Prenatal ambient air pollution exposure and child weight trajectories from the 3rd trimester of pregnancy to 2 years of age: a cohort study.

BACKGROUND: Prenatal air pollution exposure may increase risk for childhood obesity. However, few studies have evaluated in utero growth measures and infant weight trajectories. This study will evaluate the associations of prenatal exposure to ambient air pollutants with weight trajectories from the 3rd trimester through age 2 years. METHODS: We studied 490 pregnant women who were recruited from the Maternal and Development Risks from Environmental and Social Stressors (MADRES) cohort, which comprises a low-income, primarily Hispanic population in Los Angeles, California. Nitrogen dioxide (NO2), particulate matter < 10 µm (PM10), particulate matter < 2.5 µm (PM2.5), and ozone (O3) concentrations during pregnancy were estimated from regulatory air monitoring stations. Fetal weight was estimated from maternal ultrasound records. Infant/child weight measurements were extracted from medical records or measured during follow-up visits. Piecewise spline models were used to assess the effect of air pollutants on weight, overall growth, and growth during each period. RESULTS: The mean (SD) prenatal exposure concentrations for NO2, PM2.5, PM10, and O3 were 16.4 (2.9) ppb, 12.0 (1.1) µg/m3, 28.5 (4.7) µg/m3, and 26.2 (2.9) ppb, respectively. Comparing an increase in prenatal average air pollutants from the 10th to the 90th percentile, the growth rate from the 3rd trimester to age 3 months was significantly increased (1.55% [95%CI 1.20%, 1.99%] for PM2.5 and 1.64% [95%CI 1.27%, 2.13%] for NO2), the growth rate from age 6 months to age 2 years was significantly decreased (0.90% [95%CI 0.82%, 1.00%] for NO2), and the attained weight at age 2 years was significantly lower (- 7.50% [95% CI - 13.57%, - 1.02%] for PM10 and - 7.00% [95% CI - 11.86%, - 1.88%] for NO2). CONCLUSIONS: Prenatal ambient air pollution was associated with variable changes in growth rate and attained weight from the 3rd trimester to age 2 years. These results suggest continued public health benefits of reducing ambient air pollution levels, particularly in marginalized populations.

Prenatal metal mixtures and fetal size in mid-pregnancy in the MADRES study.

BACKGROUND: Fetal growth is predictive of health later in life. Both toxic and essential metals influence fetal growth, but most studies have focused on these elements individually and used birth weight as an indicator of fetal growth. The objective of the current study was to investigate the impact of a mixture of metals on fetal size in mid-pregnancy in a predominately lower income Hispanic pregnancy cohort in Los Angeles. METHODS: For our primary analysis, we focused on six elements that have previously been associated individually with fetal size, including arsenic (As), barium (Ba), cadmium (Cd), mercury (Hg), molybdenum (Mo), and tin (Sn), measured in maternal urine samples collected in early pregnancy (median: 12.4 weeks gestation). In an exploratory analysis, we additionally included cobalt (Co), nickel (Ni), antimony (Sb), and thallium (Tl). Using covariate-adjusted Bayesian Kernel Machine Regression (BKMR) as our main mixture modeling approach, we examined the impact of these metals on fetal biometry measures obtained between 18 and 22 weeks gestation, with a focus on estimated fetal weight (EFW). RESULTS: BKMR identified Mo and Ba as the mixture components that contributed most to associations with EFW. Linear associations were observed for both metals. An increase in Mo from the 25th to 75th percentile was associated with a 0.114 (95% credible interval (CI): 0.019, 0.247) SD higher EFW, equivalent to a 7.4 g difference. Similar associations were observed between Mo and the other fetal measures evaluated. In contrast, an increase in Ba from the 25th to 75th percentile was associated with a -0.076 (95% CI: 0.217, 0.066) SD lower EFW, equivalent to a 4.9 g difference. Similar inverse associations were observed for Ba in relation to abdominal circumference and biparietal diameter. BKMR also identified a possible interaction between Ba and Mo in relation to head circumference, suggesting that the positive associations between Mo and this outcome may be attenuated at high levels of Ba, which was consistent with findings from linear regression (Pinteraction = 0.03). In an exploratory analysis accounting for a larger mixture of metals, Mo and Ba consistently contributed most to associations with EFW. An inverse association was also identified between Sb and EFW. CONCLUSIONS: Our results suggest that Mo may promote fetal growth, while Ba and Sb may reduce fetal growth, in this population.

Extracellular vesicle microRNA in early versus late pregnancy with birth outcomes in the MADRES study.

Circulating miRNA may contribute to the development of adverse birth outcomes. However, few studies have investigated extracellular vesicle (EV) miRNA, which play important roles in intercellular communication, or compared miRNA at multiple time points in pregnancy. In the current study, 800 miRNA were profiled for EVs from maternal plasma collected in early (median: 12.5 weeks) and late (median: 31.8 weeks) pregnancy from 156 participants in the MADRES Study, a health disparity pregnancy cohort. Associations between miRNA and birth weight, birth weight for gestational age (GA), and GA at birth were examined using covariate-adjusted robust linear regression. Differences by infant sex and maternal BMI were also investigated. Late pregnancy measures of 13 miRNA were associated with GA at birth (PFDR<0.050). Negative associations were observed for eight miRNA (miR-4454+ miR-7975, miR-4516, let-7b-5p, miR-126-3p, miR-29b-3p, miR-15a-5p, miR-15b-5p, miR-19b-3p) and positive associations for five miRNA (miR-212-3p, miR-584-5p, miR-608, miR-210-3p, miR-188-5p). Predicted target genes were enriched (PFDR<0.050) in pathways involved in organogenesis and placental development. An additional miRNA (miR-107), measured in late pregnancy, was positively associated with GA at birth in infants born to obese women (PFDR for BMI interaction = 0.011). In primary analyses, the associations between early pregnancy miRNA and birth outcomes were not statistically significant (PFDR≥0.05). However, sex-specific associations were observed for early pregnancy measures of 37 miRNA and GA at birth (PFDR for interactions<0.050). None of the miRNA were associated with fetal growth measures (PFDR≥0.050). Our findings suggest that EV miRNA in both early and late pregnancy may influence gestational duration.

Detected prenatal perfluorooctanoic acid (PFOA) exposure is associated with decreased fetal head biometric parameters in participants experiencing higher perceived stress during pregnancy in the MADRES cohort.

Background: Perfluoroalkyl substances (PFAS) are ubiquitous synthetic chemicals with long half-lives and are known to cross the placenta during pregnancy. We examined the influence of maternal PFAS levels on in utero fetal growth trajectories and assessed whether maternal stress modified these associations. Methods: Blood serum concentrations of five PFAS (PFOS, PFHxS, PFNA, PFOA, PFDA) were measured in 335 prenatal specimens (mean gestational age (GA): 21±9 weeks) in the MADRES cohort. Fetal growth outcomes (head circumference (HC), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL), and estimated fetal weight (EFW)) were abstracted from ultrasound medical records and measured at the 3rd trimester study visit (N = 833 scans, GA range 10-42 weeks, mean 2.4 scans/participant). Adjusted linear mixed models with a GA quadratic growth curve were used for each PFAS exposure and growth outcome. PFOS and PFHxS were modeled continuously (100% sample detection), while PFOA, PFNA, and PFDA were modeled categorically (57-70% sample detection). Scores on the Perceived Stress Scale (PSS) measured in pregnancy were dichotomized at the median (<13 vs. ≥ 13) in stratified models. Results: Participants were on average 29±6 years old and predominately Hispanic (76%). Median serum concentrations of PFOS, PFHxS, PFNA, PFOA and PFDA were 1.34, 1.10, 0.07, 0.12, and 0.04 ng/mL, respectively. Participants with detected PFOA concentrations had fetuses with -2.5 mm (95% CI -4.2, -0.8) smaller HC and-0.7 mm (95% CI -1.3, -0.2) smaller BPD on average for a fixed GA than those without detected PFOA concentrations. In models stratified by PSS level, the effects of PFOA on fetal growth parameters were stronger and only significant in participants with higher stress levels (HC: ß= -3.5, 95% CI -5.8, -1.4; BPD: ß = -0.8, 95% CI -1.6, -1.1). Conclusions: Prenatal PFOA exposure adversely impacted fetal head biometric parameters in participants experiencing higher stress during pregnancy.

Prenatal Perfluorooctanoic Acid (PFOA) Exposure Is Associated With Lower Infant Birthweight Within the MADRES Pregnancy Cohort.

Introduction: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals found in household products that can cross the placenta during pregnancy. We investigated whether PFAS exposure during pregnancy was associated with infant birth outcomes in a predominantly urban Hispanic population. Methods: Serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured in 342 prenatal biospecimens (mean gestational age: 21 ± 9 weeks) from participants in the ongoing Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) cohort. PFAS compounds were modeled continuously or categorically, depending on the percentage of samples detected. The birth outcomes assessed were birthweight, gestational age at birth, and birthweight for gestational age (BW-for-GA) z-scores that accounted for parity or infant sex. Single pollutant and multipollutant linear regression models were performed to evaluate associations between PFAS exposures and birth outcomes, adjusting for sociodemographic, perinatal, and study design covariates. Results: Maternal participants (n = 342) were on average 29 ± 6 years old at study entry and were predominantly Hispanic (76%). Infants were born at a mean of 39 ± 2 weeks of gestation and weighed on average 3,278 ± 522 g. PFOS and PFHxS were detected in 100% of the samples while PFNA, PFOA, and PFDA were detected in 70%, 65%, and 57% of the samples, respectively. PFAS levels were generally lower in this cohort than in comparable cohorts. Women with detected levels of PFOA during pregnancy had infants weighing on average 119.7 g less (95% CI -216.7, -22.7) than women with undetected levels of PFOA in adjusted single pollutant models. PFOA results were also statistically significant in BW-for-GA z-score models that were specific for sex or parity. In models that were mutually adjusted for five detected PFAS compounds, PFOA results remained comparable; however, the association was only significant in BW-for-GA z-scores that were specific for parity (ß = -0.3; 95% CI -0.6, -0.01). We found no significant adjusted associations with the remaining PFAS concentrations and the birth outcomes assessed. Conclusion: Prenatal exposure to PFOA was associated with lower birthweight in infants, suggesting that exposure to these chemicals during critical periods of development might have important implications for children's health.

Prenatal Metal Mixtures and Birth Weight for Gestational Age in a Predominately Lower-Income Hispanic Pregnancy Cohort in Los Angeles.

BACKGROUND: Reduced fetal growth increases the risk for adverse health outcomes. Growing evidence suggests that metal exposures contribute to reduced fetal growth, but little is known about the effects of complex metal mixtures. OBJECTIVES: We investigated the impact of a complex mixture of metals on birth weight for gestational age (BW for GA) in the Maternal and Developmental Risks from Environmental and Social Stressors study, a predominately lower-income Hispanic pregnancy cohort in Los Angeles, California. METHODS: Cadmium (Cd), cobalt (Co), mercury (Hg), nickel (Ni), molybdenum (Mo), lead (Pb), antimony (Sb), tin (Sn), and thallium (Tl) were measured by inductively coupled plasma mass spectrometry (ICP-MS) in maternal urine samples collected in early pregnancy (median GA: 13.1 wk). Speciated urinary arsenic (As) (inorganic+monomethyl+dimethyl As) was measured by high-performance liquid chromatography coupled to ICP-MS. Primary analyses focused on a mixture of seven metals that have previously been associated individually with fetal growth (i.e., As, Cd, Co, Hg, Ni, Pb, Tl) (n=262). In exploratory analyses, we additionally examined three metals that have been less studied in relation to fetal growth (i.e., Mo, Sb, Sn). Covariate-adjusted Bayesian kernel machine regression was used to investigate metal mixture associations with BW for GA z-scores. RESULTS: In primary analyses, Hg and Ni ranked highest as predictors of BW for GA. An inverse linear association was estimated for Hg, whereas a positive association was estimated for Ni at low-to-moderate concentrations. A potential interaction between Hg and Ni was also identified. In our exploratory analysis, Sb ranked highest as a predictor of BW for GA, followed by Hg and Ni. CONCLUSIONS: Our findings suggest that in this understudied population, Hg may reduce fetal growth, whereas Ni may promote fetal growth. We also identified Sb as a potential metal of concern for this population, which merits additional investigation. https://doi.org/10.1289/EHP7201.