Anita A Panjwani1, Yuelong Ji2, Jed W Fahey1,3,4, Amanda Palmer1, Guoying Wang2, Xiumei Hong2, Barry Zuckerman5, Xiaobin Wang2,6. 1. Center for Human Nutrition, Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland. 2. Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland. 3. Cullman Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland. 4. Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. 5. Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts. 6. Division of General Pediatrics and Adolescent Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Abstract
Maternal metabolic conditions are known risk factors for child autism spectrum disorder (ASD). Branched-chain amino acids (BCAAs) are also associated with ASD. We examined the joint associations of maternal metabolic conditions and BCAAs on the risk of child ASD and whether the associations differed by child's sex. We analyzed 789 mother-infant pairs, a subset of the Boston Birth Cohort, from a predominantly urban, low-income, minority population. Maternal plasma BCAAs were measured by liquid chromatography-tandem mass spectrometry in samples collected 24-72 hr postpartum. A composite BCAA score was created using factor analysis, and prepregnancy obesity and diabetes (ob/DM) were combined into one variable. Logistic regression was used to explore the role of BCAAs as mediators or cofactors with ob/DM and child's sex on ASD risk. BCAA-ob/DM and BCAA-sex interactions were also examined. Maternal BCAAs alone were not associated with ASD and did not mediate the path between ob/DM and ASD. In the presence of maternal ob/DM, BCAA score was significantly associated with ASD (adjusted OR 2.33, 95% CI 1.18, 4.60). Interactions were present for valine with ob/DM and for valine and isoleucine with male sex on ASD risk. The odds ratio (OR) for risk of ASD was the greatest with all three risk factors combined-male sex, above median BCAA score, and ob/DM (OR 10.79, 95% CI 4.40, 26.42). Similar patterns were found for other developmental disorders, though not as strong as for ASD. Additional studies are warranted to clarify the role of maternal BCAAs, ob/DM, and child's sex in ASD. Autism Res 2019, 12: 1562-1573.
Maternal metabolic conditions are known risk factors for childautism spectrum disorder (ASD). Branched-chain amino acids (BCAAs) are also associated with ASD. We examined the joint associations of maternal metabolic conditions and BCAAs on the risk of childASD and whether the associations differed by child's sex. We analyzed 789 mother-infant pairs, a subset of the Boston Birth Cohort, from a predominantly urban, low-income, minority population. Maternal plasma BCAAs were measured by liquid chromatography-tandem mass spectrometry in samples collected 24-72 hr postpartum. A composite BCAA score was created using factor analysis, and prepregnancy obesity and diabetes (ob/DM) were combined into one variable. Logistic regression was used to explore the role of BCAAs as mediators or cofactors with ob/DM and child's sex on ASD risk. BCAA-ob/DM and BCAA-sex interactions were also examined. Maternal BCAAs alone were not associated with ASD and did not mediate the path between ob/DM and ASD. In the presence of maternal ob/DM, BCAA score was significantly associated with ASD (adjusted OR 2.33, 95% CI 1.18, 4.60). Interactions were present for valine with ob/DM and for valine and isoleucine with male sex on ASD risk. The odds ratio (OR) for risk of ASD was the greatest with all three risk factors combined-male sex, above median BCAA score, and ob/DM (OR 10.79, 95% CI 4.40, 26.42). Similar patterns were found for other developmental disorders, though not as strong as for ASD. Additional studies are warranted to clarify the role of maternal BCAAs, ob/DM, and child's sex in ASD. Autism Res 2019, 12: 1562-1573.
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