The association between maternal lipid profile after birth and offspring risk of Autism Spectrum Disorder

Background: Maternal obesity has been consistently associated with offspring risk for ASD as well as lipid metabolism derangements. However, few ASD studies have examined maternal lipids in conjunction with maternal prepregnancy body mass index (BMI).

Methods: This nested case-control study was based on the Boston Birth Cohort, a prospective cohort study of mother-child dyads recruited at the Boston Medical Center. Maternal blood samples were collected shortly after delivery and analyzed for total plasma cholesterol, HDL, and triglyceride (TG) concentrations. Low-density lipoprotein (LDL) was subsequently calculated by the Friedewald equation. Cases were identified using ASD diagnoses in children's medical records. The odds of ASD were estimated with continuous lipid levels for a linear relationship, and we further explored the non-linear relationship using the tertile of each lipid analyte with the highest tertile as the reference group. Logistic regression was used to estimate the risk of ASD adjusting for potential confounders. The analyses were performed separately for mothers with normal weight and overweight/obese based on maternal prepregnancy BMI.

Results: One standard deviation decrease in postpartum maternal LDL was associated with increased odds of ASD aOR 1.33 [1.03 - 1.75]. There were no association between postpartum maternal HDL and TG levels and ASD risk. Decreasing levels of LDL were not associated with ASD risk in normal weight mothers (aOR 1.18 [0.83 - 1.69]), but the ASD risk was more pronounced in overweight and obese mothers (aOR 1.54 [1.04 - 2.27]). Follow-up analysis of non-linear association models showed that, when compared to the highest tertile, lower maternal LDL concentrations were associated with approximately two times increased risk of ASD (first tertile: aOR 2.34 [1.22 - 4.49] and second tertile: aOR 2.63 [1.37 - 5.08]). A similar pattern was observed with overweight/obese mothers but not in normal weight mothers CONCLUSION: Lower maternal postpartum plasma LDL concentration was associated with increased odds of ASD in offspring among children born to overweight and obese mothers. Our findings suggest that both maternal BMI and lipids should be considered in assessing their role in offspring ASD risk; and additional longitudinal studies are needed to better understand maternal lipid dynamics during pregnancy among normal weight and overweight/obese mothers.

Keywords: Maternal prepregnancy BMI; autism; lipid.