Prenatal phthalate exposure quantified in meconium and cognition at 12-months: findings from the Early Autism Risk Longitudinal Investigation (EARLI) and the Prenatal Alcohol in SIDS and Stillbirth (PASS) network study

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Background/ AimPrenatal phthalate exposure may affect children’s cognitive development. Although commonly measured in urine, phthalate metabolites are also detectable in meconium, the first stool of a child, potentially reflecting more cumulative prenatal exposure. We quantified phthalate metabolites in meconium from two cohorts and evaluated associations with cognition at 12-months.MethodsPhthalate metabolites were quantified using high performance liquid chromatography- high resolution mass spectrometry in meconium from children in EARLI, a high familial autism risk pregnancy cohort (N=160, enrolled from 2009-12), and PASS, a pregnancy cohort recruited from a region at high risk for prenatal alcohol use (N=606, enrolled from 2007-15). Molar sum of di-2-ethylhexyl phthalate (∑DEHP) metabolites and an anti-androgenic (AA) score using mono-isobutyl, mono-n-butyl, mono benzyl phthalate (MBZP), and 4 DEHP metabolites were calculated. Cognition at 12-months was assessed using the Mullen Scales of Early Learning- Composite (ELC). Linear regression adjusted for a priori specified covariates and assessed associations between log-transformed metabolites and ELC. Sex-metabolite interaction terms explored effect modification in the models.Results Phthalate metabolites (8 of 13 in EARLI and 9 of 12 in PASS) were detected in over 90% of meconium samples. Few metabolites retained statistically significant associations with ELC in covariate adjusted models, but effect-modification by sex in the same direction was suggested (P < 0.2) for ∑DEHP, AA score, MBzP, and mono-2-ethylhexyl (MEHP) in both study samples. In sex-stratified analysis, ∑DEHP, AA score, MBzP, and MEHP were associated with increasing ELC among males and with decreasing ELC among females in both samples.ConclusionsPrenatal phthalate exposure was associated with early cognitive development. A subset of metabolites displayed similar sex-specific associations in both cohorts, with decrease in cognition indicating neurodevelopmental harm among females, but increase in cognition among male children.