title: Low maternal vitamin B-12 status is associated with offspring insulin resistance regardless of antenatal micronutrient supplementation in rural Nepal.
abstract: Questions have been raised about potentially negative effects of antenatal folic acid use in populations with a high prevalence of vitamin B-12 deficiency. Our objective was to examine the association between maternal folate and vitamin B-12 status in pregnancy on offspring insulin resistance and examine whether the effects of maternal micronutrient supplementation varied by baseline maternal folate and/or vitamin B-12 status. Pregnant women were cluster randomized to receive daily supplements containing vitamin A alone or with folic acid, folic acid+iron, folic acid+iron+zinc, or a multiple micronutrient. In a subsample (n = 1132), micronutrient status biomarkers were analyzed at baseline and late pregnancy. Children born to the women who participated in the trial were visited at 6-8 y of age. Fasting plasma glucose and insulin were used to estimate insulin resistance using the homeostasis model assessment (HOMA-IR). Children whose mothers were deficient in vitamin B-12 (<148 pmol/L, 27%) during early pregnancy had a 26.7% increase in HOMA-IR (P = 0.02), but there was no association with maternal folate status. Among children born to women who were vitamin B-12 deficient at baseline, the percent difference in HOMA-IR compared to the control group was 15.1% (95% CI: -35.9, 106.4), 4.9% (-41.6, 88.5), 3.3% (-38.4, 73.5), and 18.1% (-29.0, 96.7) in the folic acid, folic acid-iron, folic acid-iron-zinc, and multiple micronutrient supplementation groups, respectively, none of which were significant. Maternal vitamin B-12 deficiency is associated with an elevated risk of insulin resistance, but supplementation with folic acid or other micronutrients led to no significant change in insulin resistance in school-aged offspring.
authors.affiliation: Program in International and Community Nutrition, University of California, Davis, CA, USA. pchristi@jhsph.edu
authors.forename: Christine P
authors.initials: CP
authors.lastname: Stewart
authors.forename: Parul
authors.initials: P
authors.lastname: Christian
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Schulze
authors.forename: Margia
authors.initials: M
authors.lastname: Arguello
authors.forename: Steven C
authors.initials: SC
authors.lastname: LeClerq
authors.forename: Subarna K
authors.initials: SK
authors.lastname: Khatry
authors.forename: Keith P
authors.initials: KP
authors.lastname: West
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000150:complications / Q000517:prevention & control; D002648:Child; D015331:Cohort Studies; D019587:Dietary Supplements / Q000009:adverse effects*; D005260:Female; D005492:Folic Acid / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D005494:Folic Acid Deficiency / Q000150:complications / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D007333:Insulin Resistance; D019266:Iron, Dietary / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D009390:Nepal / Q000453:epidemiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology / Q000503:physiopathology* / Q000517:prevention & control; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000209:etiology*; D015995:Prevalence; D012423:Rural Health; D014806:Vitamin B 12 Deficiency / Q000150:complications / Q000453:epidemiology / Q000503:physiopathology* / Q000517:prevention & control; D015032:Zinc / Q000009:adverse effects / Q000172:deficiency / Q000627:therapeutic use
chemical_list: D019266:Iron, Dietary; D005492:Folic Acid; D015032:Zinc