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

Filomena Gomes¹, Seth Adu-Afarwuah², Rina Agustina³, Hasmot Ali⁴, Amrita Arcot⁵, Shams Arifeen⁶, Charles D Arnold⁷, Robert E Black⁸, Parul Christian⁹, Kathryn G Dewey⁷, Wafaie W Fawzi¹⁰, Lotta Hallamaa¹¹, John Hoddinott¹², Mihaela C Kissell⁵, Klaus Kraemer¹³, Carl Lachat¹⁴, Sophie E Moore¹⁵, Kenneth Maleta¹⁶, Carolina Pereira⁵, Dominique Roberfroid¹⁷, Saijuddin Shaikh¹⁸, Anuraj H Shankar¹⁹, Emily R Smith²⁰, Inan Subarkah²¹, Rahardjo Sunawang²¹, Dongqing Wang²², Lee S-F Wu⁹, Martin N Mwangi²³

Affiliations

¹ Healthy Mothers Healthy Babies, The Micronutrient Forum, Washington, DC, United States; NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal. Electronic address: filomena.gomes@micronutrientforum.org.
² Department of Nutrition and Food Science, University of Ghana, Legon, Accra, Ghana.
³ 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.
⁴ The JiVitA Project, Johns Hopkins University in Bangladesh, Gaibandha, Bangladesh.
⁵ Healthy Mothers Healthy Babies, The Micronutrient Forum, Washington, DC, United States.
⁶ International Centre for Diarrhoeal Diseases Research Bangladesh (ICDDR,B), Dhaka, Bangladesh.
⁷ Department of Nutrition and Institute for Global Nutrition, University of California-Davis, Davis, CA, United States.
⁸ Institute for International Programs, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
⁹ Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
¹⁰ Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
¹¹ Center for Child, Adolescent, and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
¹² Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.
¹³ Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States; Sight and Life Foundation, Basel, Switzerland.
¹⁴ Department of Food Technology, Safety and Health, Ghent University, Ghent, Belgium.
¹⁵ Department of Women & Children's Health, King's College London, London, United Kingdom; MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, The Gambia.
¹⁶ Kamuzu University of Health Sciences, Blantyre, Malawi.
¹⁷ Department of Medicine, Namur University, Namur, Belgium.
¹⁸ Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States; JiVitA Project, Rangpur, Bangladesh.
¹⁹ Oxford University Clinical Research Unit-Indonesia, Jakarta, Indonesia; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
²⁰ Department of Global Health, Milken Institute School of Public Health, The George Washington University, Washington, DC, United States.
²¹ Center for Health Research, School of Public Health, University of Indonesia, Depok, Indonesia.
²² Department of Global and Community Health, College of Public Health, George Mason University, Fairfax, VA, United States.
²³ Healthy Mothers Healthy Babies, The Micronutrient Forum, Washington, DC, United States; Global Nutrition and Health Department, Wageningen University & Research, Wageningen, The Netherlands. Electronic address: martin.mwangi@micronutrientforum.org.

PMID: 40306386
PMCID: PMC12308086
DOI: 10.1016/j.ajcnut.2025.04.022

Meta-Analysis

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

Filomena Gomes et al. Am J Clin Nutr. 2025 Jul.

. 2025 Jul;122(1):185-195.

doi: 10.1016/j.ajcnut.2025.04.022. Epub 2025 Apr 28.

Authors

Affiliations

¹ Healthy Mothers Healthy Babies, The Micronutrient Forum, Washington, DC, United States; NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal. Electronic address: filomena.gomes@micronutrientforum.org.
² Department of Nutrition and Food Science, University of Ghana, Legon, Accra, Ghana.
³ 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.
⁴ The JiVitA Project, Johns Hopkins University in Bangladesh, Gaibandha, Bangladesh.
⁵ Healthy Mothers Healthy Babies, The Micronutrient Forum, Washington, DC, United States.
⁶ International Centre for Diarrhoeal Diseases Research Bangladesh (ICDDR,B), Dhaka, Bangladesh.
⁷ Department of Nutrition and Institute for Global Nutrition, University of California-Davis, Davis, CA, United States.
⁸ Institute for International Programs, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
⁹ Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
¹⁰ Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
¹¹ Center for Child, Adolescent, and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
¹² Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.
¹³ Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States; Sight and Life Foundation, Basel, Switzerland.
¹⁴ Department of Food Technology, Safety and Health, Ghent University, Ghent, Belgium.
¹⁵ Department of Women & Children's Health, King's College London, London, United Kingdom; MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, The Gambia.
¹⁶ Kamuzu University of Health Sciences, Blantyre, Malawi.
¹⁷ Department of Medicine, Namur University, Namur, Belgium.
¹⁸ Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States; JiVitA Project, Rangpur, Bangladesh.
¹⁹ Oxford University Clinical Research Unit-Indonesia, Jakarta, Indonesia; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
²⁰ Department of Global Health, Milken Institute School of Public Health, The George Washington University, Washington, DC, United States.
²¹ Center for Health Research, School of Public Health, University of Indonesia, Depok, Indonesia.
²² Department of Global and Community Health, College of Public Health, George Mason University, Fairfax, VA, United States.
²³ Healthy Mothers Healthy Babies, The Micronutrient Forum, Washington, DC, United States; Global Nutrition and Health Department, Wageningen University & Research, Wageningen, The Netherlands. Electronic address: martin.mwangi@micronutrientforum.org.

PMID: 40306386
PMCID: PMC12308086
DOI: 10.1016/j.ajcnut.2025.04.022

Abstract

Background: Prenatal multiple micronutrient supplementation (MMS), in comparison to iron and folic acid supplementation (IFA), improves pregnancy outcomes, but less is known about their effect on infant growth.

Objectives: We conducted a systematic review of trials comparing maternal MMS to IFA and assessed the effect on infants' anthropometric outcomes at birth, 3, 6, 12, 18, and 24 mo of age.

Methods: We included trials from a Cochrane review and new studies identified through systematic literature searches in 3 databases. We calculated the pooled effect estimates with 95% confidence intervals (CIs) 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 6 mo, head circumference (HC) from birth to 12 mo, and mid-upper arm circumference (MUAC) through 3 mo. Infants born to pregnant women consuming MMS were longer at birth (mean difference: 0.05 cm; 95% CI: 0.02, 0.08 cm) and had higher length-for-age z-score at birth (0.09; 95% CI: 0.06, 0.12), 3 mo (0.09; 95% CI: 0.06, 0.12), and 6 mo (0.04; 95% CI: 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 6 mo and higher weight-for-length z-score and MUAC-for-age z-score until 3 mo. MMS reduced risk of stunting (risk ratio [RR]: 0.86; 95% CI: 0.82, 0.91), underweight (RR: 0.86; 95% CI: 0.81, 0.90), small HC (RR: 0.84; 95% CI: 0.79, 0.90), and low MUAC (RR: 0.90; 95% CI: 0.82, 0.99) at 3 mo and wasting (RR: 0.90; 95% CI: 0.85, 0.96) at birth. For some outcomes, effects were greater when MMS was continued postpartum and in settings with higher prevalence of low birthweight.

Conclusions: Prenatal MMS improves size at birth and subsequent infant growth through 6 mo of age but not thereafter. These results strengthen the evidence on MMS benefits beyond birth outcomes. This study was registered in PROSPERO as CRD42024551864.

Keywords: birth size; infant growth; length; micronutrient supplements; pregnancy.

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Conflict of interest statement

Conflict of interest PC is an Associate Editor for the American Journal of Clinical Nutrition and played no role in the Journal’s evaluation of the manuscript. MNM reports financial support was provided by Eleanor Crook Foundation. Other authors report no conflicts of interest.

References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical