Faculty Bibliography

BACKGROUND:Early-life exposure to phthalates alters behaviors in animals. However, epidemiological evidence on childhood phthalate exposure and attention-deficit/hyperactivity disorder (ADHD) behaviors is limited. METHODS:This study included 243 children from the ReCHARGE (Revisiting Childhood Autism Risks from Genetics and Environment) study, who were previously classified as having autism spectrum disorder (ASD), developmental delay, other early concerns, and typical development in the CHARGE case-control study. Twenty phthalate metabolites were measured in spot urine samples collected from children aged 2-5 years. Parents reported on children's ADHD symptoms at ages 8-18 years using Conners-3 Parent Rating Scale. Covariate-adjusted negative binomial generalized linear models were used to investigate associations between individual phthalate metabolite concentrations and raw scores. Weighted quantile sum (WQS) regression with repeated holdout validation was used to examine mixture effects of phthalate metabolites on behavioral scores. Effect modification by child sex was evaluated. RESULTS:Among 12 phthalate metabolites detected in >75% of the samples, higher mono-2-heptyl phthalate (MHPP) was associated with higher scores on Inattentive (β per doubling = 0.05, 95% confidence interval [CI]: 0.02, 0.08) and Hyperactive/Impulsive scales (β = 0.04, 95% CI: 0.00, 0.07), especially among children with ASD. Higher mono-carboxy isooctyl phthalate (MCiOP) was associated with higher Hyperactivity/Impulsivity scores (β = 0.07, 95% CI: -0.01, 0.15), especially among typically developing children. The associations of the molar sum of high molecular weight (HMW) phthalate metabolites and a phthalate metabolite mixture with Hyperactivity/Impulsivity scores were modified by sex, showing more pronounced adverse associations among females. CONCLUSION/CONCLUSIONS:Exposure to phthalates during early childhood may impact ADHD behaviors in middle childhood and adolescence, particularly among females. Although our findings may not be broadly generalizable due to the diverse diagnostic profiles within our study population, our robust findings on sex-specific associations warrant further investigations.

BACKGROUND:Phthalates are endocrine-disrupting chemicals with anti-androgenic qualities and studies reported associations between prenatal phthalate exposure and infant genitalia. This study investigated whether increased prenatal phthalate exposure is associated with decreased fetal penile measures. METHODS:Data was from the New York University Children's Health and Environment Study (2016-2019). Maternal urinary concentrations of 16 phthalate metabolites were quantified at <18 weeks gestation as a proxy for fetal exposure (n = 334 male pregnancies). We retrospectively measured penile length and width using ultrasounds conducted 18-24 weeks gestation (n = 173 fetuses). Associations of maternal urinary levels of phthalates with fetal penile length and width were determined using linear regression models. RESULTS:57.2% of women were Hispanic, 31.8% Non-Hispanic White, 6.4% Asian, 2.3% Non-Hispanic Black, and 2.3% multiple races. Mean maternal age was 32 years (standard deviation [SD] = 5.7). Mean penile length was 7.13 mm (SD = 1.47) and width was 6.16 mm (SD = 0.87). An inverse relationship was observed between maternal levels of mono-ethyl phthalate and fetal penile length, and mono-(7-carboxy-n-heptyl) phthalate and penile width, though estimates were small and not significant when considering correction for multiple comparisons. CONCLUSIONS:In our cohort we found no clinically meaningful associations between early pregnancy phthalate exposure and fetal penile length or width. IMPACT/CONCLUSIONS:First-trimester phthalate metabolites were assessed in pregnant women in New York City. Penile length and width were retrospectively measured on clinically assessed ultrasounds conducted ≥18 weeks and <24 weeks of gestation. In this cohort, no clinically meaningful associations were observed between first-trimester prenatal phthalate exposure and fetal penile length. This study contributes to the limited but growing research on the impact of prenatal phthalate exposure on male fetal genital development. The results emphasize that there may not be a clear association between prenatal phthalate exposure and fetal penile length and width, and further research on this topic may be required.

OBJECTIVE:To examine the additive or moderating influences of caregiver COVID-19-related stress, social support, and discrimination on children's behavior problems across racially diverse populations. METHOD/METHODS:In this Environmental influences on Child Health Outcomes (ECHO) cohort study (N = 1,999 caregiver/child pairs), we operationalized caregiver COVID-19-related stress in 2 ways: first, as the number of stressors (eg, financial concerns, social distancing); and second, as the level of pandemic-related traumatic stress symptoms reported via questionnaires administered between April 2020 and August 2022. At the same assessment visit, caregivers also reported their current levels of discrimination, and a subsample (n = 968) reported their emotional and instrumental support. Either concurrently or at a later assessment visit, caregivers reported on their children's internalizing and externalizing behavior problems using the Child Behavior Checklist for Ages 6-18 (CBCL/6-18). RESULTS:Multivariable analyses controlling for maternal education, marital status, child age, and child sex revealed that COVID-19-related stress (caregiver stressors and symptoms) and discrimination were positively associated, and that perceived support was negatively associated with child internalizing and externalizing behavior problems. Unexpectedly, neither emotional nor instrumental support attenuated the relationship between caregiver COVID-19-related stressors nor traumatic stress symptoms and child behavior problems. In the subset of Black American participants, caregiver perceived discrimination moderated the relationship between caregiver COVID-19 traumatic stress symptoms and child internalizing problems, such that the association was stronger at higher levels of discrimination. CONCLUSION/CONCLUSIONS:Our findings highlight the potential importance of relieving caregiver stress and increasing caregiver social support to optimize children's behavioral outcomes.

BACKGROUND:Exposure to endocrine-disrupting chemicals such as bisphenols and phthalates during pregnancy may disrupt fetal developmental programming and influence early-life growth. We hypothesized that prenatal bisphenol and phthalate exposure was associated with alterations in adiposity through 4 years. This associations might change over time. METHODS:Among 1091 mother-child pairs in a New York City birth cohort study, we measured maternal urinary concentrations of bisphenols and phthalates at three time points in pregnancy and child weight, height, and triceps and subscapular skinfold thickness at ages 1, 2, 3, and 4 years. We used linear mixed models to assess associations of prenatal individual and grouped bisphenols and phthalates with overall and time-point-specific adiposity outcomes from birth to 4 years. RESULTS:We observed associations of higher maternal urinary second trimester total bisphenol and bisphenol A concentrations in pregnancy and overall child weight between birth and 4 years only (Beta 0.10 (95 % confidence interval 0.04, 0.16) and 0.07 (0.02, 0.12) standard deviation score (SDS) change in weight per natural log increase in exposure), We reported an interaction of the exposures with time, and analysis showed associations of higher pregnancy-averaged mono-(2-carboxymethyl) phthalate with higher child weight at 3 years (0.14 (0.06, 0.22)), and of higher high-molecular-weight phthalate, di-2-ethylhexyl phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, mono-(2-carboxymethyl) phthalate, and mono-(2-ethylhexyl) phthalate with higher child weight at 4 years (0.16 (0.04, 0.28), 0.15 (0.03, 0.27), 0.19 (0.07, 0.31), 0.16 (0.07, 0.24), 0.11 (0.03, 0.19)). Higher pregnancy-averaged high-molecular-weight phthalate, di-2-ethylhexyl phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, and mono-2(ethyl-5-oxohexyl) phthalate concentrations were associated with higher child BMI at 4 years (0.20 (0.05, 0.35), 0.20 (0.05, 0.35), 0.22 (0.06, 0.37), 0.20 (0.05, 0.34), 0.20 (0.05, 0.34)). For skinfold thicknesses, we observed no associations. DISCUSSION/CONCLUSIONS:This study contributes to the evidence suggesting associations of prenatal exposure to bisphenols and high-molecular-weight phthalates on childhood weight and BMI.

Organophosphate esters (OPEs) are a class of chemicals now widely used as flame retardants and plasticizers after the phase-out of polybrominated diphenyl ethers (PBDEs). However, OPEs carry their own risk of developmental toxicity, which poses concern for recent birth cohorts as they have become ubiquitous in the environment. In this review, we summarize the literature evaluating the association between OPE exposure and maternal, perinatal, and child health outcomes. We included original articles investigating associations of OPE exposure with any health outcome on pregnant women, newborns, children, and adolescents. We found 48 articles on this topic. Of these, five addressed maternal health and pregnancy outcomes, 24 evaluated prenatal OPE exposure and child health, 18 evaluated childhood OPE exposure and child/adolescent health, and one article evaluated both prenatal and childhood OPE exposure. These studies suggest that OPE exposure is possibly associated with a wide range of adverse health outcomes, including pregnancy loss, altered gestational duration and smaller birthweight, maternal and neonatal thyroid dysfunction, child metabolic dysregulation and abnormal growth, impaired neurodevelopment, and changes in immune response. Many of the reported outcomes associated with OPE exposure varied by child sex. Findings also varied substantially by OPE metabolite and exposure time. The OPEs most frequently measured, detected, and found to be associated with health outcomes were triphenyl phosphate (TPHP, metabolized to DPHP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP, metabolized to BDCIPP). The extensive range of health outcomes associated with OPEs raises concern about their growing use in consumer products; however, these findings should be interpreted considering the limitations of these epidemiological studies, such as possible exposure misclassification, lack of generalizability, insufficient adjustment for covariates, and failure to consider chemical exposures as a mixture.

New York City (NYC) is slated to be the first jurisdiction in the USA to implement a cordon-based congestion tax, which will be levied on vehicles entering its Central Business District. Several cities around the world, for example, London and Stockholm, have had similar cordon-based pricing programmes, defined as road pricing that charges drivers a fee for entering a specified area (typically a congested urban centre). In addition to reducing congestion and creating revenue, projections suggest the NYC congestion pricing plan may yield meaningful traffic-related air quality improvements that could result in health benefits. NYC is a large city with high air pollution and substantial racial/ethnic and socioeconomic health inequities. The distinct geography and meteorological conditions of the city also suggest that the policy's impact on air quality may extend beyond the NYC metropolitan area. As such, the potential breadth, directionality and magnitude of health impacts on communities who might be heavily affected by the nation's first congestion pricing plan should be empirically investigated. We briefly review evaluation studies of other cordon-based congestion pricing policies and argue that implementation of this policy provides an excellent opportunity to employ a quasi-experimental study design to evaluate the policy's impacts on air quality and health outcomes across population subgroups using a health equity lens. We discuss why real-time evaluations of the NYC congestion pricing plan can potentially help optimise benefits for communities historically negatively affected by traffic-related air pollution. Assessing intended and unintended impacts on health equity is key to achieving these goals.

OBJECTIVE:The objective of this study was to evaluate whether the children's neighborhood quality, as a measure of place-based social determinants of health, is associated with the odds of developmental delay and developmental performance up to the age of 4 years. STUDY DESIGN/METHODS:Mothers of 5702 children from the Upstate KIDS Study, a longitudinal population-based cohort of children born from 2008 through 2010, provided questionnaire data and a subset of 573 children participated in a clinic visit. The Child Opportunity Index 2.0 was linked to home census tract at birth. Probable developmental delays were assessed by the Ages and Stages Questionnaire up to 7 times between 4 and 36 months, and developmental performance was assessed via the Battelle Developmental Inventory at the age of 4 years. RESULTS:In unadjusted models, higher neighborhood opportunity was protective against developmental delays and was associated with slightly higher development scores at age 4. After adjusting for family-level confounding variables, 10-point higher Child Opportunity Index (on a 100-point scale) remained associated with a lower odds of any developmental delay (OR = .966, 95% CI = .940-.992), and specifically delays in the personal-social domain (OR = .921, 95% CI = .886-.958), as well as better development performance in motor (B = 0.79, 95% CI = 0.11-1.48), personal-social (B = 0.64, 95% CI = 0.003-1.28), and adaptive (B = 0.69, 95% CI = 0.04-1.34) domains at age 4. CONCLUSIONS:Community-level opportunities are associated with some aspects of child development prior to school entry. Pediatric providers may find it helpful to use neighborhood quality as an indicator to inform targeted developmental screening.

Early infant growth trajectories have been linked to obesity risk. The aim of this study was to examine early infant feeding practices in association with anthropometric measures and risk of overweight/obesity in childhood. A total of 2492 children from Upstate KIDS, a population-based longitudinal cohort, were included for the analysis. Parents reported breastfeeding and complementary food introduction from 4 to 12 months on questionnaires. Weight and height were reported at 2-3 years of age and during later follow-up at 7-9 years of age. Age and sex z-scores were calculated. Linear mixed models were conducted, adjusting for maternal and child sociodemographic factors. Approximately 54% of infants were formula-fed at <5 months of age. Compared to those formula-fed, BMI- (adjusted B, -0.23; 95% CI: -0.42, -0.05) and weight-for-age z-scores (adjusted B, -0.16; -0.28, -0.03) were lower for those exclusively breastfed. Infants breastfed for ≥12 months had a lower risk of being overweight (aRR, 0.33; 0.18, 0.59) at 2-3 years, relative to formula-fed infants. Compared to introduction at <5 months, the introduction of fruits and vegetables between 5 and 8 months was associated with lower risk of obesity at 7-9 years (aRR, 0.45; 0.22, 0.93). The type and duration of breastfeeding and delayed introduction of certain complementary foods was associated with lower childhood BMI.

OBJECTIVE: DESIGN/METHODS:Pooled pregnancy cohort studies. SETTING/METHODS:Cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) consortium with births from 1999 to 2020. PARTICIPANTS/METHODS:A total of 10 800 pregnant women in twenty-three cohorts with food frequency data on fish consumption; 12 646 from thirty-five cohorts with information on supplement use. RESULTS:. never). CONCLUSIONS:-3 supplement use was uncommon, even among those who did not consume fish.

STUDY QUESTION/OBJECTIVE:Do children born to mothers with polycystic ovary syndrome (PCOS) have an adverse cardiometabolic profile including arterial stiffness at 9 years of age compared to other children? SUMMARY ANSWER/CONCLUSIONS:Children of mothers with PCOS did not have differing cardiometabolic outcomes than children without exposure. WHAT IS KNOWN ALREADY/BACKGROUND:While women with PCOS themselves have higher risk of cardiometabolic conditions such as obesity and diabetes, the evidence on intergenerational impact is unclear. Given in utero sequalae of PCOS (e.g. hyperandrogenism, insulin resistance), the increased risk could be to both boys and girls. STUDY DESIGN, SIZE, DURATION/METHODS:The Upstate KIDS cohort is a population-based birth cohort established in 2008-2010 to prospectively study the impact of infertility treatment on children's health. After ∼10 years of follow-up, 446 mothers and their 556 children attended clinical visits to measure blood pressure (BP), heart rate, arterial stiffness by pulse wave velocity (PWV), mean arterial pressure, lipids, high-sensitivity C-reactive protein (hsCRP), hemoglobin A1c (HbA1c), and anthropometrics. PARTICIPANTS/MATERIALS, SETTING, METHODS/METHODS:Women self-reported ever diagnoses of PCOS ∼4 months after delivery of their children in 2008-2010. Linear regression models applying generalized estimating equations to account for correlation within twins were used to examine associations with each childhood cardiometabolic outcome. MAIN RESULTS AND THE ROLE OF CHANCE/RESULTS:In this cohort with women oversampled on infertility treatment, ∼14% of women reported a PCOS diagnosis (n = 61). We observed similarities in BP, heart rate, PWV, lipids, hsCRP, HbA1c, and anthropometry (P-values >0.05) among children born to mothers with and without PCOS. Associations did not differ by child sex. LIMITATIONS, REASONS FOR CAUTION/CONCLUSIONS:The sample size of women with PCOS precluded further separation of subgroups (e.g. by hirsutism). The population-based approach relied on self-reported diagnosis of maternal PCOS even though self-report has been found to be valid. Participants were predominantly non-Hispanic White and a high proportion were using fertility treatment due to the original design. Differences in cardiometabolic health may be apparent later in age, such as after puberty. WIDER IMPLICATIONS OF THE FINDINGS/CONCLUSIONS:Our results provide some reassurance that cardiometabolic factors do not differ in children of women with and without self-reported PCOS during pregnancy. STUDY FUNDING/COMPETING INTEREST(S)/BACKGROUND:Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States (contracts #HHSN275201200005C, #HHSN267200700019C, #HHSN275201400013C, #HHSN275201300026I/27500004, #HHSN275201300023I/27500017). The authors have no conflicts of interest. REGISTRATION NUMBER/BACKGROUND:NCT03106493.