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



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.



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.



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).



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.



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.
Department of Population, Family, and Reproductive Health, Center on Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
Guoying
G
Wang
Departments of Nutrition and Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts3Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Frank B
FB
Hu
Division of General Pediatrics and Adolescent Medicine, Department of Pediatrics, Johns Hopkins, University School of Medicine, Baltimore, Maryland.
Kamila B
KB
Mistry
Department of Population, Family, and Reproductive Health, Center on Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland5Division of Intramural Population Health Research, Eunice Kennedy Shriver N.
Cuilin
C
Zhang
Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agriculture University, Beijing, China.
Fazheng
F
Ren
Department of Cardiology, Peking University First Hospital, Beijing, China.
Yong
Y
Huo
Department of Population, Family, and Reproductive Health, Center on Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
David
D
Paige
Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
Tami
T
Bartell
Department of Population, Family, and Reproductive Health, Center on Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
Xiumei
X
Hong
Department of Population, Family, and Reproductive Health, Center on Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
Deanna
D
Caruso
Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
Zhicheng
Z
Ji
Department of Population, Family, and Reproductive Health, Center on Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
Zhu
Z
Chen
Department of Population, Family, and Reproductive Health, Center on Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
Yuelong
Y
Ji
Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts.
Colleen
C
Pearson
Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
Hongkai
H
Ji
Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts.
Barry
B
Zuckerman
Department of Population, Family, and Reproductive Health, Center on Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland4Division of General Pediatrics and Adolescent Medicine, Department of Pedia.
Tina L
TL
Cheng
Department of Population, Family, and Reproductive Health, Center on Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland4Division of General Pediatrics and Adolescent Medicine, Department of Pedia.
Xiaobin
X
Wang
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D015992:Body Mass Index; D001900:Boston; D002648:Child; D002675:Child, Preschool; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000209:etiology*; D009765:Obesity / Q000097:blood; D050177:Overweight / Q000097:blood*; D063766:Pediatric Obesity / Q000097:blood / Q000209:etiology; D016742:Preconception Care; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood; D011297:Prenatal Exposure Delayed Effects / Q000097:blood; D011446:Prospective Studies; D014805:Vitamin B 12 / Q000378:metabolism
D015415:Biomarkers; D007328:Insulin; D020738:Leptin; D005492:Folic Acid; D014805:Vitamin B 12