Prenatal urinary concentrations of phthalate metabolites and behavioral problems in Mexican children: The Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) study

Background: Phthalate exposure has been associated with increased childhood behavioral problems. Existing studies failed to include phthalate replacements and did not account for high correlations among phthalates. Phthalates’ exposure is higher in Mexico than in U.S. locations, making it an ideal target population for this study. Aim: To examine associations between 15 maternal prenatal phthalate metabolite concentrations and children's behavioral problems. Methods: We quantified phthalate metabolites in maternal urine samples from maternal-child dyads (n = 514) enrolled in the Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) birth cohort in Mexico City. We performed least absolute shrinkage and selection operator (LASSO) regressions to identify associations between specific-gravity adjusted log₂-transformed phthalate metabolites and parent-reported 4–6 year old behavior on the Behavior Assessment System for Children (BASC-2), accounting for metabolite correlations. We adjusted for socio-demographic and birth-related factors, and examined associations stratified by sex. Results: Higher prenatal mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) urinary concentrations were associated with increased hyperactivity scores in the overall sample (β = 0.57, 95% CI = 0.17, 1.13) and in girls (β = 0.54, 95% CI = 0.16, 1.08), overall behavioral problems in boys (β = 0.58, 95% CI = 0.20, 1.15), and depression scores in boys (β = 0.44, 95% CI = 0.06, 0.88). Higher prenatal monobenzyl phthalate (MBzP) concentrations were associated with reduced hyperactivity scores in girls (ß = −0.54, 95% CI = −1.08, −0.21). Discussion: Our findings suggested that prenatal concentrations of phthalates and their replacements altered child neurodevelopment and those associations may be influenced sex.