Organochlorine Chemical Concentrations in Maternal Mid-Pregnancy Serum Samples: Association with Autism Spectrum Disorders in the Early Markers of Autism Study

Background:  Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs), widely detectable environmental contaminants in human populations, are known neurodevelopmental toxicants and have been associated with adverse developmental outcomes. Whether prenatal exposure to these pollutants influences development of autism spectrum disorder (ASD) is unknown.

Objectives: In this study, we examined whether concentrations of PCBs and OCPs measured in maternal mid-pregnancy serum samples were associated with risk of ASD in the offspring.

Methods:

Data are from the Early Markers for Autism (EMA) study, a population-based nested case control study that includes women who participated in the prenatal expanded alphafetoprotein screening program in Southern California and delivered children between 2000-2003.  Birth certificates were linked to the California Department of Developmental Services (DDS) client databases to identify children with autism and a control group with developmental delay without autism (DD). General population (GP) controls were randomly selected from the remaining birth certificates, matched to cases on child month and year of birth and sex.  Final diagnostic status, based on DSM-IV-TR criteria, was determined by expert clinical review of abstracted diagnostic and clinical information in DDS client records. Concentrations of 37 PCBs and 9 OCPs were measured in stored second trimester maternal serum samples and were available for 545 ASD, 181 DD, and 418 GP children. Analytes detectable for at least 60% of the study population were examined in further analyses; this included 11 PCBs (28, 99, 118, 138/158, 153, 170, 180, 190, 196/203, and 199, as well as their sum) and 2 pesticides (a breakdown product of dichlorophenyltrichloroethane (DDT)- p,pDDE and trans-Nonachlor, a component of oxychlordane). Descriptive statistics were compared between diagnostic groups. Conditional logistic regression was used to calculate crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) for ASD compared to GP controls by quartiles of analyte concentrations, accounting for study matching factors and potential confounding factors based on associations with the analytes and known associations with ASD.

Results:  Higher concentrations of PCBs were associated with several demographic factors (higher maternal and paternal age, maternal birthplace, lower maternal education), and several PCB congeners displayed higher geometric means in the ASD group as compared to both DD and GP groups. Overall, positive associations were found with most PCB congeners and ASD; associations remained statistically significant in adjusted analyses accounting for parental age and other demographic factors for two PCBs (for the highest quartile compared to lowest, PCB138/158 adjusted OR=1.83, 95%CI 1.12, 2.99; PCB153 adjusted OR=1.84, 95% CI 1.10, 3.07; p for trend across quartiles=0.03 for each). No significant associations were found with risk of ASD for the two OCPs examined in this study.

Conclusions:  Our results suggest that exposure to PCBs during pregnancy could increase risk of ASD. PCBs and other organohalogens should be examined further as potential risk factors for ASD during critical periods of neurodevelopment.