Effects of Prenatal Phthalate Exposure on Early Childhood Expressive Language Development Trajectories

BACKGROUND AND AIM: Phthalates are common endocrine disruptors that can impair neurodevelopment. We investigated potential links between prenatal exposure to phthalates and child language development trajectories given prior inconsistent evidence across individual phthalates. METHODS: We investigated fourteen urinary phthalate metabolites, measured in maternal urine during pregnancy, and child expressive language scores from the Mullen Scales of Early Learning (MSEL) at 6, 12, 24, and 36 months in 231 children from an enhanced autism-risk cohort (19% with autism): Early Autism Risk Longitudinal Investigation (EARLI), born 2009 - 2013 from California, Maryland, and Pennsylvania. We used multiple imputation to handle missingness in MSEL (~37%) and phthalates (~9%), and assigned children to six distinct expressive language trajectories after selecting the latent class growth analysis model with best goodness-of-fit measures. We estimated relative risk ratios (RRR) of being in different language trajectories ("high growth” as reference) associated with two-fold change in creatinine adjusted phthalates using multinomial logistic regression with Firth correction, adjusting for child sex, birth season, income, and maternal age, race, and education. RESULTS: Some low molecular weight phthalates were associated with sub-optimal language trajectories, e.g. RRRs of 1.33 or higher for mono-2-hydroxy-iso-butyl phthalate, peaking at 1.51 (1.02, 2.24) for the delayed growth low trajectory. In contrast, some high molecular weight phthalates exhibited protective effects for delayed growth trajectories but adverse effects for plateau and tracking trajectories: e.g. mono-isononyl phthalate with RRR 0.72 (0.59, 0.89) with delayed growth low but 1.29 (1.08, 1.53) with the tracking low trajectory. Some phthalates exhibited null patterns. CONCLUSIONS: Prenatal phthalate exposure may impact the trajectory of expressive language development in early childhood, with differences by individual phthalates, perhaps by molecular weight group. We observed adverse and protective influences of phthalates that may be influenced by small numbers in each trajectory class. KEYWORDS: phthalates, language development, trajectory analysis