A Prospective Birth Cohort Study on Maternal Cholesterol Levels and Offspring Attention Deficit Hyperactivity Disorder: New Insight on Sex Differences

Yuelong Ji; Anne W Riley; Li-Ching Lee; Heather Volk; Xiumei Hong; Guoying Wang; Rayris Angomas; Tom Stivers; Anastacia Wahl; Hongkai Ji; Tami R Bartell; Irina Burd; David Paige; Margaret D Fallin; Barry Zuckerman; Xiaobin Wang

doi:10.3390/brainsci8010003

A Prospective Birth Cohort Study on Maternal Cholesterol Levels and Offspring Attention Deficit Hyperactivity Disorder: New Insight on Sex Differences

Brain Sci. 2017 Dec 23;8(1):3. doi: 10.3390/brainsci8010003.

Authors

Yuelong Ji¹, Anne W Riley², Li-Ching Lee^{3

4}, Heather Volk⁵, Xiumei Hong⁶, Guoying Wang⁷, Rayris Angomas⁸, Tom Stivers⁹, Anastacia Wahl¹⁰, Hongkai Ji¹¹, Tami R Bartell¹², Irina Burd¹³, David Paige¹⁴, Margaret D Fallin^{15

16}, Barry Zuckerman¹⁷, Xiaobin Wang^{18

19}

Affiliations

¹ Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. yji7@jhu.edu.
² Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. ariley1@jhu.edu.
³ Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. hvolk1@jhu.edu.
⁴ Wendy Klag Center for Autism and Developmental Disabilities & Department of Mental Health, 615 N Wolfe St, Baltimore, MD 21205, USA. hvolk1@jhu.edu.
⁵ Wendy Klag Center for Autism and Developmental Disabilities & Department of Mental Health, 615 N Wolfe St, Baltimore, MD 21205, USA.
⁶ Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. xhong3@jhu.edu.
⁷ Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. gwang24@jhu.edu.
⁸ Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, 1 Boston Medical Center Place, Boston, MA 02118, USA. Rayris.Angomas@bmc.org.
⁹ Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, 1 Boston Medical Center Place, Boston, MA 02118, USA. Tom.Stivers@bmc.org.
¹⁰ Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, 1 Boston Medical Center Place, Boston, MA 02118, USA. awahl@bu.edu.
¹¹ Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. hji@jhu.edu.
¹² Stanley Manne Children's Research Institute, Mary Ann & J. Milburn Smith Child Health Research, Outreach and Advocacy Center, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E Chicago Avenue, Chicago, IL 60611, USA. TBartell@luriechildrens.org.
¹³ Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, 1800 Orleans St, Baltimore, MD 21287, USA. iburd@jhmi.edu.
¹⁴ Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. dpaige@jhu.edu.
¹⁵ Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. dfallin@jhu.edu.
¹⁶ Wendy Klag Center for Autism and Developmental Disabilities & Department of Mental Health, 615 N Wolfe St, Baltimore, MD 21205, USA. dfallin@jhu.edu.
¹⁷ Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, 1 Boston Medical Center Place, Boston, MA 02118, USA. barryzuckerman1@gmail.com.
¹⁸ Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. xwang82@jhu.edu.
¹⁹ Division of General Pediatrics & Adolescent Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, 1800 Orleans St, Baltimore, MD 21287, USA. xwang82@jhu.edu.

Abstract

Growing evidence suggests that maternal cholesterol levels are important in the offspring's brain growth and development. Previous studies on cholesterols and brain functions were mostly in adults. We sought to examine the prospective association between maternal cholesterol levels and the risk of attention deficit hyperactivity disorder (ADHD) in the offspring. We analyzed data from the Boston Birth Cohort, enrolled at birth and followed from birth up to age 15 years. The final analyses included 1479 mother-infant pairs: 303 children with ADHD, and 1176 neurotypical children without clinician-diagnosed neurodevelopmental disorders. The median age of the first diagnosis of ADHD was seven years. The multiple logistic regression results showed that a low maternal high-density lipoprotein level (≤60 mg/dL) was associated with an increased risk of ADHD, compared to a higher maternal high-density lipoprotein level, after adjusting for pertinent covariables. A "J" shaped relationship was observed between triglycerides and ADHD risk. The associations with ADHD for maternal high-density lipoprotein and triglycerides were more pronounced among boys. The findings based on this predominantly urban low-income minority birth cohort raise a new mechanistic perspective for understanding the origins of ADHD and the gender differences and future targets in the prevention of ADHD.

Keywords: ADHD; high-density lipoprotein; sex difference; triglyceride.

Grants and funding

R01 HD041702/HD/NICHD NIH HHS/United States