>> GOOD AFTERNOON, EVERYBODY.
WELCOME TO THE NIH DIRECTOR'S
LECTURE.
IT'S MY PLEASURE TODAY -- MY
NAME IS DARRELL, I'M THE
SCIENTIFIC DIRECTOR AT NIEHS.
IT'S MY PLEASURE TO INTRODUCE
DR. KELLEY FERGUSON AS THE
SPEAKER.
DR. FERGUSON RECEIVED HER
MPH DEGREE IN OCCUPATIONAL AND
ENVIRONMENTAL EPIDEMIOLOGY IN
2011.
AND HER PH.D. IN ENVIRONMENTAL
HEALTH SCIENCES FROM UNIVERSITY
OF MICHIGAN PUBLIC HEALTH SCHOOL
IN 2014.
SHE JOINED OUR EPIDEMIOLOGY
BRANCH AS A TENURE TRACK
INVESTIGATOR IN 2016.
SHE'S A LEADER IN HER FIELD.
HER SCIENCE FOCUSES PRIMARILY ON
ENVIRONMENTAL CHEMICAL EXPOSURES
AND BOTH PERINATAL AND EARLY
LIFE HEALTH OUTCOMES, AND SHE'S
MADE MAJOR CONTRIBUTIONS TO THE
UNDERSTANDING OF HOW EXPOSURES
TO PHTHALATE PLASTICIZERS WHICH
ARE UBIQUITOUS IN THE
ENVIRONMENT IMPACT PREGNANCY AND
THE DEVELOPMENT OF THE FETUS AND
THE CHILD.
TODAY SHE'LL TALK ABOUT SOME OF
HER RECENT WORK IN THE
RELATIONSHIP BETWEEN PHTHALATE
EXPOSURE AND PRETERM BIRTH, WORK
RECENTLY PUBLISHED IN
> JAMA
PEDIATRICS IN 2022.
THIS WAS A CULMINATION OF HER
EFFORTS TO ESTABLISH A LARGE
CONSORTIUM OF ENVIRONMENTAL
HEALTH COHORTS.
DR. FERGUSON HAS PUBLISHED OVER
140 PEER REVIEWED MANUSCRIPTS,
MANY OF WHICH HAVE APPEARED IN
THE TOP JOURNALS IN HER FIELD.
SHE'S ALSO BEEN RECOGNIZED BY
NUMEROUS AWARDS, INCLUDING THE
GILLETTE OUTSTANDING YOUNG
INVESTIGATOR AWARD IN 2020, AND
ONE OF THE 20 PIONEERS UNDER 40
IN ENVIRONMENTAL PUBLIC HEALTH
IN 2017.
AT NIEHS, SHE IS AN OUTSTANDING
MENTOR WHO HAS SUCCESSFULLY LED
NUMEROUS TRAINEES TO TENURE
TRACK POSITIONS IN ACADEMIA AND
ALSO THEIR RECEIPT OF K99/R OH
K99/R00 AWARDS.
SHE'S RECEIVED NIH TENURE ABOUT
A YEAR AND A HALF AGO, IN 2022.
SO THE TITLE OF HER TALK TODAY
IS PHTHALATE EXPOSURE IN PRETERM
BIRTH, FINDING FROM A POOLED
STUDY OF 16 U.S. COHORTS.
DR. FERGUSON.
>> THANK YOU SO MUCH FOR THAT
INTRODUCTION, DARRELL, AND THANK
YOU SO MUCH FOR THE INVITATION
TO BE HERE TODAY.
IT'S REALLY AN HONOR TO BE HERE
ON MAIN CAMPUS AND TO BE ABLE TO
SHARE SOME OF THIS WORK WITH
YOU.
SO AS DARRELL SAID, THE TITLE OF
MY TALK TODAY IS PHTHALATES IN
PRETERM BIRTH, A POOLED ANALYSIS
OF 16 U.S. COHORTS, AND I'M
GOING TO TALK ABOUT THE EFFORTS
THAT I LED TO CREATE A
CONSORTIUM TO INVESTIGATE THIS
IMPORTANT RESEARCH QUESTION.
I WANTED TO START OFF WITH AN
OVERVIEW OF MY RESEARCH GROUP
AND WHAT WE DO AT NIEHS.
MY OVERARCHING OBJECTIVE IS TO
IMPROVE THE UNDERSTANDING OF HOW
THE ENVIRONMENT IMPACTS
PREGNANCY AND CHILDHOOD HEALTH.
I STUDY ENVIRONMENTAL CHEMICAL
EXPOSURES, PARTICULARLY
NON-PERSISTENT CHEMICAL EXPOS
EXPOSURES, HOW THEY INFLUENCE
PREGNANCY AND CHILD HEALTH, AND
THE ROLE OF OXIDATIVE STRESS AND
INFLAMMATION AS POTENTIAL
MECHANISMS MEDIATING THOSE
RELATIONSHIPS.
MY OVERARCHING HYPOTHESIS IS
THAT THE ENVIRONMENTAL CHEMICAL
EXPOSURES THAT WE EXPERIENCE
DAILY ADVERSELY IMPACT PREGNANCY
AND CHILD HEALTH OUTCOMES AND
THAT OXIDATIVE STRESS AND
INFLAMMATION PLAY A PIVOTAL ROLE
IN THOSE RELATIONSHIPS.
SO THE OUTLINE FOR MY TALK
TODAY, I'M GOING TO START WITH
PHTHALATE EXPOSURE, HOW DO I
PRONOUNCE IT AND WHY SHOULD I
CARE, THEN I'M GOING TO MOVE ON
TO DESCRIBING THIS POOLED STUDY
OF PHTHALATE EXPOSURE IN PRETERM
BIRTH IN WHICH WE'VE ADDRESSED
THREE PRIMARY RESEARCH
QUESTIONS.
FIRST, WHAT IS THE ASSOCIATION
BETWEEN PHTHALATE EXPOSURE AND
PRETERM BIRTH?
SECOND, ARE THERE KEY PERIODS OF
SUSCEPTIBILITY TO A PHTHALATE
EXPOSURE FOR THIS RELATIONSHIP?
AND THIRD, HOW DO EXPOSURES TO
PHTHALATES DIFFER BY RACE AND
ETHNICITY, AND COULD THESE
DIFFERENCES CONTRIBUTE TO THE
DISPARITIES THAT WE
SIMULTANEOUSLY OBSERVE IN RATES
OF PRETERM BIRTH.
I'LL TIE UP WITH SOME MESSAGES
ABOUT THE PUBLIC HEALTH IMPACT
OF MY FINDINGS.
SO PHTHALATE EXPOSURE.
THESE ARE KNOWN AS THE
EVERYWHERE CHEMICALS.
THEY'RE FOUND IN OUR ENVIRONMENT
UBIQUITOUSLY.
THESE ARE SLIGHTLY DIFFERENT
THAN THE FOREVER CHEMICALS, LIKE
PFAS.
THEY'RE METABOLIZED QUICKLY IN
OUR BODIES, BUT NEVERTHELESS,
WE'RE EXPOSED TO THEM CONSTANTLY
ON A DAILY BASIS.
THEY'RE USED IN PLASTICS BECAUSE
THEY CAN INCREASE FLEXIBILITY
AND DURABILITY OF THE PLASTICS
THAT THEY'RE ADDED TO, AND
THEY'RE CHEAP.
SO WHEN YOU'RE LOOKING AT THE
RECYCLING SYMBOLS ON YOUR
PRODUCTS, PHTHALATES ARE
CONTAINED IN THOSE THAT ARE
LABELED WITH THE 3.
IN PERSONAL CARE PRODUCTS,
THEY'RE ALSO USED AS SOLVENTS
FOR OTHER COMPOUNDS LIKE
FRAGRANCES.
SO THEY'RE FOUND UBIQUITOUSLY IN
THE ENVIRONMENT IN FOOD AND
BEVERAGES, PERSONAL CARE
PRODUCTS AND MANY OTHER
MATERIALS AND WE'RE CONSTANTLY
EXPOSED TO THEM.
I'M GOING TO TALK A LITTLE BIT
MORE ABOUT SOME OF THE KEY
EXPOSURE PATHWAYS FOR
PHTHALATES.
PROBABLY THE MOST IMPORTANT IS
INGESTION.
PHTHALATES MAKE THEIR WAY INTO
FOOD THROUGH THE ENVIRONMENT, SO
PHTHALATES CAN BE FOUND IN SOIL,
WATER AND AIR.
THEY CAN MAKE THEIR WAY DIRECTLY
INTO THE FOOD A THAT WAY.
THEY'RE INVOLVED IN PROCESSING
MATERIALS, SO THEY CAN INTERACT
WITH FOOD THROUGH THAT AND
THEY'RE ALSO IN PLASTIC
PACKAGING OF FOODS.
ONCE THEY MAKE THEIR WAY INTO
THE BODY, THEY ARE READILY
ABSORBED THROUGH THE DIGESTIVE
TRACT INTO THE BLOODSTREAM.
"CONSUMER REPORTS" RECENTLY DID
A KIND OF MARKET BASKET SURVEY
EXAMINING LEVELS OF PHTHALATES
AS WELL AS BUSINESS PH BISPHENOD
DETECTION OF PHTHALATES IN
ALMOST ALL OF THE FOODS THAT
THEY ANALYZED.
THE ONE EXCEPTION WAS I THINK
POLAR SPRING SELL THE SELTZER W.
I WANTED TO HIGHLIGHT THIS
PARTICULAR EXPOSURE SOURCE.
ONE OF THE HIGHEST LEVELS OF
EXPOSURE THAT THEY OBSERVED IN
THEIR SURVEY WAS IN PREPARED
MEALS.
SO THESE ARE THINGS LIKE FREEZER
PIZZAS, PREPARED SOUP AND PASTAS
THAT ARE IN CANS AND OTHER
CONTAINERS.
AND THE HIGHEST CONCENTRATION
THAT THEY OBSERVED WAS IN
ANNIE'S ORGANIC CHEESY RAVIOLI
IN A CAN.
I THOUGHT THIS WAS A LITTLE
IRONIC SINCE A COUPLE YEARS AGO
ANNIE'S PLEDGED TO PURGE THIS
CLASS OF CHEMICALS FROM THEIR
FOODS BUT IT KIND OF SHOWS YOU
THE DIFFICULTY IN ADDRESSING
THIS EXPOSURE WHEN IT COMES TO
OUR FOOD SUPPLY.
ANOTHER PRIMARY ROUTE OF
PHTHALATE EXPOSURE IS THROUGH
DERMAL ABSORPTION.
PHTHALATES ARE USED AS ADDITIVES
IN MANY PERSONAL CARE PRODUCTS.
THINGS LIKE PERFUMES, SKIN
TONERS, LOTIONS AND CREAMS,
LIPSTICK, HAIR PRODUCTS, NAIL
POLISH, THEY'RE ALSO FOUND IN A
LOT OF FEMININE CARE PRODUCTS.
SO THIS PLOT ON THE RIGHT IS
FROM A RECENT PAPER WHERE THEY
ANALYZED PHTHALATES IN DIFFERENT
FEMININE CARE PRODUCTS,
INCLUDING PADS, PANTY LINERS,
TAMPONS AND WIPES AND FOUND
DETECTABLE LEVELS IN MANY OF THE
PRODUCTS THAT THEY ANALYZED.
PHTHALATES ARE READILY ABSORBED
THROUGH THE SKIN THROUGH CONTACT
WITH THESE MATERIALS.
IN ADDITION, INHALATION IS AN
IMPORTANT EXPOSURE PATHWAY.
SO PHTHALATES ARE USED AS
PLASTICIZERS IN POLLLY VINYL
CHLORIDE PLASTIC WHICH ARE
INCLUDED IN A LOT OF HOUSEHOLD
MATERIALS SUCH AT VINYL FLOORS
AND SHOWER CURTAINS.
THEY'RE NOT COVALENTLY BOUND TO
THESE MATERIALS SO THEY'RE
EASILY RELEASED INTO THE AIR AND
THEY CAN BE COMMONLY DETECTED IN
HOUSE DUST.
ONCE PHTHALATES MAKE THEIR WAY
INTO THE HUMAN BODY, THEY HAVE
SHORT HALF LIVES, ON THE COURSE
OF 12 TO 48 HOURS.
AFTER WHICH THEY'RE EXCRETED
PRIMARILY IN THE URINE.
BECAUSE OF THIS SHORT HALF-LIFE,
MEASURING CONCENTRATIONS OF
PHTHALATE METABOLITES IN A
SINGLE SAMPLE IS NOT A GREAT
ESTIMATE OF EXPOSURE.
THE GOLD STANDARD IS TO MEASURE
CONCENTRATIONS IN REPEATEDLY
COLLECTED URINE SAMPLES.
DESPITE THE RAPID ELIMINATION OF
PHTHALATES FROM THE BODY, WE
HAVE UNIVERSAL DETECTION IN
URINE SAMPLES FROM HUMAN
POPULATIONS WORLDWIDE, INCLUDING
PREGNANT PEOPLE.
I WANTED TO GIVE YOU A COUPLE OF
EXAMPLES OF THE PHTHALATES THAT
WE ANALYZE.
SO TRADITIONALLY WHEN WE'RE
DOING A STUDY ON PHTHALATES,
WE'LL MEASURE METABOLITES,
MEASURE MAYBE 10 OR 20 PHTHALATE
METABOLITES IN THE SAMPLE.
THERE'S A COUPLE I'M GOING TO
EMPHASIZE TODAY SO I WANTED TO
INTRODUCE YOU TO THEM BRIEFLY.
ONE IS DI-2ETH ILL HEX ILL
PHTHALATE, OR DEHP.
THIS IS A PHTHALATE THAT HAS
BEEN STUDIED PROBABLY THE
LONGEST AND IS THOUGHT TO BE ONE
OF THE MORE TOXIC PHTHALATES.
IT'S USED PRIMARILY TO SOFTEN
PLASTICS AND IN THE BODY IT'S
METABOLIZED INTO THESE FOUR
COMPOUNDS.
WE ANALYZE CONCENTRATIONS OF
THOSE METABOLITES IN URINE AND
I'M GOING TO PRESENT THEM AS A
SUMMED MEASURE BECAUSE THEY ALL
REPRESENT EXPO TOUR TO THE
PARENT COMPOUND DEHP.
ON THIS PLOT, I'M SHOWING
URINARY CONCENTRATIONS OF THE
SUMMED DEHP METABOLITES IN THE
NATIONAL HEALTH AND NUTRITION
EXAMINATION SURVEY IN THE GREY
BARS, AND IN A PREGNANT
POPULATION THAT I STUDY IN THE
YELLOW DOTS.
YOU CAN SEE EXPOSURE TO THESE
COMPOUNDS HAS BEEN DECREASING
OVER TIME, STARTING FROM 2007 TO
2008 TO 2017 TO 2018.
BUT DESPITE THIS DECREASE IN
EXPOSURE, WE'RE STILL ABLE TO
DETECT THESE METABOLITES IN
PREGNANT POPULATIONS.
ANOTHER COUPLE OF COMPOUNDS THAT
I'M GOING TO TALK ABOUT A LOT
ARE DI-N AND DI-ISOBUTYL
PHTHALATE.
THESE ARE USED IN BOTH PERSONAL
CARE PRODUCTS AND PLASTICS SO
THEY HAVE A MORE WIDE VARIETY OF
APPLICATIONS AND THEY'RE
METABOLIZED INTO MBP AND MIBP
RESPECTIVELY.
EXPOSURE HAS BEEN DECREASING AS
WELL BUT IT'S A LITTLE BIT MORE
CONSTANT OVER TIME COMPARED TO
WHAT WE SEE FOR DEHP.
PHTHALATES HAVE KNOWN TOXICITY.
SO THE PRIMARY TOXICITY THAT HAS
BEEN EVALUATED IN ANIMAL AS WELL
AS IN VITRO STUDIES IS THEIR
ENDOCRINE DISRUPTING ACTIVITY
AND THEY'RE KNOWN TO BE
ANTIANDROGENIC.
ADDITIONALLY THEY HAVE BEEN
SHOWN TO ACTIVATE -- ESSENTIALLY
INVOLVED IN THE EARLY INITIATION
OF LABOR.
IN EARLY CASE CONTROLLED STUDIES
OF PHTHALATE EXPOSURE AND
PRETERM BIRTH SHOW THAT
INDIVIDUALS WITH HIGHER
EXPOSURES WERE MORE LIKELY TO
DELIVER PRETERM.
THIS WORK IN THE EARLY 2000s
LED THE ESTABLISHMENT OF THIS
HYPOTHESIS THAT PRENATAL
EXPOSURE TO PHTHALATES CREATES
AN ENVIRONMENT OF INTRAUTERINE
INFLAMMATION WHICH CAN
PRECIPITATE PRETERM BIRTH.
BECAUSE OF THIS HYPOTHESIS, I
STARTED MY DISSERTATION WORK AT
THE UNIVERSITY OF MICHIGAN.
IN THAT WORK, I WORKED WITH THE
LIFECODES PREGNANCY COHORT BASED
OUT OF THE BOSTON AREA AND
INCLUDES PREGNANT WOMEN
RECRUITED FROM 2006 TO 2008.
IN THIS PROSPECTIVE COHORT, WE
SELECTED 130 CASES OF PRETERM
BIRTH AS WELL AS 350 CONTROLS
AND ANALYZED THE URINE SAMPLES
COLLECTED DURING PREGNANCY FOR
PHTHALATE METABOLITE
CONCENTRATIONS IN SAMPLES FROM
THREE DIFFERENT STUDY VISITS.
AS I SAID EARLIER, ANALYZING
CONCENTRATIONS IN A SICKLE
SAMPLE IS LIMITED, SO THIS STUDY
REALLY IMPROVED ON EXPOSURE
ASSESSMENT IN THE FIELD BY
ANALYZING CONCENTRATIONS AT
MULTIPLE TIME POINTS.
WE EXAMINED ASSOCIATIONS WITH
ODDS RATIOS OF PRETERM BIRTH AND
OBSERVED THAT MBP AS WELL AS THE
SUMMED DEHP METABOLITES WERE
ASSOCIATED WITH AN INCREASED
ODDS OF PREMATURITY.
SINCE COMING TO NIEHS, I'VE
REPLICATED THIS FINDING IN OTHER
COHORTS AS WELL.
WITHIN THE TIDE STUDY FROM 2010
TO 2012, EXAMINED ASSOCIATIONS
IN A POPULATION OF ABOUT 630
CONTROLS AND 60 PRETERM BIRTHS,
AND AGAIN, WE ANALYZED
PHTHALATES AND METABOLITE
PLEASURES FROM THREE STUDY
VISITS.
IN THIS STUDY WE ALSO OBSERVED
ASSOCIATIONS BETWEEN MBP AND DHP
METABOLITES IN PRETERM BIRTH AS
WELL AS MIBP ALTHOUGH THE
ASSOCIATIONS WERE A LITTLE BIT
LESS PRECISE BECAUSE WE HAD A
SMALLER NUMBER OF CASES COMPARED
TO THE LIFECODES STUDY.
BUT IT WAS INTERESTING TO US
THAT THE EFFECT SIZES WERE VERY
SIMILAR TO WHAT WE OBSERVED IN
LIFECODES.
ADDITIONALLY, I EXAMINED THIS
ASSOCIATION IN THE PROTECT
COHORT, WHICH IS THE PUERTO RICO
TEST SITE FOR EXPLORING
CONTAMINATION THREATS, AND THIS
IS A SUPERFUND RESEARCH PROGRAM
STUDY BASED IN PUERTO RICO.
THIS STUDY INCLUDED PARTICIPANTS
FROM 2011 TO 2017, AND HAD A
SAMPLE SIZE OF ABOUT A THOUSAND.
AND THIS STUDY, WE ALSO OBSERVED
ASSOCIATIONS BETWEEN MBP AND
MIBP IN PRETERM BIRTH.
WE DID NOT OBSERVE ASSOCIATIONS
WITH DEHP METABOLITES IN THE
STUDY POPULATION, BUT NOTABLY,
EXPOSURE LEVELS WERE
SIGNIFICANTLY LOWER THAN WHAT WE
OBSERVED IN THE OTHER STUDIES
THAT I PRESENTED ON.
SO THOSE ARE THE STUDIES THAT I
WORKED IN.
THESE ARE SOME OF THE OTHER
STUDIES UP UNTIL 2021 THAT ALSO
EXAMINED ASSOCIATIONS BETWEEN
PHTHALATE EXPOSURE IN PREGNANCY
AND GESTATIONAL AGE AT DELIVERY.
AND I WANT TO POINT OUT A COUPLE
OF CHARACTERISTICS OF THESE
STUDIES.
FIRST, MOST OF THEM HAD A VERY
SMALL NUMBER OF PRETERM BIRTHS.
THE LARGEST THAT WAS INCLUDED
WAS A STUDY WITH 134 PRETERM
BIRTHS.
SOME OF THEM DIDN'T REPORT ON
NUMBER OF PRETERM BIRTHS AT ALL.
SECOND, MOST OF THESE STUDIES
RELY ON EXPOSURE ASSESSMENT IN A
SINGLE SPOT URINE SAMPLE, WHICH
AS I SAID HAS ITS LIMITATIONS.
AND FINALLY, THE RESULTS FROM
THESE STUDIES ARE FAR FROM
CONCLUSIVE.
IN THIS TABLE, I'M SHOWING YOU
THE PHTHALATE METABOLITES THAT
WERE ASSOCIATED WITH EITHER
LONGER GESTATIONAL DURATION OR
SHORTER GESTATIONAL DURATION,
AND YOU CAN SEE IT'S KIND OF
MIXED IN BOTH DIRECTIONS, AND AN
EMPTY CELL INDICATES NULL
FINDINGS.
THERE'S A LOT OF NULL FINDINGS
IN THE FIELD AS WELL.
NEVERTHELESS, WE BELIEVE THERE'S
BIOLOGIC PLAUSIBILITY FOR
RELATIONSHIP BETWEEN PHTHALATE
EXPOSURE AND PRETERM BIRTH AND
THE PRIMARY MECHANISM THAT WE
SUSPECT TO BE INVOLVED IN
OXIDATIVE STRESS AND
INFLAMMATION IN PREGNANCY.
IN VITRO STUDIES SHOW THE
CAPACITY OF PHTHALATES TO CAUSE
OXIDATIVE STRESS AND
INFLAMMATION AND PHTHALATES HAVE
BEEN ASSOCIATED WITH OXIDATIVE
STRESS AND INFLAMMATION
BIOMARKERS IN PREGNANT WOMEN.
FINALLY, OXIDATIVE STRESS AND
INFLAMMATION PATHWAYS ARE WELL
ESTABLISHED MECHANISMS THAT LEAD
TO PRETERM BIRTH.
IN THE LIFECODES STUDY THAT I
MENTIONED EARLIER, WE
INVESTIGATED ASSOCIATIONS
BETWEEN PHTHALATE METABOLITES
AND THE OXIDATIVE STRESS
BIOMARKER 8 ICE TOE
PROSTAGLANDIN A2 ALPHA.
IN THAT STUDY WE FOUND THIS
MARKER WAS ASSOCIATED WITH
PRETERM BIRTH AND ALSO WITH
PHTHALATE EXPOSURE AND THAT IT
STA TIS TI LICK MEDIATED THE
ASSOCIATION BETWEEN PHTHALATE
EXPOSURE AND PRETERM BIRTH.
SINCE THAT TIME WE'RE EXPANDING
ON OUR INVESTIGATION OF THIS
OXYLIPIN TO STUDY OTHERS.
SO 8 ISOPROSTAGLANDIN IS
PRODUCED NON-ENZYMATICALLY BUT
THERE ARE MANY OTHERS PRODUCED
ENZYMATICALLY FROM FATTY ACIDS
THROUGH SPECIFIC ENZYMATIC
PATHWAYS.
SO WE'RE STUDYING HOW CHEMICAL
EXPOSURES ARE RELATED TO THESE
MORE SPECIFIC UPSTREAM
REGULATORS OF INFLAMMATION.
THIS IS A FIGURE FROM AN
EXPLORATORY EARLY STUDY WHERE WE
EXAMINED PHTHALATE METABOLITES
AS WELL AS OTHER CHEMICALS THAT
ARE FOUND IN PERSONAL CARE
PRODUCTS IN PLASTICS, AND
EXAMINED ASSOCIATION WITH PLASMA
MARKERS OF OXYLIPINS FROM
DIFFERENT PARENT FAT FATTY ACIDO
LIN LAKE ACID, AROCK DONG ACID,
DH AMOUNT AND EPA THROUGH
SPECIFIC ENZYMATIC PATHWAYS.
WE OBSERVED SOME INTERESTING
ASSOCIATIONS IN THIS PRELIMINARY
STUDY.
FOR EXAMPLE, BETWEEN SOME OF THE
PHTHALATE METABOLITES AND THE
EPOMES AND DIOMES.
SO THIS IS SOME OF THE
MECHANISTIC WORK WE'RE
CONTINUING TO INVESTIGATE
INDEPENDENTLY OF THE STUDY I'M
PRESENTING TODAY.
SO THIS BRINGS ME TO THE POOLED
STUDY.
WE SAW THIS KIND OF AMBIGUITY IN
THE EPIDEMIOLOGIC LITERATURE BUT
WE HAVE STRONG PLAUSIBILITY, SO
I ESTABLISHED THIS POOLED
CONSORTIUM OF 16 U.S. COHORTS TO
ADDRESS THREE PRIMARY RESEARCH
QUESTIONS.
FIRST WHAT IS THE ASSOCIATION
BETWEEN PHTHALATE EXPOSURE AND
PRETERM BIRTH.
SECOND, ARE THERE PERIODS OF
SUSCEPTIBILITY TO PHTHALATE
EXPOSURE DURING PREGNANCY.
AND THIRD, HOW DO EXPOSURES TO
PHTHALATES DIFFER BY RACE AND
ETHNICITY AND COULD THESE
DIFFERENCES CONTRIBUTE TO THE
CONCURRENT DISPARITIES THAT WE
OBSERVE IN RATES OF PRETERM
BIRTH.
TO START OFF, WE PERFORMED A
SYSTEMATIC REVIEW TO IDENTIFY
U.S. STUDIES WITH PRENATAL
URINARY PHTHALATE METABOLITE
MEASUREMENTS.
WE IDENTIFIED 21 UNIQUE
PROSPECTIVE STUDIES.
FIVE OF THESE WERE EXCLUDED
EITHER DUE TO SMALL SAMPLE SIZE
OR THERE WAS ONE CORE HORT THAT
DID NOT RESPOND.
SO OUR FINAL SAMPLE SIZE FOR
THIS STUDY INCLUDED 16 U.S.
COHORTS WITH OVER 6,000
PARTICIPANTS AND 538 CASES OF
PRETERM BIRTH.
THE NAMES OF THE STUDIES AND THE
SAMPLE SIZES ARE SHOWN HERE.
PARTICIPANTS WERE RECRUITED FROM
ACROSS THE U.S. AND FROM PUERTO
RICO.
10 OF THE 16 STUDIES RECRUITED
PARTICIPANTS IN THE FIRST HALF
OF PREGNANCY AND THE DELIVERIES
OCCURRED ACROSS THREE DECADES
STARTING IN THE 80s.
IN TERMS OF EXPOSURE ASSESSMENT,
WE INCLUDED 11 PHTHALATE
METABOLITES LISTED HERE THAT
WERE MEASURED IN 10 OR MORE OF
THE COHORTS.
AND FOR MOST STUDIES, PHTHALATE
METABOLITES WERE ANALYZED AT THE
CENTERS FOR DISEASE CONTROL AND
PREVENTION.
PHTHALATE METABOLITE
CONCENTRATIONS WERE CORRECTED
FOR URINE DILUTION AND AFTER
THAT, REPEATED MEASUREMENTS
WITHIN PARTICIPANT WERE AVERAGE.
SO FOR SOME PARTICIPANTS IN THIS
STUDY, WE HAD A SINGLE SPOT
URINE SAMPLE IN WHICH WE
ANALYZED PHTHALATES, BUT FOR
SOME PARTICIPANTS, WE HAD MORE
THAN ONE.
AND SO TO REDUCE THOSE INTO A
SINGLE EXPOSURE METRIC FOR
PARTICIPANT, WE CREATED A
GEOMETRIC AVERAGE.
THIS PIE CHART IS SHOWING YOU
THE NUMBER OR PROPORTION OF
PARTICIPANTS FOR WHICH WE HAD
ONE MEASUREMENT INCLUDED IN THE
AVERAGE VERSUS TWO, THREE OR
FOUR OR MORE.
FOR OUT COME ASSESSMENT,
GESTATIONAL AGE AT DELIVERY WAS
ESTIMATED BY SELF-REPORTED LAST
MENSTRUAL PERIOD, EARLY
PREGNANCY ULTRASOUND OR SOME
COMBINATION THERE.
AND PRETERM BIRTH WAS DEFINED AS
DELIVERY BEFORE 37 WEEKS
GESTATION.
AND WE HAD A TOTAL OF 538
PRETERM BIRTHS.
THE COVARIATES THAT WE INCLUDED
IN THE STUDY WERE A LITTLE BIT
LIMITED BECAUSE WE HAD TO
HARMONIZE THEM ACROSS ALL 16
COHORTS.
BUT THEY INCLUDED COHORT,
MATERNAL AGE, RACE/ETHNICITY,
EDUCATION LEVEL AND PREPREGNANCY
BODY MASS INDEX.
I WANTED TO BRIEFLY SHOW YOU THE
DISTRIBUTION OF PARTICIPANT
RACE/ETHNICITY IN THE POOLED
STUDY BECAUSE WE DID HAVE A
DIVERSE COHORT HERE.
ABOUT 44% OF THE PARTICIPANTS
WERE NON-HISPANIC WHITE.
13% WERE NON-HISPANIC BLACK.
38% WERE HISPANIC OR LATINA.
3% WERE ASIAN PACIFIC ISLANDER,
AND 2% REPORTED AS OTHER OR FROM
OTHER GROUPS THAT HAD SMALL
SAMPLE SIZES THAT WERE COMBINED
BECAUSE OF THAT ISSUE.
SO TO ADDRESS THE FIRST RESEARCH
QUESTION, WHAT IS THE
ASSOCIATION BETWEEN PHTHALATE
EXPOSURE AND PRETERM BIRTH, I'M
GOING TO KIND OF SKIP RIGHT TO
THE RESULTS, AND I WANT TO
HIGHLIGHT THAT THIS WORK WAS
DONE BY A FORMER POSTDOCTORAL
FELLOW IN MY GROUP, DR. BARRETT
WELCH, WHO IS NOW AN ASSISTANT
PROFESSOR AT THE UNIVERSITY OF
NEVADA-RENO.
WE OBSERVED FOR THESE NINE
DIFFERENT PHTHALATE METABOLITES
THAT THE METABOLITES MIBP, MECPP
AND MCPP WERE ASSOCIATED WITH AN
INCREASED ODDS OF PRETERM BIRTH
IN OUR ADJUSTED MODELS.
AND MECPP IS ONE OF THE DEHP
METABOLITES THAT I MENTIONED
EARLIER.
FOLLOWING OUR PRIMARY ANALYSIS,
WE WANTED TO PERFORM A MIXTURES
ANALYSIS AS WELL.
THE MOTIVATION FOR THIS IS THAT
PREGNANT WOMEN ARE EXPOSED TO
MANY PHTHALATES SIMULTANEOUSLY,
NOT JUST ONE AT A TIME.
SO THE JOINT EFFECT OF THE
MIXTURE MAY ACTUALLY BE MORE
REALISTIC FOR ESTIMATING AN OUT
COME EFFECT THAN INDIVIDUAL
EFFECT ESTIMATES.
TO ADDRESS THE JOINT EFFECTIVE
PHTHALATE EXPOSURE WITHIN OUR
MIXTURE, WE APPLIED A G
COMPUTATION METHOD, ESTIMATING
THE PROBABILITY OF PRETERM BIRTH
FOLLOWING A HYPOTHETICAL
INTERVENTION TO REDUCE
CONCENTRATIONS OF ALL EXPOSURES
IN THE MIXTURE.
AND THIS APPLICATION WAS
DEVELOPED FOR THIS STUDY BY ALEX
KEILL, WHO IS MY COLLABORATOR AT
NCI.
SO HERE WE'RE SHOWING THE JOINT
EFFECT OF ALL OF THE PHTHALATE
METABOLITES WITHIN THE MIXTURE.
WE APPLIED THE G COMPUTATION TO
THE MOST COMMONLY MEASURED
PHTHALATE METABOLITES, AND WHAT
I'M SHOWING YOU ARE THE
ESTIMATED REDUCTION IN PRETERM
BIRTHS FOR HEIG HYPOTHETICAL
INTERVENTIONS RANGING FROM A 0%
REDUCTION IN OVERALL PHTHALATE
EXPOSURE AS THE REFERENCE UP TO
90% REDUCTION IN PHTHALATE
EXPOSURE.
AND I JUST HIGHLIGHTED HERE THE
EFFECT OF REDUCING THE EXPOSURE
MIXTURE BY 50%, WHICH I THINK IS
A FEASIBLE HYPOTHETICAL
REDUCTION.
AND WHAT WE OBSERVED WITH THIS
REDUCTION IS THAT WE WOULD -- BY
REDUCING THE PHTHALATE MIXTURE
BY ABOUT 50%, WE WOULD EXPECT TO
PREVENT ROUGHLY 11 PRETERM
BIRTHS PER 1,000 LIVE BIRTHS.
SO IN CONCLUSION, I WANT TO
EMPHASIZE THE CONSEQUENCES AT
THE POPULATION LEVEL.
DESPITE THE MODEST EFFECT SIZES
THAT WE OBSERVED IN THIS
ANALYSIS, ODDS RATIOS RANGING
FROM 1.4 TO 1.6, THE HEALTH
CONSEQUENCES ON A POPULATION
SCALE COULD BE SUBSTANTIAL GIVEN
THE WIDESPREAD NATURE OF
PHTHALATE EXPOSURE AND THE HIGH
RATES OF PRETERM BIRTH THAT WE
EXPERIENCE IN THE U.S.
ADDITIONALLY, WE OBSERVED A
SIGNIFICANT IMPACT OF REDUCTIONS
IN THE EXPOSURE MIXTURE.
SO ADDITIONAL MEASURES TO
MITIGATE EXPOSURE TO PHTHALATES
AS A CLASS OF CHEMICALS COULD
HELP TO REDUCE PRETERM BIRTH
RATES.
I ALSO WANT TO GIVE A SHOUT OUT
TO A RECENT STUDY THAT JUST CAME
OUT TWO DAYS AGO, SO I ADDED IN
THIS SLIDE LAST NIGHT, THAT'S
HOT OFF THE PRESS FROM THE
ENVIRONMENTAL INFLUENCES ON
CHILD HEALTH OUTCOME STUDY.
THIS IS A CONSORTIUM STUDY THAT
INCLUDES CHILD FOLLOW-UP.
IN THIS STUDY, THEY POOLED DATA
FROM 13 COHORTS, INCLUDING 5,000
BIRTHS AS WELL AS 394 PRETERM
BIRTHS, AND SOME OF THE COHORTS
DID OVERLAP WITH THOSE INCLUDED
IN OUR POOLED STUDY.
BUT IMPORTANTLY, THEY HAD SOME
MORE RECENT DATA COLLECTION,
INCLUDING RECRUITMENT OF
PARTICIPANTS UP UNTIL 2022, WHEN
THEY WERE ABLE TO ANALYZE
SAMPLES.
SO THEY WERE ABLE TO CAPTURE
SOME OF THE MORE RECENT
EXPOSURES AS WELL.
IN THIS STUDY, THEY OBSERVED
THAT METABOLITES OF DEHP AND ITS
REPLACEMENTS INCLUDING DNOP WERE
ASSOCIATED WITH INCREASED ODDS
OF PRETERM BIRTH.
SO WE OBSERVED SOME CONSISTENCY
WITH OUR ANALYSIS WITH THE DEHP
METABOLITE, AND WE ALSO OBSERVED
AN ASSOCIATION BETWEEN MCPP,
WHICH IS A NONSPECIFIC
METABOLITE OF DNOP AND PRETERM
BIRTH SO THERE'S A LOT OF
CONSISTENCY IN OUR RESULTS.
NOW I'M GOING TO MOVE ON TO OUR
SECOND RESEARCH QUESTION.
THIS WAS TO INVESTIGATE ARE
THERE PERIODS OF SUSCEPTIBILITY
TO PHTHALATE EXPOSURE DURING
PREGNANCY?
AND THIS IS WORK THAT WAS DONE
BY ANOTHER FORMER POSTDOCTORAL
FELLOW IN MY GROUP, ALEXA
FRIEDMAN, NOW A SENIOR SCIENTIST
WORKING WITH ENVIRONMENTAL
WORKING GROUP.
THERE ARE THREE MAIN QUESTIONS
THAT WE INTEND TO ADDRESS WHEN
WE ARE ASKING ABOUT PERIODS OF
SUSCEPTIBILITY TO ENVIRONMENTAL
CHEMICAL EXPOSURES.
FIRST, WE WANT TO AID IN THE
UNDERSTANDING OF BIOLOGICAL
MECHANISMS THAT MAY BE
CONNECTING OUR EXPOSURE TO OUR
OUTCOME.
SECOND, WE'RE INTERESTED IN
REDUCING EXPOSURE
MISCLASSIFICATION, SO IF WE'RE
REALLY INTERESTED IN EXPOSURE
THAT OCCURS IN EARLY PREGNANCY
AND WE BELIEVE THAT'S THE
CRITICAL WINDOW FOR EFFECT,
MEASURING EXPOSURE ACROSS THE
ENTIRE DURATION OF PREGNANCY IS
GOING TO HAVE A LOT OF
MISCLASSIFICATION.
THIRD, WE'RE LOOKING FOR THE
POSSIBILITY OF IDENTIFYING
OPPORTUNITIES FOR INTERVENTION.
IS THERE A SPECIFIC TIME DURING
PREGNANCY WHERE WE NEED TO
INTERVENE IN ORDER TO AMELIORATE
THE EFFECTS?
SO IN THIS STUDY, WE HAD THE
ADVANTAGE OF HAVING QUITE A FEW
PHTHALATE METABOLITE
OBSERVATIONS IN EACH TRIMESTER
OF PREGNANCY.
SO ABOUT 2200 IN THE FIRST
TRIMESTER, 3700 IN THE SECOND
TRIMESTER, AND 3200 IN THE THIRD
TRIMESTER.
WE OBSERVED THAT EXPOSURE LEVELS
IN THE STUDY POPULATION WERE
VERY SIMILAR ACROSS TRIMESTERS,
SO THE RESULTS OF THIS ANALYSIS
REALLY POINT TO AN INDIVIDUAL'S
BIOLOGIC SUSCEPTIBILITY TO
EXPOSURE IN THE TRIMESTER, NOT
THE FACT THAT THEY HAVE A
DIFFERENT EXPOSURE LEVEL IN THAT
TRIMESTER.
SO WE HAVE TWO APPROACHES FOR
IDENTIFYING PERIODS OF
SUSCEPTIBILITY.
FIRST, WE SOUGHT TO VISUALIZE
THAT PHTHALATE METABOLITE
CONCENTRATIONS ACROSS PREGNANCY
IN CASES OF PRETERM BIRTH AND
COMPARE THEM TO CONTROLS.
AND SECOND, WE ESTIMATED ODDS
RATIOS OF PRETERM BIRTH IN
ASSOCIATION WITH EXPOSURE FOR
EACH TRIMESTER.
SO STRATIFIED ANALYSIS.
FIRST I'M SHOWING YOU THE
RESULTS FOR THE VISUALIZATION OF
CONCENTRATIONS ACROSS PREGNANCY
AND I'M JUST FOCUSING IN HERE ON
THE METABOLITES OF DEHP.
SO THESE PLOTS ARE SHOWING YOU
THE PREDICTED PHTHALATE
METABOLITE CONCENTRATIONS IN
CASES OF PRETERM BIRTH SHOWN IN
GREEN AND THEY'RE KIND OF THE
HIGHER LINE IN EACH PLOT, AND IN
CONTROLS, WHICH ARE SHOWN IN RED
IN THE LOWER LINE IN EACH PLOT.
WE ALSO INCLUDE 95% CONFIDENCE
INTERVALS FOR THOSE ESTIMATES.
THE Y AXIS IS THE PERCENTILE OF
EXPOSURE, SO THEY'RE KIND OF
STANDARDIZED ACROSS THE
DIFFERENT PHTHALATE METABOLITES.
AND THE X AXIS IS SHOWING YOU
THE GESTATIONAL AGE AT THE TIME
OF METABOLITE MEASUREMENT
RANGING FROM ZERO TO 40 WEEKS
GESTATION.
AND WHAT WE OBSERVED FOR THESE
DEHP METABOLITES IS THAT THE
GREATEST SEPARATION BETWEEN
CASES AND CONTROLS IS OBSERVED
EARLIER IN GESTATION.
SO YOU CAN SEE STARTING AROUND
10 WEEKS, YOU SEE SIGNIFICANT
SEPARATION OF THE CONCENTRATIONS
IN CASES COMPARED TO CONTROLS,
BUT THEY TEND TO BE MORE SIMILAR
TOWARD THE END OF PREGNANCY.
SO THIS HIGHLIGHTS EARLY
PREGNANCY AS A POTENTIALLY
SUSCEPTIBLE WINDOW.
OUR SECOND APPROACH WAS TO
EXAMINE ODDS RATIOS OF PRETERM
BIRTH BY TRIMESTER OF EXPOSURE.
AGAIN, I'M JUST SHOWING YOU THE
RESULTS FOR THE DEHP
METABOLITES, AND I'M SHOWING YOU
THE ODDS RATIOS OF PRETERM BIRTH
WITHIN EACH TRIMESTER.
WE OBSERVED THAT THE ODDS RATIOS
FOR PRETERM WERE GREATEST FOR
THE FIRST AND SECOND TRIMESTERS
FOR THE DEHP METABOLITES.
SO FOR EXAMPLE, LOOKING AT THE
MEHP METABOLITE ALL THE WAY ON
THE LEFT, WE SAW THAT THE EFFECT
ESTIMATES WERE GREATEST IN THE
FIRST AND SECOND TRIMESTER, AND
THE P VALUE FOR HETEROGENEITY
WAS .03, INDICATING THAT THE
EFFECTS ARE SIGNIFICANTLY
DIFFERENT BY TRIMESTER.
WE DIDN'T OBSERVE SIGNIFICANT
HETEROGENEITY FOR THE OTHER
PHTHALATE METABOLITES, BUT WE
DID OBSERVE THAT EFFECT
ESTIMATES TENDED TO BE GREATER
IN ASSOCIATION WITH EXPOSURE
MEASURED IN THE FIRST TRIMESTER.
SO IN CONCLUSION FROM THIS AIM,
EARLY PREGNANCY MAY BE A
SUSCEPTIBLE WINDOW TO DEHP
EXPOSURE FOR THE RELATIONSHIP
WITH PRETERM BIRTH.
WE HAD SOME LIMITATIONS TO THIS
ANALYSIS, NOTABLY NOT ALL
PARTICIPANTS HAD DATA AVAILABLE
IN EACH TRIMESTER.
ONLY ABOUT 600 OUT OF OUR 6,000
PARTICIPANTS HAD DATA AVAILABLE
IN EACH TRIMESTER.
THIS WOULD BE THE IDEAL
ANALYSIS, BUT BECAUSE THAT
SAMPLE SIZE IS SO SMALL, WE
COULDN'T REALLY COMPARE OUR
PRIMARY RESULTS TO AN ANALYSIS
WITHIN THE SUBSET.
SECOND, NOT ALL COHORTS
COLLECTED DATA IN EACH
TRIMESTER.
SO ONLY FIVE OF THE 16 COHORTS
OR 3,000 OUT OF 6,000
PARTICIPANTS HAD DATA COLLECTION
IN EACH TRIMESTER, SO THIS COULD
ALSO CREATE SOME BIAS IN THAT
SOME STUDIES DIDN'T RECRUIT
PEOPLE UNTIL THEY HAD ALREADY
MADE TO THE THIRD TRIMESTER, FOR
EXAMPLE.
OKAY.
NOW I'LL MOVE ON TO MY THIRD
AIM, WHICH WAS HOW DO EXPOSURES
TO PHTHALATE DIFFER BY RACE AND
ETHNICITY, AND COULD THESE
DIFFERENCES CONTRIBUTE TO
DISPARITIES IN RATES OF PRETERM
BIRTH?
AND AGAIN, THIS IS WORK LED BY
MY FORMER POSTDOCTORAL FELLOW
DR. BARRETT WELCH.
SO WE KNOW THAT THERE ARE
DISTINCT RACIAL AND ETHNIC
DISPARITIES IN RATES OF PRETERM
BIRTH IN THE U.S.
PRETERM BIRTH RATES AMONG BLACK
WOMEN IS 50% HIGHER THAN AMONG
ALL OTHERS.
SO IN THIS PLOT HERE, I'M
SHOWING THE RATES OF PRETERM
BIRTH OR THE PERCENTAGE OF LIVE
BIRTHS THAT WERE BORN PRETERM
FROM 2017 TO 2019, AND YOU CAN
SEE THAT HIGHEST RATES ARE
EXPERIENCED AMONG BLACK WOMEN.
WE KNOW THAT THESE DIFFERENCES
ARE NOT DUE TO GENETICS BUT
RATHER TO SOCIAL AND PHYSICAL
ENVIRONMENTAL EXPOSURE
DISPARITIES.
WHICH BRINGS INTO QUESTION THE
ROLE OF ENVIRONMENTAL CHEMICAL
EXPOSURES.
AT THE SAME TIME, THERE ARE
IMPORTANT RACIAL AND ETHNIC
DISPARITIES IN PHTHALATE
EXPOSURES.
EXPOSURES TO PHTHALATES AMONG
OTHER ENVIRONMENTAL CHEMICALS
DISPROPORTIONATELY AFFECT PEOPLE
OF COLOR INCLUDING PREGNANT
WOMEN.
IN THIS PLOT ON THE LEFT, I'M
SHOWING YOU JUST SOME QUICK DATA
ON URINARY MIBP CONCENTRATIONS
BY RACE AND ETHNICITY, AND THE
NATIONAL HEALTH AND NUTRITION
EXAMINATION SURVEY FROM 2001 TO
2012.
AND THIS IS THE GEOMETRIC MEAN
URINARY CONCENTRATION IN EACH OF
THOSE STUDY YEARS.
WHAT YOU CAN SEE CONSISTENTLY IS
THAT NON-HISPANIC WHITE
PARTICIPANTS WHO ARE SHOWN IN
THE GREEN DIAMONDS HAVE THE
LOWEST EXPOSURE LEVELS, AND
MEXICAN-AMERICAN AND
NON-HISPANIC BLACK PARTICIPANTS
HAVE THE HIGHEST EXPOSURE LEVELS
CONSISTENTLY OVER TIME.
AND THIS IS ONE OF THOSE
PHTHALATE METABOLITES THAT WAS
MOST CONSISTENTLY LINKED TO
PRETERM BIRTH IN OUR POOLED
ANALYSIS.
THESE DISPARITIES AND EXPOSURE
CAN BE CONTRIBUTED TO FACTORS
DRIVEN BY SYSTEMIC AND
INSTITUTIONALIZED RACISM, SUCH
AS PERSONAL CARE PRODUCT USE,
AND FOOD LANDSCAPES IN RACIALLY
SEGREGATED AREAS.
THE POOLED STUDY OF PHTHALATE
EXPOSURE IN PRETERM BIRTH IS
REALLY UNIQUELY POISED TO
EXAMINE RACIAL AND ETHNIC
DIFFERENCES AND EXPOSURE DURING
PREGNANCY.
BECAUSE OF ITS LARGE SAMPLE SIZE
AND DIVERSITY.
THIS PLOT IS SHOWING TH THE
DIVERSITY OF OUR POPULATION
SOMEWHAT DIFFERENTLY THAN THE
PREVIOUS PIE CHART I SHOWED.
IT DISPLAYS EACH OF THE COHORTS
THAT WERE INCLUDED IN OUR STUDY,
AND THE NUMBER OF PARTICIPANTS
WHO SELF-REPORTED AS
NON-HISPANIC WHITE, NON-HISPANIC
BLACK, HISPANIC LATINA, ASIAN
PACIFIC ISLANDER OR OTHER.
OUR FIRST STEP IN THIS STUDY WAS
TO EXAMINE RACIAL AND ETHNIC
DISPARITIES IN PHTHALATE
EXPOSURE.
AND WE DID THIS BY EXAMINING
PERCENT DIFFERENCE IN COVARIATE
ADJUSTED GEOMETRIC MEANS WITHIN
NON-HISPANIC BLACK, HISPANIC
LATINA AND ASIAN PACIFIC
ISLANDER PARTICIPANTS COMPARED
TO NON-HISPANIC WHITE
PARTICIPANTS.
IN NON-HISPANIC WHITE
PARTICIPANTS WERE SELECTED A
PRIORI AS THE REFERENCE GROUP AS
WE EXPECTED THEM TO HAVE THE
LOWEST EXPOSURE LEVELS, AND
INDEED THEY DID.
THESE ESTIMATES ARE ADJUSTED FOR
MATERNAL AGE, EDUCATION,
PREPREGNANCY BMI, DELIVERY --
AND STUDY, AS THESE ARE
SOMETIMES FACTORS THAT OTHERS
MIGHT USE TO KIND OF EXPLAIN WHY
THE DISPARITIES AND EXPOSURE
LEVELS EXIST.
SO THESE DIFFERENCES THAT I'M
SHOWING YOU EXIST AFTER
ADJUSTMENT FOR ALL OF THOSE
FACTORS.
SO THIS PLOT ON THE RIGHT IS
SHOWING YOU EACH OF THE
PHTHALATE METABOLITES THAT WE
EXAMINED IN THIS STUDY, AND IT'S
SHOWING YOU THE PERCENT
DIFFERENCE IN 95% CONFIDENCE
INTERVALS, IN EXPOSURE LEVELS IN
EACH OF THESE GROUPS COMPARED TO
NON-HISPANIC WHITE PARTICIPANTS.
WHAT YOU CAN SEE STARTING AT THE
TOP IS THAT THERE ARE MUCH
HIGHER LEVELS OF EXPOSURE IN
NON-HISPANIC BLACK PARTICIPANTS
COMPARED TO NON-HISPANIC WHITE
PARTICIPANTS.
WE ALSO OBSERVED MUCH HIGHER
LEVELS OF EXPOSURE AMONG OUR
HISPANIC LATINA PARTICIPANTS,
AND FOR ASIAN PACIFIC ISLANDER
PARTICIPANTS, EXPOSURE LEVELS
WERE MORE SIMILAR TO
NON-HISPANIC WHITE PARTICIPANTS,
BUT WE DO SEE THAT MBP AND MIBP,
WHICH ARE SOME OF THE PHTHALATES
THAT WERE ASSOCIATED WITH
PRETERM BIRTH IN OUR INITIAL
ANALYSIS, WERE HIGHER IN ASIAN
AND PACIFIC ISLANDER
PARTICIPANTS.
I KIND OF ALREADY EXPLAINED
THIS, BUT AGAIN, THE GREATEST
DIFFERENCES IN EXPOSURE THAT WE
OBSERVED WERE FOR PHTHALATES
THAT WERE TYPICALLY FOUND IN
PERSONAL CARE PRODUCTS.
SO FOR THESE COMPOUNDS,
NON-HISPANIC BLACK PARTICIPANTS
HAD 23 TO 148% HIGHER EXPOSURE
AFTER ADJUSTING FOR ALL OF THESE
OTHER FACTORS.
HISPANIC LATINA PARTICIPANTS HAD
5 TO 94% HIGHER EXPOSURE LEVELS,
AND AS I SAID FOR ASIAN PACIFIC
ISLANDER PARTICIPANTS, THEY HAD
MORE SIMILAR EXPOSURE LEVELS TO
NON-HISPANIC WHITE PARTICIPANTS.
SO WE HAD SEVERAL FOLLOW-UP
QUESTIONS AFTERR AFTER IDENTIFYS
DISPARITY EXPOSURE IN OUR POOL
POPULATION.
FIRST DO ASSOCIATIONS BETWEEN
PHTHALATE EXPOSURE AND PRETERM
BIRTH DIFFER BY MATERNAL RACE
AND ETHNICITY?
THIS IS KIND OF A TRADITIONAL
STRATIFIED EFFECT MODIFICATION
ANALYSIS, AND KIND OF THE
JUSTIFICATION FOR THIS ANALYSIS
IS THAT THERE COULD POSSIBLY BE
UNMEASURED FACTORS IN OUR STUDY
THAT ARE ASSOCIATED WITH
MATERNAL RACE AND ETHNICITY SUCH
AS PSYCHOSOCIAL STRESS DURING
PREGNANCY THAT ARE CAUSING SOME
GROUPS TO BE MORE SUSCEPTIBLE TO
THE EFFECTS OF PHTHALATE
EXPOSURE COMPARED TO OTHERS.
SO IT'S KIND OF THE UNDERLYING
JUSTIFICATION.
BUT OUR STATISTICAL APPROACH IS
TO EXAMINE ASSOCIATIONS BETWEEN
INDIVIDUAL PHTHALATE METABOLITES
IN PRETERM BIRTH IN MODELS THAT
ARE STRATIFIED BY MATERNAL RACE
AND ETHNICITY.
HERE ARE THE RESULTS FOR THAT I
AAL CYST.
THIS PLOT IS AGAIN SHOWING YOU
EACH OF THE PHTHALATE MA TAB
LIGHTS THAT WE EXAMINED AND THE
ODDS RATIO IN NON-HISPANIC WHITE
PARTICIPANTS, NON-HISPANIC BLACK
PARTICIPANTS, AND HISPANIC
LATINA PARTICIPANTS.
AND WHAT WE OBSERVED IS THAT FOR
TWO OF THE FOUR PHTHALATE
METABOLITES THAT WERE ASSOCIATED
WITH PRETERM BERM IN BIRTH IN R
PRIMARY ANALYSES -- FOR MBP THE
ODDS OF PRETERM BIRTH WERE
GREATEST AMONG HISPANIC OR
LATINA PARTICIPANTS.
AND FOR MIBP, THE ODDS OF
PRETERM BIRTH WAS GREATEST AMONG
NON-HISPANIC BLACK PARTICIPANTS.
OUR SECOND QUESTION IS A LITTLE
BIT MORE HYPOTHETICAL.
SO WE ASKED, COULD ELIMINATING
DISPARITIES IN PHTHALATE
EXPOSURE THAT EXIST BY RACE AND
ETHNICITY REDUCE RATES OF
PRETERM BIRTH?
OUR APPROACH FOR THIS WAS TO
APPLY G COMPUTATION TO ESTIMATE
THE RATES OF PRETERM BIRTH THAT
WE WOULD HAVE OBSERVED IF
NON-HISPANIC BLACK PARTICIPANTS
HAD THE SAME EXPOSURE TO
PHTHALATES AS NON-HISPANIC WHITE
PARTICIPANTS.
AND ALSO FOR HISPANIC LATINA
PARTICIPANTS.
SO WE APPLIED THIS HYPOTHETICAL
INTERVENTION WITH THE CENTRAL
QUESTION, IF WE COULD ELIMINATE
DISPARITIES IN PHTHALATE
EXPOSURE, WOULD IT SIGNIFICANTLY
IMPACT RATES OF PRETERM BIRTH?
SO UNDER THE HYPOTHETICAL
INTERVENTION, WE REDUCE EXPOSURE
LEVELS FOR EACH OF THE NINE
PHTHALATE METABOLITES IN OUR
MIXTURE IN NON-HISPANIC BLACK
PARTICIPANTS AND HISPANIC LATINA
PARTICIPANTS TO THE DISTRIBUTION
THAT WAS OBSERVED IN
NON-HISPANIC WHITE PARTICIPANTS.
SO I'M TRYING TO ILLUSTRATE THIS
HERE ON THE RIGHT.
SO WHAT YOU CAN SEE ON THE
BOTTOM IS THE DISTRIBUTION OF
ONE EXPOSURE BIOMARKER IN OUR
REFERENCE GROUP, WHICH IS
NON-HISPANIC WHITE PARTICIPANTS,
AND YOU SEE THE CURVE THEY
EXPERIENCE OF THEIR EXPOSURE.
ON THE TOP IN THE GREEN ON THE
RIGHT, THAT DISTRIBUTION IS WHAT
WE OBSERVE IN OUR STUDY
POPULATION, THE EXPOSURE
DISTRIBUTION FOR THAT PHTHALATE
METABOLITE, AMONG, FOR EXAMPLE,
NON-HISPANIC BLACK PARTICIPANTS.
THE DISTRIBUTION IS MUCH HIGHER
THAN WHAT WE OBSERVE FOR
NON-HISPANIC WHITE PARTICIPANTS.
SO UNDER THIS HYPOTHETICAL
INTERVENTION, WE SHIFT THAT
DISTRIBUTION CURVE TO THE LEFT,
SO THAT THE MEAN IS EQUIVALENT
TO THAT THAT'S OBSERVED AMONG
NON-HISPANIC WHITE PARTICIPANTS.
AND THEN WE ESTIMATE THE EFFECT
OF SHIFTING THIS CURVE, THIS
INTERVENTION ON THE PREDICTED
PRETERM BIRTH RATES WITHIN EACH
OF OUR RACIAL AND ETHNIC GROUPS.
SO IN THIS PLOT, I'M SHOWING YOU
FIRST NON-HISPANIC WHITE
PARTICIPANTS WHO EXPERIENCE NO
INTERVENTION UNDER OUR
HYPOTHETICAL FRAMEWORK, AND I'M
SHOWING YOU THE NUMBER OF
PRETERM BIRTHS PER 1,000 LIVE
BIRTHS IN THE 95% CONFIDENCE
INTERVAL IN OUR STUDY
POPULATION.
NEXT I'M SHOWING YOU THE
NON-HISPANIC BLACK PARTICIPANTS,
AND I'M SHOWING YOU THE NUMBER
OF PRETERM BIRTHS PER 1,000 LIVE
BIRTHS BEFORE THE INTERVENTION
IN THE BLUE CIRCLE AND AFTER THE
INTERVENTION, IN THE GREY
TRIANGLE.
WHAT YOU CAN SEE IS THAT OUR HIP
THET CAL INTERVENTION REDUCES
THE PERCENT PRETERM BIRTHS BY
ABOUT 13%.
SIMILARLY AMONG HISPANIC LATINA
PARTICIPANTS, AFTER THE
INTERVENTION, WE OBSERVE
DECREASE IN THE NUMBER OF
PRETERM BIRTHS BY ABOUT 9%.
NOW WE'RE NOT SAYING HERE THAT
THIS IS THE ONE FACTOR THAT IS
CREATING DISPARITIES IN PRETERM
BIRTH RATES AMONG BLACK AND
WHITE WOMEN IN THE U.S., BUT
WE'RE SAYING THAT IT COULD BE A
POSSIBLE CONTRIBUTOR AND THIS IS
AN IMPORTANT WAY TO EXAMINE THIS
DIFFERENCE AND THE CONSEQUENCES
OF EXPOSURE.
SO IN CONCLUSION IN REGARDS TO
EXPOSURE DISPARITY, WE OBSERVED
THAT NON-HISPANIC BLACK AND
HISPANIC LATINA PARTICIPANTS HAD
EXPOSURES THAT WERE AS HIGH AS
94 TO 148% HIGHER COMPARED TO
NON-HISPANIC WHITE PARTICIPANTS.
AND THIS IS AFTER ADJUSTMENT FOR
FACTORS THAT ARE ASSOCIATED WITH
BOTH RACE AND ETHNICITY AND WITH
EXPOSURE.
WE ALSO OBSERVED SIGNIFICANT
EFFECT MODIFICATION WITH LARGER
MAGNITUDES OF ASSOCIATIONS FOR
MBP AND MIBP AMONG NON-HISPANIC
BLACK OR HISPANIC LATINA
PARTICIPANTS COMPARED TO
NON-HISPANIC WHITE PARTICIPANTS.
IN TERMS OF PREVENTING PRETERM
BIRTH, OUR RESULTS PROVIDE
EVIDENCE THAT IF THESE GROUPS
HAD NEARLY EQUAL EXPOSURES
COMPARED TO NON-HISPANIC WHITE
PARTICIPANTS, THEN THEY MAY HAVE
FEWER PRETERM BIRTHS.
SO NOW I'LL MOVE INTO TALKING
ABOUT THE PUBLIC HEALTH IMPACT
BRIEFLY.
SO THE FIRST QUESTION THAT YOU
MIGHT ASK AFTER SEEING THIS DATA
IS, ARE THESE HYPOTHESIZED
REDUCTIONS WORTH PURSUING?
WE BELIEVE THE ANSWER IS YES.
PRETERM BIRTH IS A SIGNIFICANT
PUBLIC HEALTH PROBLEM IN THE
U.S. AND ELSEWHERE.
IT AISK AFFECTS ABOUT 10% OF BIS
IN THE U.S. AND THERE ARE VERY
FEW KNOWN AND PREVENTABLE RISK
FACTORS FOR PRETERM BIRTH.
THE MOST WELL-KNOWN INCLUDE
SOCIOECONOMIC STATUS, MATERNAL
AGE AND PREVIOUS PRETERM BIRTH.
THESE ARE ALL VERY DIFFICULT
FACTORS TO INTERVENE UPON.
IN THE OVERALL POPULATION,
REDUCING EXPOSURE TO PHTHALATES
BY EVEN JUST 50% IN OUR STUDY
RESULTED IN ROUGHLY 10% FEWER
PRETERM BIRTHS.
THIS WOULD BE THE EQUIVALENT OF
ABOUT 386,000 PRETERM BIRTHS IN
2021.
FINALLY, REDUCING HIGH PHTHALATE
EXPOSURES AMONG SYSTEMATICALLY
MARGINALIZED GROUPS WOULD HELP
TO REDUCE THE RACIAL DISPARITY
IN PRETERM BIRTH THAT WE
EXPERIENCE IN THE U.S.
A SECOND BIG QUESTION IS, ARE
THESE HYPOTHESIZED REDUCTIONS IN
EXPOSURE POSSIBLE?
WE ALSO THINK THE ANSWER IS YES.
AND THE INVESTIGATION OF
EXPOSURE DISPARITIES IN
PARTICULAR, THE HYPOTHETICAL
EXPOSURE DISTRIBUTIONS THAT WE
MODELED IN NON-HISPANIC BLACK
PARTICIPANTS ALREADY ACTUALLY
EXIST AMONG NON-HISPANIC WHITE
PARTICIPANTS, SO IT SHOULD BE
FEASIBLE.
IN THE OVERALL POPULATION,
REDUCTION BY 50% SEEMS FEASIBLE
AS WELL.
WE'RE NOT SEEING -- SAYING THAT
THESE EFFECTS WOULD BE OBSERVED
IF WE ELIMINATED EXPOSURE.
WE'RE SAYING IF WE REDUCE THEM
BY 50%, WE WOULD SEE SIGNIFICANT
EFFECTS.
AND THIRD, HOW CAN HYPOTHESIZED
REDUCTIONS HAPPEN?
THIS IS GOING TO REQUIRE A
COMBINED APPROACH.
SO I TALKED ABOUT THE EXPOSURE
SOURCES AT THE BEGINNING OF THIS
TALK.
THIS IS GOING TO REQUIRE
TARGETING BOTH PERSONAL CARE
PRODUCT USE AS WELL AS DIETARY
SOURCES OF EXPOSURE.
WE BELIEVE THAT PRIORITIZATION
OF ACTIONS AT THE POPULATION
LEVEL INCLUDING LEGISLATIVE
POLICIES AS WELL AS VOLUNTARY
MARKET REMOVAL RATHER THAN
INDIVIDUAL LEVEL CHANGES LIKE
IMPLEMENTING DIETS IN ORGANIC
FOOD OR USE OF FRAGRANCE-FREE
ITEMS ARE GOING TO RESULT IN
MORE EFFECTIVE CHANGE IN
PHTHALATE EXPOSURE.
AND FINALLY, INTERVENTIONS HAVE
TO ACCOUNT FOR THE
INTERSECTIONALITY OF RACISM,
SEXISM AND SOCIAL INEQUITY.
I THINK IT'S REALLY IMPORTANT TO
POINT OUT THAT PERSONAL LEVEL
BEHAVIORAL INTERVENTIONS MAY BE
INEFFECTIVE.
SO NOT ONLY ARE WE ALREADY
BURDENING PREGNANT WOMEN BY
TELLING THEM SO MANY DIFFERENT
THINGS THAT THEY NEED TO DO
DURING GESTATION, THINGS TO
AVOID AND ET CETERA, ADDING ONE
MORE TO THE LIST IS TOO MUCH IN
MY OPINION.
AND ADDITIONALLY, INDIVIDUAL
LEVEL CHANGES MAY NOT BE
EFFECTIVE.
THERE HAVE BEEN TRIALS TO SEE,
DOES CONSUMING A DIET IN FRESH
FOOD REDUCE YOUR PHTHALATE
EXPOSURE?
AND SOME OF THEM SHOW SOME
SUCCESS, BUT OTHERS DO NOT.
SIMILARLY, TRIALS TO CHANGE
PERSONAL CARE PRODUCT USE
PATTERNS, TO USE PRODUCTS THAT
ARE FRAGRANCE-FREE OR
PHTHALATE-FREE HAVE SHOWN SOME
SUCCESS BUT NOT FOR ALL
PHTHALATE METABOLITES, AND NOT
CONSISTENTLY ACROSS STUDIES.
ADDITIONALLY, BY IMPLEMENTING
PERSONAL LEVEL CHANGES, WE'RE
REALLY RELYING ON THE
INDIVIDUAL, AND SUCCESS MAY BE
DEPENDENT ON ACCESS TO
PHTHALATE-FREE PRODUCT OR TO
EDUCATION ABOUT WHAT CHEMICALS
ARE INCLUDED IN THOSE PRODUCTS.
SO BY FOCUSING ON PERSONAL LEVEL
INTERVENTION, WE COULD BE
PERPETUATING THE INEQUITIES THAT
ALREADY EXIST.
THIS FIGURE IS FROM A RECENT
PAIB IN ENVIRONMENTAL HEALTH
PERSPECTIVES BY MY COLLABORATOR,
TAMARA TODD, AND IT INVESTIGATED
THE RISK OF IDENTIFYING PERSONAL
CARE PRODUCTS THAT HAD HIGH
HAZARD SCORES IN BOSTON
NEIGHBORHOODS.
WHAT THEY OBSERVED IN THAT STUDY
IS THAT RETAILERS IN BOSTON
NEIGHBORHOODS WITH A HIGHER
PERCENT OF RES NENS OF COLOR
WERE MORE LIKELY TO SELL
PRODUCTS WITH HIGH HAZARD
SCORES.
SO THIS IS A MAP OF BOSTON, AND
YOU CAN SEE KIND OF IN THE
CENTER, NUMBER 1 REPRESENTS
BEACON HILL AND NUMBER
4 REPRESENTS THE DOWNTOWN AREA.
THOSE ARE LIGHTER SHADED AREAS
COMPARED TO THE OTHER
NEIGHBORHOODS LIKE DORCHESTER
AND ROXBURY, WHERE YOU SEE
DARKER SHADING, WHICH INDICATES
THAT THEY'RE MORE LIKELY TO
IDENTIFY PERSONAL CARE PRODUCTS
ON THE SHELVES THAT HAVE HIGH
HAZARD SCORES ACCORDING TO THE
ENVIRONMENTAL WORKING GROUP
DATABASE.
SO IN TERMS OF WHAT CAN BE DONE
OUTSIDE OF THE PERSONAL LEVEL,
PROJECT TENDR, WHICH IS AN
ORGANIZATION DEDICATED TO
ADVOCACY AROUND THE USE OF
CHEMICALS IN PRODUCTS, PUBLISHED
THIS PAPER IN 2021 THAT GAVE
SOME RECOMMENDATIONS FOR
CRITICAL POLICY REFORMS FOR THE
REDUCTION OF PHTHALATE EXPOSURE
FOR THE PROTECTION OF BRAIN
DEVELOPMENT IN CHILDREN.
SO THEY HAVE SOME REALLY NICE
EXAMPLES IN THIS PAPER OF SOME
PUBLIC HEALTH LEVEL CHANGES THAT
COULD BE MADE TO REDUCE
PHTHALATE EXPOSURE.
SOME CAN OCCUR ON THE FEDERAL
REGULATORY ACTION LEVEL.
FOR EXAMPLE, THE U.S. CONSUMER
PRODUCT SAFETY COMMISSION BANNED
USE OF EIGHT PHTHALATES IN
CHILDREN'S TOYS.
SECOND, ANOTHER EXAMPLE IS THAT
THE U.S. FDA SET MAXIMUM DEHP
CONCENTRATIONS IN BOTTLED
DRINKING WATER AT THE SAME
CONCENTRATION THAT THE EPA SET
IN DRINKING WATER.
THERE CAN ALSO BE VOLUNTARY
ACTION BY RETAILERS.
I MENTIONED THE EFFORTS THAT
ANNIE'S IS TRYING TO IMPLEMENT
EARLIER IN THE TALK.
ANOTHER EXAMPLE FROM THIS PAPER
IS THAT PANERA BREAD HAS
REPLACED VINYL GLOVES WHICH
CONTAIN PHTHALATES.
THESE ARE THINGS I THINK CAN
TRULY LEAD TO AN EQUITABLE
REDUCTION IN PHTHALATE EXPOSURE
IN THE U.S., COMPARED TO
DEMANDING INDIVIDUALS TO MAKE
CERTAIN CHANGES IN THEIR
LIFESTYLES.
SO WITH THAT, I WANT TO
ACKNOWLEDGE THE WORK OF MY
FORMER POSTDOCTORAL FELLOWS, DR.
AND THE SUPPORT OF ALEX KEILL,
WHO IS NOW IN THE DIVISION OF
CANCER EPIDEMIOLOGY AND
GENETICS, THE NCI, WHO IS MY
METHODOLOGIST, AND STATISTICIAN
ON THIS STUDY, AND HAS BEEN
REALLY HELPFUL IN UNDERSTANDING
KIND OF THE OUTPUT OF THESE
ANALYSES.
AND WE HAVE A LARGE NUMBER OF
COLLABORATORS WHO ARE IN THE
WORKING GROUPS FOR EACH OF THESE
PAPERS AND OTHER COLLABORATORS
FROM THE POOL STUDY.
I'M SO THANKFUL TO THEM FOR
CONTRIBUTING THEIR DATA AND
THEIR TIME.
THEY WERE UNCOMPENSATED FOR
THEIR EFFORTS WORKING WITH ME ON
THIS STUDY, SO I'M VERY GRATEFUL
TO THEM AND FOR ME FUNDING FROM
THE INTRAMURAL RESEARCH PROGRAM.
WITH THAT, I'LL TAKE ANY
QUESTIONS.
THANK YOU.
[APPLAUSE]
>> THANK YOU FOR THAT VERY
INTRIGUING PRESENTATION.
SO THE PEOPLE IN THE ROOM CAN
COME TO THE MICROPHONE FOR
QUESTIONS, AND IF YOU'RE
LISTENING ON THE VIDEOCAST, YOU
CAN ENTER YOUR QUESTIONS THERE.
MAYBE LET ME START WITH ONE
QUESTION.
SO YOU MENTIONED THAT THESE
COMPOUNDS ARE UBIQUITOUSLY
PRESENT.
SO WHAT COULD WOMEN WHO ARE
WANTING TO BECOME PREGNANT OR
WHO ARE IN THE EARLY STAGES OF
PREGNANCY AND WANTING TO AVOID
EXPOSURE, WHAT COULD THEY DO
OTHER THAN NOT USE PERSONAL CARE
PRODUCTS AND NOT GO TO PANERA
BREAD WHEN THEY'RE USING THE
RIGHT GLOVES?
>> THAT'S A GOOD QUESTION, AND
YOU KNOW, I HAVE A LOT OF
FRIENDS WHO ARE TRYING TO GET
PREGNANT OR WHO ARE PREGNANT OR
RECENTLY HAD CHILDREN.
SO I FREQUENTLY GET THIS
QUESTION, WHAT CAN I DO.
AND I TELL MY FRIENDS TO NOT
STRESS OUT TOO MUCH.
CHANGING A DIETARY BEHAVIOR,
CHANGING A PERSONAL CARE PRODUCT
BEHAVIOR MIGHT POSSIBLY REDUCE
YOUR EXPOSURE, BUT IT'S NOT
GUARANTEED.
THERE'S SO MANY DIFFERENT
SOURCES OF PHTHALATES IN OUR
ENVIRONMENT THAT IT'S REALLY
HARD TO REDUCE YOUR INDIVIDUAL
LEVEL EXPOSURE.
AND SO INSTEAD, I THINK WE NEED
TO THINK MORE ABOUT THE CHANGES
THAT WE CAN MAKE ON A POPULATION
LEVEL TO REMOVE OR CHANGE THE
CHEMICALS THAT WE INCLUDE IN
PRODUCTS THAT WE'RE COMING INTO
CONTACT WITH ON A DAILY BASIS.
>> GREAT.
DR. OWENS.
>> HI.
I ENJOYED YOUR TALK.
WHAT VALIDATION IS THERE THAT
THERE'S A 100% CORRELATION
BETWEEN EXPOSURE AND URINE
LEVELS?
>> THAT'S A GOOD QUESTION.
VALIDATION ON THE CORRELATION
BETWEEN INTAKE AND URINARY
CONCENTRATIONS.
THERE HAVE BEEN STUDIES IN
HUMANS WHERE THEY'VE
ADMINISTERED PHTHALATES AND
EXAMINED THE CONCENTRATIONS IN
URINE.
I'M NOT SURE -- IT SOUNDS LIKE
YOU'RE SOMEONE WHO WORKS WITH
ANIMAL MODELS, AND THINKING MORE
FROM THIS PERSPECTIVE.
>> NO, IT'S JUST THAT -- IT'S
MORE OF A WORDSMITHING ISSUE.
YOU KNOW, TO TALK ABOUT
EXPOSURES WHEN YOU'RE ACTUALLY
MEASURING URINE AND THERE'S A
LOT THAT HAPPENS BETWEEN
SOMETHING TOUCHING YOU AND
ENDING UP IN YOUR URINE.
>> RIGHT, RIGHT.
I THINK THAT THEY'RE ACCURATELY
CATCHING WHAT MAKES THEIR WAY
INTO THE HUMAN BODY, IF THAT
IS --
>> OKAY, YES, THAT WAS THE
QUESTION.
>> WE HAVE A QUESTION FROM
MIRANDA BROADNEY ONLINE.
THE QUESTION IS, YOU MAY COVER
THIS BUT WHAT DO YOU OR THE
FIELD KNOW ABOUT DIFFERENTIAL
PHTHALATE EXPOSURE ACROSS
COMMUNITIES OF BIRTHING MOTHERS?
>> THAT'S A GOOD QUESTION.
THE TERM "COMMUNITY" CAN APPLY
TO A LOT OF THINGS.
WE TEND TO STUDY KIND OF
DIFFERENCES BASED ON THE FACTORS
THAT WE COLLECT IN OUR STUDY,
WHICH ARE MORE KIND OF
DEMOGRAPHIC, YOU KNOW,
COMMUNITIES BASED ON RACE AND
ETHNICITY, SOME OF OUR STUDIES
ARE BASED IN DIFFERENT STATES,
BUT WE DON'T HAVE A LOT OF
FOCUSED GEOGRAPHIC INFORMATION
IN THESE STUDIES.
THAT'S AN AREA THAT I'VE KIND OF
BEEN INTERESTED IN.
ARE THERE NEIGHBORHOOD OR
TEMPORAL DIFFERENCES IN HOW
THESE EXPOSURE LEVELS CHANGE?
I THINK THAT'S A REALLY
IMPORTANT QUESTION FOR FUTURE
WORK.
>> AND WE HAVE A COMMENT ONLINE,
EXCELLENT LINE OF INVESTIGATION.
CLEAR PRESENTATION.
THANK YOU VERY MUCH.
AND IN THE ROOM?
>> GREAT BR PRESENTATION, KELLY.
NICE TO HEAR ABOUT ALL OF YOUR
WORK TO DATE.
COUPLE QUESTIONS HERE.
ONE IS, HAVE YOU CONSIDERED
LOOKING AT THE INTERACTION OF
THE PHTHALATE EXPOSURE WITH
OTHER RISK FACTORS FOR PRETERM
BIRTH?
AND MIGHT THE TWO TOGETHER, FOR
EXAMPLE, GIVE A WORSE PREGNANCY
OUT COME, EVEN EARLIER GESTATION
OR WORSE OUTCOMES THE A BIRTH?
>> THAT'S A REALLY GOOD
QUESTION.
IT'S SOMETHING THAT I WAS REALLY
INTERESTED IN WHEN I FIRST CAME
TO NIEHS, AND I'VE BEEN A LITTLE
BIT LIMITED IN ABILITY TO
INVESTIGATE THAT JUST BECAUSE OF
THE DATA AVAILABILITY, BUT IN
THE TIDE STUDY WHICH I MENTIONED
EARLIER, WE EXAMINED
ASSOCIATIONS BETWEEN PHTHALATES
AND PRETERM BIRTH AND OBSERVED
ASSOCIATIONS WITH SOME OF THE
SAME COMPOUNDS THAT WE DID IN
THE POOLED STUDY.
ALSO IN THAT STUDY, WE HAVE
MEASURES OF PSYCHOSOCIAL STRESS
DURING PREGNANCY AND WE KNOW
THAT CAN BE A RISK FACTOR FOR
PRETERM BIRTH.
SO I WAS INTERESTED IN IS THERE
AN INTERACTION BETWEEN THOSE TWO
EXPOSURES AND INDEED WE DID FIND
ONE IN THAT STUDY.
IT WAS A LIMITED SAMPLE SIZE,
BUT WE FOUND THAT MOTHERS WHO
EXPERIENCED STRESSFUL LIFE
EVENTS DURING PREGNANCY, WHICH
IS JUST ONE OF MANY DIFFERENT
PARAMETERIZATIONS OF
PSYCHOSOCIAL STRESS, THOSE WOMEN
EXPERIENCED AN ASSOCIATION
BETWEEN PHTHALATE EXPOSURE AND
PRETERM BIRTH, WHEREAS THOSE WHO
HAD NO STRESSFUL LIFE EVENT
DURING PREGNANCY DID NOT.
SO IT REALLY SHOWED THAT THERE
COULD BE SOME SORT OF JOINT
EFFECT OF STRESS AND PHTHALATE
EXPOSURE ON PREMATURITY.
>> AND ANOTHER QUESTION IS ABOUT
THE METABOLISM OF PHTHALATES AND
WHETHER THERE ARE ANY GENETIC
POLYMORPHISMS THAT LEAD TO
DIFFERENCES IN METABOLISM SUCH
THAT SOME PEOPLE MAY HAVE
INCREASED EXPOSURE JUST FROM
THEIR GENETIC RISKS.
>> THAT'S A REALLY GOOD QUEST
QUESTION.
WHEN I WAS WORKING ON MY
DISSERTATION WORK, THERE WAS AN
INTEREST IN LOOKING AT THE DEHP
METABOLITES, WHICH ARE
METABOLITES FIRST INTO MEHP AND
THEN SECOND INTO MEOHP, MEHPP,
MECPP, THE OXIDIZED METABOLITES.
SO THERE WAS THE IDEA THAT THIS
KIND OF THE RATIOS OF THOSE
METABOLITES COULD BE AN
INDICATOR OF HOW EFFICIENTLY THE
INDIVIDUAL IS METABOLIZING DEHP.
AND SO SEVERAL STUDIES KIND OF
EXAMINED THE RATIO OF THOSE
COMPOUNDS AS AN EFFECT MODIFIER
AND ANALYSES TO SEE IF THERE IS
MORE EFFICIENT METABOLISM INTO
THESE OXIDIZED METABOLITES, IS
THAT POSSIBLY PROTECTIVE OR
SOMETHING LIKE THAT.
AND IT WASN'T REALLY FOUND TO BE
AN IMPORTANT EFFECT MODIFIER IN
THE PAPERS THAT EXISTED.
SO IN TERMS OF DOING AN ACTUAL
GENETIC STUDY AND LOOKING AT
POLYMORPHISMS IN ASSOCIATION
WITH EXPOSURE, I'M NOT FAMILIAR
WITH THAT LITERATURE.
I DON'T KNOW IF IT EXISTS.
BUT IT'S A REALLY INTERESTING
QUESTION.
>> THANK YOU.
>> WE HAVE A COMMENT FROM DR
DR. ELISEO, HE SAYS ONE WAY TO
LOWER THE RISK FACTOR IS THROUGH
DIRECTED CACHE ASSISTANCE, WHICH
WORKS.
GREAT PRESENTATION.
>> THANK YOU VERY MUCH.
APPRECIATE IT.
>> WE HAVE ANOTHER QUESTION
ONLINE FROM NOR WHITE.
REGARDING THE RACIAL
SOCIOECONOMIC DISPARITY IN
PERSONAL CARE PRODUCT EXPOSURE,
IS THE PROBLEM THAT CHEAPER
PRODUCTS HAVE MORE PHTHALATES OR
IS THERE A CULTURAL PREFERENCE
FOR CERTAIN PRODUCTS THAT HAPPEN
TO HAVE HIGHER THAT WILL LATES
AND THAT'S THE ISSUE, OR BOTH?
>> I THINK BOTH IS THE ANSWER.
THAT'S A REALLY GOOD QUESTION,
AND SOMETHING THAT MY COLLEAGUE
AMI SOTA HAS ADDRESSED, THE
DISCUSSION AROUND CERTAIN
PERSONAL CARE PRODUCT THAT ARE
USED MORE BY COMMUNITIES OF
COLOR TENDING TO HAVE HIGHER
LEVELS OF SOME OF THESE CHEMICAL
EXPOSURES.
SO I THINK IT'S REALLY SOMETHING
TO PAY ATTENTION TO WHEN WE'RE
KIND OF INVESTIGATING HOW CAN WE
REDUCE EXPOSURE LEVELS.
>> WE HAVE A COUPLE MORE
QUESTIONS ONLINE.
ONE FROM STEVEN GILMAN.
THANK YOU SO MUCH FOR THIS
REALLY IMPORTANT TALK.
IT WOULD BE INTERESTING -- I
WOULD BE INTERESTED IN YOUR
THOUGHTS ON STUDYING PHTHALATES
IN THE CONTEXT OF EXPOSOME
APPROACHES.
THAT MAY ALSO INCORPORATE OTHER
TYPES OF CHEMICALS, INCLUDING,
FOR EXAMPLE, AIR POLLUTION,
WHICH IS ALSO ASSOCIATED WITH
PRETERM BIRTH.
>> YEAH, THAT'S A REALLY
IMPORTANT KIND OF NEXT STEP THAT
I'M INTERESTED IN MY RESEARCH
GROUP AT NIEHS.
SO WE KNOW THAT PHTHALATES ARE
JUST ONE CLASS OF CHEMICALS THAT
ARE INCLUDED IN PLASTICIZERS AND
WE'RE SIMULTANEOUSLY EXPOSED TO
MANY OTHER CHEMICALS THROUGH
PLASTICS AND OTHER CHEMICALS
BESIDES.
SO KIND OF THE JOINT EFFECTS
THAT WE TALKED ABOUT EARLIER,
LIKE UNDERSTANDING THE
COMBINATIONS OF THOSE MULTIPLE
DIFFERENT CHEMICALS TO PRETERM
BIRTH IS SOMETHING THAT I'M
REALLY INTERESTED IN
UNDERSTANDING, AND ALSO HOW THE
CORRELATIONS EXIST AMONG THESE
CHEMICALS.
SO JUST BECAUSE WE'RE ONLY
MEASURING PHTHALATES, YOU KNOW,
THERE COULD BE OTHER CHEMICALS
THAT ARE ASSOCIATED WITH
PHTHALATE EXPOSURE THAT ARE ALSO
CONTRIBUTING TO PRETERM BIRTH
AND WE NEED TO UNDERSTAND, ARE
WE INVESTIGATING THE RIGHT
CHEMICAL EXPOSURE, ARE THERE
OTHER CHEMICAL EXPOSURES OUT
THERE THAT NEED MORE ATTENTION.
>> VERY NICE TALK.
IN THE DATA YOU PRESENTED IN THE
CHANGE IN PHTHALATES OVER THE
TRIMESTERS, IT LOOKED LIKE THERE
WAS AN INCREASE AROUND WEEK 12
FOR YOUR CASES.
DO YOU HAVE AN IDEA ABOUT WHAT
THAT MIGHT BE, AND DID THAT
PATTERN HOLD UP THE SAME ACROSS
RACIAL GROUPS OR DID DIFFERENT
RACIAL GROUPS HAVE DIFFERENT
CHANGES OVER TIME DURING THEIR
PREGNANCY?
>> THAT'S A REALLY GOOD
QUESTION.
I HAVE KIND OF STAYED AWAY FROM
FOCUSING ON THE WIGGLES IN THOSE
PLOTS TOO MUCH BECAUSE WE DON'T
HAVE GREAT REPRESENTATION FROM
ALL PARTICIPANTS ACROSS EACH OF
THOSE TIME PERIODS.
SO SOME OF THE VARIABILITY THAT
YOU OBSERVE COULD JUST BE DUE TO
THE FACT THAT ONE COHORT HAS
DATA AVAILABLE IN THAT AREA.
SO WE TRIED TO LOOK AT THE
GENERAL TRENDS AND WHEN DO WE
TEND TO OBSERVE DIFFERENCES IN
CASES AND CONTROLS ACROSS
TRIMESTERS.
IN TERMS OF WHETHER OR NOT THOSE
DIFFERENCES SIMILARLY EXIST
ACROSS RACIAL AND ETHNIC GROUPS,
WE HAVEN'T EXAMINED THAT IN THE
PERIODS OF SUSCEPTIBILITY
ANALYSIS.
WE DIDN'T HAVE A STRONG REASON
TO BELIEVE OR TO SUSPECT THAT
PERIODS OF SUSCEPTIBILITY WOULD
BE DIFFERENT BY MATERNAL RACE
AND ETHNICITY, BUT IT IS
SOMETHING WE COULD EXPLORE.
GOOD IDEA.
>> WE HAVE ANOTHER QUESTION FROM
JONATHAN TALBOT.
MEDIA COVERAGE ON RECENT STUDIES
OF PHTHALATES INCLUDES CRITICISM
OF METHODOLOGIES THAT EXAMINE
MULTIPLE PHTHALATES TOGETHER.
IS THIS A LEGITIMATE CONCERN,
AND IS THERE ANOTHER WAY TO
ESTABLISH POSSIBLE ASSOCIATION?
>> YEAH, THAT'S A REALLY GOOD
QUESTION.
EXAMINING PHTHALATES TOGETHER IS
MORE REALISTIC, I BELIEVE, AND
IT DOES KIND OF REFLECT KIND OF
WHAT WE'RE GETTING AT, WHICH IS
THE IMPACT OF AN INTERVENTION TO
AVOID PHTHALATES GENERALLY, HOW
WOULD AVOIDING PHTHALATES
GENERALLY RESULT IN LOWER
EXPOSURE LEVELS IN A CHA AND A N
YOUR PREGNANCY OUT COME.
IN TERMS OF UNDERSTANDING THE
TOXICITY OF INDIVIDUAL
COMPOUNDS, I THINK IT'S REALLY
IMPORTANT THAT EVERY STUDY THAT
EXAMINES A GROUP OF CHEMICALS OR
JOINT EFFECT OF KESM KALS NEEDS
TO HE EXAMINE CHEMICALS ONE AT A
TIME.
IN ORDER TO COMBINE DATA ACROSS
PAPERS IN META-ANALYSIS IN ORDER
TO FORM RISK ASSESSMENT, IT'S
REALLY IMPORTANT TO STUDY
CHEMICALS ONE AT A TIME.
SO WHILE I THINK IT IS USEFUL TO
UNDERSTAND THE PUBLIC HEALTH
IMPACT OF EXAMINING JOINT
EFFECTS, I THINK FOCUSING ON
MAKING SURE THAT WE EXAMINE
CHEMICALS ONE AT A TIME IN OUR
ANALYSES IS IMPORTANT.
>> SO I'M JUST CURIOUS, MAYBE
SPEND A MINUTE OR TWO TALKING
ABOUT WHERE YOU THINK YOU'RE
GOING IN THE FUTURE WITH THIS.
SO WHAT ARE YOUR NEXT STEPS IN
TERMS OF EITHER THE COMBINED
COHORT OR OTHERWISE?
>> THAT'S A GOOD QUESTION.
SO THERE ARE SOME LIMITATIONS TO
WORKING IN A POOLED STUDY.
I THINK THAT THIS HAS BEEN
REALLY USEFUL FOR IDENTIFYING A
LARGE NUMBER OF PRETERM BIRTH
CASES, SOMETHING THAT WE
COULDN'T GET OUT OF, YOU KNOW, A
STUDY -- A SINGLE STUDY.
BUT THE LIMITATIONS ARE KIND OF
IN THESE OTHER DATA THAT WE'RE
INTERESTED IN THAT COULD BE
CO-OCCURRING WITH THE EXPOSURES
THAT WE'RE MEASURING.
SO EXPANDING BEYOND LOOKING AT
PHTHALATES BY THEMSELVES AND
EXAMINING OTHER CHEMICALS THAT
ARE FOUND IN PLASTICS IN THE
ENVIRONMENT AND KIND OF THE
JOINT EFFECTS OF THESE CHEMICALS
SIMULTANEOUSLY IS ONE INTEREST
AREA.
ALSO MODIFYING EFFECTS OF THINGS
LIKE PSYCHOSOCIAL STRESSORS.
I THINK THAT'S REALLY IMPORTANT,
AND INVESTIGATING THE ROLE OF
DIET.
NOBODY BROUGHT IT UP, THAT'S
USUALLY MY VERY FIRST QUESTION
WHEN I TALK ABOUT THIS RESEARCH,
IS THAT PHTHALATE EXPOSURES COME
FROM THE DIET, AND DIET IS
IMPORTANT FOR HEALTH.
SO WHAT IS THE POTENTIAL
CONFOUNDING ROLE OF DIET IN THIS
SCENARIO?
AND WE HAVE EXAMINED DIET IN
OTHER STUDIES, CALORIC INTAKE,
AMOUNT OF FRUIT AND VEGETABLE
INTAKE.
WE DON'T REALLY SEE A BIG IMPACT
OF ADJUSTING FOR THOSE FACTORS
IN OUR ANALYSES, BUT ONE OF THE
MAIN OR A BIG EXPOSURE SOURCE
FOR PHTHALATES IS ULTRAPROCESSED
FOOD.
AND I THINK THAT THERE NEEDS TO
BE MORE WORK TO UNDERSTAND HOW
THAT EXPOSURE SOURCE,
PARTICULARLY COULD BE
POTENTIALLY CONFOUNDING THE
RESULTS THAT WE'RE LOOKING AT.
SO I'M INTERESTED IN KIND OF
EXPANDING THE EXPOSURES FROM
LOOKING AT ONE CLASS OF A
CHEMICAL TO THE EXPOSOME.
I'M ALSO INTERESTED IN
UNDERSTANDING THE BIOLOGY
FURTHER.
SO AS I MENTIONED KIND OF
BRIEFLY, YOU KNOW, WE'RE
INTERESTED IN UNDERSTANDING
INFLAMMATION AND OXIDATIVE
STRESS PATHWAYS IN PREGNANCY
THAT COULD BE UPREGULATED IN
RESPONSE TO PHTHALATE AND OTHER
CHEMICAL EXPOSURES, AND HOW
THOSE PLAY A ROLE IN PRETERM
BIRTH.
SO WE'RE STUDYING THOSE MORE,
AND THAT KIND OF ALSO INVOLVES
INVESTIGATING OUR OUT COME IN
MORE DETAIL.
SO IN THE STUDY, WE EXAMINED
PRETERM BIRTH AS DELIVERY BEFORE
37 WEEKS GESTATION BUT ANY
CLINICIAN KNOWS THAT THAT IS NOT
THE BEST OUT COME TO LOOK AT.
THERE'S EARLIER PRETERM BIRTH
WHICH HAS WORSE EFFECTS FOR THE
DEVELOPING CHILD.
THERE'S ALSO DIFFERENT
PRESENTATIONS OF PRETERM BIRTH.
THERE'S A SPONTANEOUS PRETERM
BIRTH VERSUS ONE THAT IS
DELIVERED BY THE OBSTETRICIAN
BECAUSE SOMETHING IS GOING WRONG
WITH THE FETUS IN UTERO.
SO KIND OF ISOLATING THESE
DIFFERENT OUTCOMES MORE
SPECIFICALLY IS SOMETHING THAT
I'D LIKE TO FOCUS ON IN THE
FUTURE.
>> LAST QUESTION IN THE ONE
MINUTE WE HAVE LEFT FROM TANYA
WHITE.
SOMETIMES WHEN PRODUCTS ARE
REDUCED IN PRODUCTS -- CHEMICALS
ARE REDUCED IN PRODUCTS, THEY
ARE REPLACED BY PRODUCTS THAT
HAVE NOT BEEN STUDIED OR COULD
BE POTENTIALLY WORSE.
IS THIS AN AREA OF CONCERN?
>> YEAH, THIS IS DEFINITELY A
HUGE AREA OF CONCERN.
MY GROUP HAS DONE SOME WORK
LOOKING AT SOME OF THE PHTHALATE
REPLACEMENTS AND OTHER COMPOUNDS
THAT HAVE BEEN USED TO REPLACE
PRIMARILY DEHP AS A PLASTICIZER,
BECAUSE THOSE ARE BEING
INTRODUCED TO THE MARKET AND
HAVE NOT BEEN STUDIED
THOROUGHLY.
SO WE'RE KIND OF FOCUSING ON
THOSE RIGHT NOW, BUT THERE'S A
LOT OF OTHER CHEMICALS AS WELL.
SO SUGGESTING A PHASE-OUT, IF WE
SEE A TOXIC EFFECT OF A
CHEMICAL, WE STILL NEED TO
ADDRESS IT.
BUT THERE DOES NEED TO BE SOME
ATTENTION TO KIND OF WHAT'S
GOING TO COME NEXT.
>> GREAT.
SO I THINK WE'RE AT THE TOP OF
THE HOUR, SO LET'S AGAIN THANK
DR. FERGUSON FOR A WONDERFUL
TALK.
[APPLAUSE]
>> THANK YOU FOR YOUR ATTENTION.