In Utero Pyrethroid Pesticide Exposure and Child Cognitive Development from 6 to 36 Months in the Marbles Longitudinal Cohort

Background: Associations between prenatal pesticide exposure and both autism spectrum disorder (ASD) and cognitive delays have been reported. Pyrethroid pesticides have neurotoxicological properties but little is known about the effects of in utero exposure on child development.

Objectives: Assess the relationship between pyrethroid pesticide exposure during pregnancy and child cognitive development from 6 - 36 months.

Methods: Mother-child pairs (n=134) in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) longitudinal birth cohort were examined. This cohort enrolled pregnant women who already had a child with ASD and, therefore are at increased risk (up to 20%) for having another child who will develop ASD. Maternal urine samples comprising an individual spot urine and a pooled sample of 3 individual spot urine samples (each at least a week apart), from each of the latter 2 trimesters were analyzed for pyrethroid metabolite 3-phenoxybenzoic acid (3PBA). To adjust for urine dilution 3-PBA concentrations were specific gravity (SG) corrected. To assess average exposure during the pregnancy period concentrations of 3-PBA from urine samples collected during each trimester of pregnancy were averaged and the intraclass correlation coefficient (ICC) and total number of urine samples for each pregnancy were used to compute weights for linear regression models of average 3-PBA concentration during pregnancy and Mullen Scales of Early Learning (MSEL) scores.

Results: Subjects had median SG-adjusted 3-PBA concentration= 0.78 ng/ml and ICC = 0.34. After applying weights to 3PBA concentrations and adjusting for SG, child’s sex, prenatal vitamin use and maternal education, we found significantly lower MSEL Composite (β= -0.79, p=0.003), Visual Reception (β= -0.80, p=0.001), and Fine Motor (β= -0.32, p=0.02) scores at 6 months.

Conclusions: This may be the first study to assess a biomarker of pyrethroid exposure, with the use of multiple urine samples, from both the 2^nd and 3^rd trimesters during pregnancy in relation to child cognitive development from 6-36 months. We observed lower scores on the MSEL at 6 months however this effect was attenuated by 12 months. These findings suggest in utero 3-PBA concentrations are not strongly related to child cognitive development. Previous literature on this topic is inconsistent, which in part could be due to exposure misclassification because previous studies used a single spot urine sample to assess exposure. A single urine sample from pregnancy will not capture long-term exposure for pyrethroids due to their quick metabolism. A priori we had expected that if prenatal pyrethroid exposure affected child cognition, this effect would be consistent across ages. The 6-month results could be a chance finding and/or the lack of association at 12 months or older could reflect confounding factors that are influential at later ages. These are preliminary findings from an ongoing study. Results will be updated with a larger sample, more rigorous measurement error modeling approaches, results from additional urine samples, and analyses of trimester specific 3-PBA concentrations.