Faculty Bibliography

Persistent organic pollutants (POPs) are believed to alter metabolic homeostasis during fetal development, leading to childhood obesity. However, limited studies have explored how fetal chemical exposures relate to birth and infant weight outcomes in low-income Hispanic families at the highest risk of obesity. Therefore, we sought to determine associations between neonatal POPs exposure measured in newborn dried blood spots (DBS) and prenatal diet quality, birth weight, and overweight status at 18 months old. We conducted a case-control study nested within the Starting Early Program randomized controlled trial comparing POPs concentrations in infants with healthy weight (n = 46) and overweight status (n = 52) at age 18 months. Three categories of POPs, organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs) and perfluoroalkyl substances (PFASs) were measured in archived newborn DBS. We assessed correlations between prenatal diet quality and neonatal POPs concentrations. Multivariable regression analyses examined associations between POPs (dichotomized at the mean) and birth weight z-score and weight status at 18 months, controlling for confounders. Seven of eight chemicals had detectable levels in greater than 94% of the sample. Higher protein, sodium and refined grain intake during pregnancy were correlated with lower POPs in newborn DBS. We found that high concentrations of perfluorooctanesulfonate (unstandardized coefficient [B]: -0.62, 95% confidence interval [CI]: -0.96 to -0.29) and perfluorohexanesulfate (B: -0.65, 95% CI: -0.99 to -0.31) were related to lower birth weight z-scores compared to those with low concentrations. We did not find associations between PBDEs, OCPs, and the other PFASs with birth weight z-scores, or between any POPs and weight status at 18 months. In conclusion, two PFASs were associated with lower birth weight, an important indicator of child health and growth, although direct associations with infant overweight status were not found. Whether neonatal POPs exposures contribute to economic and ethnic disparities in early obesity remains unclear.

Maternal immune activity during pregnancy has been associated with risk for psychiatric disorders in offspring, but less is known about its implications for children's emotional and behavioral development. This study examined whether concentrations of five cytokines assayed from prenatal serum were associated with socioeconomic status (SES) and racial disparities in their offspring's self-regulation abilities. Participants included 1,628 women in the Collaborative Perinatal Project (CPP). Seven behavioral items conceptually related to self-regulation were rated by CPP psychologists when children were 4 years old. Concentrations of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and IL-10 were assessed. Covariates included child sex and mother's age, psychiatric disorders, and medical conditions during pregnancy. There were significant SES differences in child self-regulation, with higher SES children scoring higher on self-regulation (β = .18, 95% CI [.11, .25]), but no racial differences. The concentration of IL-8 in maternal serum was associated with higher child self-regulation, β = .09, 95% CI [.02, .16]. In mediation analyses, variation in maternal IL-8 contributed to the association between family SES and child self-regulation (β = .02, 95% CI [.003, .030]), explaining about one-tenth of the SES disparities. This study suggests pregnancy as an early sensitive period and maternal immune activity as an important context for child development.

OBJECTIVE:This study examined the extent to which maternal immune activity during pregnancy is associated with childhood adiposity, and if so, whether associations at birth differ from those in infancy and childhood. Sex-specific associations were also examined. METHODS:Participants were 1,366 singleton pregnancies from the Collaborative Perinatal Project (1959-1966). Interleukin-1β (IL-1β), IL-6, TNF-α, IL-8, and IL-10 in maternal sera were assayed repeatedly during pregnancy. Children's BMI was calculated repeatedly from birth through age 8 and derived age- and sex-normalized BMI z scores (BMIz). Linear mixed models were used to estimate the cumulative concentration of each cytokine in the second and third trimesters and then related this concentration to child BMIz. RESULTS:Children exposed to higher IL-1β, IL-6, IL-8, and IL-10 concentrations had lower BMIz at birth but higher BMIz during childhood. Higher concentrations of IL-8 and IL-1β were also associated with higher BMIz during infancy (B per log increase in IL-8 = 0.04; 95% CI: 0.02 to 0.07; B per log increase in IL-1β = 0.03; 95% CI: 0.001 to 0.06). The associations between TNF-α and BMIz were in opposing directions in boys (B = -0.13; 95% CI: -0.31 to 0.04) and girls (B = 0.14; 95% CI: 0.02 to 0.26) during childhood. CONCLUSIONS:Maternal prenatal inflammation contributes to the age- and sex-specific programming of obesity risk in childhood.

OBJECTIVES/OBJECTIVE:To identify homogenous depressive symptom trajectories over the postpartum period and the demographic and perinatal factors linked to different trajectories. METHODS:= 4866) were recruited for Upstate KIDS, a population-based birth cohort study, and provided assessments of depressive symptoms at 4, 12, 24, and 36 months postpartum. Maternal demographic and perinatal conditions were obtained from vital records and/or maternal report. RESULTS:Four depression trajectories were identified: low-stable (74.7%), characterized by low symptoms at all waves; low-increasing (8.2%), characterized by initially low but increasing symptoms; medium-decreasing (12.6%), characterized by initially moderate but remitting symptoms; and high-persistent (4.5%), characterized by high symptoms at all waves. Compared with the high-persistent group, older mothers (maximum odds ratio [OR] of the 3 comparisons: 1.10; 95% confidence interval [CI]: 1.05 to 1.15) or those with college education (maximum OR: 2.52; 95% CI: 1.36 to 4.68) were more likely to be in all other symptom groups, and mothers who had a history of mood disorder (minimum OR: 0.07; 95% CI: 0.04 to 0.10) or gestational diabetes mellitus diagnosis (minimum OR: 0.23; 95% CI: 0.08 to 0.68) were less likely to be in other symptom groups. Infertility treatment, multiple births, prepregnancy BMI, gestational hypertension, and infant sex were not differentially associated with depressive symptom trajectories. CONCLUSIONS:One-quarter of mothers in a population-based birth cohort had elevated depressive symptoms in 3 years postpartum. Screening for maternal depression beyond the postpartum period may be warranted, particularly after mood and diabetic disorders.

Experimental studies suggested per- and polyfluoroalkyl substances (PFASs) may disrupt estrogens in animals, however, the epidemiological evidence on the associations of PFASs with estrogens is sparse. We investigated the associations of legacy PFASs and their alternatives, including F-53B, the perfluorooctane sulfonate (PFOS) replacement that is specifically and commonly used in China, with estrogen concentrations in newborns. We quantified six PFASs and three estrogens in the cord sera of 942 newborns from a birth cohort in Wuhan, China, between 2013 and 2014. After adjusting for confounders and correcting for multiple comparisons, we observed that both legacy PFASs and their alternatives were associated with higher serum levels of estradiol (E2). Some of the PFASs were associated with increasing levels of estrone (E1) and estriol (E3). Analysis of PFASs in mixture using weighted quantile sum regressions showed that F-53B contributed 20.1% and 48.5% to the associations between PFASs and E1 and E2, respectively. This study provided epidemiological data on the associations between common PFAS exposures and estrogens in newborns. Additional toxicology studies are needed to fully understand the effects of PFASs on estrogens and the mechanisms.

BACKGROUND:Most pregnant women are exposed to bisphenols, a group of chemicals that can interfere with various components of the thyroid system. OBJECTIVES/OBJECTIVE:To investigate the association of maternal urinary bisphenol concentrations during pregnancy with maternal, newborn and early childhood thyroid function. METHODS:This study was embedded in Generation R, a prospective, population-based birth cohort (Rotterdam, the Netherlands). Maternal urine samples were analyzed for eight bisphenols at early (<18), mid (18-25) and late (>25 weeks) pregnancy. Maternal serum thyroid stimulating hormone (TSH), free thyroxine (FT4) and total thyroxine (TT4) were measured in early pregnancy and child TSH and FT4 were measured in cord blood and childhood. RESULTS: = 0.08). DISCUSSION/CONCLUSIONS:Our findings show that exposure to bisphenols may interfere with the thyroid system during pregnancy. Furthermore, the potential developmental toxicity of exposure to bisphenols during pregnancy could affect the thyroid system in the offspring in a sex-specific manner.

BACKGROUND:Prenatal exposures to phthalates and bisphenols are associated with impaired brain development in animals. However, epidemiological studies investigating the association between prenatal phthalate or bisphenol exposure and cognition have produced mixed findings and mostly had modest sample sizes and measured the exposure during the third trimester. OBJECTIVE:We examined the association between pregnancy maternal urinary biomarkers of phthalate or bisphenol exposure and nonverbal intelligence quotient (IQ) in children 6 years of age. METHOD/METHODS: RESULTS: CONCLUSIONS:We did not observe that maternal biomarkers of bisphenol exposure are associated with nonverbal IQ. We found that phthalate exposure in early pregnancy and DNOP exposure in late pregnancy are associated with lower nonverbal IQ scores in children. Our results might suggest that particularly early pregnancy is a sensitive window of phthalate exposure, but future studies are needed to replicate our findings. https://doi.org/10.1289/EHP6047.

OBJECTIVES/OBJECTIVE:To assess relations of prepregnancy maternal and paternal obesity with offspring behavioral problems and psychiatric symptoms at 7-8 years in the Upstate KIDS study, a prospective cohort study. STUDY DESIGN/METHODS:Maternal body mass index (BMI) was calculated from prepregnancy height and weight provided in vital records or self-report at 4 months postpartum. Mothers reported paternal height and weight. At 7-8 years, mothers indicated if their children had been diagnosed with ADHD or anxiety (n = 1915). Additionally, children's behavior was measured with the Strengths and Difficulties Questionnaire at 7 years of age (n = 1386) and the Vanderbilt ADHD Diagnostic Parent Rating Scale at 8 years of age (n = 1484). Based on Strengths and Difficulties Questionnaire scores, we identified children with borderline behavioral problems. Adjusted risk ratios (aRR) and 95% CIs were estimated with robust multivariable Poisson regression. RESULTS:had higher risks of reported ADHD (aRR, 1.14, 95% CI, 0.78-1.69; aRR, 1.96, 95% CI, 1.29-2.98; and aRR, 1.82, 95% CI,1.21-2.74, respectively). Risks of hyperactivity problems identified by the Strengths and Difficulties Questionnaire and a positive screen for inattentive or hyperactive/impulsive behavior with the Vanderbilt ADHD Diagnostic Parent Rating Scale were also higher with increasing maternal prepregnancy BMI. Paternal BMI was not associated with child outcomes. CONCLUSIONS:Our findings suggest that maternal, rather than paternal, obesity is associated with maternal report of child ADHD diagnosis and inattentive or hyperactivity problems. Further research is needed to understand how maternal obesity might influence these behavioral changes during or after pregnancy.

The aims of the NYU Children's Health and Environment Study (CHES) are to evaluate influences of prenatal non-persistent chemical exposures on fetal and postnatal growth and pool our data with the US National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Program to answer collaborative research questions on the impact of the preconceptual, prenatal, and postnatal environment on childhood obesity, neurodevelopment, pre/peri/postnatal outcomes, upper and lower airway outcomes, and positive health. Eligible women were ≥ 18 years old, < 18 weeks pregnant, had a pregnancy that is not medically threatened, and planned to deliver at NYU Langone Hospital-Manhattan, Bellevue Hospital, or NYU Langone Hospital-Brooklyn. Between March 22, 2016 and April 15, 2019, we recruited 2469 pregnant women, from whom 2193 completed an initial questionnaire and continued into NYU CHES. Of the 2193, 88 miscarried, 28 terminated, and 20 experienced stillbirth, while 57 were lost to follow up. We report here demographic and other characteristics of the 2000 live deliveries (2037 children), from whom 1624 (80%) consented to postnatal follow-up. Data collection in pregnancy was nested in clinical care, with questionnaire and specimen collection conducted during routine prenatal visits at < 18, 18-25, and > 25 weeks gestation. These have been followed by questionnaire and specimen collection at birth and regular postpartum intervals.

OBJECTIVE:To study the associations between maternal polycystic ovary syndrome (PCOS) and hirsutism with offspring attention-deficit/hyperactivity disorder (ADHD), anxiety, conduct disorder, and behavioral problems. DESIGN/METHODS:Prospective birth cohort study. SETTING/METHODS:Not applicable. PATIENT(S)/METHODS:A total of 1,915 mother-child dyads. INTERVENTION(S)/METHODS:None. MAIN OUTCOME MEASURE(S)/METHODS:Maternal report of offspring ADHD, anxiety, or conduct disorder diagnosis at 7 to 8 years; emotional symptoms, behavioral problems (including peer relationship, conduct, hyperactivity/inattention), and prosocial problems measured with the Strengths and Difficulties Questionnaire (SDQ) at 7 years. RESULT(S)/RESULTS:Prevalence of PCOS and hirsutism were 12.0% and 3.9%; 84% of women with hirsutism had PCOS. After adjustment for sociodemographic covariates, prepregnancy body mass index, and parental history of affective disorders, children born to mothers with PCOS had higher risk of anxiety (adjusted risk ratio [aRR] 1.62; 95% confidence interval [CI], 1.02-2.57) and borderline emotional symptoms (aRR 1.66; 95% CI, 1.18-2.33) compared with children born to mothers without PCOS. The associations between maternal PCOS and offspring ADHD were positive but imprecise. Maternal hirsutism was related to a higher risk of children's ADHD (aRR 2.33; 95% CI, 1.28-4.24), conduct disorder (aRR 2.54; 95% CI 1.18-5.47), borderline emotional symptoms, peer relationship problems, and conduct problems (aRRs 2.61; 95% CI, 1.69-4.05; 1.92; 95% CI, 1.16-3.17; and 2.22; 95% CI, 1.30-3.79, respectively). CONCLUSION(S)/CONCLUSIONS:Maternal PCOS was associated with offspring anxiety, and hirsutism was related to other offspring behavioral problems. These findings should be interpreted with caution as replication is needed in prospective cohort studies that assess PCOS and hirsutism diagnoses using medical records.