor. So, again, if I can buy 20 sausages for a pound—that’s
about $1.30 in today’s exchange rate—and I know they’ll eat that. God only knows what’s in those
sausages, but she knows the kids will eat it. And the…the backstory to that is you can only
afford to buy food which you know is not going to be wasted. If you take a risk and buy lots of
fresh fruit and vegetables and spend your precious dollars, pounds, on fresh fruits and vegetables,
and then they rot and get thrown away and the kids don’t eat them, then you’re in big trouble
because you’ve got nothing else to eat. So, you buy 20 sausages for a pound, knowing that they’re
probably not the best thing you can buy and feed your children. But what other choice do you have?
And then there’s the whole shopping experience, the whole, kind of, access experience. So,
women who don’t drive and she’s taking her kids shopping. And we’ve all been there. Those of us
who have ever shopped with small children will know exactly what that’s like. And…and, you know,
there’s a…you can have a lot of sympathy for the fact that she’s actually going to get herself in
and out of that shop as fast as possible, that she’s not going to spend time considering food
labels and the relative content of this over that and…and…and doing anything other than just
getting out there, having spent as little money as possible, with as much food to feed her children
as possible. And then the last one I’m always very interested in because it never occurred to me. But
if you live in a tower block or a block apartment, you’re very…and you have small children, you’re
very dependent on the lifts working. And I spent enough time in Southampton and enough time in the
tower blocks to know that the lifts are quite often not working. So, what the hell do you do?
I mean, that is a choice I’ve never really got my head around. Do you leave your kids at the bottom
in the pushchair while you take the shopping up? Or do you take the kids up and leave the shopping
at the bottom? Both of which you might risk losing on the way. I don’t know how you resolve
that conundrum, but it’s a real one for a lot of women. And I guess what that might make you do is
not buy a lot of heavy fresh fruits and vegetables because then you can take everything up at once,
up the stairs. And…and it’s another reason for…for poor women eating and choosing the way they do.
And I just…so, I put this slide in because it struck me very forcibly when I was reading and
preparing for this talk that things, of course, must be getting pretty terrible in the States,
too. The cost of living crisis is hitting all of us everywhere. And the statistics I read
from what looks like a local research group—and I don’t know anything about the Urban Institute,
but their stuff looks pretty, pretty reputable—25% of American adults reported being food insecure.
That’s shocking and striking and a terrible thing that we should be thinking about. And so, for food
insecure, read all those things that we’ve just heard about, about women and the…and families
and the difficulties they have to…the challenges they have to overcome in order to feed themselves.
So, food insecurity clearly constrains choices very profoundly…food choices and nutrition and
diets very profoundly. And there’s a quote that I am going to show you now from a tweet that I
showed Krista—and I don’t know if anyone else last year…I can't remember who else was at the meeting that I attended last
year when I met Krista—from a very famous cook in the U.K. Her name is Jack Monroe. And she
champions cooking very cheap, very good food, and she is very politically active and a defender of
poor families eating as well as they can for the money they have. And you’ll have to excuse the…the
stars. “You can cook meals from scratch with nothing—You CAN’T cook meals from scratch with
nothing. You can’t buy cheap food with nothing. The issue is not ‘skills,’ it’s 12 years of
Conservative cuts to social support.” A little political U.K. dig. “The square root of F-all is
always going to be F-all, no matter how creatively you’re told to dice it.” And I think this is a
really important point that we need to think about. You know, at what point do our choices
become so constrained that actually they’re not choices at all? And when we spend a lot of time
talking about nutrition education and teaching particularly women and young families how to cook,
we have to remember the context in which they’re trying to do that. And actually,
it’s not really about nutritional education and skills. It’s about so, so many other things,
and we must not forget that. And by making it all about nutrition educational skills, we’re
making this an individual responsibility, and it’s clearly, clearly not an individual responsibility.
Food choices, if they’re that constrained, are not an individual responsibility or choice.
So, having told you about the situation for families and the kind of things that they
have to deal with and the choices that they have to make, I want to
move on to answer some of the questions—or one of the questions—that we were asked to consider. So,
what is the most promising…or the one most promising scientific or technological opportunity
moving forward? For me, this is all about young people. And those of you who I’ve spoken to in
the last 24 hours will not be surprised by this because I beef on about young people all the time.
I think it’s about adolescent development. I think it’s about harnessing what we now know about young
people and about adolescent development and the adolescent life course theories, and I think we
are missing a massive trait. So, for me, the thing we need to do is really work with adolescents. And
there was a very good series, in which I only played a very small part…[inaudible] small
part in the Lancet recently about adolescent nutrition, which I would recommend to anyone. It’s
really broad and, in the way those Lancet series are, covers a huge amount of ground,
from what we know about growth and development and young people through to what constrains and limits
that or…contrains their food choices really across the world and also suggests some interventions
and the way we need to work with them. So, why do I think adolescents are so important? Well,
this slide, which I’m sure many of you have seen, comes from my friend Keith Godfrey’s publication
some years ago. So, you can see that this is a…a rather complicated looking but actually quite
simple idea, which is that if you invest in different stages of the life course,
your energies and your commitment to improving health and nutrition, then you get different
levels of payback at different time points. And for me, the…the thing about this grant is that
if you—sorry, this graph—is, if you invest in adolescents, you are not only investing in that
young person’s health now, you’re also changing the trajectory for that young person as they get
to become an adult, but you’re also improving the health of the next generation. You get the best
bang for your buck, for want of a better expression. The best return of your investment
by investing in adolescents. And that really is why almost all my work now is with adolescents—on
top of which, I just really like them. I think they’re great. So, just to rehearse my work with
young people, it’s also a developmental stage that affects health, as I said, not just now,
but in later life. We also know that there is great potential to effect sustained change
in behavior and lots of other things, too, in development to protect future generations’ health.
Of course, there are lots of challenges of working with young people. They do, actually,
in surveys, have the poorest health behaviors of any population group. They eat worse,
they exercise least. They experiment with drugs. They don’t sleep much, or they sleep
at the wrong time. All of the things that we would like not to do, they do in abundance.
But also, so many mental health problems are established in…in adolescence. It’s a massive…a
massive issue. So, you’re working not just for the population who actually are struggling
with their own health behaviors to stay healthy, they’re actually really struggling, many of them,
with their own mental health problems. But for me, those…that makes this an even more important time
to invest. So, we spent a lot of time talking to young people, and we have a big study called
EACH-B, Engaging Adolescents in Changing Behavior, which has taught us lots and lots of
things, and we’ve been running this for the last 6 years now. And what we have really come to realize
is what we need to understand if we’re going to improve adolescent nutrition. So, the yellow blob
really is about the fact that…that young people actually know that they need to be eating well
and looking after themselves and sleeping and exercising. This is not news to them. They know.
But the thing is, they operate through their own agenda and to a set of their own constraints. So,
these three colored blobs underneath represent the major…the major parts of the agenda that
they work to. So, I do what others do. I need…I need to meet my needs for relatedness.
I need to relate to my…to my peers. It’s very important to me. I want healthy to fit into
my life. I need to be…it needs to be…part of my general confidence. It has to be not a separate
thing. It has to work with everything else I do. And this is my life. I need to be a [inaudible].
I need to make my own decisions. So, autonomy, competence, and relatedness,
three factors which actually overlay…very nicely the theory of self-determination,
are the basic needs that young people are trying to meet when we’re trying to persuade them to
eat well and look after themselves. And this is a lovely piece of work done by my colleague, Sarah
Shaw, who looks at the impact of the food…because it’s a joint impact, it’s a social environment,
young people hanging out with their friends, and the food environment where they
shopped for independent…and made independent food choices where they went to restaurants,
and how these two environmental factors that kind of…one of those layers of the
rainbow interacted with those individual psychological basic needs that young people
have to produce their food choices. And she…she identified and tested these…these
factors, not just in qualitative but also then in quantitative surveys. And she’s done some very
interesting work following young people in real time looking at the choices that they’re making.
So, other work we’ve done with young people, where that first…very first quote I showed
you came from, is with young pregnant women. Very young mothers. And some years ago, again,
we conducted some work with 106 young women between the ages of…15 and 22,
who were interviewed by not us, because we decided very early on there was no way a bunch of
middle-class academics were going to get anywhere near the really quite disenfranchised group of
young pregnant women that we…we wanted to talk to. So, we hired a…a social enterprise to do
the interviewing for us. And they were incredibly effective. Interviewing 106 young pregnant women
in Southampton…in a very short space of time was a phenomenal thing. So, top tip for anyone who
wants to do research with communities that are quite often ignored: Get someone else to do your
talking for you, from a part of the community. Okay. So, what we learned about these young women
and their eating habits was that they fell into three kinds of groups, really. There were those
who were trying really hard. They were eating really regularly, who had…and who managed to
hang on to their aspirations for themselves and their future. And these were young women
who were making the link between what they were eating and the baby they were carrying.
We had some young women in this group who knew things weren’t getting quite right but really
wanted to eat better and eat more. And they had relationships with their midwives, and they had,
again, some aspirations for a healthy baby, and, again, were making the baby–diet link.
And then we had another group, a third group of young women, who were very disengaged,
who…really, their aspirations were very short term. They really weren’t thinking much about
what they put in their mouths and the way it was going to feed their baby, and they skipped a lot
of meals. So, we have these three women—these, sorry, three groups of young women. And the point
about these three groups is that actually, these individual differences, these group differences
between women, meant that they were going to vary very much in their engagement with the midwives
and the people who were there to support them. You can imagine that the engagement of the…the women
who were skipping meals, the skippers, was not going to be the same as the regular eaters. And
that’s, again, something we need to understand, is that one intervention doesn’t work for everybody.
You need to tailor the interventions, and you need to understand whom you are tailoring those
interventions and what is important for them before you can do that. So, this is a
rather wordy but rather lovely diagram that my colleague Sofia introduced…[inaudible] introduced
to us as…as part of this work that she was running, which really shows the intersect
between the views of the young mother and the midwives, whom we also interviewed,
who were working with these young women. And again, you can see the autonomy, competence,
and relatedness being really, really basic needs of the mother…the young mothers, and how important
it is for the midwives and the support that the young mothers were having to intersect
and to meet these basic needs that we needed to understand before we could actually design any
kind of service which was likely to support their nutrition. And I am more than happy to talk about
any of this later, but I’m going to skip on in the interest of time. So, how do we actually realize
these improvements in multigenerational health through investment in adolescence? And here are
a few quotes from the Lancet series on adolescent nutrition, and very nicely
phrased by George Patton, who sadly died last year or earlier this year, very shockingly.
He was a…a friend and a wonderful advocate for adolescent health and nutrition, and
the world of adolescent researchers will miss him greatly. But the important things about…about what
I put on this slide is really that the programs that we offer, they have to be intersectional. So,
I know we want to improve diet. But what…what the…this review was saying is that having looked
at all the evidence, we’re not going to improve young people’s diet if we just focus on health
services or nutritional services. They need to be intersectoral. They need to work with educational
settings, they need to work with the social care, they need to work, yes, with health services.
And…but they also need to work with food retailers and with local communities and, to some extent, in
domestic households. We…nutrition is…is, as we all heard yesterday, as we all commented yesterday,
is such a complex…diet is such a complex behavior and constrained by so many things that we really
need to address all of those things. We can’t just zone in. We need to be cognizant first.
And following that, logically, the most effective policies will therefore have to stretch beyond
health and nutrition. They’ll have to take in the departments of education, the departments
of business, all the government…across government—certainly in the U.K.,
across government—departments in order to actually improve the end point,
which is adolescent nutrition, particularly, as it says here, with adolescents who are the most
socioeconomic disadvantaged…advantaged. So, for the next question that we were asked to consider:
What’s the biggest scientific challenge? And I’m nearing the end of my talk now. So, for me,
aside from, “How on earth do we work with young people effectively?” which I think I’ve already
covered, it’s about finding a way of generating the high-quality evidence of effectiveness that
we need of interventions, and it’s—I’m all about interventions, as you’ve probably gathered—that
doesn’t involve our current trial processes, which are—as we talked [inaudible] go there—are large
sledgehammers cracking nuts, and we don’t ever get the response or the results that we want because
we just have the wrong methodology. At the moment, we are running big public health trials to look at
things like a…a…programs that address adolescent nutrition and finding…nothing particularly useful
at the end of it of…you know, effect size at the end of these things is…is, for public health
trials, fairly unhelpful. We need to find better, effective methods…methods of doing that. So,
that’s my…my big plea and my big beef, and it has been for some time. And the other thing
is something that Sonia introduced yesterday, is we need to include the full and diverse range of
participants in our trial. There is a shameful…a shameful history of all of us working with those
who are most keen to work with us as our research participants, which excludes all the people that
we really should be working with, the people who are most disenfranchised, most distrustful,
and most in need of support and help. And I think that that it’s more than high time that we address
that. So, to find ways of reaching the not so much hard to reach as the easy to ignore, as my
lovely colleague always puts it, that, again, is our biggest…I think, one of our biggest kinds of
challenges. And I’m going to finish now just by acknowledging all the amazing families and
awesome young people that we spoke to and who shared their thoughts and their time with us;
and all my amazing colleagues who…I can’t begin to tell you what a fantastic bunch of people I
work with in the U.K. and have done this for some years; and our funders, who put up with
me and my endless ranting about the things that I care about. Thank you very much.
[Applause]
DR. KRISTA ZANETTI: Thank you, Dr. Barker,
for a…it’s your choice. I think you’re, you’re welcome to stay there—
since you’re going to be the only one answering questions.
DR. MARY BARKER: Okay.
DR. KRISTA ZANETTI: And so, we thank you for an engaging presentation. And we will now take
questions. Again, those attending virtually, please share any questions you have in the
Q&A box. And for those in the room please raise your physical hand, and we’ll do our best to get
to as many questions as we can. So, we do have an online question, so I think we’re going to
start with our…our…our virtual participants this morning. Turn it over to Dr. Mitchell.
DR. MONTESSA MITCHELL: All right. Our first question starts off with:
“My close family member is a single mom of three kids, and I was struck by how heavily she relied
on screen time and snack foods to manage the kids’ behavior. She actually threatened
them with fruit as a snack if they didn’t behave. Do you find that parenting resources
and skills are a widespread issue potentially contributing to the overall diets of families?”
DR. MARY BARKER: That’s obviously a really good and very important question.
I mean, the things that strike me about that question are that this is a single parent of
three small children, and that woman, I suspect, if she’s anything like any of the other single
parents I know, spends a lot of time just getting by, just doing what she has to and dealing with
the things that are the most important things she has to deal with. She has to keep her kids
safe. She has to keep her kids fed. She has to go to work, presumably. She has to do all
those things that she has to do. Probably screen time, kinds of snacks they’re eating,
come about 150th on her list of really important things to think about. So…so,
I hesitate to dismiss this, and I’m not dismissing this question at all. And of course,
parenting skills are really important. But for me, maybe we could look about in terms
of parenting support. And I think the support we give young families in Western society,
which is really the [inaudible] about, is lamentable. And I think if we really,
really want to address things like the major crisis in mental health there is at the moment,
we need to support young families much, much better. And we don’t, at the moment. And the
wraparound support for single parents is just nonexistent. It just…it doesn’t exist. So,
I would hesitate to put this on the woman and say her parenting skills were lacking and point more
to the fact that we as a society and a community do not support young parents to do the…to do what
we all want them to do. To do, frankly, what they would like to do, too. And I would like
to put that back out onto us, really, our society to have a think about how we spend our resources,
and maybe redirect some of our resources towards…to more of our resources towards
developing systems which support young families, rather than blame them for being bad parents.
DR. MONTESSA MITCHELL: I’m sorry. Joe?
AUDIENCE MEMBER (JOE): That, that was a great talk. And…and I really appreciate the model you showed about how our
diet is influenced by these multilevel factors. And I…and I wonder if you have any thoughts about
whether we need to incorporate artificial intelligence into there, thinking about how food
apps and how AI is being incorporated in decisions around welfare for families. And…and just…there’s
a lot of ways that AI is going to creep into our lives in the next…you know, probably not even
decades, years, you know. And I think it could influence how, you know, some of these things
that are related to diet. And whether you and your colleagues have thought about that at all.
DR. MARY BARKER: That’s an…an amazing question, Joe. And the short answer is: No, I haven’t
thought about it at all. But I would love to hear what you think about it. I mean, how is it going
to affect…how is it going to affect the…the…the way that we feed people or the way that we—
AUDIENCE MEMBER (JOE): I mean, the thing I think about is, like, we’re…most of us…I’m,
I’m looking around. A lot of us have these fitness watches or activity tracking. You know,
people are using, you know, calorie counting apps or other diet apps. And, like, you know,
you get to the point where your watch, you know, your iPhone tells you, “You know,
you haven’t eaten blueberries in a while, so you should eat some blueberries.” Right? And
so how much of it’s going to be our choice versus the app’s choice or the, you know…?
DR. MARY BARKER: That’s, well, that’s interesting. Now you’ve honed it down onto apps. I do have,
of course, apps…views on apps and watches. They are used by a select few and almost
always by people who don’t really need the nutritional advice because they’re
probably just fine. So, actually, the people that we’re talking about who
really are needy probably don’t use the apps or the watches. And I think
people like me who use apps and watches—and people like you, presumably—we’re fine just as we are.
And actually, I’m not going to worry about us too much. I’m much, much more bothered about people
who don’t use that…have that kind of access to AI. What I thought you were going to talk about
is actually the way that maybe the kind of food marketing and food retailers work, which I am
sure there must be AI involved in the algorithms they use, or there must be algorithms they use
for supplying different areas of the country and different shops with different food. We know that
the convenience stores, for example, you know, are very clever at meeting the needs of the local…or
the demand from the local populations. And therefore, constrain access to…to—
AUDIENCE MEMBER (JOE): Well, and…and I don’t mean to dominate the conversation. I think
the last question plays into that with the mom who’s talking about, you know,
her kids on screen time. You know, it’s the, you know, the advertising that they’re exposed to—
in those apps, as well, might be targeted towards them—
DR. MARY BARKER: Yep.
AUDIENCE MEMBER (JOE): —in certain ways around their eating choices.
DR. MARY BARKER: I think there is a criminal, criminal lack of attention to the…to the way food
is marketed to children. But I think…I’d like to think…certainly in the U.K., there’s been certain
push to legislate and to…to limit the amount of food marketing to children. But it’s been
pushed backed by our glorious government often. Sorry. Don’t let me get political.
DR. ASHLEY VARGAS: So, this is a tremendous talk, and it really reminded me of all the things when
I was growing up when we didn’t have a lot of resources, and now I’m a different place. So,
thank you for, I think, bringing it back to the human. I’m wondering, as…as a biologist,
this sort of stuff seems like we can’t fix it. Like, this is just too hard to fix. All of these
limitations that people have to deal with. It’s so much easier to think about the mechanisms
and the biology and what gene is interacting with what gene. And that’s hard to know. I
wondered if you had an example where…where an intervention was successful. Because you kind
of hinted at public health interventions being difficult and challenging. And I know it’s hard
to…to…to work with the populations that we really need to work with. But is there a silver lining
or a glimmer of something that you…you have seen work or a model that you have seen work?
DR. MARY BARKER: That’s a really good question. Yes, there are. There are models. And there
are…we know there are—at a policy level, a structural level—there are things that we
know that work. Like unconditional financial benefits. We know they raise people’s health
standards and…and…improve their lives. But we don’t offer them. We know that things
like what we call Sure Start in the U.K., we know that…so, this is a bit like your Healthy Start,
very well organized. We know that the families who have a lot of engagement with Sure Start do…do so
much better. The Family Nurse Partnership, for example, that’s…or the Nurse-Family
Partnership, I think you call it here. That’s been incredibly successful long term in preventing the
children born to…to mothers who live in very difficult circumstances being sucked back into
kind of repeat cycles of deprivation. There are structural interventions which we know work. Now,
they’re a long, long way from the biology. I’m very sorry. But actually, they are…the structural
ones seem to be the interventions that work. The individual-level interventions are much,
much harder to…to…to get right. There are…and I’m talking public health here. I think if you
then hone down on particular populations who have particular clinical needs, we’re much better at
designing effective interventions and working with those groups effectively. But that’s because—in
my view—because they already have a fundamental motivation to engage. You have diabetes,
you’re much more likely to engage. You’re still not very likely to engage, but you’re much more
likely to engage than you are…when you’re a young person, you’re going to live forever,
you’re fine. Why would you engage in public health intervention? Because you’re fine. So…so
it comes down in…in terms of individual-level interventions and behavioral intervention, it
comes down to a kind of…an existing motivational state, and we know that, too. Yes, there are
glimmers of hope. But I don’t know where the biology fits into that. Sorry. That’s your job.
DR. KRISTA ZANETTI: I’m going to piggy…I’m going to piggyback really quickly off Ashley’s question.
We do have an online question, then we’ll get to you, Drew, so we have a plan. Piggybacking off
of Ashley’s question, thinking about this from the perspective of what scientific questions we should
be asking…so, going back to thinking about a path forward or strategies to improve the ability for
those people facing these constraints and their ability to focus on healthy diet and nutrition,
what do we think are scientific questions we should be asking to further explore how
to address these issues? Because I think a lot of what we’re trying to think about today is:
What are the questions we need to be asking, and how are we going to address these challenges? So,
do you have any thoughts on, you know, maybe what…what we need to ask or what
has been asked? And…and you had mentioned some other studies that, you know, maybe needs to
be redesigned as far as adolescents. It’s sort of two different things. But it…it brings me back to:
What are those key scientific questions we need to be asking to help address these
issues and individuals that are facing these constraints that seem to be over…overwhelming?
DR. MARY BARKER: So, most of my thinking about, you know, how we get this right is…is
about adolescents. And I do think adolescents are a really, really important population for
us to focus on as a scientific community because the…the potential there is so huge. So, when I’m
thinking…when we’re thinking about adolescents and we’re working with doing a particularly
interesting piece of work at the moment looking at the intersect between culture and cultural
experience. Not…not…not…it’s kind of arts and culture, rather than…creative culture rather than
any other…definition of culture. And it’s taken us down a road of thinking very much about how we
engage young people in thinking about their diet and their health and their well-being generally.
And what we have found based on two very interesting published papers, which looked
at great big cohorts very long-running cohorts—and I can find both of those papers
if anyone’s interested—is that actually, if you raise young people’s aspirations for themselves,
general aspirations, you know, “What do you want to do when you grow up?” kind of questions,
“How can we support to…to…to achieve that?” If you do that, then health benefits follow. And we know
this because raising young people’s aspirations is associated…or young people’s aspirations are
associated in observational studies, longitudinal studies, with better health and well-being long
term; better…better life satisfaction as adults, as middle-aged adults; and longevity. So…so,
the thinking that we’re doing at the moment is (a) what’s…how does that work? So, if you raise
young people’s aspirations, it seems to kind of dawn on them that actually…well, in fact, they
know. If you have these conversations with young people—and we’re working on methods of having
those conversations effectively at the moment—is it dawns on them that, actually, they have to
learn to eat properly, they have to…they have to look after themselves, they have to exercise,
they have to eat well in order to achieve those things that they want to achieve. So,
so the…the…and this is a long ways from diet and nutrition, but if you can work with educational
establishments, if you can work with cultural establishments, if you can work across the board,
as we said, with young people to raise their aspirations, then you may well have a fighting
chance of improving their diet, their health, their mental health, their general well-being.
And…and it’s about…perhaps the big scientific challenge for us, then, is how do we raise young
people’s aspirations? And I go…I go back to that adolescent nutrition paper in the Lancet, the…the
policy programs paper, which said these approaches have to be intersectional. Now, you sat here in…in
NIH are in a very good position to pull those intersectional levers. And it strikes me that
very few other organizations or institutions can do that in the way that you can. So, over to you.
DR. MONTESSA MITCHELL: All right. first,
you did get a kudos in the Q&A for your first response. They said, “Excellent response.”
And your second question is: How have you explored the impact of social determinants of health on
young mothers’ eating habits, specifically the impact of types of jobs and time for eating?
DR. MARY BARKER: Well, that’s another really, really good question. We’ve explored those
things qualitatively and quantitatively to some extent. And the…and the…the
slide that I showed…go back to it. Don’t know where it went. I actually managed to mess
up…which is the one that I wanted? This one. I don’t know how I get it back on display now.
That’s right. That one. So, that was part of an exploration of all the things that
we thought might affect young…young women’s diets and ability to feed themselves. So…so,
we did ask them in the big survey that we did with, with 372 young women with families,
about whether they work and whether they didn’t work, and about how time was an issue. And the
interesting thing about time, and it comes up when you have…in all the discussions that we’ve had,
both in the interviews and in the policy work, is that time is a kind of…everybody doesn’t
have enough time. And time is a sort of proxy for how important this is to you. Because, actually,
all of us find time for things that are really, really important to us. And I think we just come
back to the point that having…not having time to cook is probably more to do with the fact
that other things are more important, like the fact that you have to run two jobs or like the
fact that actually you…you…you scoot in on your heels to pick up your kids from school to get them
home. They’re starving. You feed them whatever you can as fast as possible because otherwise
you get earache. So…so, time is a funny thing, and it’s the first thing that we all say that
we don’t have, we don’t have access to. But very often, it’s a…it’s a relative
response to…to what it is. So, it’s more about…if we’re going to then work with families,
it’s more about working with their priorities. So, what are your priorities? What do you have
to do first? How could we support you so that you can find time to do this cooking that you want to
do? And…and having those conversations. And we have developed a…a very good method of having
conversations with large numbers of people, which I can talk about later, to support them
to make those changes. Does that answer the question? Good. Drew had a question for us.
DR. KRISTA ZANETTI: Yes, Drew. I think we have time for one more.
AUDIENCE MEMBER (DREW): Yes. And this is more of a…more of a comment than
a question. And…and first of all, Mary, thank you. This is—
AUDIENCE MEMBER (DREW): —super important. And…and to follow on what Ashley mentioned
and…and what you had talked about, there was…schools are another venue where…where
there is opportunity for…for interventions in the…in the…nutrition space. And that’s…and…and
that became quite evident during COVID when…when kids lost access to school.
DR. MARY BARKER: Yeah.
AUDIENCE MEMBER (DREW): And I…what I…what I really appreciate about…about your…your lens, Mary, is
we…we spent a lot of time yesterday really focused on the…on…on the early part of the first 1,000
days, and that’s super important. But that…those next 1,000 weeks, or 7,000 days, you know, into
adolescence, you know, is also, as you mentioned, incredibly important. And that’s…and that’s often
a gap of when we think about longitudinal research and think…and think about cohorts,
we often focus on…on the parents and the children, but…but not…not the…not the children as they
grow up. And so, I think it’s…it’s…as…as we think about, you know, moving…moving the field forward,
you know, that…that…that adolescent…that early childhood/adolescent period is extraordinarily
important. And that’s often a group of individuals that…that gets lost in…in the research space.
DR. MARY BARKER: It absolutely does. And thank you for bringing that up. And I meant to say that
earlier, is that we have ignored adolescents for a very long time. We’ve…in…in the research field,
we kind of just assume that they’re kind of big kids or small adults. And they’re not. There…there
is a distinct and discrete life course phase. It has its very own developmental trajectory.
Astonishing things happen physiologically and psychologically during adolescence. You know,
their brains basically melt and get completely reformed. And, sorry, somebody once quoted me
that…on that, and I felt mortified that I’d actually said that, so, please don’t ever quote
me. Melting brains. I just lose all my kudos as a psychologist if I go on saying that.
But I think…I think, you know, the opportunity…it’s…it’s the…it’s the second critical
life course phase, which we have paid almost no attention to. And I can’t quite understand why,
except that a lot of people find adolescents quite scary and difficult to deal with.
Yeah, they are, but, you know, it’s fun. Does that answer? Okay. Thank you.
DR. KRISTA ZANETTI: Well, I think for…to keep us on time, even though I…I’m sure
there are…there’s much more to discuss, that was really a, you know, an excellent presentation and
great discussion. So, I want to thank everybody who contributed to the discussion and thank Dr.
Barker for her thoughtful feedback and a great talk. And you set the stage quite nicely for
our day two presentations and discussions that are going to focus on nutritional influences
beyond individuals. So, we’re looking forward to the rest of the day. So, having said that,
I am going to turn it over to our third session, to Dr. Somdat Mahabir from the
National Cancer Institute. Oh, yes. Sorry. Let’s give Dr. Barker a round of applause.
And I will now turn it over to Dr. Somdat Mahabir from the National Cancer Institute
to introduce the next session and our speakers. And…and thank you all.
DR. SOMDAT MAHABIR: Good morning, again. Thank you very much, Krista. That was a great session.
I think most of us could…can relate to the things that were said there. In fact, most people.
So, welcome to session three. And this session is on family and society-level aspects of
multigenerational influence of nutrition. And I am Somdat from the National Cancer Institute. I’ll
be your moderator for this session. I’m also a member of the planning committee, and I’m
really happy the way how this meeting has kind of turned out and look forward to all the sessions.
Also like to thank Dr. Kellie Casavale from FDA who has been assisting me here. She will
be serving as my copilot. Hopefully, we’ll run the session smoothly. So,
Dr. Merilee Brockaway will begin the session and join us virtually from the University of Calgary,
with a presentation on maternal health, delivery method, and lactation-related influences.
The rest of her session will be presented from right here in the room, at the NIH campus that
we’re in here, in this room. And Dr. Kristen Stowers from the University of Connecticut
will be present on food, environment, and environmental justice. Very interesting
topic. Then we’ll move onto Dr. Joseph Brown from Brown University School of Public Health.
And his presentation will be on food contaminants that have multigenerational
effects and nutrition-related outcomes. Last but not least, we’ll then listen to Dr. Carrie
Breton from the Keck School of Medicine of the University of Southern California,
and she’ll present on the effects of the built environment on multigenerational nutrition-related
health and disease. So, I will now turn it over to Dr. Brockaway to get us started.
DR. MERILEE (MEREDITH) BROCKWAY: Thank you very much. Can everyone see my presentation screen? All
right. Well, I want to thank you for inviting me to present. Thank you to Ashley and Krista,
and I want to highlight that I’m going to be talking about maternal health, delivery,
but really centered around lactation and that impact it has on infant health and long term
health outcomes. So, I do want to acknowledge that I do have some funding and thank my funders,
but none of my funding is in conflict with what I’m presenting today. Also, coming from Calgary,
it is our tradition in Canada to acknowledge the traditional territories from which we come. So,
here in Calgary is the traditional territories of the people of Treaty 7 region, in southern
Alberta, and the city of Calgary is also home to the Métis Nation of Alberta, Region 3. And
we thank our traditional peoples for their…for their lens. So what we’re going to discuss today
is we’re going to discuss how breastfeeding and human milk feeding impact child health outcomes.
We’re going to explore maternal factors in human milk and how human milk composition and breastmilk
production are informed by those. We’re going to explore the impact of labor and delivery
on breastfeeding and the microbiome. We’re going to explore breastfeeding supplementation options
because we know not all infants can breastfeed. And then we’re going to talk about the challenges
and opportunities in lactation and breastfeeding research. So, I think we’re all familiar with the
World Health Organization recommendations and many health organization recommendations about
breastfeeding exclusivity for the first 6 months of life, and then continued and
sustained breastfeeding for 2 years and beyond. And likely you’re all familiar with the hierarchy
of evidence, but when we overlay that with the child health benefits related to breastfeeding,
we can see that there’s varied evidence…levels of evidence for how breastfeeding relates to child
health outcomes. So we have strong evidence for things like necrotising enterocolitis
in pre-term infants, ear infections, respiratory infections, and GI infections.
Those are systematic reviews. We’ve actually got systematic reviews of systematic reviews
on that. And then medium-level evidence where we may have a few systematic reviews not quite
so many studies or clear associations between things like asthma and allergies, SIDS, obesity,
things like that and breastfeeding. And then much weaker evidence looking at cognitive development,
type II diabetes, and metabolic issues, and dental carries with breastfeeding. And I’ve just taken
the liberty of moving asthma and allergy…allergy into the medium levels of evidence because we’re
starting to see quite a good…bit more good evidence come out supporting the relationship
with breastfeeding, and I’m going to talk about that later. But we do have to be careful that
historically our information and our evidence around breastfeeding is pretty much based on
observational data, clearly because it’s hard to do experimental research in human populations.
But we have started to see some very good research come out about breastfeeding,
and one example I’m going to highlight here is the child study out of Canada. There’s other
cohort studies similar across the world. But for us in our context, the child study, it’s a large
cohort study, of about 3,000 families. It was one of the first studies to actually ask good
questions about breastfeeding and then look at biological outcomes such as stool samples,
blood draws, things like that, and start to look at mechanistic effects.
So, what they really have sought out—and part of this child program—is looking at how breastfeeding
relates to those health outcomes that we have seen with the levels of evidence and trying to identify
mechanisms of how breastfeeding and breastmilk can form those outcomes. Things like gut microbiota,
epigenetics, metabolism, lung function, immunity—things we heard about yesterday.
And a lot of that clearly comes from milk composition. So what’s in the milk? The
microbiota, the human milk oligosaccharides, immune factors, fatty acids, hormones,
and vitamins, and how those impact the mechanisms of child health. But of course, we have a pretty
good understanding that maternal health, both physically, mentally, and socially, do impact milk
composition and…and subsequently those mechanisms. And we have modifiable health issues…aspects like
obesity, nutrition and then…confidence and lifestyle choices. And then we have fixed
aspects that can inform milk composition, like age, genetics, ethnicity. And also,
those do also inform biologically infant health outcomes and successfully the breastfeeding that
can—if mom is successful with breastfeeding—and can sustain it for as long as possible. So when
we compare human milk composition or breastmilk composition to formula, we can see—and I have two
different descriptions here…or pictures—we can see formula originally was created as a nutritional
replacement. So the macro…micronutrients of breastmilk, back when we didn’t have a very
good understanding of all the different components in breastmilk. But now we know breastmilk has a
variety of biotic components, it’s got immuno components, it’s got hormones and vitamins,
and things we’re really trying to work hard now to replicate in different formula products. And so,
as we start to produce different formula products that have these different components, we’re very
interested now in looking at breastmilk to see what is in breastmilk and…and how we can study it.
So, with that in mind, in our postdoc lab—I did a postdoc with Dr. Meghan Azad out of the University
Manitoba—we asked the question: how does human milk composition inform child growth? And I have
to tell you, this was an overly ambitious question. We conducted a systematic review
and ended up reviewing almost 10,000 abstracts for screening and ended up with three distinct
manuscripts, one of which has been published—it’s up here—looking at micronutrients. So we had 28
articles looking at micronutrients, 57 looking at macronutrients, and 75 looking at bioactives.
So I’m not really going to talk about the results we found because actually, in a lot
of situations we struggled to identify consistent associations between many human milk components,
specifically the bioactives, and infant growth. And that’s because we found that over…over 85
percent of those studies really struggled with quality. They were either moderate or low quality.
And a lot of that was really…really related to failing to adequately account for confounding,
specifically breastfeeding exclusivity and maternal factors that inform human
milk composition. So those are two very important aspects of breastfeeding and human lactation that
really were missed by a lot of studies exploring human milk composition and in…infant growth.
So with that, I want to move onto talking about maternal
factors that play a role in human milk composition but also in breastfeeding.
So, I think it became apparent from Dr. Barker’s presentation that nutrition is complex, there’s
lots of different social influences, and that is also true with breastfeeding. So breastfeeding is
a complex interplay between mother and infant and the environment. And Dr. Lars Bode has posed it as
kind of a triadic relationship, not only between mother and infant and…but also the human milk. So,
it’s kind of a triadic relationship. But there’s also other things to consider,
such as environmental influences. So, what mom is exposed to can influence milk composition.
Social influences can influence how successful mom is with breastfeeding,
perceived milk insufficiency, or if they choose to continue breastfeeding long term or exclusively.
And then, of course, economic influences. We consistently see in the literature that
mothers who are of higher socio-economic status tend to be more successful with breastfeeding.
And then cultural influences, as well. When you look across countries globally, we see
much different breastfeeding rates. The UK, for example, has very low breastfeeding rates. Canada,
we have quite high. And the U.S. is in the…the 80s for initiation. So, really culture has a big
role to play on that. But when we think about the direct effects of maternal health on breastfeeding
behaviors, human milk production, and composition, we have limited evidence. So, with nutrition it
would…you would think that what mom eats would directly impact the milk composition, but that’s
not necessarily true. In fact, we only have pretty strong evidence looking at fatty acids,
such as fish composition. That does improve DHA in human milk composition. Vitamin C is another one.
And I’ve just highlighted one study that looks at fructose, because we have a lot more fructose in
our diet, and actually, fructose transports right into the breastmilk, and we do see quite high
fructose levels in breastmilk, so that’s something that’s interesting. Obesity is another issue that
interplays with human milk composition but also with breastfeeding. So we know that mothers who
are obese tend to have issues with lactogenesis, so they have delayed milk production and often
tend to supplement a lot more than mothers who are not obese. We also have seen some evidence that
there’s higher fat concentrations and higher lactose concentrations in their breastmilk.
Mothers who have endocrine issues such as diabetes, thyroid, or polycystic ovarian syndrome,
really struggle with lactogenesis. So if those are untreated or not managed well, we see that
these mothers tend to supplement or struggle with breastfeeding, and so their babies tend to get
less breastmilk. We’ve also done some research looking at mothers who have chronic illness, and
if their symptoms aren’t well managed, they tend to stop breastfeeding a lot earlier than mothers
who don’t have chronic illness, and they also are less likely to exclusively breastfeed. So we see
some challenges there. And then mental health is an interesting one and a hard conundrum to nail
down because we see that moms with mood disorders, such as depression, are less likely to breastfeed.
But we’re not sure which to really…way that relationship goes. We don’t know if breastfeeding
leads to lower…or…sorry, if breastfeeding leads to reduced depression, or if depression leads to
reduced breastfeeding. So we’re not sure if…if the chicken comes before the egg on that one.
And then the social environment, of course. So breastfeeding success is very contingent
on the social surroundings. So, if mothers are surrounded by mothers and aunties and sisters
that have breastfed, they’re likely more…more likely to continue to breastfeed and be more
successful compared to mothers who are not surrounded by those who breastfeed.
So thinking about…going forward about the impacts of labor and delivery, the impacts on mom and baby
and breastfeeding success, but also, I’m going to thread that into the microbiome,
because a lot of my work looks at the microbiome and infant health. So we learned yesterday, and
I’m sure all of you are aware, that the microbiome is very important for developing infant health.
There’s that critical window of about 1,000 days from conception to 2 years of age, whereas if we
have a dysbiotic microbiome, we’re going to see likely some adverse childhood health outcomes
as opposed to if we have a eubiotic or a good microbiome. And we all know early life exposures
can really inform that microbiome. But also, we have to understand that the experience of birth
in hospital can inform breastfeeding outcomes as well. So if breastfeeding is successful. So
this is kind of multifaceted. So I just want to highlight a typical birthing experience in North
America. It’s pretty similar to Canada in the United States, but I tried to make the numbers as
U.S.-centric as possible. So about 98% of births happen in hospital, and about 30% of those births
are born via C-section. So we know C-section deliveries are sterile, and we have a disruption
to the microbiome there. And you’ll see later, they’re also very disruptive to breastfeeding.
And then the antibiotic exposure piece. We have about 40% of infants who are exposed to
antibiotics in labor or early in life. So that’s through group B strep prophylaxis that’s possibly
due to premature prolonged rupture of membranes. If moms have a fever and if moms have a C-section,
we often give antibiotics prophylactically. So a lot of infants are exposed to antibiotics.
And then if we look at breastfeeding—so initiation rates, they vary a little bit,
but in Canada, they’re about 96%, and in the U.S. they’re 9…or 83%. But regardless of that,
we see that Caesarean-section babies get supplemented to a much higher extent than
babies who are born vaginally. And that makes sense, because a Caesarean-section, it’s major
abdominal surgery, mom’s had a lot of fluids on board, so there’s a lot of aspects that can
disrupt breastfeeding in the short term, which in turn turns to earlier cessation of breastfeeding
and less exclusive breastfeeding. So, we see that the C-section deliveries can significantly impact
the success of breastfeeding. But also, when you think about it from a microbiome perspective,
you can see that a lot of infants not only have one adverse exposure to their microbiome early in
life, but they can actually have multiple ones. So bringing this back to the context of human milk,
I just want to focus on that antibiotic exposure piece. And I just came back from a really great
microbiome conference where this paper was presented. Again, this is from the child study,
and it really is looking at Bifidobacterium longum subspecies infantis. And this
microbio…microbe came up multiple times during this conference. So, it’s really starting to show
evidence that this particular microbe, now that we can do that shallow shotgun deep sequencing, keeps
coming up as something that is related to good infant health outcomes. And this study found that
breastfeeding was protective of childhood asthma when infants were exposed to antibiotics. So, if
the infants were breastfeeding while they received antibiotics, they virtually had no increased risk
of asthma, but if they weren’t breastfeeding, they were three times more likely to develop asthma.
So, when they explored this from a microbiome perspective, they found it was really related
to that B-longum infantis, which clustered well with some various HMOs: the DFLNT, 3’SL. I’m not
going to read them all. But…so we were seeing some really nice activity that they consumed those HMOs
quite specifically. And we saw multiple studies come out and talk about this B-infantis being
quite a protective organism. The interesting thing is it’s starting to become a missing microbe.
So, in Canada, in several of our cohort studies, we only see this B-infantis in 14 to 16% of the
population of infants. And in the U.S., it’s less than 10%. However, when we look at non-Western
infants, it’s between 60 and 80%. So we’re starting to see that microbe disappear in
certain Western cultures. And if you think about the experiences with Caesarian-section birth,
with antibiotics exposure, and the disruptions we’ve had over generations of breastfeeding,
it is possible that those influences have cut down on the prevalence of this microbe.
So, when we consider the more…main factors around the establishment of the gut microbiome—so
antibiotics, mode of delivery, gestational age, and infant feeding—we have pretty good
evidence to show that human milk and breastmilk feeding can actually recover the microbiome,
be pre…protective against those long-term health effects. But it’s important to consider are we
losing important microbes from multigenerational overuse of antibiotics or lack of breastfeeding.
Some questions to…to consider is can we replenish these missing microbiomes and is evolution going
to compensate? We don’t know. So, it…it…this is quite an interesting, new, and very novel finding.
So, I want to move on to discuss…because we know that not all infants can breastfeed or
do breastfeed, and some mothers do struggle with breastfeeding. So, thinking about supplementation
options and how those compare to kind of the gold standard of direct breastfeeding. So when we look
at direct breastfeeding, we see that there’s lots of probiotic bacteria, prebiotics evident in human
milk oligosaccharides, but the skin-to-skin contact and the act of the infant latching
on the breast actually results in something called retrograde flow—an exchange of the oral microbiome
of the infant with the mammary glands—so you get that direct exchange of microbiome between mom and
infant. So, when we think about pumping breastmilk and serving it raw, we still have very similar
probiotic, macro and micronutrients, immunological factors, but we don’t get that exchange of the
microbiome between mom and infant, but still quite good as far as the other components. But
if we start to intervene with that milk and freeze it, then we start to reduce on the components and
they start to degrade. So, our probiotics start to die off. The prebiotics and postbiotics remain
relatively stable. We start to see a reduction in those immunological factors. Immunoglobulins are
pretty temperamental, so they do degrade quite quickly. And then, pasteurized donor human milk
is becoming more common and more prevalent. And it’s a very good alternative to breastfeeding when
moms can’t breastfeed, but we do see with the processing of pasteurization—the freeze-thaws,
the tube…moving the milk through the tubes, and the pasteurization process—we have virtually no
probiotic activity, but our prebiotics and postbiotics remain relatively stable. Our
immunological factors drop considerably, and our macro and micronutrients do degrade a bit.
And then of course, formula. We have pretty good evidence to show that formula can be disruptive
to the microbiome. They’re starting to add in some pro- and prebiotic aspects, but again,
the evidence on that is pretty new and not well explored. And again, the immunological factors,
the responsiveness of human milk to the infant’s environment, we don’t get that with formula. And
the reason why I highlight those last two is that is my program of research—comparing
pasteurized donor human milk to formula milk when we have to supplement infants.
So, moving on to the two slides that everybody’s talked about throughout this conference, is what
is the biggest scientific challenge that needs to be addressed? And for me, it’s that quality of
breastfeeding evidence. We’ve historically under researched and under reported breastfeeding. We
haven’t done a good job assessing breastfeeding, or, when we’re doing house research, we don’t
account for breastfeeding. So, we don’t even think to ask about it. And actually,
this is really interesting, and it’s surprising to a lot of people. We don’t have a consistent,
well-validated infant feeding assessment tool. Most of us use the World Health Organization,
or Miriam Labbok’s work on…of assessing breastfeeding, but we all ask the questions
a little bit differently. So we really need to come up with a consistent and well-validated
infant feeding tool we can use across studies. And then again, a lot of studies…the majority of
studies really don’t look at that confounding…or potential confounding, such as maternal factors or
that…looking at the environmental aspects that can influence breastfeeding as well. And then this is
a really tough one, because human studies are hard to do experimentally with breastfeeding research.
But with the increased availability of donor milk, we are able to do randomized control trials. Donor
milk is not as good as, like, raw breastmilk, but we can still look at that human milk,
exclusive human milk diet. But because we’re dealing with this experimental design barrier,
we still deal with a lot of skepticism about the evidence of breastfeeding in the clinical
environment. So, the big piece I want to nail home there is that our challenge right now is still
that quality of evidence. So moving forward, what do we have to look forward to? There is
definitely increased momentum and a shift that is value…valuing the importance of human milk
and breastfeeding on infant and maternal health outcomes. We’re starting to see some prominent
human milk and breastfeeding scientists emerge. There’s the International Human Milk Institute
down at UC San Diego—and I saw Drew down there in April—so that’s a really, really exciting
development. And we’re also starting to see increasing priority around women’s health. So
more funding for research in this really important area. That being said, we really need to balance
our biomedical research with a…a humanistic lens so that we adequately incorp…adequately
incorporate the role of mothers and how they can influence lactation and breastfeeding science.
And the other thing is, is we tend to look at human milk singularly, rather than as a
contingent of a larger group or a network of components that work together. So long term,
we have some really amazing technology right now that we can get in, deeply phenotype the…the
different biological measures that we’re looking at, especially with the microbiome. And looking
at these longitudinal studies and getting deeper and deeper, as that one study of the child did, to
see…you know, it’s these particular bugs that are really important or these particular metabolites
that are really important over a series of repeated assessments. So our…really working
down into that deep phenotyping and then bringing it back to the larger, kind of, picture. And then,
this is one of Meghan Azad’s, kind of, soapboxes, but really using machine learning to develop a
complex, interactive system of understanding human milk as it works as a network, rather
than those individual pieces, and then how that interplays with breastfeeding and health outcomes.
So with that, I want to thank you for the opportunity to give you this firehose of
information about human milk and lactation. And I’ll pass it on to the next speaker.
DR. SOMDAT MAHABIR: Thank you. Thank you very much.
In the interest of time, we’ll move right on to our next speaker, Dr. Stowers from the University
of Connecticut. As she’s going to get set up here, I just want to ask our speakers to please
keep track of time. One of the challenges, as you know, in moderating a session, which
is partially in and virtual is that we don’t have the opportunity to give them the clue to wrap up,
and they don’t really see the flashing red light as well. So, in some way, the speakers here are
kind of at disadvantage. But nevertheless, we look forward to hearing the next session.
DR. KRISTEN COOKSEY STOWERS: Good morning, everyone. I’m Kristen Cooksey Stowers. I’m
an assistant professor at UConn with the Rudd Center for Food Policy and now Health, it used
to be Obesity. And I just want to start with a huge thanks for the Office of Nutrition Research
for putting this event on and for inviting me. Yesterday, I learned so much and have learned
so much from the talks already. So, it’s truly a pleasure. Today, I’ll be presenting on advancing
nutrition and health equity via CDPR research on neighborhood food environments. I just wanted to
provide a brief overview of where I’ll go today. I want to level set with some language on defining
health equity. I wanted to give a brief overview of some important health equity health frameworks
that address food and nutrition. I provide some very quick, short examples of my own food swamp
research situated in health equity frameworks. I wanted to share a few tools and theoretical
frameworks from authentic community and resident engagement literature that I think folks in this
room would find particularly helpful, just as sort of an FYI for later. And then, of course,
as requested, I’ll end with the…directions. So, what is health equity? It’s a principle that’s
underlying or commitment to reduce and ultimately eliminate disparities in health and its social
determinants. So, I think what’s interesting is the terms health equity and health disparities
are often used inter…interchangeably. But they’re not quite synonymous. They’re related. But health
inequities or health disparity is rooted in social disadvantage. So, to improve health inequities,
we have to in…address social context. And I really love sharing this quote, that “If an effort does
not address poverty, discrimination, or their health-damaging consequences for groups of people
who have…who have historically been excluded or marginalized, it’s probably not a health
equity effort.” So it’s a little gut check that I like to also sort of anchor myself and my lab in.
Folks, now, we have seen this visual many times, I’ll just briefly address…what
I wanted to highlight here is that health equity research is about intentionality and meeting
people where they are. So, there’s often a bit of a…a…a tension between a quality framework that are
concerned with getting everything…every population the same thing regardless of outcome. Right? So,
I tend to look at these boxes here as resources, investments, funding. All of the resources and
things that we…we give in our space, sometimes we can be more concerned with making sure everyone
has the same thing, even if it doesn’t get us to the…the optimal health outcome, nutrition equity.
Equity is about meeting people where they are and giving that concentrated time, focus, research,
and investment to the populations that need it. Liberation of…of course, getting to a point in
society where we have no barriers to health. I…I think that, like, to look at the…picture as a
symbol of that. But we have this call to action, honestly, this reality of where we are now,
where we…where we continuously have research and focus on the same populations over and over,
where there are some populations that remain understudied and undersupported. Just briefly,
in…in health equity spaces, we have this “first do no harm” principle, so this idea that without
careful design and implementation, PSE strategies may inadvertently widen health inequities. So,
we may not…you know, we don’t want to do that. But every…every action and decision is a health
equity–related action and decision, whether we are intentional and thoughtful about it or not. So,
it behooves us to think…to leverage some of these theoretical frameworks and thoughtfulness that
have…about issues that…around social determinants that we don’t make matters worse.
So, this brings me to my first point of the day, which is: Health equity researchers and
multigenerational nutritional researchers need to talk. Health equity and social determinants of
health frameworks have limited multigenerational perspectives and vice…and vice-versa. These
frameworks are so rich in terms of understanding [inaudible] and history, and organizational
behaviors, and policy. But they should better integrate it in nutritional…multigenerational
nutrition research moving forward, if we truly want to tackle social resources and the causes
of the issue. So, one of my favorite frameworks in this space is the Sonar…Solar/Irwin model from the
World Health Organization. And they identified the social determinants of health as being the social,
economic, and political contexts. That’s going to be policy, government, and I think a crucial
one is cultural societal value. That’s one that we kind of can miss from time to time. Socioeconomic
position is just where we think about race and we think about intersectionality and citizenship
status. All of these aspects sort of drive a lot of what we see at the material…circumstance
level and intermediary determinant of…of level of health and…and so, this is where we finally
get to food availability. And all of these factors then drive health equity impacts and well-being.
This version…I’m sorry…it’s a bit cut off here. This version of the social determinants
of health framework I…I like a lot because it gives a head nod to the interconnectedness of
them. Right? Some of the versions sort of map them out all separately but they don’t talk to
each other. They have nothing to do with each other. But aren’t they the same population,
the same households, and in a lot of cases the same individuals? So, I think what this
does nicely is it makes us think about: What is that intersection between neighborhoods, food,
and transportation; and neighborhood, food, and race and identity; and neighborhood, food, and
the health care sector? It helps us to line up how we might finally get out of our silo…silo. What it
doesn’t do as clearly is to help us to think about…well, the…the topic of this conference,
time, generations. Right? So I think it…the information is there. [audio interference] So,
I also wanted to highlight fundamental cause theory—another really important theory that
we ground our…our health equity work in. Fundamental cause theory is this idea that
flexible resources, money, power, prestige, neighborhood context, social connectedness,
create and maintain the wicked health inequities that all of us are trying to address.
Social racism has…has been identified as one of those key root causes and cultural resources
that we need to pay attention to and incorporate in our research. Relatedly, racial residential
segregation is an environmental play space fundamental cause that is well documented as being
important for the nutrition equity and health equity. I’ll just briefly share this quote that I
think is helpful: “Neighborhoods bundle together beneficial or less than beneficial sets of
circumstances, such as the availability of helpful foods and good medical care. The importance
of neighborhoods and understanding racial differences in health is hard to overstate.”
So, this brings me to the “place, not race” paradigm that we talk a lot about in the
health equity idea. And this research suggests that it’s more so the racial disparities in…in
types of environments than the individual racial groups themselves or [inaudible]
the racial groups themselves. So, this is a study from Southwest Baltimore,
where they looked at integrated neighborhoods and what happened to the health outcomes and
the racial experience when…when it’s more sort of a level set. In this case, the disparities between
White and Black Americans in terms of obesity and diabetes…dissipate. So, when the environment is…is
comparable and we have integrated neighborhoods, then it…it…it is an advancement to health equity.
Another important study is the Moving to Opportunity study, which is…was led by the…the…the
Housing…the Department of Housing and Urban Development. In this study, over 4,000 mothers
with low income had the opportunity to move from a neighborhood with a high level of poverty to
one with a lower level of poverty. This is one of the most notable interventions and experiments on
improving extreme obesity and diabetes, and it wasn’t an obesity intervention at all. Right?
So this makes us…or at least by intent, right? And…but the…the mechanisms are not understood. So,
this gets…this gets me excited because this…this tells us that we should be paying attention to
policy, neighborhood context, right? For us, all…all of the interventions and changes in the
social context, we can consider interventions for multigenerational…understanding wealth
as a generational effect. Another study that I think is really important to flag here is one from
the PHRESH Study, which…which…it included a supermarket in a food desert. And what’s really
interesting about this is that there were, in fact, increases in improvements to diet
quality in the study, but they weren’t related to the supermarket at all. Right? Be…and…and
the research…documents that because the uptake of the supermarket wasn’t high enough for it to
really have translated to effect. What…what drove the improvements in diet quality were seeing the
neighborhood being revitalized…that…and that lowered stress and that improved neighborhood
satisfaction and then people felt better and they ate better. So, again, continuing this theme of we
need to keep our eyes on what may not commonly be perceived as nutrition interventions as absolutely
being related to what we do. So, this brings me to my second point:
More research on the multigenerational effects and drivers of food swamps is needed. So, these are
just some…some…some pictures from some newspaper articles that I’ve covered my work on food swamps.
And as you can see from the headlines, they’re really leaning to the equity-oriented aspects
of food environments, as well as their impacts on Black populations and Hispanic populations.
So, just to step…back a moment and define food swamps, a lot of folks are more familiar with
the term “food desert,” which are defined as areas that lack access to a supermarket.
I was at the USDA as an econ intern when the Food Desert Locator Map dropped, and I was like, wow!
This is amazing, these new terms. So, that’s what my lived experience was.
However, what the food desert measure and metaphor does not capture is everything else
in the built food environment. The intent is to map spatially access to supermarkets. It’s not
meant to demonstrate relative balance or sort of a more comprehensive assessment of equity between
food store types, like food swamp measures. So, a big…so one of the key things that I’ve
aimed to do in my work is to contribute to the measurement and identification of food
swamps to build upon food desert research…food desert research. These are both important.
Never have food swamps have been associated with obesity-related disparities among adults,
and I’m including some of my work. I published another paper in 2020 that shows that…that
food swamp exposure nationally was linked to…increased adverse diet outcomes—or habits,
rather—and that Black Americans were particularly at risk for this. Food swamps have been linked
to dietary habits among Black adults and teenage girls in Baltimore. Diabetes-related
hospitalization—so, not just diagnoses of…of prevalence, but being hospitalized for diabetes.
And then also they’ve been linked to differences in exterior…unhealthy
marketing at the restaurant level. And…and lastly, diet quality among preschoolers and foods served
within family childcare homes. So, that’s one of the studies that I’ll briefly share some details
about in a moment. Food swamps have also been linked to other neighborhood level disparities.
A little bit of…for example, residential segregation, and neighborhood blight and
housing vacancy. So, again, going back to that framework where we need to start to
think about the inter…interconnectedness of…of the social determinants of health.
Also, food swamps have been linked to neighborhood crime and social disorder.
So, one of the studies that I…that I published, and mentioned just…just now,
demonstrated that food swamps were a stronger predictor of obesity prevalence
and geographic disparity in obesity…obesity prevalence compared to food deserts. This is
a national sample of all counties in the U.S., and what we see is when we think about transportation
systems, where again, that interconnectedness, the food swamp effects was higher in areas
where the community was less mobile. So, where there was lower car…vehicle ownership or there
was less reliable public transport, the food swamp effects and obesity was much higher. So,
we can imagine…so, that tells us that the local environment, the walkable environment, is…in…that
surround folks’ home where they live, workplace, worship is really important to think about.
Having formatting issues here. A…a common argument or common concern in health equity
work is economic status and wealth inequality. These are common things we talk about. So,
I wanted to test how that played into these built environment disparities. And the results show that
regardless of wealth inequality measured by the Gini coefficient, the food…the food swamp
effect in obesity persists. So, that means that they’re both important. That means even
if we improve income and wealth inequality, that will not get us away from addressing the
built environment issues that we see. Here’s a study that was funded by NHLBI…excuse me.
The R01 parent grant for this study is…the PIs are Dr. Jiang and Patty Risica…my collaborators and
mentors on the grant, and they did a randomized control trial of family childcare homes,
and an improvement environment, the physical activity and food environments within those homes.
So, I added a secondary analysis to look at the built food environment surrounding those
homes to better understand what we saw them in…in, within the food…the family,
childcare homes, and ultimately what these young…the young kids consumed.
Just briefly about…in terms of the demographics, there were over 300 children enrolled or assessed
in this study. A very ethnically diverse sample of over 58% Hispanic. We think about
a lot about that…that…that combination or intersectionality of culture and race.
So, there was 16% Black in the…in the sample. But as you can see,
toddlers are spending a lot of time in family childcare homes, childcare centers in general.
But this warrants…this warrants additional attention, right? Because 73% of the children,
their parents reported that they are there 8 hours a day or more,
right? And 84% eat breakfast there, 97% eat lunch there, and 8% actually stay for dinner.
So, just briefly, a little bit more about the…the data set. The research team went in,
they observed the food environment within the family childcare home. They did place
weights. They watched what the kids ate, consumed, and then ATI scores were computed.
ATI 2015 scores were computed. The provider demographics come from the provider survey,
and the child demographics come from the parent survey. So, in terms of key findings, about 12% of
the family childcare homes were located in food deserts; 58% were located in food swamps. So,
again, it’s both/and, right? We have areas that are one or the other. They’re both.
They’re neither. There’s a term “food oasis” where they’re neither; 26% of the family childcare homes
were in high food crop–exposure areas. Meaning 67% to 88% of all food retail surrounding the
family childcare home were considered unhealthy. Fast food restaurant, the Brown Bag restaurant,
just outlets not serving majority healthy options. Higher neighborhood food swamp exposure
surrounding the family childcare home was related to the family childcare providers serving more
fried foods, including potatoes, higher-sugar, and high-fat foods, as well as low-fat…fat meat.
The lower diet…the child diet quality scores were also lower, and we looked at the…the
specific categories within the scores and saw there was more vegetable consumption for kids
that are in family childcare homes in food swamps and higher intake of saturated fats.
Another study that I wanted to briefly mention is one that my colleague at Harvard,
Dr. Juliana Cohen, graciously added me to…allowed me to add a follow-up study
to her K that was funded by NIDDK, where she was looking at quick-service restaurant environments
and then parent–child diet to see what they chose and consume within the quick-service restaurant.
By the neighborhood research, I say, “Oh, you know, I wonder, are there spatial differences
if your neighborhood environment primes you up for a certain level of behavior?” So,
we were able to collaborate and…and explore this a bit together. In terms of key methods
to keep in mind, just briefly, the…these are four quick-service restaurants in the New England area.
After sort of all…of the different caveats, the…the…the analytics sample of children was 149,
and as I said, these are…this is observational data, so the research team going into the
quick-service restaurant and watching what the parent–child diets do. In terms of key findings,
sugary drink consumption among children in QSR was just much higher than we expected, just
descriptively, right? So the line the…the line here of 25 is what the American Heart Association
recommends of 25 grams of sugar a day for a kid, and the blue dots are where the kids were in terms
of their…the sugar in their drinks, right? So, that’s a red flag for us to keep in mind.
The regression results interestingly found no difference though in neighborhood status. So,
they just were high in…in food service restaurants. It didn’t change by neighborhood
status. But importantly, Latinx children were more likely than non-Latinx children to consume sugary
drinks in a quick-service restaurant. Just to flag a cue…to…to flag a…a few key takeaways from this
study, is the children are more likely to acquire and consume sugary drinks and QSRs relative to
healthy alternatives. I think this work elevates some of the policy efforts that are around, like
healthier default for food service restaurants. And…but further investigation is needed when you
think about ethnic disparities in sugary drink consumption among young kids. So, briefly,
food for thought, how much should researchers rely on communities and residents to design
and implement studies examining multigenerational influences on nutrition-related health inequities?
Full alert, I’ll share what I think about this. We can absolutely better leverage CBPR
methods and authentic resident engagement tools to…I just spoke to it, right, yesterday. I’m
looking at Sonia, who looks at the stage grade from…yesterday, improving the recruitment and
retention of communities of color and other historically marginalized populations. So,
the methods can help us do that. And importantly, advance health equity in a sustainable, authentic
root cause–oriented way. This is just a website that I think for later…FYI, screenshot it please,
or…or whatever you do to keep notes. I’ve been working with Healthy Food Policy Project for 7
years now, and this is a tool that…that focuses on food access and policy change through authentic
resident engagement. You can take some of these tools and do an assessment with yourself and your
lab to assess: Where are we on the spectrum? How ready are we to engage with the community? So,
I think it’s just a very helpful tool. Here’s a brief definition of authentic resident engagement.
Ultimately, it’s about inclusivity at all stages of the research and policy change.
The working principles I want to flag is that in our work, we need to consider addressing power
imbalance, building trust, using an asset-based approach, right? To acknowledge the resilience
that the communities and residents and patients have had before we even showed up. And to take an
anti-racism stance. This tool demonstrates that community engagement is a spectrum. It’s not
that…you know, you’re all the way there or you’re not. It’s…you can…you can jump in at any point.
You can absolutely grow. It’s a dynamic, iterative process of looking to see: Are we ignoring in the
community? Are we informing the community? Are we consulting, involving, collaborating, all the way
to deferring to the community, where the community and the residents are really driving the questions
and even the interpretation and dissemination of the data? And this one gets a little tricky. This
is what is causing us to even be participatory in how we budget with our grants. Briefly, this
is a CBPR, an example of some of my CBPR work in Hartford. I won’t go into the weeds too much, but
I wanted to share, you know, just some highlights of what dissemination and co-development with…with
residents look like. These are the communities I work with. It is a federally designation of
Hartford…Promise Zones. So, I wanted to flag that. North Hartford was designated a Promise
Zone under the Obama administration, so that really just sort of should, you know, give you a
visual in mind of the level of this investment and level of poverty in the community that I’m working
with on a day-to-day basis. A lot is going on in Hartford in terms of, they want the supermarket.
There are…there’s revitalization efforts. There’s policy change happening with the city council.
They just put out a resolution to sort of in food deserts and address food swamps in the north end.
But for this audience, I wanted to flag my relationship with this work. This is not…my work
is not post-intervention at this time. I am at the table sometimes at 10:00, 11:00 at night at the Y
with the community, trying to help infuse evidence and research into the decisions to begin with,
right? Because sometimes by the time we show up, so much has been determined that we’re…right,
as researchers, we’re just trying to catch up. So, I’m bringing all this evidence to bear and
inform this work to help steer and support the community in figuring out what they want done.
These are the aspects of the [inaudible] work…we’ve done audits, we’ve done resident
surveys. I conduct photo voice research, which is a qualitative study, but photos are the data and
the community tells their story. And I also did a policy audit. These are pictures from the audit.
And ultimately, I co-developed these community resources. So, of course, the manuscript,
the…the professional conferences. We did all that. But we also co-developed these translation of
these materials with residents in the community. We have a social media campaign based on some of
this work. And in this…this side of the slide, you might be able to see the neighborhood profiles,
who took the data from the Food Swamp Audit, created maps, and worked with the community to
help tell the story that they wanted told about their own community. How do you want this shared?
And they said, “We want you to lead with our resilience and our assets. Before you get to
the problem, or the calls to action, please tell about the rich history of North Hartford.” These
are pictures from the photo voice…just in terms of community assets and talking about transportation,
but talking about the emotional and mental health impacts of hearing that a supermarket or a healthy
outlet was going to open and just seeing it lay barren for years and years and years.
We ran the resident survey and found the residents of food swamps are less likely
to experience both types of food insecurity. We looked at COVID-related food insecurity,
which is an interesting one, and we…we’ll do follow-up research to explore this because
what we suspect is that residents of food swamps are just perceiving a variety of food,
but not necessarily getting that type of food. Right…that’s where the, sort of,
the…the nutrition and…and food insecurity, hunger paradigm come together. Hispanics were more likely
to experience COVID-related food insecurity, and non-Hispanics were more likely to go to a
food pantry more frequently. We think this has to do with perceived safety…is there a safe place?
Post the former administration, there’s certain populations that…that they’re reporting fearful
to show back up in food…food pantry, and we have no reason to believe that they don’t need it. But
there’s just a perceived safety issue that is something keep in mind. These are pictures from
the photo voice…gallery walk that I co-developed with the community at the city hall. The mayor
showed up, the city hall…city council folks showed up to…to…to discuss important research
and important to discuss the change that should follow it. And this brings me to my conclusion.
In terms of the number one challenge that I see in this area at the moment, is our relationship with
our…as researchers with historically oppressed, marginalized communities that are underrepresented
in nutrition work due to recruitment and retention issues. As researchers, when we
take the time to build and maintain trust, given our competing deadlines for promotion, and tenure,
and our grant deadlines, we’ll take the time to build diverse research teams with representation
from the community. Sometimes recruiting and hiring directly from the community will absolutely
help folks answer your call, open their door for you, and you’re elevating training and resources
in that same community. When we take the time to share resources and…and power with the community,
with residents and patients…this is a tricky one because then we’re sharing budget…budget
information and being transparent, those things. In terms of opportunities, multigenerational
nutritional researchers should leverage CBPR methods and principles. It helps to maximize
impact in a sustainable way and elevate voices. We can think of ourselves as playing a support
role to policy makers and decision makers that, as I said before, in the…personal harm slide.
We are making decisions that impact health equity, whether we are being cognizant and calling it that
or not. So, we should work with them. We should say, “Hey, we’re here with our skills and training
and resources. Let us help make this decision.” And another opportunity that I think is exciting
is that we can expand the comprehensive measures of neighborhood food environments,
including but not limited to food…to food swamps, but also validated measures on consumer-level food
environments like the one that discussed today, childcare setting, the quick-service restaurant.
And we should absolutely…because we’re…we’re not out of the woods completely. But we should
leverage what…what we’ve just been through with COVID, and the…revitalization efforts,
like the Biden American Rescue Plan, to think of natural experiments that can help us understand
these societal policy neighborhoods and social changes over time, but also across generations.
With that, I’d like to thank, again, the office of Nutrition Research for inviting me here,
the funders, my academic collaborators, community partners, including my resident advisors,
and my training from the…from my Health Equity for the People Lab. Thank you.
DR. SOMDAT MAHABIR:
Thank you very much. We are now running way short of time, so I don’t want to put
too much pressure on the other speakers. Maybe we’ll have to chew into some of our lunchtime
so that we can get some good questions and so forth. So, next speaker is Dr. Joseph Braun.
DR. JOSEPH BRAUN: All right, well thank you to the organizers,
to Kristen and Ashley for inviting me here today.
It’s…it’s my pleasure to be here, and it’s been a really interesting series of talks to hear so far.
I just want to start out by disclaiming that I have been financially compensated as an
expert witness for plaintiffs and litigation related to PFAS-contaminated drinking water
in New Hampshire. And PFAS is the chemical we’re going to be talking about most today.
So, I want to start out by bringing this idea forward that chemical exposures can make us obese,
and this idea isn’t new. Nicholas Kristof from the New York Times wrote about this over 10
years ago—“Warnings From a Flabby Mouse”—where he highlighted a study from Retha Newbold, who was at
the National Toxicology Program, where these two mice were exposed in utero to either nothing or
diethylstilbestrol, which is a synthetic estrogen. And you can guess which…which mouse is exposed
to the…to the DES. It was the fatter, larger mouse there. Bruce Blumberg and Leo Trasande,
both researchers have written books about the obesogen effect or other endocrine-disrupting
chemicals and how they can impact the risk of obesity and related diseases. And this
really shouldn’t be—I…I think biologically there’s…there’s good reason to suspect that
this is happening. We know from pharmaceuticals that there is actually pharmaceutical obesogens
and thiazolidinediones are an example of this. These are a class of drugs that are used to treat
type 2 diabetes, Rosiglitazone and pioglitazone being two of them used here in the United States.
And these are PPAR-gamma agonists, so they actually bind to the PPAR receptor inside our body
and impact metabolism. And they can actually cause an on average 11-pound weight gain among diabetics
who take this, which is a paradoxical effect if you have diabetes, you’d think. But what’s really
interesting is actually weight gain in these persons is…is correlating with better metabolic
control. And it’s thought that largely this is due to the fact that these drugs help take fat
away from the inside around the organs and move it to the periphery of the body, which is where
it could be “healthier fat.” So, there’s this redistribution phenomenon. So, what about chemical
exposures? Well, we’re exposed to a…a…a…a large number of endocrine-disrupting chemicals, and I’ll
talk about PFAS today, as well as some others, and we think that many of the mechanisms that they can
impact obesity are similar to what might be going on with thiazolidinediones, like PPAR agonism,
but also general endocrine disruption that can impact metabolism and energy homeostasis, as
well as appetite and satiety. We also think that there may be…some of these chemicals can inhibit
11-β-hydroxysteroid dehydrogenase 2, and thus increase cortisol levels and possibly also impact
DNA methylation and other epigenetic mechanisms to affect gene expression. And the net result of this
is that we end up with adipose tissue accrual and alterations in metabolic function. The class of
chemicals that I’ve been studying with…with regard to this are PFAS or polyfluoroalkyl substances.
And PFAS are a…also known as the “Forever Chemicals.” This is a diverse class of…of …of
thousands of chemicals that are characterized by having these—this long carbon chain that’s only
fully or partially fluorinated. And these chemicals have very high environmental persistence
and in some cases may stay in the environment for the…the rest of the planet’s history.
They’re designed to be persistent. And they have these desirable chemical and physical properties
that make them useful for a lot of products that we use in our everyday lives. They’re used in
stain and water-repellent textiles, like vortex. They’re used in food packaging, like popcorn
bags and grease-proof wrappers. They’re used to manufacture non-stick cookware, as well as stain
resistant—other textiles, rugs, and furniture. They’re used in cosmetic products and in aqueous
film forming foams or firefighting foams that are used on a military bases or civilian airfields.
These chemicals have long biologic half-lives in our bodies, ranging from 3 to 7 years for some
of them. So, they stick around in us for…for a long time. Thus, the name the Forever Chemicals.
They’re extensively used. It’s estimated that they’re used in thousands of products. I just
gave you a few highlights there, but they’re used in these obscure things too, like guitar strings.
You know, they coat guitar strings with PFAS. They get…they’re used in…in anti-fog coatings
on goggles and glasses. And they’ve also been widely distributed in our environment. Here in the
United States, it’s estimated that they’re used at over 57,000 sites—industrial or commercial sites.
And hundreds of millions of people are in this country are exposed to two of these compounds,
PFOA and PFOS, at levels above a provisional guideline being set by the EPA for drinking
water limits. And they’re detected in the blood of everyone here in the United States and largely
in other industrial countries, as well. As I mentioned, they persist in our body for years.
Now, the tie to diet is that, there’s…it’s…at least half of our exposure to some of these PFAS
comes from diet, and in some cases, it’s close to 95%. This can be from contaminated fish, eggs,
and meat, but also from food contact materials. So, things like grease,
food wrappers that I mentioned, or popcorn bags or other plastic bottles that are
fluorinated and coated in order to impart better…decrease their permeability. So,
we can be exposed to these chemicals not only from our food but our food containers. Drinking water
is also a major source of exposure, particularly for infants. This includes from trans-lactational
transfer for…for breastfed infants, as well as formula made with contaminated water.
Now, in terms of obesity related diseases, there’s been a…a number of studies examining
PFAS in relationship to cardiometabolic disease in adults. The last time we did a review of this,
in the last year, we found that there’s at least four studies and…and the majority of
these suggesting that mid-adulthood exposure to PFAS or mixtures of PFAS—because there’s not
just one of them—is associated with increased risk of type 2 diabetes.
They’ve also been consistently associated with dyslipidemia, and there’s some evidence that
lifestyle interventions may ameliorate their effects, such that having better diet and more
physical activity may decrease the…the effects of PFAS on the risk of type 2 diabetes, which
is some work that was done by Andreas Cardenas and highlighted in the lower right panel here.
More recently, there was a paper by Wen and colleagues that published in EHP showing that
PFAS may be associated with premature mortality. This is data linking NHANES data to the National
Death Index and showing that increasing levels of PFAS in people’s…in people’s PFOS, which is one of
these PFAS, was associated with increased hazard of mortality from either heart disease or cancer.
And they did some counterfactual calculations to estimate the attributable number of deaths
that we could avoid if we move the top third of people in the PFOS distribution
to the bottom third, and estimated that there’s somewhere over 200,000
deaths that could have been prevented. Now there’s lots of assumptions baked into that,
I know, but this is…this is a highlight that there could be a really large
attributable fraction here that has a…a pretty profound absolute effect on…on mortality.
So, our research group has been thinking about early life origins of cardiometabolic disease and
obesity and really focusing on PFAS lately, and I—you know, this intersects very nicely with diet
because we think for…for PFAS, there’s—diet is one of the primary sources of our exposure to these
chemicals. And in addition, diet has an…an…an important impact on our life, both prenatally
and…and inter-generationally. A lot of the work we’re doing comes from the health outcomes and
measures of the environment study or home study. This is a prospective pregnancy and birth cohort
study in the Cincinnati, Ohio, area that was initiated in 2003 to 2006, and we follow—have
been following—up approximately 400 children from the second trimester of pregnancy until now, 16
to 18 years of age. We’re doing ongoing follow-up visits right now with them and have brought about
100 back in. They’re actually grownups now. So, we come back in and we don’t…we don’t consent their
mom…we don’t have to get them…consent from their moms anymore. It’s from them. And we
have really detailed health phenotyping of these children, beginning as early as one year of age,
really focused on neurodevelopment. And then in these later years we’ve been focusing on
cardiometabolic health, bone health, as well as mental health, like anxiety and depression.
A paper we published a few years ago by a…a former postdoc Nan Li,
was looking at prenatal exposure to PFOA, which was one of these polyfluoroalkyl substances,
in relationship to cardiometabolic disease at age 12. And we created a cardiometabolic risk score,
which is shown over on the…on the left panel there. Can I get a laser here?
Laser? Nope. Nope. That’s up and down. No. Oh, okay. I don’t get, I don’t get the laser. Okay.
So, PFAS concentrations, PFOA concentrations are on the…in the mom’s blood are on the x-axis,
and on the y-axis there’s this cardiometabolic risk score,
and we see this sort of nonlinear association with increasing cardiometabolic risk, with
increasing PFOA. We saw similar associations with fat mass that we measured with…with a DEXA scan.
And we also looked at this mixture of four PFAS and found that PFOA was really driving
the association between cardiometabolic risk and…and this mixture of PFAS.
My colleague Jessie Buckley has also been looking at prenatal PFAS exposure in relationship to bone
health, and in these same kids at age 12, we looked at bone mineral density at multiple sites
and found that higher levels of PFOA, as well as this PFAS mixture, were associated with lower bone
density, and that these associations were somewhat stronger in males and at cortical bone sites,
with the implication of this then being that we may be setting kids on this trajectory towards
lower bone mass early in life, and thus at increased risk of osteoporosis later in life.
We’ve also been doing work to investigate relation—biological mechanisms underlying
this. And in this work published by postdoc Jamie Liu, we looked at DNA methylation in cord blood
leukocytes at—or in leukocytes at delivery, as well as age 12 years of age in these children,
and found that several PFAS were associated with CpG methylation, and we were actually
able to replicate several of these in another…in another independent cohort. And many of these
genes were related to cancers, cognitive health, cardiovascular and kidney disease;
nothing specifically related to cardiometabolic disease or obesity, much like some of the work
Rick…Rick Pilsner was talking about yesterday. But…but broadly that they suggested there
could be these implications more globally for health. So, what was notable here is that these
associations with DNA methylation and PFO—PFAS concentrations—in pregnancy were persistent. So,
they persisted out to age 12 years of age. So, we saw increases or decreases
in methylation that persisted across the life span up until we had measured.
We’ve also been using the ECHO Cohorts to investigate associations between PFAS
and, and BMI in work using over 1300 kids from eight of these cohorts. We’ve looked
at prenatal PFOA concentrations or prenatal PFAS concentrations in relationship to BMI at ages two
to five in children from ECHO. And in this work published by Jamie Liu, just, just recently in the
last couple months here, we found some evidence a little bit mixed that PFAS concentrations were
associated with increased BMI—which is on the left panel there—and then risk of overweight or
obesity on the right axis. And these were…we looked at quintiles of PFAS concentrations,
as well as their mixture. We did see strong evidence of a mixture effect, but we did find
that some individual PFAS were associated with increased risk of obesity, like PFOS—there was a
trend suggesting that—as well as for some of these longer chain PFAS, like PFUNDA and NMFOSAA . Not
always consistent evidence of dose response, some cases a threshold, but, again, sort of this…this
evidence again that…that these chemicals could have these long-term health effects on child BMI.
Another thing that we’ve been investigating are how can we prevent PFAS exposure and related
health effects. And I think this goes to what, you know, I was really happy to see Dr. Barker talking
about interventions and…and we were talking about this last night, and…and the slides that have
been shown sort of about, you know, what’s the health effects versus the cost and difficulty of
doing these, you know, with preventing exposure way on the left there—although maybe the cost
and difficulty we talked last night might be far higher than we…we…we’d like to think—but
that, you know, we…we can certainly get more bang for our buck if we can prevent exposure.
We’ve done some work to start to think about ways to decrease PFAS exposure in our environment. So,
we did a quasi-experimental study actually at our School of Public Health a couple of years
ago where we installed Corsi-Rosenthal boxes, which were indoor air filtration system that
was designed by Richard Corsi and Jim Rosenthal; two air quality engineers. These were developed in
response to COVID pandemic to improve indoor air quality. So, these are just four consumer-grade
filters that are taped together with duct tape and a box…a box fan on the top. You turn it on,
and it increases air change…air change in the room. And they’re really effective.
They’re more effective than a commercial air filter that you can buy, you know, online.
And so we dropped these into these 17 rooms. We did monitoring for exposure before and after the
intervention. This was our little exposure rig here. We’re also measuring…so we could measure
PFAS and other semivolatile compounds in the air. We also measured temperature and relative
humidity. And we found actually that we were able to lower concentrations of six PFAS by
30 to 60% in the air with this intervention. And so…and this plot here is showing you the before
and during intervention distribution of these six PFAS concentrations,
as well as each individual room change in PFAS concentrations before versus during intervention.
And these were really pretty profound effects for…for air—for reducing the indoor air
concentrations. You know, we were able to get, you know, about…reduce it by about half on average.
So, this is…this is pretty big. Now, the, the real question now that we’re trying to follow
up with this is to determine whether or not this translates into measurable reductions in
exposure that we can—in, in our bodies. Air isn’t a major pathway of PFAS exposure for most of us;
however, for young children it could be since they spend more time closer to the
ground. They’re also…so they have a different breathing zone. And we might also be pulling
some of the PFAS that would be in the dust or in other places out of the air when we do this. So,
we’re…we’re interested and we’re seeking funding to go and try to do these sorts of intervention
studies with the Corsi boxes and see if we can reduce body burden and improve health.
Related to diet, there’s, you know, packaged and processed foods could be a source of PFAS
exposure as well as other EDCs. We know that these chemicals are used in food packaging and
processing, and as I said earlier, they also contaminate the…the food supply.
Two studies have suggested that processed and packaged food consumptions related to
higher levels of phthalates, which Rick was talking…Rick was talking about yesterday,
as well as phenols. There’s not been any studies of PFAS that I’m aware of. And this study I’m
highlighting on the right here was developed with Menichetti and colleagues developed a new
processing index of food based on the NOVA Index that uses a machine learning algorithm
to classify foods into their degree of processing. And then they looked at this food processing index
in terms of consumption of individuals in relationship to a variety of diseases,
and then some chemical exposures, as well as other health-related biomarkers. This is the NHANES.
This is cross-sectional data, but the…the food processing index was associated with these disease
outcomes, as well as some exposures that we think may be found in…in foods or food packaging.
And my colleague Jessie Buckley has also published a study…a study showing that sandwiches, burgers,
French fries, potato products, and ice cream pops are associated with higher levels of
urinary phthalates in individuals. So, it seems that there’s specific food items as well as
markers of the degree of processing that seems to
be related to these chemical exposures and possibly also cardiometabolic
disease. We recently have been thinking about also how do we prevent exposure related disease? And
for PFAS, this is really important because, you know, once these get into our body, it’s
virtually impossible to get rid of them. You know, so you can’t do anything about
the exposure to PFAS that you’ve had in terms of getting rid of it. So, we need to do something
for populations who have been exposed but want to reduce their disease risk. So,
as I mentioned earlier, some of these studies in adults have found that better diets and physical
activity seems to buffer the effects of PFAS exposure and risk of type 2 diabetes. And so,
we looked at this in a…in our cohort, where we found that children with higher physical
activity at age 12, we didn’t see this association between PFOA concentrations and cardiometabolic
risk among those children with higher physical activity—which is the orange dash line and
confidence interval. Whereas those children with lower physical activity, we saw increased
cardiometabolic risk with increasing prenatal PFOA concentrations, suggesting that physical activity
may buffer some of the effects of prenatal exposure to PFOA on cardiometabolic risk.
And this interaction…interaction was significant, and it was really driven by insulin resistance
and adiponectin leptin ratio, as well as visceral fat content. And some suggestion too,
that this physical activity modified this association for the PFAS mixture.
So, in terms of some of the challenges and opportunities we have, so I think…I think…thinking
about signal-to-noise ratio here with intergenerational effects is really important.
And I liken this to the…to butterfly wings and sledgehammers. You know, we have some exposures
that we…are probably have like sort of butterfly wing effects, right? They’re not very big.
They…they can…that doesn’t mean they’re not important, but they’re going to be
hard to detect in most studies. And then there’s the sledgehammers, right? You know,
smoking is a big sledgehammer. Diethylstilbestrol in exposure in utero. That’s a sledgehammer.
So, when we’re looking at these studies, we really need to think about like,
what sort of effect size are we expecting with this exposure? How long do we expect to see
it for? What’s our sample size? You know, it’s sort of going back to some basic epidemiologic
questions. I think we got…and…and the study design principles. We have to be really thoughtful about
that because we may miss things otherwise, or we…and, and we also need to show that there’s
some proof of principle here. So, I think looking at sledgehammers is a good place to start. I know
it was…it’s not as sexy and exciting to look at sledgehammers—like we don’t need another study
telling us that smoking is bad—but I think as proof of concept, it’s really important,
because if you don’t see stuff with the sledgehammers, there may not be something
there for the phthalates or the PFAS or the other things. Exposure data quality is really
important—especially, you know, whether it’s diet or chemical exposures, often these historical
cohorts don’t have this collective. Even some things like air pollution are really…you know,
we can’t measure going back historically because we didn’t measure it back then. You know. So,
this is important to think about is what sort of exposure data…what’s the quality of this? And then
as I was alluding to sort of what’s the long-term effects of this? So, we often see things. These
health effects manifest in childhood, but do they persist out into adolescence, adulthood,
and on? And if they’re not persisting there, would they persist inter-generationally? So,
I think those are…those…those are important studies that we need to do.
I think there’s opportunities…Rick was pointing out, you know, we can determine if dads matter.
I think I…we...and I’ll…and I’ll talk a little bit about this.
We can utilize existing studies like the collaborative Perinatal project and ECHO or use,
you know, these natural and existing experiments that have been done, like the Overkalix study.
And I think more interventions to identify ways to reduce or prevent exposure. And I think diet
is a great place to do this with chemical exposures because we can kill two birds
with one stone by improving people’s diet. You know, we can get them better macro and
micronutrient profiles in terms of what they’re eating and also reduce their chemical exposures.
PFAS is just one of many potential obesogens. You know, there’s a laundry list that have been…that
have been thought of that may be obesogens, like phthalates, brominated flame retardants,
[inaudible]. So, I think we need to be also thinking very much more comprehensively
about this chemical soup we live in and these mixtures and what their health effects are.
And in terms of some of the intergenerational effects and how this may impact human health in
terms of relative to dads, we have some data that is—this is hot off the presses and unpublished—but
we have been doing…following children who are born to couples seeking fertility treatment
from a clinic in…in Massachusetts General Hospital and looking at maternal and paternal preconception
and prenatal phthalate exposures, and had done follow-up now on about 200 children,
age 6 to 10 years of age. We have data on about 100 fathers in terms—both in terms of
their exposure and then some follow-up data on them as well. And we’ve been finding that higher
levels of some of these pthalates in dad’s urine before pregnancy is associated with alterations
in children’s eating behaviors, where they have more of these food approach behaviors that would
be associated with more obesogenic on…with being obesogenic. So this is, this is work that we’re,
that a grad student, Jordana Leader, is just about to submit for publication. I
think she might have submitted yesterday, in fact. So this…stay tuned for this. So,
I just want to close by acknowledging a long, a long list of colleagues and…and mentors who
have helped me over the years with all this, as well as funding from the National Institute
of Environmental Health Sciences and then study participants from home and…and the PEACE studies.
DR. SOMDAT MAHABIR: Thank you.
Right. Thank you very much. So, our next speaker is Dr. Carrie Breton.
DR. CARRIE BRETON: All right. Well, thank you so much for inviting me here today,
and I will be wrapping up this session and pretty much the only thing between you and lunch.
UNIDENTIFIED SPEAKER: [inaudible].
DR. CARRIE BRETON: …And Q&A, sorry. (laughs) So I will…I’ll try to be brief here.
And, so I’m going to be talking a little bit about built environments and how the built
environment and different aspects of neighborhood characteristics can affect multi…multigenerational
nutrition-related health. Before I start, I really want to highlight again some of the challenges we
pricked a little bit about these both yesterday and today, and particularly relevant for the topic
that I’m going to address in the next few minutes. But when we think about multigenerational studies,
time is not always on our side, so a long time period is needed to observe changes across
multiple generations. And another point that we definitely heard yesterday and again today is that
there’s generally been a lack of standardization of methodology,
both in exposure assessments and also when we talk about phenotyping health outcomes. So this
makes it hard to compare across cohorts, but it also makes it hard to compare across time.
Families also tend to have lived…shared living environments and shared behavior. So teasing
apart the…across the generation, the effects from one particular generation or another when we have
correlated environments and shared environments is a challenge. And perhaps, most germane to my
talk right now, that there is a need to balance individual responsibility for health with the
structural and societal responsibility for health. So I want to start by defining what I
mean by the built environment, because these are changeable, manmade aspects of the environment.
They can include things like urban design, land use, transportation systems.
So they have the potential to support or constrain eating behavior and activity behavior.
Examples include access to grocery stores, food vendors, food swamps that you’ve heard about, but
also it seems like walkability in a neighborhood, greenness, tree cover, transportation networks,
transportation density, and even the pollution that may come with proximity to transportation.
And last year there was a scoping review that was published that specifically was looking at the
built environment in relation to diet, physical activity, and obesity. So I wanted to start there,
sharing some of those results. While this was a…a review that really looked at the evidence of the
data within a single generation, not necessarily across generation, I…I think there’s some key
points worth mentioning. Quality of dietary intake appeared to be associated with the availability of
grocery stores. Higher levels of physical activity appeared to be most consistently associated with
greater walkability, and lower weight status was associated with greater diversity in land use mix.
The authors of this review also presented some concerns again tended to
revolve around methodology and methodological limitations, including some concerns over poor
quality of existing studies, and advocated for stronger study design and stronger
standardization of definitions that we use across the study, along with valid and reliable measure.
Just to share, in a little bit more detail, two of the figures from this review, this one shows
the primary characteristics of the environment and the built environment that were associated
with physical activity. And the top ones included walkability, recreational facilities,
nearby shops and services, as well as proximity to park and trails. And when we looked at weight
or when they looked at weight status, aspects of the…of the built environment, such land use mix,
the aesthetic of the environment around you, the overall food environment, and again, availability
of parks and playgrounds, these were all some of the highest predictors of weight status.
So again, that didn’t address multigenerationality at all. But I did want to highlight a study,
that came out almost 10 years ago now that really was one…one of the first that I
could find looking at some aspect of the social environment in…across multiple generations. And
this was the Aberdeen children was a 1950s study. They had three generations, so they
looked…and…and we’re really asking the question about what might predict offspring size at first,
looking at the grandmother’s generation as well as the parent generation. And their main takeaway
from the study was that the social environment, as well as the mother’s own growth, were the two
biggest predictors of offspring size. So I wanted to share with you a quote that I thought quite
germane 10 years ago for…for where we are right now, and I’ll let you read it.
But the…the …the major take home is that, you know, we need to balance individual
characteristics that we know we can intervene on with the social environment and really think
about our structural environment and how, how we as individuals interact with that environment.
and I’ll just caveat that in this setting, social environment was really just defined
as social class. So, I think there’s a lot more that we can do, but it does provide a
nice starting point illustrating the…that we can try to look across generations.
So, I would like to share with you some research that we’ve been doing in Los
Angeles. This is in our MADRES pregnancy cohort, part of an environmental health disparity center
that we’ve been running in LA for the last 7 or 8 years. So, we have enrolled about just over 1,100
pregnant women in the greater Los Angeles area. The neighborhoods are illustrated on this map
of greater Los Angeles, shaded in pink with the darker colors, just having a greater density of
participants in that urban core of Los Angeles. We recruit in early pregnancy, and we follow mothers
and children for…through about 4 to 5 years of the child’s life. So we have started to really
look at neighborhood-level characteristics of our population. On the left is a map, again,
these are all…will all be the maps of sort of the greater Los Angeles area. Outlined in pink are the
neighborhoods in which our participants reside, and on the left is…are our neighborhoods overlaid
with census-based data for race and ethnicity, where purple are Asian…from Asian communities,
green are predominantly Hispanic communities, and yellow predominantly Black or African American
communities. So I think what you can see just visually is that our population…the majority of
our population lives in neighborhoods that are predominantly Hispanic. And in fact, 75% or so
of our population self-identify…self-identified as Hispanic. On the right, we’ve overlaid those
same neighborhoods with historical redlining information from 1930s in Los Angeles. The redline
neighborhoods are shown in yellow and red. And so also, I think what’s striking is that many of
our neighborhoods are…our participants are living in neighborhoods that were historically redlined.
So, there are many different characteristics that we can look at and think about when we
talk about neighborhoods. And this—we’ve been doing work in our center that’s been
led by my colleague and co-investigator, Rima Habre, who’s an exposure scientist.
So outlined here in the diagram are really several different aspects of neighborhoods that
we can look at. They expand from demographics to socioeconomics to the built environment,
which is my focus today, as well as the chemical environment and physical environment. And then,
in terms of social environments, specific indices that we can map onto our residential addresses
are things such as the walkability index, greenness and tree cover indices, food deserts,
transportation networks, food insecurity, food swamps should be added to this list. And then
on the right, you can see the distribution to some of the metrics in our population and
about 800 of our MADRES participants. The top one shown on the right is actually the
CES score. This is the CalEnviroScreen score, which is a cumulative index of neighborhood
burden for the state of California. And I’ll show you more on that in the next slide. In fact—so
the CalEnviroScreen is really—the overall burden score ranges from zero to 100, with 100 showing…or
indicating sort of the most environmentally burdened neighborhoods across the state of
California. This is comprised of two subscores that are multiplied together. One of them is a
population susceptibility score, so this…some exposures such as—thinking about crime rates,
asthma prevalence rate, poverty. And then the pollution burden score really tries to get at
proximity to hazardous chemicals, industrial waste sites, air pollution levels, and things like that.
So, the highest levels are shown in pink and red. And I think what you can see is that many of our
neighborhoods were very highly in the pink and red, indicated on this index. So really indicating
total sets of population susceptibility point of view and from pollution point of view that,
our participants are living in neighborhoods that are highly burdened. In fact, 60% of our
participants live in the 10% most highly burdened neighborhoods across the state of California.
But we can also look at things like distance to supermarkets. So,
on the left is a zoomed-out version of LA, and our neighborhoods are outlined in blue,
with yellow indicating the supermarkets, and green areas…areas of green are shaded.
Our proximity was in a 1-mile walk to one or more supermarkets. And the righthand side is
the zoomed-in area, in LA, just to sort of show you more specifically that the
areas of concern would actually be the areas that are yellow with the red dots. So these
are areas that do not have supermarket access within that 1-mile walk. There…this is more of
a…you can access a supermarket within about a 10-minute drive from your home. So…so we can
start to look at some of these indices and try and release them to health…health outcomes. And so,
one of our interests has been looking at obesity risks and infant fat and lean mass early in life.
And so, we have begun measuring infant fat and lean mass using an instrument known as an EchoMRI,
which measures full body fat mass, lean mass, free water, and total water. This image is of the
machine shown right here. And it takes 3 minutes to do. It’s a quantitative measure, it’s not an
imaging MRI. And it…and it’s no radiation. So unlike [inaudible] we don't have any radiation concerns. So, to date, we have done
about 111 infants. We put them in and measure their fat and lean mass at about 1 month of age.
And we have started to look at some of these built environment characteristics
in relation to infant fat and lean mass. And what we’re seeing in preliminary data,
is that when we look at tree canopy, for no matter what cluster we use to sort of—around the home to
quantify the tree canopy—we’re seeing a positive association between presence and density of tree
canopy with lean mass in…in them. But we don’t see any associations with fat mass. And when we
looked at food deserts, we also don’t…haven’t seen any strong associations with fat or lean
mass. Not strictly built environment, but looking at the Gini Index, which you heard
about before, more of a socioeconomic indicator. We also were looking at…so
this proportion of income inequality in a given neighborhood and whether it might relate to infant
characteristics and found that higher Gini Index in pregnancies negatively correlated
with newborn adiponectin levels…adiponectin levels. So, adiponectin is interesting because
it’s an anti-inflammatory molecule produced by fat tissues. It can affect many different
organ systems, and most notably, I think, in thinking about nutrition and metabolic health,
it can help regulate lipid and glucose problems in…in the liver. So, we don’t yet know what
this means. We don’t know the implications of…of changing, adiponectin levels in this population
at 1 month of age, but this is something that, I think it’s preliminary and intriguing and,
something that we’re going to follow up on.
I have a postdoc, Nancy, who has also been very interested in looking at growth trajectories of
our infants through the first 2 years of life. So I want to, wanted to just share
with you some of this work, really looking at the combination of maternal diet in
the third trimester of pregnancy in the context of child neighborhood characteristics, which is
the Childhood Opportunity Index, which really just tries to, quantify the quality of a neighborhood
in which a child lives and how much opportunity is in the neighborhood. And I think what’s most
striking…so this…the plot that you see here are growth trajectory starting in utero. So it’s a
combination of fetal growth in the third trimester through birth weight, through 2 years of life.
And, almost immediately, in the third trimester of pregnancy, you see a divergence of the green
and brown curve from the blue and red. And really that represents the difference between
communities…children who were born in communities with high COI versus low COI. So green and brown
trajectories are the trajectories of children born in the high COI neighborhoods,
whereas blue and red are in low COI neighborhoods. Now, the more modest differences are seen with the
dietary pattern, which we identified as high in fruits, oils, and vegetables. and so if we compare
the highest quartile to the lowest quartile of this dietary pattern, we see modest reductions in
the growth and attained weight at 2 years within each of those categories. But I think by far the
most striking observation is that there’s these diverging growth patterns, from the get-go in
children, depending on the opportunity of the neighborhoods in which they are born.
If we now take a step broader and look nationwide, there…I wanted to share with
you a couple different publications coming out of Echo, which have addressed characteristics of the
built environment and thinking about birth outcomes and weight trajectories. And so,
published last year by Sheena Martenies, was a…was a publication really looking at an
index similar to the CalEnviroScreen but created on a national level, and whether
children who were born in high…communities with higher overall burden, whether there’s
differences in birth outcomes, and what they observed was that indeed,
there was lower birthweight and earlier gestational age at birth in children who
were born in communities with these…with higher scores on this burden index.
Similarly, in another paper that came out last year, they were interested in looking at two
different aspects of neighborhood vulnerabilities. Again, one of them was the COI, the Child
Opportunity Index that’s shown on the left. The other was the Social Vulnerability Index, which
is created by the CDC. And both of these were looking at growth trajectories…BMI trajectories
from birth through 20 years of life, and both…in looking at both measures, they really saw similar
pattern of [inaudible], which is that residence and neighborhoods with higher opportunity or lower
social vulnerability in early life were associated with an overall lower BMI trajectory and lower
risk of obesity. And I think what’s most striking is that they looked at these indices at different
time points, and the strongest associations were at birth. That maternal environment, in utero,
mattered. It mattered a lot for a 20-year trajectory of growth.
And the last bit of data I wanted to share, also coming out of Echo just this year was looking
at the effects of a policy intervention on a national level. And so this was…the
goal here was to look at the trends in BMI nationally in children after…before and after
implementation of the Healthy Hunger-Free Kids Act of 2010. And so this act was really meant
to intervene on school lunches and try to improve the quality of school lunches. And I think what
you see pretty strikingly in this slide is that BMI trajectories on the left in sort of the white
shaded area, and in the blue and dark blue lines, that’s the overall trajectory of BMI from about,
what, 2005 to 2016, so trending slightly upward over time. And then after the intervention,
you see a…a marked change in that trajectory of BMI compared to sort of the dashed lines,
which is where it was projected to have gone had there not been any policy intervention.
So, I’ll just end with my own thoughts about the challenges and…and opportunities for the
future. And, I think…you know, we have plenty of literature on aspects of the built environment
within a single generation. I showed just very…just a very quick glimpse at some of what
that might look like. But as I think we’ve heard thematically throughout yesterday and today, there
are…there’s just a lot less that’s known across generations, specifically when I think about the
built environment. And our ability to track that in a standardized fashion across generations is
also a…I think remains a huge challenge. And then I would just sort augment on to that, that our…we
need to do our due diligence to try to tease apart the shared environment that will cross,
you know, that does cross across generations to really try to understand,
the effect within each generation and then also across each generation.
So, opportunities that exist to do this though, I think,
really lie in…in thinking about the intersection of how we individually interact then with the
environment around us. And, and I would argue that there’s probably a role for 1. looking and trying
to take advantage of mobility setting. I think we saw one example of that a little bit earlier,
in both directions. So if we can, you know…as families either hopefully go more upwardly mobile,
can we take advantage of the change across the different environments and really look
at whether we can see and disentangle some of these effects. But I think there’s also a role for
more personalized type study designs looking at ecological momentary assessment type designs,
for instance, where you can really capture in real time and a snapshot and of an individual response
to their environment around that. And so then you get that perception of the environment and not
just the GIS-based sort of index or…or assessment of the neighborhood defined by some sort of buffer
around a residential address. And with that, I will end with acknowledgement to a large number of
collaborators and staff and students and postdocs that make all of this work possible. Thank you.
DR. SOMDAT MAHABIR: Thank you very much. So, I’d like to take this opportunity to
invite all the speakers to come and sit up front here so we can start our Q&A.
I think you would agree with me that this was really a wonderful session. Kind of varied,
and we’ll try not to tie it together. Disparities [inaudible] to built environment.
So, I think the way we’ll start to do this,
let’s give the people online the opportunity first. So, we’ll…one online, one in house.
DR. KELLIE CASAVALE: How much time do we have today?
All right. We do have a number of questions that have come in online. So,
hi. Thank you again for the session. That was really, really fabulous.
And to everybody listening online, I’m Kellie Casavale from FDA. And so the first question
that we have, I…I think is for Merilee who is online. And the question is, “Regarding the
composition of human milk, what is the influence of maternal insulin on insulin content in human
milk and insulin, and the infants, which we know influences fetal growth and metabolism?”
DR. MERILEE (MEREDITH) BROCKWAY: That’s a great question. And insulin is…definitely, can be
impactful for the infant nutrition. So, it hasn’t been well examined because a. we try to keep,
obviously, maternal diabetes well controlled, so we don’t like to have high insulin levels in
moms. Therefore, it won’t be as prevalent in milk. And then also, in uncontrolled diabetes,
those mothers are not that successful in breastfeeding. So, my understanding is that
insulin will pass through the breast milk, but I don’t think we have very good evidence around
what the impact of that is on infants. I can look into that and get back to you with a more
comprehensive answer if you want to pop your email into the chat and I can give you a better answer.
But as I mentioned before, the level of evidence and the data around it is pretty sparse, I think.
DR. SOMDAT MAHABIR: Thank you. Any question from the audience here? Oh, it’s not yet done.
DR. KELLIE CASAVALE: [inaudible] DR. SOMDAT MAHABIR: Okay, Kelly.
DR. KELLIE CASAVALE: Okay. Anybody in the audience have a question before I ask mine? Okay. Go ahead, Mary.
DR. MARY BARKER: I’m trying to decide which of my list of questions to start with.
I’m going to start with Kristen’s question. That was a great talk. I loved it. I was going to love
it, wasn’t I? But I did, so that’s good. I loved the…the framing that you put on everything. I was
very, very interested in your descriptions of the non-nutrition–specific interventions, which
had nutritional outcomes. I think non-nutrition specific, as in nutrition-sensitive interventions,
are probably the way to go. So, the global kind of more structural, broader interventions,
which address a whole load of issues which have nutritional impacts. What was really
interesting is that they measured nutritional outcomes in that study you talked about. I’ve
had a quick look for it and can’t find it, so I’m going to come and see you later and
I want your list…all your references from your talk. Can you tell me about…anything more about
that study about why they ended up measuring nutritional outcomes when actually they didn’t
set out to measure any or didn’t set out to assess them? It was the one…it was the study
where they planted a new supermarket into a neighborhood where there was no supermarket.
The one…no, sorry. It was the one where they moved…they moved. No, it wasn’t actually that
one. I was wrong. It’s the place…it’s the study where they moved…relocated a load
of families into a slightly less disadvantaged neighborhood and found reduction in obesity and…
DR. KRISTEN COOKSEY STOWERS: The moving to opportunity study? Yes.
Okay. So the technology distracted me one more time for the actual question.
DR. MARY BARKER: I just…can you tell me more about it? Can you tell me more about it, because I’m
really interested in the whole nutrition-sensitive interventions rather than nutrition-specific
interventions. How do they…how do they end up measuring nutritional outcomes?
DR. KRISTEN COOKSEY STOWERS: Yeah. So, I think…great question and
I mean the…the affluent tent of, like, big picture because so many papers and so many analysis.
DR. KRISTEN COOKSEY STOWERS: I mean, it’s one of the biggest in terms of housing research
and segregation and those kinds of things. So, hundreds of …I mean, I can’t even…right?
DR. MARY BARKER: Okay. That’s interesting.
DR. KRISTEN COOKSEY STOWERS: Yeah. So…so, but the…the initial intent of the study was
to understand, really, how to…how to manage concentrated poverty. And I think some of
the research leveraging, you know, the history of structural racism as it relates to policy is that,
you know, the government sort of, you know, trying to see, like, how should…how
should we best manage clusters of poverty? Do we want to sort of allow it to spread or should
we think and test…do an experiment to see, you know, who built it up so high? I’m from Chicago,
so they’re…they’re called projects and they’re short, hence their nickname “projects,” and people
that live there forget that it was…like, projects are not just sort of a by chance name. They were
actual projects by the housing department to explore poverty and housing among young,
low-income mothers and really, plainly put, what to do with them. Right? Do we stack them
up yay high? Do we allow them…give them back [inaudible] get…gave a head nod to do this
socioeconomic status, right? Because we all, even in nutrition, should give vouchers. Should we give
double bucks? Should we give coupons and, you know, and…and wish them many blessings, if you
will. That’s great. But we also have spatial-built neighborhood aspects that we have to tackle. So,
it’s another one of those both-end questions. So, there’s so many…happy to [inaudible]—
DR. MARY BARKER: Okay. I—[overlapping voices]
DR. KRISTEN COOKSEY STOWERS: —so many papers that come out of this.
DR. MARY BARKER: So, what’s really interesting is…is
that you’ve drawn our attention to a…a major housing study. A study about housing, which
has the additional implications, which I think for all of us, there’s a kind of wakeup call,
but there are areas of literature we would not go to. I don’t know anything about the housing
literature, but clearly, I should and…and to be much broader in our…in our looking. And Joe,
so would that be a… [Inaudible cross-talk]
DR. JOSEPH BRAUN: But you know, it’s interesting because, you know,
I think housing is an interesting aspect because, you know, we have studies we’re going through
right now where we’ve done some interventions [inaudible] originally targeting less, but now
we’re trying to see if it affects other chemicals in the environment because it’s cleaned up.
And so housing may be again, a way to go after multiple things.
DR. MARY BARKER: Yeah. DR. JOSEPH BRAUN: Nutrition,
indoor chemical exposures that are coming from emanating indoor environments and built
materials. So, I think…I think, you know, you’re right, the home is a really important aspect that
centers on a lot of things, you spend a lot of time there. So there’s a lot of things we can do.
DR. MARY BARKER: And where your home is, which I think…
DR. KRISTEN COOKSEY STOWERS: Yeah, and I…and I would add…I would add to those points,
water. This is where some of my work is evolving, right? When we…when we sort of frame it as a,
you know, a sugary drink issue, even…even addressing disparities,
you know, if we stay in our house nutrition, forget the impact of the housing piece that
we look at the qualitative research. It’s not just simple as folks don’t know. They have no intention
to drink water. There are actual legitimate concerns about drinking water from their home,
and issues like Flint, Michigan, that elevated all types of things. And I think…I think…and it’s
a thing that started yesterday, right? Getting out of silos, getting…going across departments
and…and…and sort of why highlighted again, both are cross-cultural determinants because
it’s not as clean. And, you know, one or the other, they’re all interconnected.
DR. KELLIE CASAVALE: All right, so in the interest of time, we’re going to move on to
the next question. I could literally talk about that topic for at least two hours with you guys.
Getting all sorts of good ideas. So, the next question, I think, is also primarily…and it’s
related to the measures that you mentioned as being gaps in the end. And the question is,
“do you have any thoughts about the questionnaires used in CDC’s infant feeding practices study as a
solution to adequately assessing infant and early childhood diet? That…I know I had a very similar
question because I also work in this area of acquiring adequate federal data in the space.
DR. MERILEE (MEREDITH) BROCKWAY: Yeah, it’s an excellent question. And the CDC questionnaire is a
beautiful questionnaire. It really comprehensively looks at infant feeding. The challenge is…is
because it’s a large questionnaire, so participant burden is a concern. So, when we’re working with
cohort studies or intervention trials and looking at infant feeding as an outcome,
that questionnaire is…it would really add to participant burden. So, I think if we were to
develop kind of a consistent questionnaire that is just kind of a short form, I guess,
that would be ideal, that it’s just a series of like four or five questions and are able to
capture similar information but not as granular for those larger cohort studies.
DR. KELLIE CASAVALE: All right, great, thank you. Okay. And now
I’m going to ask my question from in the room, and this question is for Joseph, and
I’m also going to use your sledgehammer analogy because I do…I do like that. So, in your talk
you mentioned utilizing existing studies. And the National Health and Nutrition Examination
Study measures many different data points that are related to PFAS for ages 1 year and older. And so,
what kind of bio samples or other measures—so for infants—do you think would help elucidate
those sledgehammers in infant exposures to PFAS and also other environmental chemicals?
DR. JOSEPH BRAUN: I…I mean the…the…I mean there are bio…there are bank biospecimens from NHANES
as far as I’m aware. You know, the…the biomonitoring program for NHANES though,
I don’t remember the exact details for every exposure, every micronutrient they measure, but
that doesn’t encompass always down to infancy. So, a lot of factors aren’t measured down in early—
DR. KELLIE CASAVALE: So, I’ll just…I’ll just add to that that they don’t collect
blood, for example, on infants at all.
DR. JOSEPH BRAUN: No, no, no. It’s only done at one.
DR. KELLIE CASAVALE: So, what kind of bio samples do you think would be most valuable?
DR. JOSEPH BRAUN: I…I mean, blood is valuable, but so is, you know, we can measure a lot of
things in urine. Increasingly, people are doing some stuff with hair. It’s…it doesn’t
work for everything though. So I think those are reasonable places to start. You know,
the other thing…the other things just to collect are things like, you know, there’re…people are
using the…the exposome wristbands that can absorb lots of things from the environment. But the issue
is whether those are actually indicative of exposure. It’s not also something you can
put on an infant. You got to find a way to, you know, put it on them that…that doesn’t involve
going around their wrist because it won’t stay there. So I think…I think there’re…but I think,
again, urine is probably the best bet to get at a lot of things, particularly because I
think a lot of manufacturers who have made these persistent pollutants are switching
to making things less persistent, which means they’re going to get excreted in the urine more.
DR. SOMDAT MAHABIR: Wonderful. I…just for Joseph, as well, and Carrie, I’m going to have…make a
quick comment—you may not be familiar with some of these resources—and then a question. So,
I’m glad to hear your talk on PFAS. And sometime when you think about nutrition, people don’t tend
to think about these two together and the built environment as well. At the National Cancer
Institute, we have a program, which is now in the second year, where we have funded five large-scale
prospective cohorts. This is called the…the Cohorts for Environmental Exposures and Cancer
Risk. I’m leading that program and PFAS is one of the things that we are working on. These are
large-scale efforts. We do have a pregnancy cohort as well. So, I agree with you that urine is a good
sample and the PDMS wrist band and so forth—these are new tools that are being used to address these
things. So, my question to you is, in terms of food contaminants, in addition to PFAS,
there are other food contaminants that are chemicals and then we have additive effects.
Do you…what are your thoughts about some of these in terms of obesity and other outcomes?
DR. JOSEPH BRAUN: Oh,
I…I think in terms of the…I think one of the…one of the promising technologies out
there right now are use of these high-resolution mass spec platforms to do non-targeted analysis,
you know, to measure lots of things, whether it’s in urine or blood or…or serum.
So that’s one route to go to get individual-level exposure. You know, you can do similar things with
dust or air samples as well, or these…or these...for these wristbands. You know, the other…the other piece,
and this is an FDA thing, crosses into FDA’s territory is, you know, food contaminants,
and doing a better job monitoring those. And so, I…I think there’s…I think there’s a lot
of promise in using nontargeted analysis, and then, you know, a lot of biostatistical methods
have been developed to look at mixture effects, whether they’re antagonistic or agonistic or…or
aggregate effects. And so, I think there’s, you know, the…the, we have caught up in that way,
and in fact, there’s probably too many methods now, biostatistically speaking. And so I think,
you know, we…we have a lot of tools now at our disposal to look at lots of these things. The…the
key is going to be having the data…the…the large-scale data resources to do it with.
DR. CARRIE BRETON: I would, also just add that…I mean, I think we
know metals are a good example of known…known contaminants in…in some of the food supply. And
so while we can…I think…it’s a great effort to identify more contaminants that we don’t
necessarily know of. We also could still push the envelope and do more work to
reduce the levels of the things we do know about at, you know, either, especially maybe
targeting some of these vulnerable windows of…of development, whether that’s adolescents,
whether that’s, you know, fetal development. So, I…I think there’s room to grow there as well.
DR. SOMDAT MAHABIR: Wonderful. And…and some of the work related to the built environment,
I think the California teachers study, just where you sit, I am also very much active…that’s,
over 120,000 participants. They’re doing a lot of this fancy work as well,
and I think it’s time for us to think how to integrate the food there as well.
DR. CARRIE BRETON: Yeah. The nice thing about the built…you know, a lot of the built environment
is that you can at least start…as long as you gather residential history, and I would argue
do it more than once, and then you can capture mobility, and then you can start to look across
them. But then you have…that opens your door to so many of these things pretty easily.
DR. KRISTEN COOKSEY STOWERS: I also just wanted make another shameless plug for equity considerations with this,
and honestly, you know, the…the issues of toxins and these types of environmental exposures
are a key motive…a motivator for me, having been interested in food swamp environments because
they’re literally a spatial clustering in context to disproportionately impact certain populations
than others. And so, I’m sure, you know, there’s tons of work, you know, and there’s seeds in place
that would just advocate for paying attention to these issues as drivers of place-based inequities.
DR. SOMDAT MAHABIR: Yeah. I mean…and I can tell you for sure,
in all of these large-scale studies, you have multiethnic population. I
like to tell people we cannot study health disparities with just one type
of individual…groups. Right? One population. It’s not going to work. Anyway, Dr. Manuela.
DR. MANUELA ORJUELA-GRIMM: Thank you. I mean, just a really phenomenal panel like
everyone has said, and I just wanted to raise one…one topic that I…I think maybe alludes to
some…some aspects that were being discussed, but that I think we haven’t discussed specifically,
which is the aspect of food preparation, which I think touches on modifying exposure,
and has to do with the built environment, the indoor environment, and I just wondered…and…and
that also is an equity issue because there are…are lots of variations. It’s something that we’ve done
work on, but I am…sort of stumbled onto exposures that we didn’t realize were happening because of
collecting data on how…who was on 24-hour recalls and then realizing, “Oh, this is actually how
they’re preparing it.” This is just opening up opportunities for thinking about exposure.
I just wondered if the panel could talk about that element or the food utilization aspect.
DR. JOSEPH BRAUN: I…I mean the classic example, sort of, you know, the lead…lead-based cookware
and…and pottery that’s used in Mexico or in other, you know, traditional South and Latin
American cooking. That would be one example of that. I’m not aware of it for sort of…I mean, for
other contaminants I guess could creep, you know, using plastics and products and things like that.
So yeah, I think it…but I think you’re right. It…it…it adds in another layer of that…of…of
where can…where we can be exposed to things and how that modifies diets and…and exposures.
DR. CARRIE BRETON:
I guess I would just ask the question sort of back it—do we have a great instrument
or tool for even assessing this, and it’s one to be so population specific to that?
I…I would imagine we need to do some work on that area.
DR. KRISTEN COOKSEY STOWERS: I would
just say…add, you know, going back to, [inaudible]. I would just go back to...well, you know,
my comment with you just now about, like, clustering and like place/space drivers,
and certain behaviors. So, there’s going to be literally geographic areas
and neighborhoods that are more designed for, you know, cooking at home to start,
let alone in…versus areas that are designed for becuase of the space and food environment
and a variety of advertising and all type of stuff, it’s primed for a lot of eating out and,
you know, restaurant food which, again, food supply issues, contamination. So again, these
are these issues that are…been…have disparities and clustering that we should pay attention.
DR. KELLIE CASAVALE: Thank you. All right, we’re going to take one more question from online.
And this question is, “Are there any specific recommendations for
the nutrition support of pregnant women with chronic illnesses?
OB-GYN units typically do not provide specific recommendations to these high-risk pregnant women,
and the metabolic consequences for their babies are high.”
Oh, yes, please go ahead, Marilee.
DR. MERILEE (MEREDITH) BROCKWAY: Okay. I can take a crack at that one. So, I think that speaks to
kind of the fracturing of care for pregnant women with chronic diseases, because often,
OB-GYNs don’t feel that they’re well-prepared to support pregnant women with a chronic disease with
specific needs, and then their care provider who is going with the chronic disease care maybe isn’t
as comfortable with the pregnancy aspect. So, there is definitely a disconnect with
the nutritional requirements for specific needs. I think, kind of, the generic response is just
to eat healthy and do as well as you can. Just linking back to the presentation that I talked
about with chronic illnesses and lactation, a big issue was symptom management in pregnancy. So,
if the symptoms weren’t well managed in pregnancy, those women were less likely to breastfeed. So,
I think that’s also a concern that OB-GYNs don’t feel comfortable with…what…as well is that using
medications to manage symptoms in such a high-risk population.
So, I don’t have a good answer, essentially.
DR. CARRIE BRETON: I would…I would just add that, at least anecdotally, that…and some practitioners
might refer out to like a nutritionist, but then access to nutritionists is…is not
necessarily timely, or at least not right now. And…I mean…so…so then…and time is of the essence
if you’re trying to intervene in a, you know, especially in…in a pregnancy. So I feel like,
I mean, that’s a challenge that, I mean, I’m no expert in, but would be worth thinking about.
DR. KRISTEN COOKSEY STOWERS: [inaudible]
The better integration between health care systems and food banking systems and these kinds of more
systemic changes seem promising. Like there are a lot…there’s a lot more sort of discussion around
health care systems, screening for social determinants of health, and things of that nature.
And I think that this is a population where if we really invest on the intervention of the response
to someone’s screening of a social determinant of health, like food insecure…like moving beyond,
“Okay, where here’s a referral list to find your pantry,” right? Or “Here’s a list of social….”
If we can get beyond that and really better understand like how to respond to the unique
needs of that…that patient…that pregnant mother, what they tell us, they have an issue in the
social determinants of health realm. It’s really promising in that way. Right now, the integration
is there, but it’s just more like an FYI information sheet. We need to think more broadly
about integrating from a social determinants, structural determinants of health standpoint.
DR. SOMDAT MAHABIR: Thank you all very much. If there is no final
question from the audience here, I would like to call this session a close. So,
thank you all, speakers, and those who ask questions. Thanks a lot. Lunch time.
[Applause]
I think we need to be back here, 1:40. Have a great lunch.
MS. KIMBERLEA GIBBS: Welcome to session four, which is Next Steps for Multigenerational Nutrition Studies. I’m
Lieutenant Commander Gibbs, and I work in NICHD. I’ll be your moderator for this
session. I’d like to welcome and introduce Dr. Janina Galler from Harvard University,
who will present on Lessons Learned in Multigenerational Nutrition Studies. Ma’am.
DR. JANINA GALLER: Hi. I wanted to first, thank you all for inviting me to this very exciting meeting and challenging
meeting, and I’m going to, today, summarize my own work on multigenerational malnutrition,
and…and end with the challenges and opportunities
that the meeting for the past 2 days has presented us with in that light.
This is an overview of what I will be talking about. I’m
going to go through very quickly because of the time limitations.
One out of three children globally under the age of 5 years suffers from malnutrition,
and I’m going to be talking today about a very long-term multigenerational study which
has been carried on now for over 50 years. The classic definition, according to UNICEF and WHO,
of malnutrition is the combination of stunting and wasting, and roughly 30% of the global child
population under the age of 5 suffers from this condition. And as you can see, the definition,
strictly speaking, is under two standard deviations below median weight for age. The
prevalence of undernutrition in young children globally has declined, but is nowhere near what
our original goals were for the beginning of the century. As you can see, in 2020,
20.8% of children were still impacted, and most of these lived in sub-Saharan Africa and in Asia.
And again, this is a distribution of the global…of the percentages of children
globally, and the prevalence of childhood malnutrition. And again, you can see, where
the major concentrations are, but malnutrition continues to occur in all parts of the world.
In the U.S., although we don’t specifically identify an issue with undernutrition, even
the New York Times identified the extreme problem that we have in this country with hunger. Hunger
which carries on for any sustained period of time can, of course, result in overt undernutrition.
In 2020, food insecurity and undernutrition impacted one…one of four—and by some studies, one
of five—U.S. children; approximately 16 million children have been impacted. And I think what
we all cannot forget, and since this is my first meeting since the end of the COVID crisis, during
the COVID pandemic, these figures escalated, and we really don’t have a present count of what the
prevalence is in the United States or elsewhere, but we can only assume that’s substantially worse.
I would like to draw your attention to a slide that many others in this
meeting have…have presented similarly, talking about critical periods of brain development,
and what we understand this to be are periods when the brain grows most…most rapidly and is therefore
most vulnerable to nutritional insult. What is important about this is that it’s generally
been accepted that if malnutrition in humans occurs anywhere between the second trimester of
pregnancy and 2 years of age, the findings are generally thought to be irreversible. I think
that’s an important point, and I will carry out this theme throughout my presentation.
Also, it’s important in thinking about translational studies to look at what
rapid periods of brain growth are, because they are different in different species
and it’s important to have, obviously, a comparable period of rapid brain growth.
The Barbados Nutrition Study is a study that Frank Ramsey and I actually started together in 1973,
but it was based on a cohort of children that were first identified by him in 1967 to 1972. In 1966,
Barbados became an independent country. For those of you who have not been in Barbados, it’s
a tiny little island in the Eastern Caribbean, and it’s approximately 15 by 20 miles big, and
it has a population of about 285,000 individuals, most of whom are of lower-middle-class background.
There are very few people in upper class backgrounds, although this is now changing.
In 1966, when the…country became independent, the first Prime Minister recognized that malnutrition
was one of the major childhood issues on the island, and he identified and declared the need
to tackle this particular problem, and identified Frank Ramsey, my colleague from Barbados,
to establish a study to track these children.
So, in 1973, when I joined the study part B, we…we actually started to not just collect the children,
but also to think of this in terms of a study, and the study participants actually include children
with exposure to grade two, grade three protein energy malnutrition restricted to the first year
of life, so all of the kids had normal birth weights, and early childhood histories that
you know, had them with Apgars of greater than 8. They had no birth complications, they had regular
prenatal care, and no childhood encephalopathic events. Controls were from the same neighborhoods
and classrooms, and they were matched by age, gender, and handedness to the PEM group,
and we, as you can see, highlighted in red the children were exposed only for a year or less,
early in their lives, and thereafter, were involved in a nationally supported intervention
program, which provided nutrition education, nutrition supplementation, a stipulation program,
which was roughly two to three mornings a week that was available to the children.
They had all the routine health care through the national nutrition center until 12 years
of age and had regular visits by home…by public health care givers. So, these kids were heavily
engaged in what we considered at that point to be the state-of-the-art intervention program,
and…and therefore were documented as never suffering from malnutrition again.
We collected these children, and these children are now roughly 55 years of age, and we’ve
tracked them throughout their lives, and we also have extensive data on their mothers, and also
on their offspring who were…are now roughly 30 years of age, ranging from 6 to 30 years of age.
The etiology of childhood malnutrition in Barbados in 1966 really arose from
several…for several reasons, some of which were addressed previously about why children
develop malnutrition. First of all, there was no government policy supporting breastfeeding
or child…a child leave policy, so mothers had to return to work almost immediately.
Socioeconomic conditions in a sugar-rearing country are very tenuous. If sugar markets are
high, there are no issues, and if sugar markets are low, there is poverty on the island. So,
just to give you an example, in 1967, when…when the data collection was started on the sample,
80% of the income of the family went to food and housing, so that’s very little wiggle room if…you
know, if there are issues in terms of the cost and availability of sugar globally. There were
major cultural factors that played a role. There is…continues to be a practice of early weaning
to bush teas, and also Barbados is a matriarchal society, so it’s highly dependent on the women as
the providers in that society, and male support is not necessarily available. And, finally,
health conditions played an important role. We all know about the important role of infections,
including diarrhea and measles as a precipitance in a marginally nourished…population. And also,
as was mentioned earlier, maternal depression also leads to the early cessation of breastfeeding,
and results in malnutrition in populations, and was certainly a factor here. On this slide,
I hope to show a popular Calypso song at the time, which talks about another cultural
factor. “Endorse de cou cou and gi me another share, dem children en wuk no way.” And again,
it’s the demand by the man of the household to get the cou because the children are not working,
and so again, the focus and the priority would not have been on the children. This is a summary
of our multidisciplinary research focus in this in the Barbados nutrition study, and seven waves
of data collection that allowed us to collect a wide range of data on mental health and behavioral
outcomes, cognitive functions, a comprehensive assessment of medical health and ecology factors,
epigenetics, and more recently, neuroimaging, including qEEG and… and NIRS on this population.
This is a summary of 50 years of work in this population in one slide,
and basically, what I want to emphasize here is that there are changes across the board,
but the really important changes that we observed were a fourfold increase in attention deficits in
the population—and I’m mentioning this because, at the time we started to work in Barbados,
attention deficit disorder was only recognized as being a Western disorder. So, ours was the
first paper published in the Journal of Child and Adolescent Psychiatry that talked about attention
deficits in a developing country. So, I think that’s an extremely important point. And also,
we didn’t come in with a preconceived notion. What we did was we created this to identify
the…this issue. We had a classroom questionnaire, which describes lots of behaviors that would be
typical of children of this age and basically, you know, used principal components analysis to
reduce the data, and what emerged was what looked for…for the likes of…of anything else, looked like
the attention deficit disorders that were also seen in this country. The percentages were such
that 15% of the control and 60% of the children with histories of malnutrition in the first year
of life had an attention deficit disorder. We replicated this finding, and I’ll describe some
of the replications many times, at least five times over the…life span of the individual,
and the attention deficit disorders continued into adulthood. There were also conduct problems,
maladaptive personality traits, depressive symptoms, and in the area of neuropsychological
testing, IQ deficits for school performance and lots of changes in relationship to the executive
functioning of these children. An important point in the long-term longitudinal study is
that we recently have documented a severalfold rise in accelerated cognitive decline in the
population at age 55. And it is closely linked to the early diagnosis at age 5 of attention deficits
in the population. So, having a diagnosis in this setting of an attention deficit disorders predict
cognitive decline at a very early stage in this population.
Again, there were also health concerns; diabetes was elevated, especially in females;
metabolic syndrome; and a decline in social status, which…which…which was very significant.
In the next generation, in generation two, and…and I’m only going to report 16 to 30,
so there the…the data are directly comparable with the adults in the previous slide.
We also reported attention deficit disorders, personality traits being altered, depressive
symptoms being…being altered. What we did not diagnose at this particular stage of development
was any change in BMI or metabolic syndrome, but again, they are only 30, and we don’t know yet,
you know, what…what will emerge at a later point in time. So, what it appears is that
some of the behavioral findings that we observed in the first generation do carry over,
even with carefully adjusting for not only socioeconomic factors, age, and sex, but also
a range of extra nutritional factors that we have documented carefully in this population. Because
of my background as a child psychiatrist, we also collected extensive data on maternal depression
and child maltreatment. So, all the findings that you see reported will have been adjusted for those
other early adversities, as well. So, this is a summary of the slides, specifically one of our
slides on the CAARS, which is the Conner’s Adult Attention Deficit Rating Scale, and
this is, actually a study that was conducted intergenerationally by one of my daughters,
[inaudible], and basically, what you can see here is that the darker bars represent the
first generation, and the lighter bars represent the second generation. And you can see comparable
differences, again, in…in the various categories of, especially inattentiveness and DSM-IV
ADHD symptoms, between the…the various groups. Now, to supplement a lot of this work,
which originally started out really as a study of behavior cognition, brain, and health,
as newer technologies evolved and were available, we became very multidisciplinary.
One of our important collaborations have been with [inaudible] at…at Mount Sinai, with whom we’ve
been working on epigenetics effects. And I…again, I just want to summarize very quickly,
this is a paper we had published in Biological Psychiatry showing that in both G1 and G2, there
were many methylation changes. I think what’s important about this paper in particular is that
to…to our knowledge, it was the first paper that actually correlated these changes with attention
deficits and IQ deficits in the population. So, there was a significant correlation between the
genes that we saw across the board. A particularly interesting gene…let me start on the next slide,
which is specifically a slide talking about the 74 G2 offspring. Some of the important genes
were the DPPA5, which is a very potent developmental gene that has to do with early
brain development, a HOXB gene, HLA-DPA, but what was really exciting for us was to see that, there
were…was significant enrichment in 183 impacted genes that relate to immune function. So, this
was, a really interesting finding, and something that we’re continuing to work on at this point.
Now, there are other aspects of our research having to do with neuroimaging,
which is a more recent focus, NIRS, which we’ve been conducting in this population, as well, but
what I want to spend a few minutes talking about our…is our translational research. In addition
to the…the work, the 50-year Barbados Nutrition Study, we also conduct animal…studies of animal
models of…of protein malnutrition, and the first series of studies that I was involved in concerned
a colony that I inherited from [inaudible] Stewart at the London School of Tropical Hygiene and
Medicine. In 1973, I flew over a colony of rats with 20 generations of malnutrition from London,
where they lived for a number of years at MIT, and because the opportunity of…of following this very
important colony transgenerationally. And the bottom line to that series of studies is that
there were multiple changes in…in a range of behaviors, and whereas females seem to
recover within two generations, it took males four generations to recover, so there was
definitely a gender difference, and also talks of the importance of studying both genders in…in all
these area studies. I mention that because it’s not unusual in rodent studies in particular to
focus on male rats, and I know NIH has tried to encourage everybody to…to also look at females,
but it’s not done as often because of the varying complexities, and also being able to…to
look at them outside of hormonal changes, but we clearly see cognitive differences in that study.
So, just a couple of quick findings that corroborate the attentional findings that we
have found in our youth population. This is a.. a 2000–2019 study that we published, looking at the
acts of glucose uptake in the prefrontal cortex, and what you see here is that…that executive
functions are selectively impacted in the brain of rodents that have been exposed to both prenatal
and longer-term malnutrition. And this paper by one of our more junior faculty in 2020 was
particularly exciting because what it shows is that it isn’t that there are deficits, it’s the
fact that the brain actually reorganizes itself, very much like what happens to the heart after
a myocardial infarction. It actually develops alternate pathways, and he was able to…document
that NR rodents, whereas the normal pathway during sustained attention paths would have been through
the prefrontal cortex, which was not operating in the previously malnourished rodents. They were,
however, using a pathway through the right hippocampus, the right hippocampal formation, and
were able to achieve the same outcome, which is extremely interesting and, you know…and may have,
you know, further translational opportunities as we think about intervention. Okay, so let me just
summarize some of our key findings real quickly, and then move on to…to the…to our larger overview.
Our work in Barbados, again, which my collaboration with Frank Ramsey until his death,
which was roughly 15 years ago. As a result of our work, we were able to eliminate childhood
malnutrition completely from Barbados by 1980. Frank Ramsey was knighted for that work, and,
you know, it’s probably the greatest achievement from my perspective of…of my work in Barbados.
Number two, despite a 12-year national intervention program, the BNS shows that
early malnutrition limited to the first year of life still impacts mental health, cognitive,
and health outcomes over the life span and across generations. These findings parallel our early
intergenerational studies in a rodent model, and I think this is extremely important, and…and it
goes back to that slide I showed you of critical timing of brain development. But what is really
interesting is the transgenerational impact. Attention deficits and impaired executive control
are probably the most pervasive effects, even after controlling for extra nutritional factors.
Importantly, we have a series of papers on this. The attentional deficits lead to poor
performance at age 11, when there’s a national examination called the Common Entrance Exam,
which dictates whether you go to an…an academic high school or a trade school.
That attention deficits at age 5 predict how the child does at age 11 on this national exam,
which in turn predicts what the social status and economic earning potential is at age 4.
So, there’s an incredible impact of the history of early childhood malnutrition, and resulting
in a decline in earning potential and social status, which only gets worse over generations.
I talked previously about the epigenetic changes. What I’m excited about is the fact that it allows
us to think about potentially reversible effects, that’s what so exciting, I think,
for all of us here, in that particular area, we have not worked on microbiomes,
and as I shared with some of you yesterday, it’s partially because of cultural restrictions in
Barbados we can’t collect those…those samples as much as we’d like to.
Finally, multidisciplinary research really can contribute to…to the early identification
of high risk and resilient individuals. I would like to emphasize that even though
we do see 60% of children in childhood—and up to 45% in adulthood—with attention deficits,
you still have 40 to 50% of the population that did not have these outcomes,
these adverse outcomes, and I think that one thing our translational research, focus has…has
led us to is this whole concept of looking at resilience in these individuals as a way of
identifying ways to culturally and appropriately intervene. So, the malnutrition-poverty cycle.
My mentor in the 19…’60s, actually, from 1968 until his death in 1973 was Herbert Birch.
This is a…a very well-known figure, which I have modified over time, which he published as…as a
theoretical figure. Because I think what…what you all may not realize is that until the late 1960s,
all children globally with malnutrition were dying, and it was not until UNICEF contributed
for oral rehydration therapy that these children finally began to survive, and the question of
quality of life became a significant issue, and it was at that time that this particular version of
this slide was published. What we have done over the past 50 years is basically fill in the pieces
of this entire picture in terms of trying to look at how the generational process continues. And
if you look under the word “malnutrition” and a couple of other places, I have indicated
areas where I think, you know, we have a lot of opportunity in terms of further…
further research studies, specifically looking at mechanisms underlying how these effects occur
and…and how we understand the whole concept of resilience. So, I’d like to take the next few
minutes to talk about what I’ve heard the last couple of days and how it relates to my own
experience with…with having worked for 50 years in…in several multigenerational venues. So, again,
you know, you may want to just take this home and, you know, read it, or…or not read it, as the case
may be, but I think we all talked for the last 2 days about how important multigenerational studies
of nutrition are in terms of looking at health outcomes of children and into the next generation.
Again, one of the important take-home messages from the BNS, from the Barbados Nutrition Study,
is that it’s not only limited to the prenatal period. And…and again you know, even Barker many
times, you know, referred to the fact that, that early postnatal environment is equally
important. It really is the entire period from the second trimester to age 2. It’s not just…just the
prenatal period. Everyone talks about the need to standardize methods, which…which we all agree
would be necessary. Many of the very important studies, including studies such as the Dutch
famine and some of the other major famine studies, have a major problem in that the children were
never examined at the time, and we don’t really have precise measures of their nutritional status
at the time that they experienced, the history of malnutrition. It’s really by history, and
by history of exposure, so that was the reason, in part, for undertaking this particular study, which
is a prospective study. So, standardizing methods is…is very important, including measures of other
factors that can influence individuals when they’re exposed to these issues is very important,
so you have to also look at…at other aspects of the environment. We heard a lot this morning about
the broader context of shared environments, neighborhoods, and, most importantly to me,
public policy. I’ve spent a lot of time trying to convince a lot of people that this is all very
meaningful, and we need money to support research in this area and to support interventions in this
area. Do dads matter? Another very important and salient topic, some of our early rodent studies
show that yes, they do, and we’ve heard a lot of really exciting work about yes, they do,
you know, from…from several researchers in the last 2 days. We need to consider both
paternal and maternal contributions as much as possible, and both genetically and otherwise.
The interaction between nutrition and other exposures, including food contaminants, is…is
another very important area. Food can mitigate the effects of…of certain food contaminants,
of proper nutrition, but also the contamination of undernutrition of other exposures is problematic.
Translational research can identify underlying mechanisms and generate hypotheses because
testing in human populations…without our rat work, I wouldn’t have known where to go. It…it
really would have been a fishing expedition, and so, you know, again, I think it’s vitally
important that we support this work, you know, that…that you really need to go from the lab,
you know, to…to…to the larger population and the larger community, which has always been NICHD’s
focus from the get-go. Okay, interdisciplinary approach is critical. Again, as we get more and
more complex and have more and more technology, we have to work in a multidisciplinary way. You know,
I was one of the first people who really pulled in people from a wide array of backgrounds, mostly
because of, you know just wanting to expand and extend, you know, the breadth of our… of our work.
But now, with new technology, we can really do this effectively. We have to think about targeted
intervention programs that are actionable. This has to be a priority. Prevention is the biggest
dimension, but I don’t know that we’re going to be able to prevent undernutrition—especially,
you know, with the COVID experience the last 3 years, it’s out of our control. But we therefore
need to think about certainly early interventions, but I thought Dr. Barker’s, you know, attention
earlier today to opportunities during adolescence are well taken. In 2015, you know, I participated
in an NICHD conference on the interaction between early nutrition and inflammatory factors,
and we actually published a paper on adolescence in Pediatrics, and there’s really no better time
to think of that, intervention for so many reasons. And finally, there is the need,
the ongoing, ever-present need to change public policy. We need to support…we have the opportunity
to support analysis of previously collected data. There is a lot of data that has been collected
multigenerationally, long term that has just been left out there without support, and I think it
would be…this is the time to call it back in, I think we can make use…I’m not saying that you
should not be doing new studies, but I think you can also make use of existing data. And finally,
I’m thrilled to see people here, you know, with K awards you know, at…at junior stages of their
careers because that’s the way to the future is to support the next generation. Finally,
I’d like to, you know…this is just a quick list of all the horrible things that can happen in
multigenerational research. I thought I would…I was originally going to talk about lemons to
lemonade, but I’m actually doing the reverse right now. So, these, these are things that
have happened to me, and everyone else who’s worked in this type of research, and yet we
continue with it because of how important it is. There are attrition factors. The great thing about
the BNS is that we know where 80 to 90% of our population is: 60% of them remain in Barbados,
the rest of them live in Toronto, for the most part. So, it’s been…that’s been a positive thing,
but not… not something a lot of people have benefited from. Not only is there an issue with
methodology and unique, more precise measures, but the other big headache is the fact that
measures change over time. You have different gold standards over time. And so, we have had to…in…in
our multiple waves of data collection, frequently have had to retest using the old measure,
and also include the new measures to be able to see how they compare in the very same populations,
and you’re obligated to do that, but it’s a headache. It’s one of the lovely things about
doing, you know, long-term and multigenerational research. Changing data analytic approaches,
how we deal with missing data, mixed models, all of this is important. I’ve, you know, had to learn
the SAS inside out to be able to…to deal with some of the, data issues. Missing data’s a very big
piece of it. We find, sometimes, retrospectively that we forgot to collect data on certain people,
or they didn’t show up for a particular phase of the study because they had a beauty parlor
appointment. I had that most recently, you know, when we doing our, our NIRS qEEG work.
Another interesting and important challenge is the multidisciplinary approaches because you as a
researcher have to learn new languages, so that’s a real push sometimes. You know, I was sharing
with some of my colleagues yesterday that, you know, when I started to work with my very dear,
wonderful neuro anatomist and learned that they were using [inaudible] to publish, you know,
these highly quoted papers, and here we are, you know, being told that an N of, you know, roughly
550 individuals is too small because there are all these studies out there, you heard it yesterday,
you know, going up to 60,000. You know, it’s learning those languages, not only about ends, but
strategy, and kind of talk to one another, and so on, has…has always been an interesting challenge.
Leadership plans and staff retention are critical. You know, I’ve heard a number…I have a dear
colleague who had an office next to mine, had a 50-year study, and passed away without you know,
leaving someone to…to take over. And NIH usually requires when you’re doing grants to identify,
you know, who the next person in line is, but not everybody takes that seriously. Staff retention,
is a very important piece in a longitudinal study. I have been blessed in Barbados with people
who worked on the study in the 1960s and…and continued until their death, basically, you know,
on the project, but that’s not usual, and staff turnover is a nightmare. IRB challenges people.
IRB challenges with maintaining long-term data is an insurmountable headache, and I am very thankful
for the IRB at Mass General for not giving me a hard time about this. Changes in government
policy. I can remember in 1980, when…when Reagan, took over and I was a U.S. Senate Fellow at that
time, that suddenly we went from a country, you know, under Kennedy, etc., you know, including
focused on nutrition of children in this country, to being told that there is no nutrition issue
anymore. You know, government policy changes all the time, and when you’re working in developing
countries, or working in communities that are at…at greater risk, government policy is a
very big deal. So, I’d just like to conclude with my last three comments, which have…are
a direct statement to NIH, which are, number one, please remember, you’re talking about and thinking
about multigeneration studies. The lack of continuity and funding leads to subject attrition
and loss of staff, and irrevocable changes to a longitudinal study. It can’t happen [inaudible].
Stable funding is urgently needed, and the usual models for NIH of the 5-year limit and the cap. I
mean, we never used to have a cap, now there’s a cap. It’s really problematic when you’re talking
about not only long-term studies, but studies that should be translational and should be
multidisciplinary. These are…are…it’s, it’s very hard to get your epigenetic colleagues
to do anything under $250,000 a year, I can tell you. And finally, grant review.
I mean, you do this all the time, but these multigeneration studies really have
the need for special review process because the ordinary, you know…and…and again, I’ve been on
over 100 study sections, I’ve chaired three of them. We don’t know anything about, you know,
multigenerational, you know, research, and you need…you need a group of reviewers who really can
you know, decipher this, etc. Anyway, that’s it for today, and thank you very much.
MS. KIMBERLEA GIBBS: Thank you so much, Dr. Galler. I invite you to come sit, and—
DR. JANINA GALLER: Okay.
MS. KIMBERLEA GIBBS: We’ll have a quick question and answer session. To our audience,
if you have any questions and you’re online, please drop them in the question and answer
box. I’d like to thank also Dr. Vargas for helping me to navigate and prioritize the questions. So,
let’s get started. We can start in the room and then we’ll transfer over to our virtual
audience. Does anyone have any questions or comments for her? Yes, of course.
DR. ASHLEY VARGAS: Okay. Ashley Vargas. So, Dr. Galler, I can’t talk and see you,
but fantastic presentation. I have a hard question for you, which maybe is no surprise.
We’ve heard a lot about what we know, what we don’t know, we need more observational studies,
we need more intervention. If you had to pick one…or, can you make an argument for why we
need to do more intervention research, are we ready for that? Even policy level,
individual level, whatever, or do you really think the best bang for
the buck is in more observational and more discovery science at this stage?
DR. JANINA GALLER: So, I don’t think you really have to make that choice in the sense that,
you know, I really think that well planned intervention and,
you know, really have…you have the ability to capture a
lot of this information by both looking at intervened and…and non-intervened individuals so,
you know, that’s an opportunity to be able to, to look here. But I really think that, at this point
in time, I think the best bang for the buck is to begin to think about, you know, research that
also drives you know, intervention [inaudible]. I think that we…we need to be able to do that,
and I think we should be able to document all of the various dimensions that have been talked about
the last 2 days, you know, by doing that. Whether it leads to public policy—I would hope as such.
AUDIENCE MEMBER:
Yes. Sure. [inaudible]
Yeah. I was glad to hear about Barbados study. I am from the part of the world. It is really
that malnutrition has been eliminated in Barbados? What about undernutrition? Barbados is a part of
CARICOM, as you may know, is the group of nations, and they have a big problem with
undernutrition. I don’t know about malnutrition. And this varies by ethnicity. they…You know,
CARICOM countries are very multi…multiethnic, so can you talk about the dimensions of that?
DR. JANINA GALLER: Yeah. So, Barbados is a little unusual in that it’s 99% homogenous.
It’s…it’s…it’s not like Trinidad or even Jamaica in terms of…of…of diversity. It’s not particularly
diverse. And 1% are White, and 99% are of African ORIGIN, North…North African…origin, so,
we have less diversity than in other places. There is not a problem with undernutrition at
this point. The problem in Barbados is…is what we have seen globally, which is with overnutrition,
at this point. So, we actually have a…a study funded by a Toronto foundation at this very
moment, you know, look…looking specifically at…at the impact of not only overnutrition,
but the over-representation in our population of…of overnutrition. So, as you know,
the flipside of malnutrition is that when people recover from malnutrition, they frequently enter
a phase of overnutrition, which is exactly what we’re seeing on the island at this point. Now,
in CARICOM countries, there continues to be an issue, indeed, with undernutrition and not so
much frank malnutrition, but with undernutrition, but Barbados has been spared. Barbados actually
is 58 of 189 countries, and it’s actually, believe it or not, much to my consternation,
considered an upper-income country, which means that are not eligible for any funding from
Fogarty. It has been the bane of my existence. It’s really been very, very difficult because,
on the one hand, we…we are classified as a developing country. On the other hand, they’re
seen as an upper-income country. So, its health statistics in terms of mortality, morbidity,
maternal…mortality, in particular, are really excellent, comparable to the U.S. population.
MS. KIMBERLEA GIBBS: Thank you, and we’ll move to our last question. Dr. Buffington?
DR. SHELLY BUFFINGTON: Dr. Galler, excellent talk. And so, I remember from our conversation
yesterday, and then you showing the parameters here on your chart, that you first tried to do
these EEGs, and kind of the larger neuro measurements in the ’70s, and I see this
40-year gap, but I saw another check mark in, you know, the 2010s, right? And so, were…how
were you able to change the cultural perception of those tests, and, obviously coming from an
interest in microbiome [inaudible], they’re not really willing to consider giving fecal samples
so it can be analyzed. Is there any sort of, I guess, lesson to be learned, you know, in your
experience with the EEGs that could be ultimately applied toward, you know, fecal sampling?
DR. JANINA GALLER: That…that’s a really interesting you know, perspective, and…and…and
a great question. So, what we were talking about is the fact that some of the mothers, early on,
when we did EEGs of the children in 1977—they were 5–11 years of age—actually told us that their
children developed, you know, significant migraine headaches a result, you know, they had seizures,
you know, resulting from the EEGs. There were a lot of cultural taboos, you know, insofar
as the work. I…I think what’s changed things is the fact that, you know, exposure to, you know,
the internet, media in general, we provided…we have maintained a terrific communication with
the community, you know, educating them when we publish papers. They are not only given
copies of…of the papers, but we actually talk about it. I give public lectures on the island,
so we really familiarized them with…with the work, and I think that has helped to…for them
to overcome. And when we did the most recent, you know, redo of the qEEG we…we unfortunately don’t
have any really good MRI units on the island, and it’s too complicated to take them off the island,
so we can’t…we can’t do that. But they were…they were more than willing to…to participate with us.
And…and the answer is yes. I mean, I think that over time, they may be more open to…to things
like microbiome studies as more scientific studies on the island are…are published about the benefits
of it. You know, many of the people, not even the physicians, you know, listen in on University of
Miami Medical Center Grand Rounds, and, you know, people are at a very different place in education.
I thought someone was going to, in fact, comment on why the CAARS scores were so much higher the
second generation, and the theory behind that is that the kids all grew up being exposed to
computers and iPads. They…they are each given a computer when they go to school; they have one.
So you know…and again, it’s known that CAARS and attention deficits are higher when kids are using,
you know, this type of medium. So, I…I think there’s an opportunity, but we’re really not there
at this point. In fact, we can’t even collect fecal samples, you know, for…for epigenetics.
They won’t…that’s something else that’s not culturally allowed. We can do tape recordings,
let’s say, of interviews that I have with individuals. But I think that the best solution,
really, is not only their personal education, but also retaining…and again, a very important piece
of the multigenerational long-term study, you have to maintain a connection with the population,
and they have to feel that they are the priority and you’re not simply there in a
colonial way collecting data from them, and not giving them…nothing in return. Unfortunately,
that has been the case in other studies, but not…you know, not in ours, so, yeah.
MS. KIMBERLEA GIBBS: Wow. So, you are getting kudos in the…from,
from the virtual audience. I’ll read it. This is a splendid talk, thank you so much for it,
and I’ll echo that sentiment. Thank you so much. We are going to take a 5-minute break in the room.
[Applause]
We’ll take a 5-minute break in the room and we’ll invite our virtual audience to join us at 3:40.
DR. ASHLEY VARGAS: So, for the virtual audience, us in the room, we’re going to do a breakout session and report
back to you all at 3:40, so that’s why we’re asking you to come back. For those of you in
the room, please hold tight as we work towards getting you together in groups. Thank you,
again. Okay, everyone, Ashley Vargas, NICHD. We’re here to report out from the wonderful
breakout sessions we’ve had in-house here with our speakers, and we want to first thank
the speakers for their time and expertise today, and over the past 2 days, really,
and this all comes to a culmination, hopefully, in these breakout sessions. So, I’m going to start,
and then I’ll have my colleagues who also helped to moderate the breakout sessions introduce
themselves briefly before they do their report out. So, one of the first questions we asked were:
What are the overarching scientific questions that are needed…oops, can’t see that word. To
advance, we’ll go with, the field of multi[generational effects related]
to nutrition forward? So in the first breakout group, we had a couple points. So, the first was
improving the understanding of parents, including fathers, at the biological level and behavioral
levels, and they…the speakers specifically emphasize the effects moderation of parents
on child health outcomes and making sure we capture both mothers and fathers. There was
also an interest in integrating multiple levels, so I think we saw a great break to…yesterday about
more biologically focused individual-level things, and today we focused on family and multilevel
interventions. And so, the speakers emphasized that we needed to bring all of those together
and develop meaningful understanding of how nutrition affects individuals and families
and societies across generations—so, a big task. We also were high…we also were advised
to improve and develop methods that really allow us to identify those critical windows. And so,
we know some of them, but those vary, probably, on an individual situation, and we need to develop
better methods for improving our ability to measure those. And then the very last one is…I…I
almost captured this verbatim, so you can see. We have a speaker who would really love to see
a model where you can effectively layer all these comorbidities into a score. And so, we know that
there are things like the child vulnerability score, and there are some scores out there,
but we wanted to emphasize the opportunities we have to improve on that with a growing body of
knowledge. So, with that, we also had a couple other breakout sessions on this same question,
so I’m going to turn this over to my colleague, Dr. Kellie Casavale from FDA, to take over.
DR. KELLIE CASAVALE: All right, thank you, Ashley. I’m Kellie Casavale, senior science advisor for
nutrition at FDA CFSAN, and if we can go onto the next slide…oh, it’s on…oh, it’s me? Okay. So, we
did hear some of the similar things that speakers in Ashley’s group described, and so multiple
speakers mentioned a number of things, but we also had a lot of variety across the group. And so,
one of the topics that speakers mentioned were also related to the role of the male contribution,
but also, when addressing dyads, to consider not just the mothers, also the mother and father, as
well as including both societal as well biological influences that are influenced by fathers.
There also was some discussion around preclinical models really with a focus on the persistent
effects that may not have been…been teased out, or paid attention to in the past, and really
thinking about those persistent effects from the perspective of the timing of those pieces.
So, there was also comments around work being done on girls, but less being done with boys,
and to understand timing and reproductive health, to go beyond just discussing reproductive health,
focusing just on females, and to focus on both boys and girls because of the
generations of parents. We talked a lot about reversible effects underlying the models,
and so the speakers were very interested in understanding more and studying more about,
you know, there are insults and deficits that occur early in life, but…that have effects,
but are there things that can happen in other stages of life that are positive and can help
to reverse or address those early insults or deficits? There was points made around
in adolescence as being an unappreciated window in this regard on how nutrition
and other inventions—interventions—can be an opportunity. In addition, school-aged children
were thought to be more ignored, with the focus currently being more on preschool and adolescence,
so the data is not really captured kind of consistently across those early life stages.
Similar to the comment that Ashley heard, there was some interest in scales or severity
of acute malnutrition and how that differs from other events that influence outcomes.
There was a comment regarding nutrient and toxic interactions being part of studies,
not just one side or the other. And then, how do we learn…use machine learning to integrate
all of the -omics of this, of what we have learned from past studies to use them as predictors and to
identify those critical windows? And this is our second slide. There’s interest in having a proof
of concept for key exposures, the quote-unquote “sledgehammers,” noting that through the
discussions in this workshop, there’s a…a lot of information being focused on prenatal, F1 and F2,
but not the proof of concept for what those key sledgehammer exposures are multigenerationally.
And then disentangling the genetic from those environmental effects using studies that may use
twin studies and then other methodologies that can help to really identify the…environmental effects.
There’s interest in really looking at natural experiments,
and so, understanding that our world is not static, that things are constantly changing,
and we are constantly living in natural experiments, and so how can we learn from
those situations about what has worked and what has not worked, including what has worked at the
population and policy levels versus more focused individual intervention–level interventions?
And so, really, there was additional comments about focusing on the most vulnerable, but having
those most vulnerable really being the ones that are vulnerable to the multigenerational effects.
There’s interest in studies around the vehicle of transmission of those multigenerational effects.
And then focusing on historical issues. What are the current issues, and how are they a result of
historical issues? And in this regard, there were comments around distinguishing between issues that
are social versus biological drivers, and the interactions of those, specifically over time,
historically leading to the current point in time. As an example of this, evolution of
food marketing, food environments, food cost, and how those impacts have changed over time,
and over generations, and are not static. It was also described that when it comes to studying
disparities and…and…inequalities, that there’s a lack of theoretical bases and frameworks that can
be used to help identify drivers across studies. And I believe that was it, all of that loveliness.
MS. KIMBERLEA GIBBS: Okay, we’ll turn it over to Dr. Sonia…or Dr. Montessa Mitchell to take over.
DR. MONTESSA MITCHELL: So…That’s very low. So, we proposed the second question, which was:
What do you now think are the most immediate actions that should be taken over the next 5
years to move multigenerational effects related to nutrition forward? And with our group,
we really heard that there is a desire to discover which investment stages of
life yield the highest return—so, where do we get the best bang for our buck, as was said earlier?
And they want to identify [audio drop]. So, to wrap it up, the best way to assess nutritional
status over time is still a struggle, and we need to look at what would be most useful in advancing
this area, as well as ideal and…consistent ways to talk to each other to make it easier,
too. There was also interest in exploring innovative markers of nutritional status that are
relevant for capturing multigenerational effects, as well. And so, I’ll go ahead and turn it over.
DR. SONIA ARTEAGA: Hello. I’m Sonia Arteaga. I’m cohort lead with the ECHO Program. So, first I want to say thank you,
because this was really fun. It was fast and furious, and the ideas were flowing,
so that was great, so thank you. Okay, so…so, what did we talk about in the room? So,
one of the first things that came up was have a…a PACE for multigenerational cohorts—and no
one could remember what PACE stands for. I don’t know if anyone now can remember what PACE stands
for, but it’s birth epigenetic cohorts, I believe, at NIEHS, and the idea is getting
all of these multigenerational cohorts together, and how many do we have? Like,
do an…an assessment of that. We also talked about proof of concept with sledgehammer,
so that came up in the first group, too. The importance of standardizing biospecimen
collection, and then providing recommendations for other groups to also do very similar things.
Similar to PACE, finding existing cohorts that have kids and recruiting the parents,
and this comes up later, also. It’s this idea of let’s find those cohorts that have…that
have been ongoing, assess the participants, then assess the grandparent and assess the child,
so you get this three-gen effect. And some examples include GUTS,
which is…I don’t…Growing Up Today Study from the Nurse’s Health Study, and then
the children’s centers at NIEHS could…those are examples of where some of these…we…we
could recruit the children and assess them and their parents and children. The idea was brought
up: Can we do something with electronic health records to construct a multigenerational cohort?
So, that’s another idea. How about supplements to existing original cohort studies to do extra work?
We talked about standardizing protocols and this idea of going backwards and forwards,
like I mentioned—participant, grandmother or grandfather,
and then the child. The idea of developing an equity-based framework for nutrition
research—that really is multigenerational in…in its work, so taking time into account.
Then I…The idea of assessing what is the low-hanging fruit for community-based work? What
is really important for the community? And that can help us with [inaudible]
making the…the results more meaningful and impactful for participants. We also talked
about developing predictive biomarker…biomarkers to identify highest…the highest-risk individuals.
The idea of looking at links between early nutrition and attention challenges in children.
Recruiting more diverse participants—recruiting, retaining, engaging more diverse participants.
Leveraging other epigenetic clocks, how to integrate predictive information. Also,
this idea came up of geographical mobility and assessing the impact on nutrition. How
do we capture it? So, how do we develop a tool to do that? So, it’s the idea that someone’s
parents came from Mexico, then they moved to California, and now their kids are in Maryland,
or something like that. How do we assess those contextual geographical variables?
Also, talking to methodologists to develop better methods,
especially when it comes to interventions. More opportunities for us to get together,
not…for different disciplines. So, this gets to the intersectoral collaborations, so, how do
you allow behavioral and social sciences to all come together. Looking at…outcomes that
are just…that are just [inaudible], but also other outcomes that are of…of interest to participants,
such as quality of life, education. The idea, also, of doing these…we do multisite trials
all the time. How about doing multisite animal studies with some of our controls?
Doing more…replication studies. And this one I did not put down, but it did come up: Leverage
ECHO to do a lot of what has been mentioned up above. Like I said, I did not mention that;
someone else did. So, that’s why it’s up. So, yeah. So, that’s what our group discussed.
UNIDENTIFIED SPEAKER: Okay. I want to thank our moderators and our notetakers and our participants.
These are all individual ideas that speakers came up with, not a consensus, but NIH is really
appreciative of all these different ideas, and I hope that the audience is also appreciative of
this ideas, and we’ll see some really great grants coming in eventually from some of you, leveraging
from the…the connections you’ve made today or yesterday with your multidisciplinary colleagues.
So, with that, I’m going to turn it back over to Dr. Krista Zanetti to close us.
DR. KRISTA ZANETTI: Okay.
So, I think after the last 2 days, we realize that we can honestly probably spend an entire
5 days discussing this topic or more. But at the same time, we all have day jobs, and we have a lot
of things going on, so we had to, you know, really think about what we could fit in to reasonable a
2-day meeting to think about the breadth of what is in this space. So, it was a lot, and I think
that we’ve learned a lot, and I think that we have a lot of really good feedback and individual ideas
that came in. The potential ideas and things to be considered to move this field forward.
And I know it’s also tough, the hybrid format, and…and I know a lot of people broadcasted,
and I want to thank you all for hanging in there with us; it’s been a long time since we’ve put one
of these meetings on. So, we’ve been really…we were really excited to have the opportunity to
bring speakers into the NIH and have them here, and we were also really thrilled to have the
opportunity to broadcast it out to all of you. So, we know there were some technical difficulties,
and we appreciate your patience and hanging in there with us, and we thank you so much for
attending. So, having said that, I’m going to move on to some additional thank yous. First, I want to
thank the organizing [committee]. I’m not going to read all the individual names out, as it’s a lot
and it’s the end of the day, and here we have it on the slide. But what I do…I’d rather take that
time to say thank you so much to the organizing committee. My sincerest gratitude to you. You
have been amazing to work with. And we have had meetings of almost every week for the last 5
months, and the individuals you see listed here really stepped up to the plate, and they were
committed to make this meeting happen. They were fantastic to work with. They were…it was fun…the
meetings just talking about this, thinking about how to have this meeting and thinking
about the…the commitment and ideas and everything that kind of goes into whether or not you want to
spend, you know, an hour-plus a week when you have many things on your plate to keep meeting
and meeting. You know, sometimes it’s asking a lot, and these individuals really…I couldn’t have
been happier to work with them, so thank you all so much, and I want to give a special shout-out
to Kimberly Barch, and she did all of the logistics for the meeting, as far as the emailing
and making sure that Dr. Vargas and I dotted our i’s and crossed our t’s and made sure we didn’t
forget anything. And I also want to send a special shoutout to Janiya Peters, who was also logistics
and made sure everything ran, our Zoom was up and going, thinking of everything from getting
the room, making sure it was set up, and all of those little things that sometimes we forget
to make sure that this meeting happened, and it happened very well, so I want to thank all of you.
And I couldn’t get them up here…and then, I also, of course,
want to thank our speakers. We know that it’s the middle of summer. We know that some of you
had to shift around for your vacations and time with family, and some of you were able to come
one day but not the other because you already had commitments, but you said, “Hey, I will fly in in
the morning, I will present, I will fly out in the evening, I will jump on Zoom the next day to the
breakout sessions and to watch,” and…and I know we asked a lot for you being in the middle of July,
but we couldn’t be happier that you all accepted our invitation to participate, to present, and
to give us a lot to think about. And I think that we…we saw so…so much in how much goes into this,
you know, multigenerational nutritional influences space over the last 2 days,
and we couldn’t have done it without all of you, and I thank you so much for…for…for coming,
for presenting, for letting us pick your brains during the breakout sessions. We thank you.
[Applause]
So…and I know that after 2 days, we are all tired, and I know the participants watching
in…watching the broadcast are also probably tired because it was a lot,
so I don’t want to belabor the point. I think we can wrap up this…yes, Drew?
AUDIENCE MEMBER (DREW): Oh, how about Krista and Ashley?
DR. KRISTA ZANETTI: Thank you very much.
I will say, it is very easy to work with Ashley, so that’s what makes…that’s what made this a lot
easier. Very, very easy. Very easy to work with Ashley, so it’s a joy. So, you know, I…I know
we all…all want to…get onto flights and trains and things, and…and…and…you know, and for those
of us in D.C., get back into the traffic and get home, so for those of you that are participating
virtually, thank you so much. We thank you for coming. Oh, we have a question. Mary.
AUDIENCE MEMBER (MARY): I just want to ask, what happens next?
DR. KRISTA ZANETTI: Oh. Well, we will evaluate the information, we will look at it, and we will…you
know, think about what those next steps are. A lot of that…a lot goes into that, including,
you know, planning, and we will be in touch after, so, you know, a lot goes into,
kind of…we will be thinking forward, and you all will probably be getting emails from us
in the not-too-distant future. So, are there any other questions before we wrap up? Yes,
one in the back? It’s like, you’re like, as soon as I’m ready to wrap up,
there’s going to be a hand. One more. Do you want to turn your microphone on?
AUDIENCE MEMBER: A few of us have been chatting…over the last couple of days about the workshop,
paper, for…that…not just involves NIH staff but also some of us who,
of course, would volunteer. Will one of those emails be a solicitation, or…?
DR. KRISTA ZANETTI: Yes, I think if the speakers want to write white papers, of course, we’re
not…we’re not going to not support that. We’re going to support that wholeheartedly. So, that
will be some of the future emails that you get. So, those of you that are in the room, be thinking
about whether you want to participate in that. And also, you know, you have a long flight home or a
train ride; think about, maybe, some of the ideas on what a white paper you might want to write is.
You know, even though you’re all probably going to want to just take a nap. But think about that
on the way out. So, I think we have a lot to look forward to, and it’s been a long 2 days for us,
and I want to wrap up. And I just want to thank you all again, and we look forward to continuing
to think about this important space. So, everybody have a great rest of your day.
[Applause]