Newborn micronutrient status biomarkers in a cluster-randomized trial of antenatal multiple micronutrient compared with iron folic acid supplementation in rural Bangladesh

Kerry J Schulze, Alison D Gernand, Afreen Zaman Khan, Lee S-F Wu, Sucheta Mehra, Saijuddin Shaikh, Hasmot Ali, Abu Ahmed Shamim, Pongtorn Sungpuag, Emorn Udomkesmalee, Alain B Labrique, Keith P West, Parul Christian, Kerry J Schulze, Alison D Gernand, Afreen Zaman Khan, Lee S-F Wu, Sucheta Mehra, Saijuddin Shaikh, Hasmot Ali, Abu Ahmed Shamim, Pongtorn Sungpuag, Emorn Udomkesmalee, Alain B Labrique, Keith P West, Parul Christian

Abstract

Background: Daily antenatal multiple micronutrient (MM) compared with iron folic acid (IFA) supplementation from early pregnancy improved birth outcomes and maternal micronutrient status in rural Bangladesh, but effects on newborn status are unknown.

Objective: We examined cord blood micronutrient biomarkers in relation to antenatal MM and IFA supplementation and maternal gestational micronutrient status in rural Bangladeshi newborns.

Design: In a double-blinded, cluster-randomized trial of antenatal IFA or MM (with the same IFA content), we analyzed cord blood plasma from 333 singleton births, and corresponding maternal plasma at 32.5 ± 2.6 wk of gestation, for ferritin (iron stores), folate, cobalamin (vitamin B-12), retinol (vitamin A), 25-hydroxyvitamin D [25(OH)D, vitamin D status], α-tocopherol (vitamin E), zinc, thyroglobulin, and free thyroxine (iodine status). Intervention effects and associations were determined using linear regression, exploring maternal status as a mediator of intervention effects on cord biomarkers.

Results: The MM intervention increased cord ferritin (mean: +12.4%; 95% CI: 1.3, 24.6%), 25(OH)D (mean: +14.7%; 95% CI: 4.8, 25.6%), and zinc (mean: +5.8%; 95% CI: 1.0, 10.8%). Cord folate (mean: +26.8%; 95% CI: 19.6, 34.5%), cobalamin (mean: +31.3%; 95% CI: 24.6, 38.3%), 25(OH)D (mean: +26.7%; 95% CI: 23.2, 30.3%), α-tocopherol (mean: +8.7%; 95% CI: 3.6, 13.7%), zinc (mean: +2.3%; 95% CI: 0.5, 4.2%), thyroglobulin (mean: +20.1%; 95% CI: 9.0, 32.2%) and thyroxine (mean: +1.5%; 95% CI: 0.0, 3.0%) increased per 1-SD increment in maternal status (all P < 0.05); ferritin and retinol changed by +2.0%; 95% CI: -8.9, 14.3%; P = 0.72; and +3.5%; 95% CI: -0.4, 7.3%; P = 0.07, respectively. Ferritin, folate, cobalamin, zinc, and thyroglobulin averaged 1.57-6.75 times higher and retinol, α-tocopherol, and 25(OH)D 0.30-0.84 times lower in cord than maternal plasma, suggesting preferential maternal-fetal transfer of iron, folate, cobalamin, and zinc; limited transfer of fat-soluble vitamins; and high fetal iodine demand.

Conclusions: Antenatal MM supplementation increased newborn ferritin, 25(OH)D, and zinc, while maternal and newborn folate, vitamins B-12, D, and E, zinc, and iodine biomarkers were positively related. Despite limited effects of MM, better maternal micronutrient status was associated with improved micronutrient status of Bangladeshi newborns. This trial was registered at clinicaltrials.gov as NCT00860470.

Keywords: Bangladesh; cord blood; micronutrients; newborn; pregnancy.

Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.

Figures

FIGURE 1
FIGURE 1
Associations of cord blood micronutrient status biomarkers with maternal micronutrient biomarkers assessed at 32 wk of gestation among mother–newborn pairs in rural Bangladesh in the context of a trial of antenatal IFA and MM supplementation. Micronutrient status biomarkers include ferritin (A), folate (B), vitamin B-12 (C), retinol (D), 25(OH)D (E), α-tocopherol (F), zinc (G), thyroglobulin (H), and free thyroxine (I). Scatterplots and best fit lines are shown by intervention group such that open circles and dashed lines denote the IFA group and solid lines and closed circles denote the MM group. The gray line that diagonally crosses each image represents where maternal and newborn biomarker concentrations are the same. IFA, iron folic acid; MM, multiple micronutrients; 25(OH)D, 25-hydroxyvitamin D.

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