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

Authors

• 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.

APA Citation

Smith, Emily R.; Gomes, Filomena; Adu-Afarwuah, Seth; Aguayo, Victor M.; El Arifeen, Shams; Bhutta, Zulfiqar A.; Caniglia, Ellen C.; Christian, Parul; Devakumar, Delanjathan; Dewey, Kathryn G.; Fawzi, Wafaie W.; Friis, Henrik; Gomo, Exnevia; Guindo, Ousmane; Hallamaa, Lotta; Isanaka, Sheila; Kæstel, Pernille; Lachat, Carl; Maleta, Ken; Moore, Sophie E.; Oakley, Erin M.; Osrin, David; Rahman, Anisur; Rana, Ziaul; Rizvi, Arjumand; Roberfroid, Dominique; Shaikh, Saijuddin; Sonko, Bakary; Soofi, Sajid Bashir; Subarkah, Inan; Sunawang, Rahardjo; and Wang, Dongqing, "Contribution of maternal adherence to the effect of multiple micronutrient supplementation during pregnancy: a systematic review and individual participant data meta-analysis" (2025). GW Authored Works. Paper 7186.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7186

Department

Health, Human Function, and Rehabilitation Sciences