Maternal Insecticide Exposure during Pregnancy and Risk of Autism in Offspring from a National Birth Cohort

Background: Dichlorodiphenyl dichloroethene (DDE) is a metabolite of the insecticide DDT and is a persistent organic pollutant. Despite declining levels with time, ongoing prenatal exposure potential exists for nearly all children. DDE is transferred across the placenta, demonstrated by high correlations between levels of this pollutant in maternal serum and placenta and maternal and cord serum. Maternal prenatal serum DDE levels have been correlated with lower scores on standardized early childhood neurocognitive tests and low birthweight.

Objectives: We sought to examine whether elevated maternal DDE levels during pregnancy were related to an increased risk of childhood autism in a large sample of offspring from a national birth cohort.

Methods:  The study is based on a nested case-control design. Cases with autism were identified from the national Finnish Hospital Discharge Registry and linked to the Finnish Maternity Cohort, which includes archived maternal serum specimens from virtually all pregnancies in Finland (over 1.5 million). Cases were born from 1987-2005 and followed up until 2007. Cases were matched 1:1 to controls drawn from the birth cohort who were without ASD (N=750 matched pairs) on date of birth, sex, birthplace, and residence in Finland. The samples were assayed for DDE using gas chromatography tandem mass spectrometry (GC-MS/MS). In each batch of samples a control serum sample from the National Institute of Standards and Technology was included. In previous work the detection rate for DDE was >96%. DDE was classified as a dichotomous variable, with the cut-point at the 75^th percentile of the control distribution. Data were analyzed using conditional logistic regression for matched pairs.

Results: In a preliminary analysis we demonstrated that maternal exposure to DDE levels in the highest quartile are associated with a 41% increased risk of childhood autism (OR=1.41, 95% CI=1.11-1.80, p=0.005). We will also present results from assays of polychlorinated biphenyls (PCBs) in maternal serum samples of autism cases and controls, and from multivariate analyses adjusting for covariates. In addition, we shall report findings on whether the association between maternal DDE and autism is mediated by perinatal complications and increased growth velocity of head circumference.

Conclusions: We found an increased risk of autism among subjects who were exposed during pregnancy to elevated levels of DDE, a metabolite of DDT. These preliminary data suggest that prenatal exposure to this insecticide is related to the risk of autism in offspring. Strengths of the study include a large, population-based, national sample and prospective measures of exposure. Since this persistent organic pollutant has been related to neurocognitive and other early life abnormalities, this work may ultimately lead to an improved understanding of the neurodevelopmental mechanisms that underlie autism and suggest preventive strategies.