Background A large body of evidence has documented the effects of ortho-phthalates, additives to soft plastic used in food packaging, on premature birth. Ortho-phthalates are increasingly replaced with alternatives including tere-phthalates and di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH). A limited toxicological literature suggests that DINCH metabolites disrupt sex hormones and promote oxidant stress known to contribute to adverse birth outcomes, and epidemiologic studies have also been limited in sample size, inclusivity of different populations and measurements at different time points in pregnancy. Methods We leveraged a large American cohort comprised of mother-child dyads from twenty-two cohorts to assess associations of trimester-specific and pregnancy-wide DINCH metabolites with birth weight (BW) and gestational age (GA). Findings Average prenatal urinary DINCH was inversely associated with birth length, birthweight, and birthweight for gestational age z-scores, but not GA. A tenfold increase in the pregnancy-averaged DINCH metabolite cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (MCOCH) was associated with a decrease of 27.43 g (95%CI: -54.81, -0.04) in birthweight. Trimester-specific analyses revealed stronger associations for third trimester DINCH exposure with birth outcomes. Interpretation In a large American cohort representing a broad range of backgrounds, we identified an inverse association of DINCH with standardized measures of birth size, but not gestational age. Further studies should examine joint exposures to DINCH, tere- and orthophthalates, and repeated measures across pregnancy.
