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Original Investigation
August 1, 2016

Association Between Maternal Prepregnancy Body Mass Index and Plasma Folate Concentrations With Child Metabolic Health

Author Affiliations
  • 1Department of Population, Family, and Reproductive Health, Center on Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
  • 2Departments of Nutrition and Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
  • 3Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 4Division of General Pediatrics and Adolescent Medicine, Department of Pediatrics, Johns Hopkins, University School of Medicine, Baltimore, Maryland
  • 5Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
  • 6Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agriculture University, Beijing, China
  • 7Department of Cardiology, Peking University First Hospital, Beijing, China
  • 8Stanley Manne Children’s Research Institute, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois
  • 9Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
  • 10Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts

Copyright 2016 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA Pediatr. 2016;170(8):e160845. doi:10.1001/jamapediatrics.2016.0845

Importance  Previous reports have linked maternal prepregnancy obesity with low folate concentrations and child overweight or obesity (OWO) in separate studies. To our knowledge, the role of maternal folate concentrations, alone or in combination with maternal OWO, in child metabolic health has not been examined in a prospective birth cohort.

Objective  To test the hypotheses that maternal folate concentrations can significantly affect child metabolic health and that sufficient maternal folate concentrations can mitigate prepregnancy obesity-induced child metabolic risk.

Design, Setting, and Participants  This prospective birth cohort study was conducted at the Boston Medical Center, Boston, Massachusetts. It included 1517 mother-child dyads recruited at birth from 1998 to 2012 and followed up prospectively up to 9 years from 2003 to 2014.

Main Outcomes and Measures  Child body mass index z score calculated according to US reference data, OWO defined as a body mass index in the 85th percentile or greater for age and sex, and metabolic biomarkers (leptin, insulin, and adiponectin).

Results  The mean (SD) age was 28.6 (6.5) years for mothers and 6.2 (2.4) years for the children. An L-shaped association between maternal folate concentrations and child OWO was observed: the risk for OWO was higher among those in the lowest quartile (Q1) as compared with those in Q2 through Q4, with an odds ratio of 1.45 (95% CI, 1.13-1.87). The highest risk for child OWO was found among children of obese mothers with low folate concentrations (odds ratio, 3.05; 95% CI, 1.91-4.86) compared with children of normal-weight mothers with folate concentrations in Q2 through Q4 after accounting for multiple covariables. Among children of obese mothers, their risk for OWO was associated with a 43% reduction (odds ratio, 0.57; 95% CI, 0.34-0.95) if their mothers had folate concentrations in Q2 through Q4 compared with Q1. Similar patterns were observed for child metabolic biomarkers.

Conclusions and Relevance  In this urban low-income prospective birth cohort, we demonstrated an L-shaped association between maternal plasma folate concentrations and child OWO and the benefit of sufficient folate concentrations, especially among obese mothers. The threshold concentration identified in this study exceeded the clinical definition of folate deficiency, which was primarily based on the hematological effect of folate. Our findings underscore the need to establish optimal rather than minimal folate concentrations for preventing adverse metabolic outcomes in the offspring.