The Association of Maternal Lipid Levels and Autism Spectrum Disorder Risk.
Background: Maternal obesity and gestational diabetes are conditions of increasing concern among pregnant women in the United States. Emerging evidence also links these metabolic dysregulations with risk of autism spectrum disorder (ASD), which affects more than 1% of children in the United States. Recent research identified maternal obesity and gestational diabetes as ASD risk factors. However, little is known about how the biological indicators of metabolic dysregulations are associated with ASD risk.
Objectives: We measured maternal serum lipid levels to examine the association with ASD risk stratified by maternal BMI categories.
Methods: We performed a nested case-control study drawing on the Boston Birth Cohort (BBC), an urban minority prospective birth cohort. BBC children with at least 1 inpatient, outpatient, or emergency room visit to the Boston Medical Center between 2003 and 2015 were eligible for inclusion in our analysis. Electronic medical record ICD-9-CM diagnosis codes were used to identify ASD cases and neurotypical controls among BBC participants. Maternal non-fasting serum lipids (triglyceride (TG), high density lipoprotein (HDL), total cholesterol, and calculated low density lipoprotein (LDL)) were obtained from blood samples collected after delivery. Logistic regression was used to assess the association between ASD risk and lipid measurement. Maternal lipid quantiles were use to examine non-linear associations. Models were also stratified by maternal pre-pregnancy BMI groups (normal, overweight and obese) to assess interaction.
Results: A total of 99 children with ASD and 698 neurotypical children were identified among mother-child dyads with lipid measurements. There was no association between maternal total cholesterol, HDL and TG with ASD risk. However maternal LDL level was associated with increased ASD risk in both the lowest (<92 mg/dL; OR 2.4 [CI: 1.3-4.4]) and highest (>250 mg/dL; OR 1.9 [CI: 1.1-3.6]) tertiles compared to the middle tertile (92-250 mg/dL) after adjusting for gestational age, sex, maternal age, education and birthweight. When stratified by maternal BMI groups, maternal LDL association with ASD risk did not persist in the normal and overweight groups but was still seen among obese mothers. Interestingly a similar U-shaped pattern of ASD risk was observed among children born to obese mothers (Lowest tertile OR 5.2 [CI: 1.4-25.2], Highest tertile OR 5.3 [CI: 1.4-26.9]).
Conclusions: Our study shows that both low and high maternal LDL levels are associated with ASD risk compare to the middle LDL range, particularly among obese mothers. Optimal maternal lipid levels during pregnancy are not well established and more study is needed to better understand the role of maternal LDL and ASD risk.