Methylparaben in Meconium and Risk of Maternal Thyroid Dysfunction, Adverse Birth Outcomes, and Attention-Deficit Hyperactivity Disorder

Abstract

Background Parabens are detected ubiquitously in human urine samples, but the effects of prenatal exposure are unclear, partially due to inadequate exposure assessment in maternal urine, which may fail to capture fetal exposure. We examined the association of meconium methylparaben detection with preterm birth, gestational age, birthweight, maternal thyroid hormones, and child attention-deficit hyperactivity disorder (ADHD) at 6-7 years. Methods Methylparaben was measured in meconium with ultraperformance liquid chromatography mass spectrometry and dichotomized (detect/non-detect) for 345 children in the Gestation and the Environment cohort in Sherbrooke, Quebec, Canada, Birth outcomes and maternal thyroid hormones (T3, T4, and thyroid stimulating hormone [TSH]) at <20 weeks gestation were measured at the Centre Hospitalier Universitaire de Sherbrooke. ADHD diagnosis at age 6-7 was determined at follow-up or from medical records. Associations were estimated with logistic and linear regressions, and the potential for mediation by birthweight and preterm birth of the effect of methylparaben on ADHD was modeled with causal mediation analysis. Results Meconium methylparaben detection was associated with increased odds of preterm birth (odds ratio [OR]=4.81; 95% CI [2.29, 10.10]), decreased gestational age (beta [β]=-0.61 weeks; 95% CI [-0.93, -0.29]) and decreased birthweight (β=-0.12 kilograms; 95% CI [-0.21, -0.03]). Associations were also found with decreased maternal TSH (relative concentration [RC]=0.76; 95% CI [0.58, 0.99]) and total T3 (RC=0.84; 95% CI [0.75, 0.96]), but increased total T4 (RC=1.10; 95% CI [1.01, 1.19]). Mothers of infants with detectable meconium methylparaben had increased odds of hypothyroxinemia (OR=2.50, 95% CI [1.01, 6.22]), and children were more likely to be diagnosed with ADHD at age 6-7 (OR=2.33, 95% CI [1.45, 3.76]). Preterm birth and birthweight mediated 20% and 13% of the effect of methylparaben on ADHD respectively. Conclusions This adverse association between methylparaben and ADHD, partially mediated by birth outcomes, warrants further research into fetal methylparaben exposure.