HHS Public Access Author manuscript Author Manuscript
JAMA Pediatr. Author manuscript; available in PMC 2017 August 01. Published in final edited form as: JAMA Pediatr. 2016 August 01; 170(8): e160845. doi:10.1001/jamapediatrics.2016.0845.
Association of Maternal Prepregnancy BMI and Plasma Folate concentrations with Child Metabolic Health
Author Manuscript
Guoying Wang, MD PhD1, Frank B. Hu, MD PhD2, Kamila B. Mistry, PhD MPH3, Cuilin Zhang, MD PhD1,4, Fazheng Ren, PhD5, Yong Huo, MD6, David Paige, MD1, Tami Bartell, BS7, Xiumei Hong, MD PhD1, Deanna Caruso, MS1, Zhicheng Ji, BS8, Zhu Chen, PhD1, Yuelong Ji, MSPH1, Colleen Pearson, BA9, Hongkai Ji, PhD8, Barry Zuckerman, MD9, Tina L. Cheng, MD1,3, and Xiaobin Wang, MD MPH, ScD1,3 1Department
of Population, Family and Reproductive Health, Center on Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
2Departments
of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA 3Division
of General Pediatrics & Adolescent Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
4Division
of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
Author Manuscript
5Beijing
Advanced Innovation Center for Food Nutrition and Human Health, China Agriculture University, Beijing, China
6Department
of Cardiology, Peking University First Hospital, Beijing, China
7Stanley
Manne Children’s Research Institute, Ann & Robert H Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA
8Department
of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
#
Author Manuscript
Correspondence and reprint requests should be addressed to: Xiaobin Wang, MD, MPH, ScD, Zanvyl Krieger Professor, Director, Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, [email protected], Phone: 410-955-5824, Fax: 410-502-5831. Author contribution: Dr. X Wang is the principal investigator of the Boston Birth Cohort (the parent study), and has full access to all of the study data and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: G Wang, X Wang, Acquisition of data: Pearson, Chen, Y Ji, Zuckerman, G Wang, X Wang Analysis and interpretation of data: G Wang, Hong, Mistry, Paige, Cheng, Z Ji, H Ji, Hu, Zhang, Ren, Hou, X Wang Drafting of the manuscript: G Wang, Cheng, Bartell, X Wang Critical revision of the manuscript for important intellectual content: Hong, Pearson, Caruso, Paige, Z Ji, Zuckerman, Cheng, Mistry, Ren, Hou, Hu, Zhang, Bartell, X Wang Data management and statistical analysis: Hong, Z Ji, H Ji, Caruso, Pearson, G Wang, X Wang Administrative, technical, and/or material support: Chen, Y Ji, Caruso, Pearson Study supervision: X Wang Funding: X Wang Conflicts of interests: The authors have declared that no conflicting interests exist.
Wang et al.
Page 2
9Department
Author Manuscript
of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, USA
Abstract Importance—Previous reports have linked maternal prepregnancy obesity with low folate concentrations and child overweight or obesity (OWO) in separate studies. 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—We tested the hypotheses that maternal folate concentrations can significantly affect child metabolic health and that maternal sufficient folate concentrations can mitigate prepregnancy obesity-induced child metabolic risk.
Author Manuscript
Design—Prospective birth cohort study Setting—The Boston Medical Center, MA, USA Participants—This study included 1517 mother-child dyads recruited at birth from 1998–2012 and followed prospectively up to 9 years (median age: 6.2 years, range: 2–9 years). Main Outcomes and Measures—Child BMI z-score calculated according to U.S. reference data, OWO defined as BMI≥85th percentile for age and gender, and metabolic biomarkers (leptin, insulin, and adiponectin).
Author Manuscript
Results—An “L-shaped” relationship between maternal folate concentrations and child OWO was observed: the risk of OWO was higher in the lowest quartile (Q1) as compared to Q2–Q4 with an odds ratio (OR) of 1.45 (95% confidence interval [CI], 1.13 to 1.87). The highest risk of child OWO was found among children of obese mothers with low folate concentrations (OR, 3.05, 95%CI, 1.91 to 4.86) compared to children of normal weight mothers with folate concentrations in Q2–Q4 after accounting for multiple covariables. Among children of obese mothers, their risk of OWO was associated with 43% reduction (OR, 0.57, 95%CI, 0.34–0.95) if their mothers had folate concentrations in Q2–Q4 compared to Q1. Similar patterns were observed for child metabolic biomarkers.
Author Manuscript
Conclusions and Relevance—In this urban low-income prospective birth cohort, we demonstrated an L-shaped relationship 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 far exceeded the clinical definition of folate deficiency (
JAMA Pediatr. Author manuscript; available in PMC 2017 August 01. Published in final edited form as: JAMA Pediatr. 2016 August 01; 170(8): e160845. doi:10.1001/jamapediatrics.2016.0845.
Association of Maternal Prepregnancy BMI and Plasma Folate concentrations with Child Metabolic Health
Author Manuscript
Guoying Wang, MD PhD1, Frank B. Hu, MD PhD2, Kamila B. Mistry, PhD MPH3, Cuilin Zhang, MD PhD1,4, Fazheng Ren, PhD5, Yong Huo, MD6, David Paige, MD1, Tami Bartell, BS7, Xiumei Hong, MD PhD1, Deanna Caruso, MS1, Zhicheng Ji, BS8, Zhu Chen, PhD1, Yuelong Ji, MSPH1, Colleen Pearson, BA9, Hongkai Ji, PhD8, Barry Zuckerman, MD9, Tina L. Cheng, MD1,3, and Xiaobin Wang, MD MPH, ScD1,3 1Department
of Population, Family and Reproductive Health, Center on Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
2Departments
of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA 3Division
of General Pediatrics & Adolescent Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
4Division
of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
Author Manuscript
5Beijing
Advanced Innovation Center for Food Nutrition and Human Health, China Agriculture University, Beijing, China
6Department
of Cardiology, Peking University First Hospital, Beijing, China
7Stanley
Manne Children’s Research Institute, Ann & Robert H Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA
8Department
of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
#
Author Manuscript
Correspondence and reprint requests should be addressed to: Xiaobin Wang, MD, MPH, ScD, Zanvyl Krieger Professor, Director, Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, [email protected], Phone: 410-955-5824, Fax: 410-502-5831. Author contribution: Dr. X Wang is the principal investigator of the Boston Birth Cohort (the parent study), and has full access to all of the study data and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: G Wang, X Wang, Acquisition of data: Pearson, Chen, Y Ji, Zuckerman, G Wang, X Wang Analysis and interpretation of data: G Wang, Hong, Mistry, Paige, Cheng, Z Ji, H Ji, Hu, Zhang, Ren, Hou, X Wang Drafting of the manuscript: G Wang, Cheng, Bartell, X Wang Critical revision of the manuscript for important intellectual content: Hong, Pearson, Caruso, Paige, Z Ji, Zuckerman, Cheng, Mistry, Ren, Hou, Hu, Zhang, Bartell, X Wang Data management and statistical analysis: Hong, Z Ji, H Ji, Caruso, Pearson, G Wang, X Wang Administrative, technical, and/or material support: Chen, Y Ji, Caruso, Pearson Study supervision: X Wang Funding: X Wang Conflicts of interests: The authors have declared that no conflicting interests exist.
Wang et al.
Page 2
9Department
Author Manuscript
of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, USA
Abstract Importance—Previous reports have linked maternal prepregnancy obesity with low folate concentrations and child overweight or obesity (OWO) in separate studies. 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—We tested the hypotheses that maternal folate concentrations can significantly affect child metabolic health and that maternal sufficient folate concentrations can mitigate prepregnancy obesity-induced child metabolic risk.
Author Manuscript
Design—Prospective birth cohort study Setting—The Boston Medical Center, MA, USA Participants—This study included 1517 mother-child dyads recruited at birth from 1998–2012 and followed prospectively up to 9 years (median age: 6.2 years, range: 2–9 years). Main Outcomes and Measures—Child BMI z-score calculated according to U.S. reference data, OWO defined as BMI≥85th percentile for age and gender, and metabolic biomarkers (leptin, insulin, and adiponectin).
Author Manuscript
Results—An “L-shaped” relationship between maternal folate concentrations and child OWO was observed: the risk of OWO was higher in the lowest quartile (Q1) as compared to Q2–Q4 with an odds ratio (OR) of 1.45 (95% confidence interval [CI], 1.13 to 1.87). The highest risk of child OWO was found among children of obese mothers with low folate concentrations (OR, 3.05, 95%CI, 1.91 to 4.86) compared to children of normal weight mothers with folate concentrations in Q2–Q4 after accounting for multiple covariables. Among children of obese mothers, their risk of OWO was associated with 43% reduction (OR, 0.57, 95%CI, 0.34–0.95) if their mothers had folate concentrations in Q2–Q4 compared to Q1. Similar patterns were observed for child metabolic biomarkers.
Author Manuscript
Conclusions and Relevance—In this urban low-income prospective birth cohort, we demonstrated an L-shaped relationship 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 far exceeded the clinical definition of folate deficiency (
