Leonardo Trasande

The prenatal period is a critical window for neurodevelopment, during which maternal metabolic processes are increasingly recognized to shape later behavioral and autism-related traits. We examined associations between targeted maternal urinary metabolomic profiles across pregnancy and preschool emotional, behavioral, and autism-related outcomes in the New York University Children’s Health and Environment Study (NYU CHES), a large prospective birth cohort. Targeted metabolomics was conducted on maternal urine samples collected in early, mid, and late pregnancy. Child outcomes were assessed at a mean age of 2.3 years using the Child Behavior Checklist (CBCL) total and DSM-5–oriented autism spectrum disorder (ASD) subscale scores. We applied two-stage mixed-effects models to assess overall pregnancy metabolite levels and timepoint-specific negative binomial models to evaluate trimester-specific associations, with covariate adjustment, sex-stratification, and false discovery rate (FDR) correction. Few associations were observed two-stage models. In timepoint-specific analyses, a robust sex- and timing-specific association emerged: among males, higher third-trimester urinary lysoPC a C26:1 was associated with lower CBCL total and ASD subscale scores, surviving stringent FDR correction and remaining robust after adjustment for maternal diet quality. Additional associations involving taurine, inflammatory markers, and acylcarnitines were observed primarily in sex-stratified or diet-adjusted models but were less robust to multiple testing correction. These findings suggest that prenatal metabolic profiles, particularly lipid- and mitochondrial energy-related pathways in late gestation, may contribute to early behavioral and autism-related traits in a sex-specific manner, underscoring the importance of exposure timing and maternal metabolism in the etiology of neurodevelopmental outcomes.

Background: Both poor sleep health and hypertensive disorders of pregnancy (HDP) are independent risk factors for cardiovascular disease. Whether poor postpartum sleep contributes to the relationship between HDP and future cardiovascular disease is unknown. This pilot study evaluated the feasibility and acceptability of studying sleep health using a wearable device (Oura ring) among mothers of young children. Objective: We evaluated indices of sleep health both objectively with the Oura ring and subjectively via questionnaires and qualitative interviews among mothers with and without a history of HDP. We also aimed to compare cardiovascular health (CVH) among mothers with vs without a prior history of HDP. Methods: Women who were 3 to 7 years after childbirth completed baseline questionnaires (the Pittsburgh Sleep Quality Index [PSQI], Mediterranean Eating Pattern for Americans tool, and 7-item International Physical Activity Questionnaire) and wore the Oura ring continuously for 2 weeks to monitor sleep. Optimal sleep health was defined as a sleep duration of ≥7 hours, a PSQI score of ≤5, sleep timing with a sleep midpoint between 2 AM and 4 AM, a sleep efficiency of >85%, and a sleep onset variability of P= .22). Average sleep duration was suboptimal (6.7, SD 0.8 hours), with no difference between groups. Approximately half (n=23, 47%) had abnormal sleep timing, which was more common among those with a prior normotensive pregnancy. Sleep onset variability was high (mean 1.2, SD 0.5 hours), with no significant differences by HDP status. The mean CVH score fell within the moderate range (70.7, SD 12.8), with no differences between groups. The components of the CVH score that were lowest (ie, worst) among the entire cohort were diet (mean 37.3, SD 25.6) and BMI (mean 50.8, SD 35.4 kg/m ² ). Common barriers to sleep included parenting, work, and household responsibilities. The study met our criteria for the feasibility and acceptability of using the Oura ring to study sleep in this population. Conclusions: Among postpartum women, sleep health was suboptimal regardless of HDP history. Interventions to improve sleep and CVH should target all mothers during the first decade after childbirth.

BackgroundEmerging evidence suggests endocrine disrupting chemicals, including bisphenols and phthalates, may affect behavioral development in children and adolescents. Risk behavior constitutes a potentially sex hormone sensitive behavioral construct. Here, we examined longitudinal associations of phthalate and bisphenol exposure with performance-based tasks and self-reported risk-taking behaviors.MethodsWithin a population-based birth cohort in the Netherlands, urinary bisphenols and phthalate metabolite concentrations were measured in women during pregnancy (three times, n=1379) and in children (once at 6 years, n=775). At 10 years, child risk-taking behavior was assessed with the computerized experimental Columbia Card Task (CCT). At 14 years, adolescents completed a computerized self-assessment of real-life risk-taking behaviors. Linear regression and hurdle models adjusted for confounders were applied in the whole sample and stratified by sex at birth.ResultsIn girls, prenatal mono-isobutyl phthalate was associated with a higher average CCT-score, indicting more risk-taking (B per 10-fold increase in creatinine-adjusted average prenatal levels= 2.10, 95% CI: 0.68,3.51). In boys, higher prenatal and childhood mono-[(2-carboxymethyl)hexyl] phthalate levels were associated with a higher CCT-score (prenatal B=6.21, 95% CI: 1.57,10.47; childhood B=6.02, 95% CI: 1.57,10.47). No associations were observed for bisphenol exposure nor for self-reported risk-taking.ConclusionsPrenatal phthalate exposure was associated with more risk-taking in an experimental task at 10 years-of-age, with sex-specific differences. The task reflects risky decision-making, which may be a hormonally sensitive construct. Risky decision making potentially precedes real-life risk-taking, which was captured by the self-reported measure and was limited in this young sample.

Oxidative stress (OS), an imbalance between reactive oxygen species and antioxidants, has been linked to impaired placental function and suboptimal fetal growth, yet trimester-specific associations remain poorly understood. We examined 561 mother–infant pairs from The Infant Development and Environmental Study, measuring maternal urinary biomarkers of DNA oxidation (8-hydroxydeoxyguanosine (8-OHdG)), lipid peroxidation (malondialdehyde (MDA) and F2-isoprostanes), and protein oxidation (dityrosine (diY)) at first and second trimesters. Using generalized linear models, we examined prospective associations between OS and ultrasound-derived growth velocities. Early pregnancy OS biomarkers were persistently associated with reduced second and third trimester growth velocities. First trimester lipid peroxidation markers (8-PGF2α, 15-PGF2α, and 8,15-PGF2α) were associated with slower estimated fetal weight (EFW) growth velocity in both second trimester (−0.81, −0.93, and −1.72 g/week per log-unit increase, respectively) and third trimester (−4.25, −5.60, and −6.74 g/week). Similarly, first trimester 8-OHdG and diY were associated with both second trimester (−1.31 and −1.17 g/week, respectively) and third trimester EFW velocity (−8.01 and −6.75 g/week, respectively). Second trimester 8-OHdG and MDA were associated with slower third trimester EFW velocity (−8.57 and −9.25 g/week, respectively). These results provide novel insights into trimester-specific associations between OS and fetal growth.