Prenatal exposure to per- and polyfluoroalkyl substances and cognitive development in infancy and toddlerhood

Abstract

Background/objective: Per- and polyfluoroalkyl substances (PFAS) have neurobehavioral toxicity in experimental studies. Evidence on associations between prenatal PFAS exposure and child's cognitive development is inconsistent partly due to differences in assessment time points and tools. We examined associations of prenatal maternal serum PFAS concentrations with child's cognitive development assessed at multiple time points in infancy and toddlerhood.

Methods: We included 140 mother-child pairs from MARBLES (Markers of Autism Risk in Babies - Learning Early Signs), a longitudinal cohort of children with a first degree relative who was diagnosed with autism spectrum disorder followed from birth. Study children's cognitive development was assessed at 6, 12, 24, and 36 months of age using the Mullen Scales of Early Learning (MSEL) which provides an overall Early Learning Composite (normative mean of 100 and SD of 15) and four subscales (i.e., fine motor, visual reception, receptive language, and expressive language abilities; normative mean of 50 and SD of 10). Nine PFAS were quantified in maternal serum collected during pregnancy. We examined associations of log 2-transformed prenatal maternal serum PFAS concentrations with the MSEL Composite and each of the subscale scores at each time point as well as longitudinal changes in the scores over the four time points. We also classified trajectories into low- and high-score groups and fit Poisson regression models to estimate associations expressed as relative risks (RR).

Results: Among six PFAS detected in more than 60% of the samples, prenatal maternal serum perfluorooctanoate (PFOA) was inversely associated with child's Composite score at 24 months (β = -5.22, 95% CI: -8.27, -2.17) and 36 months of age (β = -5.18, 95% CI: -9.46, -0.91), while other five PFAS were not strongly associated with Composite score at any time points. When assessing longitudinal changes in the scores over the four time points, PFOA was associated with trajectories having a negative slope for Composite scores and all four subscales. When examining trajectories of the scores between low- and high-score groups, PFOA was associated with having lower and/or decreasing Composite scores (RR = 1.49, 95% CI: 1.09, 2.03).

Conclusions: Prenatal PFOA appears to adversely affect child's cognitive development in toddlerhood in this study population. Because a large fraction of MARBLES children is at risk for atypical development, population-based studies are needed to confirm our findings.

Keywords: Cognitive function; Per- and polyfluoroalkyl substances; Prenatal exposure; Serum.

Figure 1.

Distributions of MSEL Composite scores and T-scores of four subscales at 6, 12, 24, and 36 months of age for 140 children included in the current study. Red crosses denote mean values at each time point. Blue asterisks denote differences in mean scores with other time points identified by the postestimation test with Bonferroni correction following the linear mixed model at the significance level of 0.05. Composite scores have a normative mean of 100 and an SD of 15 and T-scores of each subscale have a normative mean of 50 and an SD of 10.

Figure 2.

Adjusted mean differences (β) in MSEL Composite scores and T-scores of subscales of children at 6, 12, 24, and 36 months of age in association with a unit increase in log 2-transformed prenatal maternal serum concentrations of six PFAS and two PCs. Models were adjusted for child’s sex, parity, maternal pre-pregnancy BMI, gestational diabetes, maternal education, and breastfeeding duration. Red shaded areas represent associations with a p-value < 0.05.

Figure 3.

Trajectories of child’s Composite scores from 6 to 36 months of age for low- and high-score groups. Solid lines represent trajectories of group mean, and fine lines and dots represent trajectories of individuals.