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Original Investigation |

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

Guoying Wang, MD, PhD1; Frank B. Hu, MD, PhD2,3; Kamila B. Mistry, PhD, MPH4; Cuilin Zhang, MD, PhD1,5; Fazheng Ren, PhD6; Yong Huo, MD7; David Paige, MD1; Tami Bartell, BS8; Xiumei Hong, MD, PhD1; Deanna Caruso, MS1; Zhicheng Ji, BS9; Zhu Chen, PhD1; Yuelong Ji, MSPH1; Colleen Pearson, BA10; Hongkai Ji, PhD9; Barry Zuckerman, MD10; Tina L. Cheng, MD1,4; Xiaobin Wang, MD, MPH, ScD1,4
[+] 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
JAMA Pediatr. 2016;170(8):e160845. doi:10.1001/jamapediatrics.2016.0845.
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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.

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Figure 1.
Association Between Maternal Plasma Folate Concentrations and Offspring Body Mass Index (BMI) z Score and Probability of Overweight or Obesity (OWO) During Childhood in the Boston Birth Cohorta

A, The graph displays the crude association between maternal plasma folate concentration and offspring BMI z score. Owing to a small sample size, the curve is truncated at 35 ng/mL (mean BMI z score among children with maternal plasma folate concentration >35 ng/mL was 0.60; 95% CI, 0.22-0.98; n = 51). B, The graph displays the crude association between maternal plasma folate concentration and the probability of OWO. Owing to a small sample size, the curve is truncated at 35 ng/mL (the proportion of OWO among children with maternal folate >35 ng/mL was 37.3%; 95% CI, 24.1-51.9; n = 51). For both panels, the curves (95% CIs, indicated by thin black lines) were derived from smoothing plots (PROC LOESS). To convert folate to nanomoles per liter, multiply by 2.266. Body mass index is calculated as weight in kilograms divided by height in meters squared.

aThe Boston Birth Cohort uses a rolling enrollment; the study sample consists of children enrolled from 1998 to 2012 who have been followed up from birth up to the last visit recorded by electronic medical record.

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Figure 2.
Combined Effect of Maternal Plasma Folate Status and Maternal Prepregnancy Body Mass Index (BMI) Categories on Child’s BMI z Score and Proportion of Overweight or Obesity (OWO) in the Boston Birth Cohorta

A, The y-axis presents least square means and 95% CIs of child BMI z score, estimated from a generalized linear model with adjustment for maternal age, race/ethnicity, education, smoking, parity, perceived stress during pregnancy, diabetes, and plasma vitamin B12 concentration during pregnancy and infant’s gestational age category, birth weight, and breastfeeding status. There was no significant interaction between maternal folate status and prepregnancy obesity (P > .05). B, The y-axis presents adjusted probabilities and 95% CIs of child OWO, estimated from a logistic regression model with adjustment for the previously mentioned covariables. There was no significant interaction between maternal folate status and prepregnancy obesity (P > .05). Body mass index is calculated as weight in kilograms divided by height in meters squared.

aThe Boston Birth Cohort uses a rolling enrollment; the study sample consists of children enrolled from 1998 to 2012 who have been followed up from birth up to the last visit recorded by electronic medical record. The quartile (Q) 1 folate concentration range is 2.9-<9.0 ng/mL; Q2-Q4 folate concentration range, 9.0-81.9 ng/mL. Maternal prepregnancy BMI was categorized into 3 groups: normal weight, 18.5-24.9; overweight, 25-29.9; and obese, ≥30. To convert folate to nanomoles per liter, multiply by 2.266.

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