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Cited by 86Folate and B Vitamins ResearchBirth, Development, and HealthObesity, Physical Activity, Diet

Association between Maternal Prepregnancy Body Mass Index and Plasma Folate Concentrations with Child Metabolic Health

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Wang, Guoying, Hu, Frank B., Mistry, Kamila B., Zhang, Cuilin, Ren, Fazheng, Huo, Yong, Paige, David, Bartell, Tami +10 more·2016·JAMA Pediatrics
DOI 10.1001/jamapediatrics.2016.0845PMC PMC5147730
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Abstract

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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  • Children of overweight or obese mothers with adequate folate plasma concentrations showed a 43% reduction in obesity risk.

    “The children of overweight or obese mothers with adequate folate plasma concentrations showed a 43% reduction in obesity risk.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [114]

    The Results section reports a 43% lower risk of child overweight or obesity (OWO) among children of obese mothers with adequate folate concentrations, compared with children of obese mothers with low folate concentrations (OR 0.57). The claim extends this finding to overweight mothers and describes the outcome as obesity alone; the cited result specifies obese mothers and the combined OWO outcome. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • A nine-year prospective study in Boston involving 1517 mother-son couples of different ethnicities has shown that folic acid deficiency was involved in a transgenerational transition of obesity and that its supplementation improved the offspring's metabolic parameters.

    “A nine-year prospective study carried out in Boston involving 1517 mother–son couples of different ethnicities has shown how folic acid deficiency was involved in a transgenerational transition of obesity and how its supplementation improved the offspring’s metabolic parameters.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [114]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Low maternal plasma folate is linked to insulin and leptin concentration and to a reduction in the leptin/adiponectin ratio.

    “Low maternal plasma folate is linked to insulin and leptin concentration and to a reduction in the leptin/adiponectin ratio.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [114]

    The Results section reports that low maternal folate was associated with higher insulin and leptin concentrations in offspring. It reports a reduction in the adiponectin/leptin ratio, however, not the leptin/adiponectin ratio stated in the claim. (LLM, conf=0.94)

    Experimental — accuracy not yet measured

  • Adequate maternal folate status protects against neural tube defects and supports proper brain development, while deficiency is associated with persistent alterations in offspring neurodevelopment and an increased risk of obesity and insulin resistance later in life.

    “Adequate maternal folate status protects against neural tube defects and supports proper brain development, while deficiency is associated with persistent alterations in offspring neurodevelopment and an increased risk of obesity and insulin resistance later in life [112,113,114].”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [114]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • In that study, maternal folic acid concentration was inversely proportional to the Z-score of the BMI of the baby, with a stronger association when mothers were overweight or obese.

    “Respectively, 29% and 25% of women were overweight or obese before pregnancy and showed lower folate concentration compared to normal-weight women; 38% of children were overweight at the age of 2–9 years, indicating that maternal folic acid concentration is inversely proportional to the Z-score (number of standard deviation) of the BMI of the baby.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [114]

    The Results report an inverse association between maternal plasma folate and child BMI z-score, but explicitly describe it as nonlinear, not proportional. They also report a combined effect of low folate and maternal obesity, but no significant interaction; the claim that the folate–BMI association was stronger among overweight or obese mothers is therefore not established. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Authors
Wang, G., Hu, F. B., Mistry, K. B., Zhang, C., Ren, F., Huo, Y., Paige, D., Bartell, T., Hong, X., Caruso, D., Ji, Z., Chen, Z., Ji, Y., Pearson, C., Ji, H., Zuckerman, B., Cheng, T. L., & Wang, X.
Affiliations
  • Johns Hopkins University (US)
  • Brigham and Women's Hospital (US)
  • National Institutes of Health (US)
  • Beijing Advanced Innovation Center for Food Nutrition and Human Health (CN)
  • Peking University First Hospital (CN)
  • Lurie Children's Hospital (US)
  • Boston University (US)
Corresponding author
Wang, Xiaobin
ORCID
Venue
JAMA Pediatrics
Publisher
American Medical Association (AMA)
Published
2016-08-01
Volume
170
Issue
8
Pages
e160845
ISSN
  • 1072-4710 (ISSN-L)
  • 2168-6203
DOI
10.1001/jamapediatrics.2016.0845
PMC
PMC5147730
OpenAlex
W2436994948
Cited by
86
References
41
Citations by year
2026: 5 · 2025: 4 · 2024: 6 · 2023: 8 · 2022: 13 · 2021: 8 · 2020: 11 · 2019: 12 · 2018: 11 · 2017: 6 · 2016: 2
FWCI
11.00
Type
journal article
Language
en
Open access
Locations
  • Archives of Pediatrics and Adolescent Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Allergy and Infectious Diseases (U01AI090727, R21AI079872)
  • National Institute of Environmental Health Sciences (R21ES011666)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R21HD066471, R01HD086013, R01HD041702)
Topics
  • Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Obesity, Physical Activity, Diet
Keywords
childhood obesity, leptin, insulin, adiponectin, L-shaped association, maternal obesity, birth cohort, metabolic biomarkers, prenatal nutrition, Boston Medical Center, Boston, low-income mothers
MeSH terms
Adult, Boston, Child, Child, Preschool, Female, Folic Acid, Humans, Insulin, Male, Metabolic Diseases, Obesity, Pregnancy, Pregnancy Complications, Prenatal Exposure Delayed Effects, Prospective Studies, Vitamin B 12, Biomarkers, Body Mass Index, Preconception Care, Leptin, Overweight, Pediatric Obesity

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