Evaluating associations of bisphenol and phthalate exposure with time to pregnancy and subfecundity in a New York City pregnancy cohort.

It is important to understand the impact of consumer chemical exposure and fecundity, a couple's measure of probability of successful conception, given approximately 15% of couples experience infertility. Prior research has generally found null associations between bisphenol and phthalate exposure and fecundability, measured via time to pregnancy (TTP). However, this research has not been updated with current chemical exposures and have often lacked diversity in their study populations. We evaluated the associations between common bisphenol and phthalate chemical exposure groups and TTP as well as subfecundity (TTP>12 months) in the New York University Children's Health Study, a diverse pregnancy cohort from 2016 onward. Using first-trimester spot-urine samples to measure chemical exposure and self-reported TTP from first-trimester questionnaires, we observed a significant adverse association between total bisphenol exposure and certain phthalate groups on TTP and odds of subfecundity. Furthermore, in a mixtures analysis to explore the joint effects of the chemical groups on the outcomes, we found evidence of a potential interaction between total bisphenol exposure and low-molecular weight phthalates on TTP. Future research should continue to update our knowledge regarding the complex and potentially interacting effects of these chemicals on reproductive health.

Longitudinal study of birthweight, blood pressure, and markers of arterial stiffness in children age six among the TIDES cohort.

OBJECTIVE: Although some studies have observed an association between birthweight and cardiovascular disease in adulthood, fewer have investigated whether birthweight is linked to cardiovascular health in early childhood. This study assesses the association between birthweight and cardiovascular outcomes in children 6 years of age. STUDY DESIGN: Birthweight, blood pressure (BP), and markers of arterial stiffness in children, including brachial artery distensibility and carotid-femoral pulse wave velocity (cfPWV), were obtained from 324 participants in The Infant Development and the Environment Study, a prospective multisite pregnancy cohort. Birthweight was converted into sex-specific birthweight-for-gestational-age (bw/ga) z -scores based on the INTERGROWTH-21st standard. Following 2017 American Academy of Pediatrics guidelines, SBP and DBP were transformed into sex, age, and height-specific z -scores. Associations between birthweight and cardiovascular outcomes were assessed using nested multivariable linear regression models among the overall and sex-stratified samples. RESULTS: Among the overall sample, bw/ga z -score was positively associated with cfPWV [b = 0.11 m/s, 95% confidence interval (CI): 0.01 m/s, 0.21 m/s] in crude and adjusted models. No associations between birthweight and cardiovascular outcomes were detected among the sex-stratified analyses. CONCLUSION: Overall, birthweight was not related to cardiovascular outcomes in children 6 years old. However, infants born with a higher birthweight may be at risk for higher cfPWV in childhood. Early intervention in pregnant people at risk of delivering high birthweight infants may be warranted if results are replicated.

Longitudinal trajectories in recovery capital and associations with substance use among adult drug treatment court clients.

BACKGROUND: Recovery capital (RC) refers to the resources individuals use to support substance use disorder (SUD) recovery. Individuals with SUD who are involved with the criminal justice system often have limited RC. Drug treatment courts (DTCs), including traditional drug treatment courts (tDTCs) and opioid intervention courts (OICs), can link clients to important sources of RC in the short-term, but few studies have assessed RC longitudinally. METHODS: The current study analyzed five waves of data from a one-year longitudinal study on substance use and RC collected from clients of tDTCs and OICs (n=165, 52% male, 75% non-Hispanic White, Age=21-67 years). Mixed-effects models examined (1) within-person trends over time in RC, (2) individual characteristics associated with differences and changes in RC, and (3) patterns of relationships between RC and substance use over time. We also tested differences by court type. RESULTS: First, OIC participants had lower RC at baseline relative to tDTC participants, and there was considerable within-person variability in RC over time. Second, the effect of a high school diploma/GED at baseline on RC change over time was greater for OIC relative to tDTC participants. Third, there was a negative concurrent within-person association between drug use and RC that became stronger over time for OIC relative to tDTC participants. CONCLUSIONS: This study is among the first to examine longitudinal, within-person trajectories in RC. Results revealed important within-person variability over time in RC that was linked to education and drug use, particularly among OIC clients. Findings could help inform DTC treatment approaches.

Urinary concentrations of phthalate metabolites in relation to preeclampsia and other hypertensive disorders of pregnancy in the environmental influences on child health outcomes (ECHO) program.

BACKGROUND: Phthalate exposure may contribute to hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PE/E), but epidemiologic studies are lacking. OBJECTIVES: To evaluate associations of pregnancy phthalate exposure with development of PE/E and HDP. METHODS: Using data from 3,430 participants in eight Environmental influences on Child Health Outcomes (ECHO) Program cohorts (enrolled from 1999 to 2019), we quantified concentrations of 13 phthalate metabolites (8 measured in all cohorts, 13 in a subset of four cohorts) in urine samples collected at least once during pregnancy. We operationalized outcomes as PE/E and composite HDP (PE/E and/or gestational hypertension). After correcting phthalate metabolite concentrations for urinary dilution, we evaluated covariate-adjusted associations of individual phthalates with odds of PE/E or composite HDP via generalized estimating equations, and the phthalate mixture via quantile-based g-computation. We also explored effect measure modification by fetal sex using stratified models. Effect estimates are reported as odds ratios (OR) with 95% confidence intervals (95% CIs). RESULTS: In adjusted analyses, a doubling of mono-benzyl phthalate (MBzP) and of mono (3-carboxypropyl) phthalate (MCPP) concentrations was associated with higher odds of PE/E as well as composite HDP, with somewhat larger associations for PE/E. For example, a doubling of MCPP was associated with 1.12 times the odds of PE/E (95%CI 1.00, 1.24) and 1.02 times the odds of composite HDP (95%CI 1.00, 1.05). A quartile increase in the phthalate mixture was associated with 1.27 times the odds of PE/E (95%CI 0.94, 1.70). A doubling of mono-carboxy isononyl phthalate (MCiNP) and of mono-carboxy isooctyl phthalate (MCiOP) concentrations were associated with 1.08 (95%CI 1.00, 1.17) and 1.11 (95%CI 1.03, 1.19) times the odds of PE/E. Effect estimates for PE/E were generally larger among pregnancies carrying female fetuses. DISCUSSION: In this study, multiple phthalates were associated with higher odds of PE/E and HDP. Estimates were precise and some were low in magnitude. Interventions to reduce phthalate exposures during pregnancy may help mitigate risk of these conditions.

Fetal bisphenol and phthalate exposure and early childhood growth in a New York City birth cohort.

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: This study contributes to the evidence suggesting associations of prenatal exposure to bisphenols and high-molecular-weight phthalates on childhood weight and BMI.

Perinatal exposure to polychlorinated biphenyls (PCBs) and child neurodevelopment: A comprehensive systematic review of outcomes and methodological approaches.

BACKGROUND: Polychlorinated biphenyls (PCBs), extensively used in various products, prompt ongoing concern despite reduced exposure since the 1970s. This systematic review explores prenatal PCB and hydroxylated metabolites (OH-PCBs) exposure's association with child neurodevelopment. Encompassing cognitive, motor development, behavior, attention, ADHD, and ASD risks, it also evaluates diverse methodological approaches in studies. METHODS: PubMed, Embase, PsycINFO, and Web of Science databases were searched through August 23, 2023, by predefined search strings. Peer-reviewed studies published in English were included. The inclusion criteria were: (i) PCBs/OH-PCBs measured directly in maternal and cord blood, placenta or breast milk collected in the perinatal period; (ii) outcomes of cognitive development, motor development, attention, behavior, attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) among children≤18 years old. Quality assessment followed the National Heart, Lung, and Blood Institute's tool. RESULTS: Overall, 87 studies were included in this review. We found evidence for the association between perinatal PCB exposure and adverse cognitive development and attention issues in middle childhood. There appeared to be no or negligible link between perinatal PCB exposure and early childhood motor development or the risk of ADHD/ASD. There was an indication of a sex-specific association with worse cognition and attention scores among boys. Some individual studies suggested a possible association between prenatal exposure to OH-PCBs and neurodevelopmental outcomes. There was significant heterogeneity between the studies in exposure markers, exposure assessment timing, outcome assessment, and statistical analysis. CONCLUSIONS: Significant methodological, clinical and statistical heterogeneity existed in the included studies. Adverse effects on cognitive development and attention were observed in middle childhood. Little or no apparent link on both motor development and risk of ADHD/ASD was observed in early childhood. Inconclusive evidence prevailed regarding other neurodevelopmental aspects due to limited studies. Future research could further explore sex-specific associations and evaluate associations at lower exposure levels post-PCB ban in the US. It should also consider OH-PCB metabolites, co-pollutants, mixtures, and their potential interactions.

Prevalence and factors associated with second hand smoke exposure among a sample of pregnant women in Cairo, Egypt.

PURPOSE: This study estimated the prevalence of and factors associated with secondhand smoke (SHS) exposure, and assessed attitudes and knowledge about SHS among pregnant women in Cairo, Egypt. METHODS: Pregnant women in the third trimester were recruited to participate in a survey assessing tobacco smoking and SHS exposure during their current pregnancy. Participants were recruited from three antenatal clinics in Cairo, Egypt, from June 2015 to May 2016. We examined differences in sociodemographic characteristics and SHS exposure, attitudes, and knowledge by smoking/SHS status. We used multivariable ordinary least squares regression to examine the association between husbands' smoking and pregnant women's mean daily hours of SHS exposure, adjusting for women's smoking status, age group, education, and urban (vs. suburban/rural) residence. RESULTS: Of two hundred pregnant women aged 16-37 years, about two-thirds (69%) had a husband who smoked tobacco. During their current pregnancy, most women reported being non-smokers (71%), and 38% of non-smokers reported being SHS-exposed. Non-smokers exposed to SHS tended to live in more rural areas and have husbands who smoked in the home. In adjusted analyses, having a husband who smoked was significantly associated with a greater mean number of hours of SHS exposure per day exposed, and this difference was driven by husbands who smoked in the home (p < 0.001). Women in the SHS-exposed group were less likely than other groups to agree that SHS exposure was harmful to their own or their future child's health; however, all groups agreed that SHS was harmful to newborn health. CONCLUSION: Among our sample of pregnant women in Cairo, Egypt, there was a high rate of SHS exposure as well as misconceptions about the safety of SHS exposure to a developing fetus. Our findings suggest a need for targeted education and gender-sensitive messaging about SHS exposure, along with improved enforcement of existing tobacco control policies.

Exposure to secondhand smoke (SHS) remains a major contributor to health problems in pregnant women and their children. Using a survey, this study sought to estimate how many pregnant women in Cairo Metropolitan Area, Egypt, were exposed to SHS and the factors contributing to that exposure, and to assess attitudes towards SHS. During their current pregnancy, 38% of non-smokers reported being exposed to SHS. Non-smokers exposed to SHS tended to live in more rural areas and have husbands who smoked in the home. Having a husband who smoked as well as a husband who smoked in the home was significantly associated with a greater average number of SHS exposure hours per day. Women in the SHS-exposed group were less likely than other groups to agree that SHS exposure was harmful to their own or their future child's health; however, all groups agreed that SHS was harmful to newborn health. Among pregnant women in Cairo, Egypt, there is a high rate of SHS exposure­often driven by SHS exposure in the home­as well as misconceptions about the safety of SHS exposure to a developing fetus. There is a need for targeted education and gender-sensitive messaging about SHS exposure along, with improved enforcement of existing tobacco control policies.

Associations of Organophosphate Ester Flame Retardant Exposures during Pregnancy with Gestational Duration and Fetal Growth: The Environmental influences on Child Health Outcomes (ECHO) Program.

BACKGROUND: Widespread exposure to organophosphate ester (OPE) flame retardants with potential reproductive toxicity raises concern regarding the impacts of gestational exposure on birth outcomes. Previous studies of prenatal OPE exposure and birth outcomes had limited sample sizes, with inconclusive results. OBJECTIVES: We conducted a collaborative analysis of associations between gestational OPE exposures and adverse birth outcomes and tested whether associations were modified by sex. METHODS: We included 6,646 pregnant participants from 16 cohorts in the Environmental influences on Child Health Outcomes (ECHO) Program. Nine OPE biomarkers were quantified in maternal urine samples collected primarily during the second and third trimester and modeled as log2-transformed continuous, categorized (high/low/nondetect), or dichotomous (detect/nondetect) variables depending on detection frequency. We used covariate-adjusted linear, logistic, and multinomial regression with generalized estimating equations, accounting for cohort-level clustering, to estimate associations of OPE biomarkers with gestational length and birth weight outcomes. Secondarily, we assessed effect modification by sex. RESULTS: Three OPE biomarkers [diphenyl phosphate (DPHP), a composite of dibutyl phosphate and di-isobutyl phosphate (DBUP/DIBP), and bis(1,3-dichloro-2-propyl) phosphate] were detected in >85% of participants. In adjusted models, DBUP/DIBP [odds ratio (OR) per doubling=1.07; 95% confidence interval (CI): 1.02, 1.12] and bis(butoxyethyl) phosphate (OR for high vs. nondetect=1.25; 95% CI: 1.06, 1.46), but not other OPE biomarkers, were associated with higher odds of preterm birth. We observed effect modification by sex for associations of DPHP and high bis(2-chloroethyl) phosphate with completed gestational weeks and odds of preterm birth, with adverse associations among females. In addition, newborns of mothers with detectable bis(1-chloro-2-propyl) phosphate, bis(2-methylphenyl) phosphate, and dipropyl phosphate had higher birth weight-for-gestational-age z-scores (ß for detect vs. nondetect=0.04-0.07); other chemicals showed null associations. DISCUSSION: In the largest study to date, we find gestational exposures to several OPEs are associated with earlier timing of birth, especially among female neonates, or with greater fetal growth. https://doi.org/10.1289/EHP13182.

Prenatal phthalate exposure and fetal penile length and width.

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: 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.

Prenatal sleep health and risk of offspring ADHD symptomatology and associated phenotypes: a prospective analysis of timing and sex differences in the ECHO cohort.

Background: Sleep difficulties are common in pregnancy, yet poor prenatal sleep may be related to negative long-term outcomes for the offspring, including risk for attention-deficit/hyperactivity disorder (ADHD). Existing studies are few and have not examined timing of exposure effects or offspring sex moderation. We thus aimed to test the hypotheses that poor sleep health in pregnancy is associated with increased risk for ADHD symptoms and offspring sleep problems at approximately 4 years of age. Methods: Participants were 794 mother-child dyads enrolled in the NIH Environmental Influences on Child Health Outcomes Study (ECHO). Participants self-reported on sleep duration, quality, and disturbances during pregnancy and on children's ADHD symptoms and sleep problems on the Child Behaviour Checklist. Findings: Pregnant participants were 32.30 ± 5.50 years and children were 46% female. 44 percent of pregnant participants identified as Hispanic or Latine; 49% identified as White. Second-trimester sleep duration was associated with offspring ADHD symptoms (b = -0.35 [95% CI = -0.57, -0.13], p = 0.026), such that shorter duration was associated with greater symptomatology. Poorer sleep quality in the second trimester was also associated with increased ADHD symptomatology (b = 0.66 [95% CI = 0.18, 1.14], p = 0.037). Greater sleep disturbances in the first trimester were associated with offspring ADHD (b = 1.03 [95% CI = 0.32, 1.03], p = 0.037) and in the second trimester with sleep problems (b = 1.53 [95% CI = 0.42, 2.92], p = 0.026). We did not document substantial offspring sex moderation. Interpretation: Poor prenatal sleep health, particularly quality and duration in the second trimester, may be associated with offspring risk of neurodevelopmental disorders and sleep problems in early childhood. Further research is needed to understand mechanisms, yet our study suggests that prenatal maternal sleep may be a modifiable target for interventions aimed at optimizing early neurodevelopment. Funding: NIH grants U2COD023375, U24OD023382, U24OD023319, UH3OD023320, UH3OD023305, UH3OD023349, UH3OD023313, UH3OD023272, UH3OD023328, UH3OD023290, K08MH117452 and NARSAD Young Investigator Award 28545.

Associations between area-level arsenic exposure and adverse birth outcomes: An Echo-wide cohort analysis.

BACKGROUND: Drinking water is a common source of exposure to inorganic arsenic. In the US, the Safe Drinking Water Act (SDWA) was enacted to protect consumers from exposure to contaminants, including arsenic, in public water systems (PWS). The reproductive effects of preconception and prenatal arsenic exposure in regions with low to moderate arsenic concentrations are not well understood. OBJECTIVES: This study examined associations between preconception and prenatal exposure to arsenic violations in water, measured via residence in a county with an arsenic violation in a regulated PWS during pregnancy, and five birth outcomes: birth weight, gestational age at birth, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). METHODS: Data for arsenic violations in PWS, defined as concentrations exceeding 10 parts per billion, were obtained from the Safe Drinking Water Information System. Participants of the Environmental influences on Child Health Outcomes Cohort Study were matched to arsenic violations by time and location based on residential history data. Multivariable, mixed effects regression models were used to assess the relationship between preconception and prenatal exposure to arsenic violations in drinking water and birth outcomes. RESULTS: Compared to unexposed infants, continuous exposure to arsenic from three months prior to conception through birth was associated with 88.8 g higher mean birth weight (95% CI: 8.2, 169.5), after adjusting for individual-level confounders. No statistically significant associations were observed between any preconception or prenatal violations exposure and gestational age at birth, preterm birth, SGA, or LGA. CONCLUSIONS: Our study did not identify associations between preconception and prenatal arsenic exposure, defined by drinking water exceedances, and adverse birth outcomes. Exposure to arsenic violations in drinking water was associated with higher birth weight. Future studies would benefit from more precise geodata of water system service areas, direct household drinking water measurements, and exposure biomarkers.

Leveraging Systematic Reviews to Explore Disease Burden and Costs of Per- and Polyfluoroalkyl Substance Exposures in the United States.

Accelerating evidence confirms the contribution of per- and polyfluoroalkyl substances (PFAS) to disease burden and disability across the lifespan. Given that policy makers raise the high cost of remediation and of substituting PFAS with safer alternatives in consumer products as barriers to confronting adverse health outcomes associated with PFAS exposure, it is important to document the costs of inaction even in the presence of uncertainty. We therefore quantified disease burdens and related economic costs due to legacy PFAS exposures in the US in 2018. We leveraged systematic reviews and used meta-analytic inputs whenever possible, identified previously published exposure-response relationships, and calculated PFOA- and PFOS-attributable increases in 13 conditions. These increments were then applied to census data to determine total annual PFOA- and PFOS-attributable cases of disease, from which we calculated economic costs due to medical care and lost productivity using previously published cost-of-illness data. We identified PFAS-attributable disease costs in the US of $5.52 billion across five primary disease endpoints shown to be associated with PFAS exposure in meta-analyses. This estimate represented the lower bound, with sensitivity analyses revealing as much as $62.6 billion in overall costs. While further work is needed to assess probability of causation and establish with greater certainty effects of the broader category of PFAS, the results confirm further that public health and policy interventions are still necessary to reduce exposure to PFOA and PFOS and their endocrine-disrupting effects. This study demonstrates the large potential economic implications of regulatory inaction. Supplementary Information: The online version contains supplementary material available at 10.1007/s12403-022-00496-y.

State-specific fertility rate changes across the USA following the first two waves of COVID-19.

STUDY QUESTION: How did the first two coronavirus disease 2019 (COVID-19) waves affect fertility rates in the USA? SUMMARY ANSWER: States differed widely in how their fertility rates changed following the COVID-19 outbreak and these changes were influenced more by state-level economic, racial, political, and social factors than by COVID-19 wave severity. WHAT IS KNOWN ALREADY: The outbreak of the COVID-19 pandemic contributed to already declining fertility rates in the USA, but not equally across states. Identifying drivers of differential changes in fertility rates can help explain variations in demographic shifts across states in the USA and motivate policies that support families in general, not only during crises. STUDY DESIGN, SIZE, DURATION: This is an ecological study using state-level data from 50 US states and the District of Columbia (n = 51). The study period extends from 2020 to 2021 with historical data from 2016 to 2019. We identified Wave 1 as the first apex for each state after February 2020 and Wave 2 as the second apex, during Fall/Winter 2020-2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: State-level COVID-19 wave severity, defined as case acceleration during each 3-month COVID-19 wave (cases/100 000 population/month), was derived from 7-day weekly moving average COVID-19 case rates from the US Centers for Disease Control and Prevention (CDC). State-level fertility rate changes (change in average monthly fertility rate/100 000 women of reproductive age (WRA)/year) were derived from the CDC Bureau of Vital Statistics and from 2020 US Census and University of Virginia 2021 population estimates 9 months after each COVID-19 wave. We performed univariate analyses to describe national and state-level fertility rate changes following each wave, and simple and multivariable linear regression analyses to assess the relation of COVID-19 wave severity and other state-level characteristics with fertility rate changes. MAIN RESULTS AND THE ROLE OF CHANCE: Nationwide, fertility dropped by 17.5 births/month/100 000 WRA/year following Wave 1 and 9.2 births/month/100 000 WRA/year following Wave 2. The declines following Wave 1 were largest among majority-Democrat, more non-White states where people practiced greater social distancing. Greater COVID-19 wave severity was associated with steeper fertility rate decline post-Wave 1 in simple regression, but the association was attenuated when adjusted for other covariates. Adjusting for the economic impact of the pandemic (hypothesized mediator) also attenuated the effect. There was no relation between COVID-19 wave severity and fertility rate change following Wave 2. LIMITATIONS, REASONS FOR CAUTION: Our study harnesses state-level data so individual-level conclusions cannot be inferred. There may be residual confounding in our multivariable regression and we were underpowered to detect some effects. WIDER IMPLICATIONS OF THE FINDINGS: The COVID-19 pandemic initially impacted the national fertility rate but, overall, the fertility rate rebounded to the pre-pandemic level following Wave 2. Consistent with prior literature, COVID-19 wave severity did not appear to predict fertility rate change. Economic, racial, political, and social factors influenced state-specific fertility rates during the pandemic more than the severity of the outbreak alone. Future studies in other countries should also consider whether these factors account for internal heterogeneity when examining the impact of the COVID-19 pandemic and other crises on fertility. STUDY FUNDING/COMPETING INTEREST(S): L.G.K. received funding from the National Institute of Environmental Health Sciences (R00ES030403), M.C. from the National Science Foundation Graduate Research Fellowship Program (20-A0-00-1005789), and M.L. and E.S. from the National Institute of Environmental Health Sciences (R01ES032808). None of the authors have competing interests. TRIAL REGISTRATION NUMBER: N/A.

Maternal urinary bisphenols and phthalates in relation to estimated fetal weight across mid to late pregnancy.

BACKGROUND: Bisphenols and phthalates are high production volume chemicals used as additives in a variety of plastic consumer products leading to near ubiquitous human exposure. These chemicals have established endocrine disrupting properties and have been linked to a range of adverse reproductive and developmental outcomes. Here, we investigated exposure in relation to fetal growth. METHODS: Participants included 855 mother-fetal pairs enrolled in the population-based New York University Children's Health and Environment Study (NYU CHES). Bisphenols and phthalates were measured in maternal urine collected repeatedly during pregnancy. Analyses included 15 phthalate metabolites and 2 bisphenols that were detected in 50 % of participants or more. Fetal biometry data were extracted from electronic ultrasonography records and estimated fetal weight (EFW) was predicted for all fetuses at 20, 30, and 36 weeks gestation. We used quantile regression adjusted for covariates to model exposure-outcome relations across percentiles of fetal weight at each gestational timepoint. We examined sex differences using stratified models. RESULTS: Few statistically significant associations were observed across chemicals, gestational time periods, percentiles, and sexes. However, within gestational timepoints, we found that among females, the molar sums of the phthalates DiNP and DnOP were generally associated with decreases in EFW among smaller babies and increases in EFW among larger babies. Among males, the opposite trend was observed. However, confidence intervals were generally wide at the tails of the distribution. CONCLUSION: In this sample, exposure to bisphenols and phthalates was associated with small sex-specific shifts in fetal growth; however, few associations were observed at the median of fetal weight and confidence intervals in the tails were wide. Findings were strongest for DiNP and DnOP, which are increasingly used as replacements for DEHP, supporting the need for future research on these contaminants.

Chronotype and sleep duration interact to influence time to pregnancy: Results from a New York City cohort.

STUDY OBJECTIVE: To study associations between nighttime sleep characteristics and time to pregnancy. METHODS: Pregnant people age ≥18 years and<18 weeks' gestation were recruited from 3 New York University Grossman School of Medicine affiliated hospitals in Manhattan and Brooklyn (n = 1428) and enrolled into the New York University Children's Health and Environment Study. Participants in the first trimester of pregnancy were asked to recall their time to pregnancy and their sleep characteristics in the 3 months before conception. RESULTS: Participants who reported sleeping<7 hours per night tended to have shorter time to pregnancy than those who slept 7-9 hours per night (adjusted fecundability odds ratio = 1.16, 95% confidence interval: 0.94, 1.41). Participants with a sleep midpoint of 4 AM or later tended to have longer time to pregnancy compared with those with earlier sleep midpoints (before 4 AM) (adjusted fecundability odds ratio = 0.88, 95% confidence interval: 0.74, 1.04). When stratified by sleep midpoint, sleeping<7 hours was significantly associated with shorter time to pregnancy only among those whose sleep midpoint was before 4 AM (adjusted fecundability odds ratio = 1.33, 95% confidence interval: 1.07, 1.67). CONCLUSIONS: The association of sleep duration with time to pregnancy was modified by chronotype, suggesting that both biological and behavioral aspects of sleep may influence fecundability.

Analysis of Pregnancy Complications and Epigenetic Gestational Age of Newborns.

Importance: Preeclampsia, gestational hypertension, and gestational diabetes, the most common pregnancy complications, are associated with substantial morbidity and mortality in mothers and children. Little is known about the biological processes that link the occurrence of these pregnancy complications with adverse child outcomes; altered biological aging of the growing fetus up to birth is one molecular pathway of increasing interest. Objective: To evaluate whether exposure to each of these 3 pregnancy complications (gestational diabetes, gestational hypertension, and preeclampsia) is associated with accelerated or decelerated gestational biological age in children at birth. Design, Setting, and Participants: Children included in these analyses were born between 1998 and 2018 and spanned multiple geographic areas of the US. Pregnancy complication information was obtained from maternal self-report and/or medical record data. DNA methylation measures were obtained from blood biospecimens collected from offspring at birth. The study used data from the national Environmental Influences on Child Health Outcomes (ECHO) multisite cohort study collected and recorded as of the August 31, 2021, data lock date. Data analysis was performed from September 2021 to December 2022. Exposures: Three pregnancy conditions were examined: gestational hypertension, preeclampsia, and gestational diabetes. Main Outcomes and Measures: Accelerated or decelerated biological gestational age at birth, estimated using existing epigenetic gestational age clock algorithms. Results: A total of 1801 child participants (880 male [48.9%]; median [range] chronological gestational age at birth, 39 [30-43] weeks) from 12 ECHO cohorts met the analytic inclusion criteria. Reported races included Asian (49 participants [2.7%]), Black (390 participants [21.7%]), White (1026 participants [57.0%]), and other races (92 participants [5.1%]) (ie, American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, multiple races, and other race not specified). In total, 524 participants (29.0%) reported Hispanic ethnicity. Maternal ages ranged from 16 to 45 years of age with a median of 29 in the analytic sample. A range of maternal education levels, from less than high school (260 participants [14.4%]) to Bachelor's degree and above (629 participants [34.9%]), were reported. In adjusted regression models, prenatal exposure to maternal gestational diabetes (ß, -0.423; 95% CI, -0.709 to -0.138) and preeclampsia (ß, -0.513; 95% CI, -0.857 to -0.170), but not gestational hypertension (ß, 0.003; 95% CI, -0.338 to 0.344), were associated with decelerated epigenetic aging among exposed neonates vs those who were unexposed. Modification of these associations, by sex, was observed with exposure to preeclampsia (ß, -0.700; 95% CI, -1.189 to -0.210) and gestational diabetes (ß, -0.636; 95% CI, -1.070 to -0.200), with associations observed among female but not male participants. Conclusions and Relevance: This US cohort study of neonate biological changes related to exposure to maternal pregnancy conditions found evidence that preeclampsia and gestational diabetes delay biological maturity, especially in female offspring.

Prenatal weight and regional body composition trajectories and neonatal body composition: The NICHD Foetal Growth Studies.

BACKGROUND: Gestational weight gain (GWG) and anthropometric trajectories may affect foetal programming and are potentially modifiable. OBJECTIVES: To assess concomitant patterns of change in weight, circumferences and adiposity across gestation as an integrated prenatal exposure, and determine how they relate to neonatal body composition. METHODS: Data are from a prospective cohort of singleton pregnancies (n = 2182) enrolled in United States perinatal centres, 2009-2013. Overall and by prepregnancy BMI group (overweight/obesity and healthy weight), joint latent trajectory models were fit with prenatal weight, mid-upper arm circumference (MUAC), triceps (TSF) and subscapular (SSF) skinfolds. Differences in neonatal body composition by trajectory class were assessed via weighted least squares. RESULTS: Six trajectory patterns reflecting co-occurring changes in weight and MUAC, SSF and TSF across pregnancy were identified overall and by body mass index (BMI) group. Among people with a healthy weight BMI, some differences were observed for neonatal subcutaneous adipose tissue, and among individuals with overweight/obesity some differences in neonatal lean mass were found. Neonatal adiposity measures were higher among infants born to individuals with prepregnancy overweight/obesity. CONCLUSIONS: Six integrated trajectory patterns of prenatal weight, subcutaneous adipose tissue and circumferences were observed that were minimally associated with neonatal body composition, suggesting a stronger influence of prepregnancy BMI.