Contribution of maternal adherence to the effect of multiple micronutrient supplementation during pregnancy: a systematic review and individual participant data meta-analysis

Emily R. Smith, Department of Global Health, Exercise and Nutrition Sciences, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
Filomena Gomes, The New York Academy of Science, New York, NY, USA; NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal; Micronutrient Forum, Washington, DC, USA.
Seth Adu-Afarwuah, Department of Nutrition and Food Science, University of Ghana, Legon, Accra, Ghana.
Victor M. Aguayo, Child Nutrition and Development, UNICEF, New York, NY, USA.
Shams El Arifeen, Maternal and Child Health Division, International Centre for Diarrhoeal Diseases Research Bangladesh (ICDDR,B), Dhaka, Bangladesh.
Zulfiqar A. Bhutta, Center of Excellence in Women and Child Health, The Aga Khan University, Karachi, Pakistan; Department of Pediatrics & Child Health, The Aga Khan University, Karachi, Pakistan; Institute of Global Health & Development, The Aga Khan University, Karachi, Pakistan.
Ellen C. Caniglia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Parul Christian, Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; The JiVitA Project, Johns Hopkins University in Bangladesh, Gaibandha, Bangladesh.
Delanjathan Devakumar, Institute for Global Health, University College London, London, UK.
Kathryn G. Dewey, Department of Nutrition and Institute for Global Nutrition, University of California, Davis, Davis, CA, USA.
Wafaie W. Fawzi, Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Henrik Friis, Department of Nutrition Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
Exnevia Gomo, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe.
Ousmane Guindo, Epicentre, Maradi, Niger.
Lotta Hallamaa, Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Sheila Isanaka, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Epicentre, Paris, France.
Pernille Kæstel, Department of Nutrition Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
Carl Lachat, Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium.
Ken Maleta, School of Public Health and Family Medicine, University of Malawi College of Medicine, Blantyre, Malawi.
Sophie E. Moore, Department of Women & Children's Health, King's College London, London, UK; Medical Research Council Unit The Gambia, London School of Hygiene and Tropical Medicine, Fajara, The Gambia.
Erin M. Oakley, Department of Global Health, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
David Osrin, Institute for Global Health, University College London, London, UK.
Anisur Rahman, Maternal and Child Health Division, International Centre for Diarrhoeal Diseases Research Bangladesh (ICDDR,B), Dhaka, Bangladesh.
Ziaul Rana, The New York Academy of Science, New York, NY, USA.
Arjumand Rizvi, Department of Pediatrics & Child Health, The Aga Khan University, Karachi, Pakistan; Institute of Global Health & Development, The Aga Khan University, Karachi, Pakistan.
Dominique Roberfroid, Department of Medicine, Namur University, Namur, Belgium.
Saijuddin Shaikh, The JiVitA Project, Johns Hopkins University in Bangladesh, Gaibandha, Bangladesh.
Bakary Sonko, Medical Research Council Unit The Gambia, London School of Hygiene and Tropical Medicine, Fajara, The Gambia.
Sajid Bashir Soofi, Center of Excellence in Women and Child Health, The Aga Khan University, Karachi, Pakistan; Department of Pediatrics & Child Health, The Aga Khan University, Karachi, Pakistan.
Inan Subarkah, Center for Health Research, School of Public Health, University of Indonesia, Depok, Indonesia.
Rahardjo 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, VA, USA.

Document Type

Journal Article

Publication Date

5-30-2025

Journal

Advances in nutrition (Bethesda, Md.)

DOI

10.1016/j.advnut.2025.100455

Keywords

antenatal care; individual participant data meta-analysis; multiple micronutrient supplements; pregnancy

Abstract

Multiple micronutrient supplements (MMS) in pregnancy reduces the risk of infant low birthweight (LBW) and improves other maternal and infant outcomes as compared to iron-folic acid supplements (IFA) alone. However, the impact of timing of initiation and adherence on the MMS effectiveness in real-world programs remains unclear. To address this, we conducted a two-stage individual participant data meta-analysis that included 15 randomized trials (61,204 pregnant women) and assessed whether the relative effect of MMS differed by: adherence alone; adherence in combination with gestational age at initiation; and the total number of tablets taken. We also evaluated the observational association of these factors with outcomes among participants who received MMS. Compared to IFA; the relative effect of MMS on the primary outcome of continuous birthweight was greater with higher adherence (p-value for interaction<0.05). Among women who took ≥90% of supplements, MMS increased birthweight by 56g (95%CI: 45, 67g), while among women who took <60% of supplements, there was no difference in birthweight between MMS and IFA (mean difference (MD): 9g; 95%CI: -17, 35). Higher adherence was also associated with greater effect of MMS on LBW and birthweight-for-gestational age centile and women who took more supplements experienced a greater relative impact of MMS on birthweight-for-gestational age centile and small-for-gestational age births (SGA) as compared to IFA. Observational analyses among participants who received MMS showed that ≥90% adherence was associated with increased birthweight (MD: 44g; 95%CI: 31, 56) and lower risk of LBW (RR: 0.93; 95%CI: 0.88, 0.98) and SGA (RR: 0.95; 95%CI: 0.93, 0.98), while <75% adherence was associated with a greater risk of stillbirth (RR: 1.43; 95%CI: 1.12, 1.83) and maternal anemia (RR: 1.26; 95%CI: 1.11, 1.43) as compared to 75-90% adherence. Programs should invest in strategies that promote early initiation and high adherence to MMS. PROSPERO ID: CRD42022319207 INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO) ID: CRD42022319207.

Department

Health, Human Function, and Rehabilitation Sciences

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