Maternal Dyslipidemia, Plasma Branched-Chain Amino Acids, and the Risk of Child Autism Spectrum Disorder: Evidence of Sex Difference

  • Anita A. Panjwani
  • Yuelong Ji
  • Jed W. Fahey
  • Amanda Palmer
  • Guoying Wang
  • Xiumei Hong
  • Barry Zuckerman
  • Xiaobin WangEmail author
Original Paper


In contrast to the well-observed associations between obesity, diabetes, and autism spectrum disorder (ASD), the roles of maternal dyslipidemia and sex disparity in ASD have not been well-studied. We examined the joint associations of maternal plasma cholesterols, branched-chain amino acids (BCAAs) and child sex on child ASD risk. We analyzed data from 756 mother-infant pairs (86 ASD) from the Boston Birth Cohort. Maternal plasma cholesterols and BCAAs were measured in samples collected 24–72 h postpartum. We found that in this urban, low-income prospective birth cohort, low maternal high-density lipoprotein cholesterol (HDL-C), above-median maternal plasma BCAA concentrations, and male sex additively or synergistically increased risk of ASD. Additional studies are necessary to confirm our findings.


Autism spectrum disorder Maternal cholesterols Pre- and perinatal risk factors Sex differences Branched-chain amino acids Metabolomics 



The authors would like to thank all the study participants and staff as the study would not have been possible without their support and participation. This work is supported by the Health Resources and Services Administration (HRSA) of the US Department of Health and Human Services (HHS) under Grant Numbers R40MC27443 and UJ2MC31074. The Boston Birth Cohort (parent study) is supported in part by the March of Dimes PERI Grants (20-FY02-56, #21-FY07-605); and the National Institutes of Health (NIH) Grants (R21ES011666, 2R01HD041702, R21HD066471, U01AI090727, R21AI079872, and R01HD086013). This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS, or the U.S. Government. The authors do not have any conflicts of interest to disclose.

Author contributions

AAP conceptualized the study, performed the statistical analysis, participated in the interpretation of the data, and drafted the manuscript. YJ conceptualized the study and assisted in statistical analysis and interpretation of the data. JWF and AP conceptualized the study and participated in the interpretation of the data. GW and XH participated in the design and coordination of the study and data cleaning. BZ oversaw and managed participant recruitment, follow-up, and data collection. XW is the founder and principal investigator of the Boston Birth Cohort and oversaw participant recruitment, follow-up and data collection, conceptualized the study, and provided critical input on study design, data analyses, interpretation of data, and initial draft of the manuscript. All authors critically reviewed and approved the final manuscript.

Compliance with Ethical Standards

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Supplementary material

10803_2019_4264_MOESM1_ESM.docx (3.9 mb)
Supplementary material 1 (DOCX 4029 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of International Health, Center for Human NutritionJohns Hopkins University Bloomberg School of Public HealthBaltimoreUSA
  2. 2.Department of Population, Family and Reproductive Health, Center on the Early Life Origins of DiseaseJohns Hopkins University Bloomberg School of Public HealthBaltimoreUSA
  3. 3.Department of Pharmacology and Molecular Sciences, Cullman Chemoprotection CenterJohns Hopkins University School of MedicineBaltimoreUSA
  4. 4.Division of Clinical Pharmacology, Department of MedicineJohns Hopkins University School of MedicineBaltimoreUSA
  5. 5.Department of Pediatrics, School of Medicine and Boston Medical CenterBoston UniversityBostonUSA
  6. 6.Division of General Pediatrics & Adolescent Medicine, Department of PediatricsJohns Hopkins University School of MedicineBaltimoreUSA

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