Multiple micronutrient supplements versus iron-folic acid supplements and maternal anemia outcomes: an iron dose analysis

Filomena Gomes, Rina Agustina, Robert E Black, Parul Christian, Kathryn G Dewey, Klaus Kraemer, Anuraj H Shankar, Emily R Smith, Andrew Thorne-Lyman, Alison Tumilowicz, Megan W Bourassa, Filomena Gomes, Rina Agustina, Robert E Black, Parul Christian, Kathryn G Dewey, Klaus Kraemer, Anuraj H Shankar, Emily R Smith, Andrew Thorne-Lyman, Alison Tumilowicz, Megan W Bourassa

Abstract

Antenatal multiple micronutrient supplements (MMS) are more effective than iron and folic acid (IFA) supplements in reducing adverse pregnancy outcomes. Questions remain, however, about the ability of MMS to prevent anemia as effectively as IFA, especially at a lower dose of daily iron and in areas of high anemia prevalence. Analyzing data from 11 trials from a recent Cochrane review, we compared MMS to IFA, delivering either 30 or 60 mg of iron, in sustaining hemoglobin and preventing third trimester anemia and iron deficiency anemia (IDA), accounting for daily iron dose, total supplemental iron intake, and baseline prevalence of anemia. There were no differences between MMS and IFA in third trimester hemoglobin concentration or risks of anemia or IDA by iron dose or total supplemental iron consumed. MMS providing 30 mg of iron was comparable to IFA with 60 mg of iron: mean hemoglobin difference of -0.26 g/L (95% CI: -1.41 to 0.89), risk ratios of 0.99 (95% CI: 0.92-1.07) for anemia, and 1.31 (95% CI: 0.66-2.60) for IDA. Baseline prevalence of anemia did not explain heterogeneity in findings. Compared to IFA, MMS results in comparable hemoglobin concentration and protection against anemia during pregnancy, independently of iron dose.

Keywords: anemia; iron; iron deficiency anemia; micronutrient supplements; pregnancy.

© 2022 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.

References

    1. Black, R.E. , Victora C.G., Walker S.P., et al. 2013. Maternal and child undernutrition and overweight in low‐income and middle‐income countries. Lancet 382: 427–451.
    1. Gernand, A.D. , Schulze K.J., Stewart C.P., et al. 2016. Micronutrient deficiencies in pregnancy worldwide: health effects and prevention. Nat. Rev. Endocrinol. 12: 274–289.
    1. Bourassa, M.W. , Osendarp S.J.M.M., Adu‐Afarwuah S., et al. 2019. Review of the evidence regarding the use of antenatal multiple micronutrient supplementation in low‐ and middle‐income countries. Ann. N.Y. Acad. Sci. 1444: 6–21.
    1. Keats, E.C. , Haider B.A., Tam E., et al. 2019. Multiple‐micronutrient supplementation for women during pregnancy. Cochrane Database Syst. Rev. 3: CD004905.
    1. Smith, E.R. , Shankar A.H., Wu L.S.‐F., et al. 2017. Modifiers of the effect of maternal multiple micronutrient supplementation on stillbirth, birth outcomes, and infant mortality: a meta‐analysis of individual patient data from 17 randomised trials in low‐income and middle‐income countries. Lancet Glob. Health 5: e1090–e1100.
    1. Engle‐Stone, R. , Kumordzie S., Meinzen‐Dick L., et al. 2019. Replacing iron‐folic acid with multiple micronutrient supplements among pregnant women in Bangladesh and Burkina Fasso: single‐year assessment of costs, impacts, and cost‐effectiveness. Ann. N.Y. Acad. Sci. 1444: 35–51. 10.1111/nyas.14132. Epub 2019 May 27. PMID: 31134641; PMCID: PMC6771790
    1. Gernand, A.D. 2019. The upper level: examining the risk of excess micronutrient intake in pregnancy from antenatal supplements. Ann. N.Y. Acad. Sci. 1444: 22–34.
    1. World Health Organization . 2020. WHO Antenatal Care Recommendations for a Positive Pregnancy Experience. Nutritional Interventions Update: Multiple Micronutrient Supplements During Pregnancy. Geneva: WHO.
    1. World Health Organization . 2016. World Health Organization Recommendation on Antenatal Care for Positive Pregnancy Experience. Geneva: WHO.
    1. World Health Organization, UNICEF & United Nations University . 1999. Composition of a multi‐micronutrient supplement to be used in pilot programmes among pregnant women in developing countries. New York: WHO.
    1. The New York Academy of Sciences . 2018. Accessed October 1, 2021. .
    1. Ramakrishnan, U. , Gonzalez‐Cossio T., Neufeld L.M., et al. 2003. Multiple micronutrient supplementation during pregnancy does not lead to greater infant birth size than does iron‐only supplementation: a randomized controlled trial in a semirural community in Mexico. Am. J. Clin. Nutr. 77: 720–725.
    1. Ramakrishnan, U. , Neufeld L.M., González‐Cossío T., et al. 2004. Multiple micronutrient supplements during pregnancy do not reduce anemia or improve iron status compared to iron‐only supplements in semirural Mexico. J. Nutr. 134: 898–903.
    1. Brough, L. , Rees G.A., Crawford M.A., et al. 2010. Effect of multiple‐micronutrient supplementation on maternal nutrient status, infant birth weight and gestational age at birth in a low‐income, multi‐ethnic population. Br. J. Nutr. 104: 437–445.
    1. Ashorn, P. , Alho L., Ashorn U., et al. 2015. Supplementation of maternal diets during pregnancy and for 6 months postpartum and infant diets thereafter with small‐quantity lipid‐based nutrient supplements does not promote child growth by 18 months of age in rural Malawi: a randomized controlled trial. J. Nutr. 145: 1345–1353.
    1. Jorgensen, J.M. , Ashorn P., Ashorn U., et al. 2018. Effects of lipid‐based nutrient supplements or multiple micronutrient supplements compared with iron and folic acid supplements during pregnancy on maternal haemoglobin and iron status. Matern. Child Nutr. 14: e12640.
    1. Adu‐Afarwuah, S. , Lartey A., Okronipa H., et al. 2015. Lipid‐based nutrient supplement increases the birth size of infants of primiparous women in Ghana. Am. J. Clin. Nutr. 101: 835–846.
    1. Adu‐Afarwuah, S. , Lartey A., Okronipa H., et al. 2017. Impact of small‐quantity lipid‐based nutrient supplement on hemoglobin, iron status and biomarkers of inflammation in pregnant Ghanaian women. Matern. Child Nutr. 13: e12262.
    1. Christian, P. , Khatry S.K., Katz J., et al. 2003. Effects of alternative maternal micronutrient supplements. Br. Med. J. 326: 571–577.
    1. Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT) Study Group . 2008. Effect of maternal multiple micronutrient supplementation on fetal loss and infant death in Indonesia: a double‐blind cluster‐randomised trial. Lancet 371: 215–227.
    1. Sunawang, B. Utomo, Hidayat A., et al. 2009. Preventing low birthweight through maternal multiple micronutrient supplementation: a cluster‐randomized, controlled trial in Indramayu, West Java. Food Nutr. Bull. 30: S488–S495.
    1. West, K.P., Jr. , Shamim A.A., Mehra S., et al. 2014. Effect of maternal multiple micronutrient vs iron–folic acid supplementation on infant mortality and adverse birth outcomes in rural Bangladesh: the JiVitA‐3 randomized trial. JAMA 312: 2649–2658.
    1. Zeng, L. , Dibley M.J., Cheng Y., et al. 2008. Impact of micronutrient supplementation during pregnancy on birth weight, duration of gestation, and perinatal mortality in rural western China: double blind cluster randomised controlled trial. Br. Med. J. 337: 1211–1215.
    1. DerSimonian, R. & Laird N.. 1986. Meta‐analysis in clinical trials. Control. Clin. Trials 7: 177–188.
    1. Higgins, J. , Eldridge S. & Li T.. 2021. Approximate analyses of cluster‐randomized trials for a meta‐analysis: effective sample sizes. In Cochrane Handbook for Systematic Reviews Version 6.2.
    1. Higgins, J.P. , Eldridge S. & Li T.. 2021. How to include multiple groups from one study. In Cochrane Handbook for Systematic Reviews Version 6.2.
    1. Liu, J. , Mei Z., Ye R., et al. 2013. Micronutrient supplementation and pregnancy outcomes: double‐blind randomized controlled trial in China. JAMA Intern. Med. 173: 276–282.
    1. Johnson, W. , Darboe M.K., Prentice A.M., et al. 2017. Association of prenatal lipid‐based nutritional supplementation with fetal growth in rural Gambia. Matern. Child Nutr. 13: e12367.
    1. Moore, S.E. , Fulford A.J.C., Sosseh F., et al. 2019. Thymic size is increased by infancy, but not pregnancy, nutritional supplementation in rural Gambian children: a randomized clinical trial. BMC Med. 17: 38.
    1. Tofail, F. , Persson L.Å., Arifeen S.E., et al. 2008. Effects of prenatal food and micronutrient supplementation on infant development: a randomized trial from the Maternal and Infant Nutrition Interventions, Matlab (MINIMat) study. Am. J. Clin. Nutr. 87: 704–711.
    1. Persson, L.Å. , Arifeen S., Ekström E.‐C., et al. 2012. Effects of prenatal micronutrient and early food supplementation on maternal hemoglobin, birth weight, and infant mortality among children in Bangladesh: the MINIMat randomized trial. JAMA 307: 2050–2059.
    1. Hanieh, S. , Ha T.T., Simpson J.A., et al. 2013. The effect of intermittent antenatal iron supplementation on maternal and infant outcomes in rural Viet Nam: a cluster randomised trial. PLoS Med. 10: e1001470.
    1. Bhutta, Z.A. , Rizvi A., Raza F., et al. 2009. A comparative evaluation of multiple micronutrient and iron‐folic acid supplementation during pregnancy in Pakistan: impact on pregnancy outcomes. Food Nutr. Bull. 30: S496–S505.
    1. Fawzi, W.W. , Msamanga G.I., Urassa W., et al. 2007. Vitamins and perinatal outcomes among HIV‐negative women in Tanzania. N. Engl. J. Med. 356: 1423–1431.
    1. Kaestel, P. , Michaelsen K.F., Aaby P., et al. 2005. Effects of prenatal multimicronutrient supplements on birth weight and perinatal mortality: a randomised, controlled trial in Guinea‐Bissau. Eur. J. Clin. Nutr. 59: 1081–1089.
    1. Zagre, N.M. , Desplats G., Adou P., et al. 2007. Prenatal multiple micronutrient supplementation has greater impact on birthweight than supplementation with iron and folic acid. Food Nutr. Bull. 28: 317–327.
    1. Friis, H. , Gomo E., Nyazema N., et al. 2004. Effect of multimicronutrient supplementation on gestational length and birth size: a randomized, placebo‐controlled, double‐blind effectiveness trial in Zimbabwe. Am. J. Clin. Nutr. 80: 178–184.
    1. Mei, Z. , Serdula M.K., Liu J., et al. 2014. Iron‐containing micronutrient supplementation of Chinese women with no or mild anemia during pregnancy improved iron status but did not affect perinatal anemia. J. Nutr. 144: 943–948.
    1. Roberfroid, D. , Huybregts L., Lanou H., et al. 2008. Effects of maternal multiple micronutrient supplementation on fetal growth: a double‐blind randomized controlled trial in rural Burkina Faso. Am. J. Clin. Nutr. 88: 1330–1340.
    1. Osrin, D. , Vaidya A., Shrestha Y., et al. 2005. Effects of antenatal multiple micronutrient supplementation on birthweight and gestational duration in Nepal: double‐blind, randomised controlled trial. Lancet 365: 955–962.
    1. Milman, N. , Bergholt T., Eriksen L., et al. 2005. Iron prophylaxis during pregnancy – how much iron is needed? A randomized dose–response study of 20–80 mg ferrous iron daily in pregnant women. Acta Obstet. Gynecol. Scand. 84: 238–247.
    1. Zhou, S.J. , Gibson R.A., Crowther C.A., et al. 2009. Should we lower the dose of iron when treating anaemia in pregnancy? A randomized dose–response trial. Eur. J. Clin. Nutr. 63: 183–190.
    1. Oregon State University . 2016. Pregnancy and lactation. Accessed April 8, 2021. .
    1. Behere, R.V. , Deshmukh A.S., Otiv S., et al. 2021. Maternal vitamin B12 status during pregnancy and its association with outcomes of pregnancy and health of the offspring: a systematic review and implications for policy in India. Front. Endocrinol. 12: 288.
    1. Suharno, D. , West C.E., Muhilal, et al. 1993. Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia. Lancet 342: 1325–1328.
    1. Stoffel, N.U. , von Siebenthal H.K., Moretti D., et al. 2020. Oral iron supplementation in iron‐deficient women: how much and how often? Mol. Aspects Med. 75: 100865.
    1. Karakochuk, C.D. , Whitfield K.C., Barr S.I., et al. 2015. Genetic hemoglobin disorders rather than iron deficiency are a major predictor of hemoglobin concentration in women of reproductive age in rural prey Veng, Cambodia. J. Nutr. 145: 134–142.
    1. Fischer, J.A.J. , Pei L.X., Goldfarb D.M., et al. 2020. Is untargeted iron supplementation harmful when iron deficiency is not the major cause of anaemia? Study protocol for a double‐blind, randomised controlled trial among non‐pregnant Cambodian women. BMJ Open 10: e037232.
    1. Brannon, P.M. , Stover P.J. & Taylor C.L.. 2017. Integrating themes, evidence gaps, and research needs identified by workshop on iron screening and supplementation in iron‐replete pregnant women and young children. Am. J. Clin. Nutr. 106: 1703S–1712S.
    1. Zhang, C. & Rawal S.. 2017. Dietary iron intake, iron status, and gestational diabetes. Am. J. Clin. Nutr. 106: 1672S–1680S.
    1. Lu, Z.M. , Goldenberg R.L., Cliver S.P., et al. 1991. The relationship between maternal hematocrit and pregnancy outcome. Obstet. Gynecol. 77: 190–194.
    1. Oaks, B.M. , Jorgensen J.M., Baldiviez L.M., et al. 2019. Prenatal iron deficiency and replete iron status are associated with adverse birth outcomes, but associations differ in Ghana and Malawi. J. Nutr. 149: 513–521.
    1. Dewey, K.G. & Oaks B.M.. 2017. U‐shaped curve for risk associated with maternal hemoglobin, iron status, or iron supplementation. Am. J. Clin. Nutr. 106: 1694S–1702S.
    1. Paganini, D. & Zimmermann M.B.. 2017. The effects of iron fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review. Am. J. Clin. Nutr. 106: 1688S–1693S.
    1. Lönnerdal, B. 2017. Excess iron intake as a factor in growth, infections, and development of infants and young children. Am. J. Clin. Nutr. 106: 1681S–1687S.
    1. Zhang, X. , Wu M., Zhong C., et al. 2021. Association between maternal plasma ferritin concentration, iron supplement use, and the risk of gestational diabetes: a prospective cohort study. Am. J. Clin. Nutr. 114: 1100–1106.
    1. Merrill, R.D. , Shamim A.A., Ali H., et al. 2012. High prevalence of anemia with lack of iron deficiency among women in rural Bangladesh: a role for thalassemia and iron in groundwater. Asia Pac. J. Clin. Nutr. 21: 416–424.
    1. World Health Organization . 2019. Accessed January 9, 2021. .
    1. Ohuma, E.O. , Young M.F., Martorell R., et al. 2020. International values for haemoglobin distributions in healthy pregnant women. EClinicalMedicine 29‐30: 100660.

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