Faculty Bibliography

Early in the pandemic, in the North American epicenter, we investigated associations between sociodemographic factors and rates of pediatric COVID-19 diagnoses in a non-clinical setting and whether symptoms varied by child age. From 20 April-31 August 2020, COVID-19-related data were collected on 2694 children aged ≤ 18 years living in households participating in the New York University Children's Health and Environment Study. We examined differences in rates of subjective and objective diagnoses according to sociodemographic characteristics and differences in reported symptoms by child age. Children of women who were non-Hispanic White, had private health insurance, higher income, or more education were more likely to be diagnosed via WHO criteria or healthcare provider. Children of women who were Hispanic or Asian, reported low income, had less education, or were/lived with an essential worker were more likely to test positive. Older children were less likely to experience cough or runny nose and more likely to experience muscle/body aches, sore throat, headache, and loss of smell or taste than younger children. In conclusion, relying on subjective disease ascertainment methods, especially in the early stage of an outbreak when testing is not universally available, may misrepresent the true prevalence of disease among sociodemographic subgroups. Variations in symptoms by child age should be considered when determining diagnostic criteria.

Women are nearly twice as likely to develop mood disorders compared with men, and incidence is greatest during reproductive transitions, including pregnancy and postpartum. Because these periods are characterized by dramatic hormonal and physiologic changes, there is heightened susceptibility to external factors, such as exposure to environmental toxicants, which may play a role in maternal psychopathology. The purpose of this scoping review was to provide an overview of studies conducted in humans and animal models on the effects of nonoccupational exposure to environmental chemicals on maternal psychopathology during the perinatal period. The largest number of studies examined exposure to environmental tobacco smoke and antenatal depression and showed consistently positive findings, although more prospective studies using biomarkers for exposure assessment are needed. The few studies examining persistent organic pollutants such as polybrominated diphenyl ethers and perinatal depression were consistent in showing associations with increased depressive symptoms. Results were mixed for exposure to heavy metals and non-persistent chemicals, but a strong literature in animal models supported an association between bisphenols and phthalates and reduced maternal behavior and care of pups after parturition. Biological mechanisms may include endocrine disruption, neurotransmitter system impairment, alterations in gene expression, and immune activation and inflammation. Additional longitudinal studies that include biospecimen collection are essential to furthering the understanding of how environmental toxicants during pregnancy may affect perinatal psychopathology and the underlying mechanisms of action. Future work should also leverage the parallels between animal and human maternal behavior, thereby highlighting the opportunity for multidisciplinary work in this avenue.

CONTEXT/BACKGROUND:In preclinical studies, high androgen levels during pregnancy are associated with low birth weight and rapid postnatal weight gain in the offspring. However, human data linking prenatal androgens with birth weight and early life weight gain in the offspring are scarce. DESIGN/METHODS:We evaluated 516 mother-child pairs enrolled in the New England birth cohorts of the Collaborative Perinatal Project (1959-1966). We assayed androgen bioactivity in maternal sera during third-trimester using a receptor-mediated luciferase expression bioassay. Age and sex-specific BMI Z-scores (BMIz), defined using established standards, were assessed at birth, 4 months, 1 year, 4 years, and 7 years. We used linear mixed models to evaluate the relation of maternal androgens with childhood BMIz overall and by sex. We examined the association of maternal androgens with fetal growth restriction. The association of weight trajectories with maternal androgens was examined using multinomial logistic regression. RESULTS:Higher maternal androgen levels associated with lower BMIz at birth (β = - 0.39, 95% CI: - 0.73, - 0.06); this relation was sex-dependent, such that maternal androgens significantly associated with BMIz at birth in girls alone (β = - 0.72, 95% CI: - 1.40, - 0.04). The relation of maternal androgens with fetal growth restriction revealed dose threshold effects that differed by sex. There was no significant association between maternal androgens and weight trajectory overall. However, we found a significant sex interaction (p = 0.01); higher maternal androgen levels associated with accelerated catch-up growth in boys (aOR = 2.14, 95% CI: 1.14, 4.03). CONCLUSION/CONCLUSIONS:Our findings provide evidence that maternal androgens may have differential effects on the programming of intrauterine growth and postnatal weight gain depending on fetal sex.

Maternal diet, prior to and during pregnancy, plays an important role in the immediate and long-term health of the mother and her offspring. Our objectives were to assess diet quality among a large, diverse, urban cohort of pregnant women, and examine associations with sociodemographic and health behavior characteristics. Data were from 1,325 pregnant women enrolled in New York University Children's Health and Environment Study (NYU CHES). Diet quality was assessed using the Healthy Eating Index (HEI)-2015. Mean total HEI-2015 score was 74.9 (SD = 8.5); 376 (28%), 612 (46%), 263 (20%), and 74 (6%) of women had scores that fell into the grade range of A/B, C, D, and F, respectively. Mean HEI-2015 component scores were high for fruit and whole grains and low for protein-related, sodium, and fat-related components. In multivariable linear regression models, Hispanic women scored 1.65 points higher on the total HEI-2015 (95% CI: 0.21, 3.10) compared to non-Hispanic White women, while younger age (<30 years), parity, single status, pre-pregnancy obesity, smoking, pre-existing hypertension, moderate/severe depressive symptoms, not meeting physical activity recommendations, and not taking a vitamin before pregnancy were associated with ~1.5-5-point lower mean total HEI-2015 scores. Diet is a modifiable behavior; our results suggest a continued need for pre-conceptional and prenatal nutritional counseling.

Pregnant women are widely exposed to organophosphate (OP) pesticides, which are potentially neurotoxicant for the developing fetus. We aimed to identify principal demographic and dietary predictors of OP pesticide exposure among 450 pregnant women participating in the New York University Children's Health and Environment Study (enrolled 2016-19). Urinary concentrations of six dialkyl phosphate (DAP) metabolites (3 dimethyl (DM) metabolites and 3 diethyl (DE) metabolites) of OP pesticides were determined at three time points across pregnancy. At mid-gestation, the Diet History Questionnaire II was used to assess women's dietary intake over the past year. Demographic characteristics were obtained using questionnaires and/or electronic health records. We used linear mixed models to evaluate the associations of demographic and food groups with DAP metabolite levels, and partial-linear single-index (PLSI) models to analyze the contribution proportions of food groups to DAP metabolite concentrations and the dose-response relationships between them. We observed that pregnant women in NYC had lower levels of OP pesticide metabolites than pregnant populations in Europe, Asia, and other regions in the U.S. Having lower pre-pregnancy body mass index and being Asian, employed, and single were associated with higher DAP metabolite concentrations. Fruit and grain intakes were associated with higher ∑DM, ∑DE, and ∑DAP levels. ∑DE concentrations increased 9.0% (95% confidence interval (CI) = 1.2%, 17.4%) per two-fold increase in dairy consumption, whereas ∑DE concentrations decreased 1.8% (95%CI = -3.1%, -0.4%) per two-fold increase in seafood consumption. The PLSI model indicated that among the food mixture, fruit and grains were the main food groups contributed to higher levels of ∑DAP, while meat contributed to lower levels of ∑DAP. The contribution proportions of fruit, grains, and meat were 18.7%, 17.9%, and 39.3%, respectively. Our results suggest that fruit, grains, and meat are major dietary components associated with OP pesticide exposure in urban pregnant women.

OBJECTIVE:To investigate whether deoxyribonucleic acid (DNA) methylation at birth and in childhood differ by conception using assisted reproductive technologies (ART) or ovulation induction compared with those in children conceived without fertility treatment. DESIGN/METHODS:Upstate KIDS is a matched exposure cohort which oversampled on newborns conceived by treatment. SETTING/METHODS:New York State (excluding New York City). PATIENT(S)/METHODS:This analysis included 855 newborns and 152 children at approximately 9 years of age. INTERVENTION(S)/METHODS:None. MAIN OUTCOME MEASURE(S)/METHODS:DNA methylation levels were measured using the Illumina EPIC platform. Single CpG and regional analyses at imprinting genes were conducted. RESULT(S)/RESULTS:Compared to no fertility treatment, ART was associated with lower mean DNA methylation levels at birth in 11 CpGs (located in/near SYCE1, SPRN, KIAA2013, MYO1D, GET1/WRB-SH4BGR, IGF1R, SORD, NECAB3/ACTL10, and GET1) and higher mean methylation level in 1 CpG (KLK4; all false discovery rate P<.05). The strongest association (cg17676129) was located at SYCE1, which codes for a synaptonemal complex that plays a role in meiosis and therefore infertility. This CpG remained associated with newborn hypomethylation when the analysis was limited to those conceived with ICSI, but this may be because of underlying male infertility. In addition, nine regions in maternally imprinted genes (IGF1R, PPIEL, SVOPL GNAS, L3MBTL, BLCAP, HYMAI/PLAGL1, SNU13, and MEST) were observed to have decreased mean DNA methylation levels among newborns conceived by ART. In childhood, hypomethylation of the maternally imprinted gene, GNAS, persisted. No CpGs or regions were associated with ovulation induction. CONCLUSION(S)/CONCLUSIONS:ART but not ovulation induction was associated with hypomethylation at birth, but only one difference at an imprinting region appeared to persist in childhood.

OBJECTIVE: The aim of this study is to model the association between gestational age at birth and early child development through 3 years of age. STUDY DESIGN/METHODS: Development of 5,868 children in Upstate KIDS (New York State; 2008-2014) was assessed at 7 time points using the Ages and Stages Questionnaire (ASQ). The ASQ was implemented using gestational age corrected dates of birth at 4, 8, 12, 18, 24, 30, and 36 months. Whether children were eligible for developmental services from the Early Intervention Program was determined through linkage. Gestational age was based on vital records. Statistical models adjusted for covariates including sociodemographic factors, maternal smoking, and plurality. RESULTS: Compared with gestational age of 39 weeks, adjusted odds ratios (aOR) and 95% confidence intervals of failing the ASQ for children delivered at <32, 32-34, 35-36, 37, 38, and 40 weeks of gestational age were 5.32 (3.42-8.28), 2.43 (1.60-3.69), 1.38 (1.00-1.90), 1.37 (0.98-1.90), 1.29 (0.99-1.67), 0.73 (0.55-0.96), and 0.51 (0.32-0.82). Similar risks of being eligible for Early Intervention Program services were observed (aOR: 4.19, 2.10, 1.29, 1.20, 1.01, 1.00 [ref], 0.92, and 0.78 respectively for <32, 32-34, 37, 38, 39 [ref], 40, and 41 weeks). CONCLUSION/CONCLUSIONS: Gestational age was inversely associated with developmental delays for all gestational ages. Evidence from our study is potentially informative for low-risk deliveries at 39 weeks, but it is notable that deliveries at 40 weeks exhibited further lower risk.

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.

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.