Phthalate Metabolites and Neurodevelopmental Disorders
Authors:   , Mathew Leny , Newschaffer Craig J. , Dodge Kristen Lyall 
Published: June 2022

Aims: Phthalates are multifunctional chemicals widely used in varied industrial applications and resulting in ubiquitous human exposure. Prenatal phthalate exposure maybe detrimental to child neurodevelopment and is commonly measured in urine and associations studied in general population samples. Phthalate metabolites are also detectable in meconium, the first stool of a newborn. Meconium accumulates in the fetus from approximately 12th week of gestation and may better represent cumulative fetal exposure over pregnancy. The aim of this dissertation was to explore the utility of meconium to quantify prenatal phthalate exposure and evaluate the association of exposure quantified in maternal urine and in meconium with child neurodevelopment among children at higher risk for adverse neurodevelopment. Methods: Studies were based on data from two high risk pregnancy cohorts, one comprised of children born in communities with very high community levels of prenatal alcohol consumption (the Prenatal Alcohol in SIDS and Stillbirth, PASS, network study) and the other comprised of children with an older sibling diagnosed with an autism spectrum disorder (the Early Autism Risk Longitudinal Investigation, EARLI). In PASS, phthalates were quantified in meconium and outcome was cognitive functioning at 12 months, and in EARLI phthalates were quantified in maternal urine and meconium, and in addition to cognitive functioning at 12 months, social responsiveness at 36 months was also assessed. Results: Phthalate metabolites were quantified in meconium from both study samples and expected correlation patterns were detected in them, but urine quantified metabolites in EARLI displayed weak correlations with the same metabolites in meconium. A subset of metabolites in urine and meconium were associated with cognitive function at 12-months and similar set of metabolites in meconium from both cohorts were associated with cognitive function in a sexually dimorphic manner with decrease in cognition among females and increase among males. A subset of metabolites from third trimester urine were associated with higher autism related traits and some were associated in a sexually dimorphic manner indicating increase in autism related traits among females and decrease among males. Conclusion: Meconium is useful to quantify phthalate metabolites, but measured levels may not correlate well with urine quantified exposure from a discrete point in gestation. There was evidence that prenatal phthalate exposure affects child neurodevelopment among children at higher risk for adverse neurodevelopment, but results varied by phthalate metabolite, shape, and direction of associations. The evidence of effect modification by child's sex was stronger and consistent for cognitive function, and to a lesser extent for autism related traits. So, we conclude that there is modest evidence that prenatal phthalate exposure quantified in both urine and meconium is associated with child neurodevelopment and may be expressed in a sexually dimorphic manner. Additional research is needed to clarify the sexually dimorphic pathways behind such associations. Since this is the first study to evaluate these associations using meconium measured metabolites, results should be replicated in future studies. Future pregnancy cohort studies could use meconium as a matrix to capture prenatal exposure to phthalates.