Effect of prenatal multiple micronutrient supplementation vs iron and folic acid supplementation on size at birth and subsequent growth through 24 months of age: a systematic review and meta-analysis

Filomena Gomes, Healthy Mothers Healthy Babies, The Micronutrient Forum, Washington, DC, USA; NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal. Electronic address: filomena.gomes@micronutrientforum.org.
Seth Adu-Afarwuah, Department of Nutrition and Food Science, University of Ghana, Legon, Accra, Ghana.
Rina Agustina, Department of Nutrition, Faculty of Medicine, Universitas Indonesia - Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; Human Nutrition Research Center, Indonesian Medical Education and Research Institute (HNRC-IMERI), Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Hasmot Ali, The JiVitA Project, Johns Hopkins University in Bangladesh, Gaibandha, Bangladesh.
Amrita Arcot, Healthy Mothers Healthy Babies, The Micronutrient Forum, Washington, DC, USA.
Shams Arifeen, International Centre for Diarrhoeal Diseases Research Bangladesh (ICDDR,B), Dhaka, Bangladesh.
Charles D. Arnold, Department of Nutrition and Institute for Global Nutrition, University of California-Davis, Davis, CA, USA.
Robert E. Black, Institute for International Programs, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Parul Christian, Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Kathryn G. Dewey, Department of Nutrition and Institute for Global Nutrition, University of California-Davis, Davis, CA, USA.
Wafaie Fawzi, Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Lotta Hallamaa, Center for Child, Adolescent, and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
John Hoddinott, Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA.
Mihaela C. Kissell, Healthy Mothers Healthy Babies, The Micronutrient Forum, Washington, DC, USA.
Klaus Kraemer, Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Sight and Life Foundation, Basel, Switzerland.
Carl Lachat, Department of Food Technology, Safety and Health, Ghent University, Ghent, Belgium.
Sophie E. Moore, Department of Women & Children's Health, King's College London, London, UK; MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, The Gambia.
Kenneth Maleta, Kamuzu University of Health Sciences, Blantyre, Malawi.
Carolina Pereira, Healthy Mothers Healthy Babies, The Micronutrient Forum, Washington, DC, USA.
Dominique Roberfroid, Department of Medicine, Namur University, Namur, Belgium.
Saijuddin Shaikh, Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; JiVitA Project, Rangpur, Bangladesh.
Anuraj H. Shankar, Oxford University Clinical Research Unit-Indonesia, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Emily R. Smith, Department of Global Health, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
Subarkah, Center for Health Research, School of Public Health, University of Indonesia, Depok, Indonesia.
Sunawang, Center for Health Research, School of Public Health, University of Indonesia, Depok, Indonesia.
Dongqing Wang, Department of Global and Community Health, College of Public Health, George Mason University, Fairfax, Virginia, USA.
Lee S-F Wu, Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Martin N. Mwangi, Healthy Mothers Healthy Babies, The Micronutrient Forum, Washington, DC, USA; Global Nutrition and Health Department, Wageningen University & Research, Wageningen, The Netherlands. Electronic address: martin.mwangi@micronutrientforum.org.

Document Type

Journal Article

Publication Date

4-28-2025

Journal

The American journal of clinical nutrition

DOI

10.1016/j.ajcnut.2025.04.022

Keywords

birth size; infant growth; length; micronutrient supplements; pregnancy

Abstract

BACKGROUND: Prenatal multiple micronutrient supplements (MMS), in comparison to iron and folic acid (IFA) supplements, improve pregnancy outcomes, but less is known about their effect on infant growth. OBJECTIVE: We conducted a systematic review of trials comparing maternal MMS to IFA and assessed the effect on infants' anthropometric outcomes at birth, three, six, 12, 18, and 24 months of age. METHODS: We included trials from a Cochrane review and new studies identified through systematic literature searches in three databases. We calculated the pooled effect estimates with 95% confidence intervals (CI) using a generic inverse variance method, with fixed (primary analysis) and random effects, and assessed subgroup differences. RESULTS: The 19 included trials showed that MMS, compared to IFA, led to significantly greater: length and weight from birth to six months, head circumference (HC) from birth to 12 months, and mid-upper arm circumference (MUAC) through three months. Infants born to pregnant women taking MMS were longer at birth (mean difference: 0.05 cm (95% CI 0.02, 0.08)), and had higher length-for-age Z-score at birth (0.09 (0.06, 0.12)), three (0.09, (0.06, 0.12)) and six-months (0.04, (0.01, 0.07)) of age, but not thereafter. MMS resulted in significantly higher weight-for-age Z-score and HC-for-age Z-score until six months, and higher weight-for-length Z-score and MUAC-for-age- Z-score until three months. MMS reduced the risk of stunting (Risk Ratio (RR) 0.86, 95% CI 0.82-0.91), underweight (0.86 (0.81- 0.90)), small HC (0.84 (0.79, 0.90)), and low MUAC (0.90 (0.82, 0.99)) at three months, and wasting (0.90 (0.85, 0.96)) at birth. For some outcomes, effects were greater when MMS continued postpartum and in settings with higher prevalence of low birthweight. CONCLUSIONS: Prenatal MMS improved size at birth and subsequent infant growth through six months of age, but not thereafter. Results strengthen the evidence on MMS benefits beyond birth outcomes. PROSPERO REGISTRATION NUMBER: CRD42024551864.

Department

Global Health

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