Gestational Exposure to 10 Classes of Priority Chemicals and Birth Outcomes in the ECHO Cohort

IMPORTANCE Gestational environmental chemical exposures are widespread. Some chemicals are known to adversely affect birth outcomes, but many remain understudied. OBJECTIVE To evaluate associations of gestational exposure to a priori identified chemicals in 10 classes with birth outcomes in a large, diverse US cohort. DESIGN, SETTING, AND PARTICIPANTS In the prospective Environmental influences on Child Health Outcomes Cohort study, 5318 mother-child pairs were enrolled from January 1, 2000, to December 31, 2021, with data on gestational urinary chemical concentrations, gestational age at birth, and birth weight. Statistical analysis was performed from January 2024 to February 2026. EXPOSURES In single, midgestation (median, 25 weeks [IQR, 21-30 weeks]) urine samples, concentrations of 113 analytes (chemicals or their metabolites) from 10 chemical classes were simultaneously measured: fungicides and herbicides (n = 11), insecticides (n = 20), halogenated phenols (n = 5), organophosphate esters (n = 10), benzophenones (n = 6), bisphenols (n = 14), parabens (n = 6), antimicrobials (n = 2), phthalates or alternative plasticizers (n = 32), and polycyclic aromatic hydrocarbons (PAHs) (n = 7). MAIN OUTCOMES AND MEASURES Linear mixed-effects regression models with a random effect for site were used to estimate covariate-adjusted differences in gestational age at birth (days) and birth weight-for-gestational age (BW-GA) z scores per IQR increase in urinary analyte concentrations. In secondary analyses, odds ratios (ORs) for preterm birth and small for gestational age (SGA) were estimated. RESULTS In the sample of 5318 mother-child pairs, most infants (2667 female [50%]; median gestational age at birth, 39.0 weeks [IQR, 38.0-40.0 weeks]) were born to college-educated (67% [3218 of 4785]), parous (56%[2815 of 5007]) mothers (median age at delivery, 30.7 years [IQR, 26.1- 34.3 years]). A total of 43 of 113 analytes (38%) were detected in 50% or more of samples. Multiple phthalates or alternative plasticizers were associated with younger gestational age at birth or lower BW-GA z scores; for example, summed diisononyl phthalate metabolites were associated with a 0.6-day (95%CI, −1.0 to −0.1 days) younger gestational age (preterm birth OR, 1.16 [95%CI, 1.01-1.34]), and summed phthalate or alternative plasticizers were associated with a 0.06 (95%CI, −0.11 to −0.02) lower BW-GA z score (SGA OR, 1.09 [95%CI, 0.93-1.27]). Two halogenated phenols, benzophenone 8, bisphenol F, and several PAHs were associated with lower BW-GA z scores; forexample, 1- and 9-hydroxphenanthrene were associated with a 0.04 (95%CI, −0.08 to −0.01) lower BW-GA z score (SGA OR, 1.13 [95%CI, 1.01-1.27]). CONCLUSIONS AND RELEVANCE This large cohort study of diverse US pregnancies found widespread exposure to 10 classes of environmental chemicals, many of which were associated with differences in gestational age at birth or lowerBW-GA z scores. These findings indicate that reducing gestational exposure to chemicals, particularly phthalates or alternative plasticizers and PAHs, could promote healthy deliveries and better child outcomes.