Multiple micronutrient supplementation for maternal anemia prevention (MMS-MAP): an individually randomized trial of higher-dose iron (60 mg, 45 mg) compared to low-dose iron (30 mg) in multiple micronutrient supplements in pregnancy
Abstract Background Antenatal multiple micronutrient supplementation (MMS) has been shown to be more effective than iron-folic acid (IFA) alone in reducing adverse pregnancy and birth outcomes. However, there is a concern that MMS containing 30 mg of iron may be less effective in reducing maternal a...
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2025-06-01
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| Online Access: | https://doi.org/10.1186/s13063-025-08906-7 |
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| author | Emily R. Smith Alfa Muhihi Blair J. Wylie Sabina Mugusi Said Aboud Mohamed Bakari Wafaie Fawzi Shabani Kinyogoli Erin M. Oakley Qing Pan Mary M. Sando Victoria S. Brownlee Andrea B. Pembe Christopher R. Sudfeld Honorati Masanja |
| author_facet | Emily R. Smith Alfa Muhihi Blair J. Wylie Sabina Mugusi Said Aboud Mohamed Bakari Wafaie Fawzi Shabani Kinyogoli Erin M. Oakley Qing Pan Mary M. Sando Victoria S. Brownlee Andrea B. Pembe Christopher R. Sudfeld Honorati Masanja |
| author_sort | Emily R. Smith |
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| description | Abstract Background Antenatal multiple micronutrient supplementation (MMS) has been shown to be more effective than iron-folic acid (IFA) alone in reducing adverse pregnancy and birth outcomes. However, there is a concern that MMS containing 30 mg of iron may be less effective in reducing maternal anemia compared to IFA supplements containing 60 mg of iron. This poses a clinical and programmatic dilemma for countries with a high burden of maternal anemia (> 40% prevalence) where the World Health Organization (WHO) recommends using IFA with 60 mg of iron. Methods/design We will conduct an individually randomized, quadruple-blind superiority trial of daily antenatal MMS in Dar es Salaam, Tanzania (n = 6381 pregnant women). Participants will be randomized to receive a daily MMS regimen during pregnancy containing 60 mg iron, 45 mg iron, or 30 mg iron at a ratio of 1:1:1. The trial participants, outcome assessors (research staff and care providers), investigators, trial statistician, and data analysts will be blinded. Pregnant women will be enrolled in the trial before 20 weeks of gestation and will receive the randomized MMS regimen from enrollment until the time of pregnancy outcome/delivery. The primary outcome is maternal third-trimester moderate or severe anemia (Hb < 10.0 g/dL). The proportion of women who have moderate or severe anemia at 32 weeks of gestation will be compared between MMS containing 60 mg iron versus MMS containing 30 mg iron, as well as MMS containing 45 mg iron versus MMS containing 30 mg iron. Secondary outcomes include maternal hemoglobin concentration, anemia, maternal iron deficiency, and maternal iron deficiency anemia at 32 weeks gestation and 6 weeks postpartum; preeclampsia, antepartum bleeding, postpartum hemorrhage, maternal peripartum infection, pregnancy-related death, symptoms consistent with depression, fatigue, and maternal malaria during pregnancy and 42 days following; fetal death, stillbirth, birth weight, low birthweight, gestational age at birth, preterm birth, birthweight for gestational age, and small-for-gestational age birth; infant hemoglobin concentrations, infant iron status, neonatal death, and infant death at 6 weeks of age; and maternal side effects. Relative risks for binomial outcomes and mean differences for continuous outcomes and their 95% confidence intervals will be calculated for all the primary and secondary outcomes. Discussion This study will produce causal evidence on whether MMS containing 60 or 45 mg of iron is superior to MMS containing 30 mg of iron in reducing maternal anemia and improving other important maternal and infant health outcomes. The findings of this study will inform Tanzania and similar contexts on the optimal formulation of MMS as many countries begin transitioning from IFA to MMS. Trial registration ClinicalTrials.gov NCT06079918. Registered on 2023–10-06. Trial status The trial is recruiting. We report protocol version 1.7 dated March 2, 2025. Recruitment started with the first patient enrolled on March 3, 2025. At the submission of this manuscript on April 10, 2025, 111 participants have been randomized. Recruitment is ongoing and should be completed by December 2026. |
| format | Article |
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| publishDate | 2025-06-01 |
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| spelling | doaj-art-52821d46ab5d4e90a90cbfb565de7f4e2025-08-20T02:40:15ZengBMCTrials1745-62152025-06-0126111210.1186/s13063-025-08906-7Multiple micronutrient supplementation for maternal anemia prevention (MMS-MAP): an individually randomized trial of higher-dose iron (60 mg, 45 mg) compared to low-dose iron (30 mg) in multiple micronutrient supplements in pregnancyEmily R. Smith0Alfa Muhihi1Blair J. Wylie2Sabina Mugusi3Said Aboud4Mohamed Bakari5Wafaie Fawzi6Shabani Kinyogoli7Erin M. Oakley8Qing Pan9Mary M. Sando10Victoria S. Brownlee11Andrea B. Pembe12Christopher R. Sudfeld13Honorati Masanja14Department of Global Health, The Milken Institute School of Public Health, The George Washington UniversityAfrica Academy for Public HealthColumbia University Medical School, Columbia UniversityDepartment of Clinical Pharmacology, Muhimbili University of Health and Allied SciencesDepartment of Microbiology and Immunology, Muhimbili University of Health and Allied SciencesDepartment of Pediatrics and Child Health, Muhimbili University of Health and Allied SciencesHarvard University T.H. Chan School of Public Health, Harvard UniversityAfrica Academy for Public HealthDepartment of Global Health, The Milken Institute School of Public Health, The George Washington UniversityDepartment of Statistics, Columbian College of Arts & Science, The George Washington UniversityAfrica Academy for Public HealthDepartment of Global Health, The Milken Institute School of Public Health, The George Washington UniversityDepartment of Obstetrics and Gynaecology, Muhimbili University of Health and Allied SciencesHarvard University T.H. Chan School of Public Health, Harvard UniversityIfakara Health InstituteAbstract Background Antenatal multiple micronutrient supplementation (MMS) has been shown to be more effective than iron-folic acid (IFA) alone in reducing adverse pregnancy and birth outcomes. However, there is a concern that MMS containing 30 mg of iron may be less effective in reducing maternal anemia compared to IFA supplements containing 60 mg of iron. This poses a clinical and programmatic dilemma for countries with a high burden of maternal anemia (> 40% prevalence) where the World Health Organization (WHO) recommends using IFA with 60 mg of iron. Methods/design We will conduct an individually randomized, quadruple-blind superiority trial of daily antenatal MMS in Dar es Salaam, Tanzania (n = 6381 pregnant women). Participants will be randomized to receive a daily MMS regimen during pregnancy containing 60 mg iron, 45 mg iron, or 30 mg iron at a ratio of 1:1:1. The trial participants, outcome assessors (research staff and care providers), investigators, trial statistician, and data analysts will be blinded. Pregnant women will be enrolled in the trial before 20 weeks of gestation and will receive the randomized MMS regimen from enrollment until the time of pregnancy outcome/delivery. The primary outcome is maternal third-trimester moderate or severe anemia (Hb < 10.0 g/dL). The proportion of women who have moderate or severe anemia at 32 weeks of gestation will be compared between MMS containing 60 mg iron versus MMS containing 30 mg iron, as well as MMS containing 45 mg iron versus MMS containing 30 mg iron. Secondary outcomes include maternal hemoglobin concentration, anemia, maternal iron deficiency, and maternal iron deficiency anemia at 32 weeks gestation and 6 weeks postpartum; preeclampsia, antepartum bleeding, postpartum hemorrhage, maternal peripartum infection, pregnancy-related death, symptoms consistent with depression, fatigue, and maternal malaria during pregnancy and 42 days following; fetal death, stillbirth, birth weight, low birthweight, gestational age at birth, preterm birth, birthweight for gestational age, and small-for-gestational age birth; infant hemoglobin concentrations, infant iron status, neonatal death, and infant death at 6 weeks of age; and maternal side effects. Relative risks for binomial outcomes and mean differences for continuous outcomes and their 95% confidence intervals will be calculated for all the primary and secondary outcomes. Discussion This study will produce causal evidence on whether MMS containing 60 or 45 mg of iron is superior to MMS containing 30 mg of iron in reducing maternal anemia and improving other important maternal and infant health outcomes. The findings of this study will inform Tanzania and similar contexts on the optimal formulation of MMS as many countries begin transitioning from IFA to MMS. Trial registration ClinicalTrials.gov NCT06079918. Registered on 2023–10-06. Trial status The trial is recruiting. We report protocol version 1.7 dated March 2, 2025. Recruitment started with the first patient enrolled on March 3, 2025. At the submission of this manuscript on April 10, 2025, 111 participants have been randomized. Recruitment is ongoing and should be completed by December 2026.https://doi.org/10.1186/s13063-025-08906-7Multiple micronutrient supplementsDietary supplementsPregnancyPregnancy complicationsAnemiaIron |
| spellingShingle | Emily R. Smith Alfa Muhihi Blair J. Wylie Sabina Mugusi Said Aboud Mohamed Bakari Wafaie Fawzi Shabani Kinyogoli Erin M. Oakley Qing Pan Mary M. Sando Victoria S. Brownlee Andrea B. Pembe Christopher R. Sudfeld Honorati Masanja Multiple micronutrient supplementation for maternal anemia prevention (MMS-MAP): an individually randomized trial of higher-dose iron (60 mg, 45 mg) compared to low-dose iron (30 mg) in multiple micronutrient supplements in pregnancy Trials Multiple micronutrient supplements Dietary supplements Pregnancy Pregnancy complications Anemia Iron |
| title | Multiple micronutrient supplementation for maternal anemia prevention (MMS-MAP): an individually randomized trial of higher-dose iron (60 mg, 45 mg) compared to low-dose iron (30 mg) in multiple micronutrient supplements in pregnancy |
| title_full | Multiple micronutrient supplementation for maternal anemia prevention (MMS-MAP): an individually randomized trial of higher-dose iron (60 mg, 45 mg) compared to low-dose iron (30 mg) in multiple micronutrient supplements in pregnancy |
| title_fullStr | Multiple micronutrient supplementation for maternal anemia prevention (MMS-MAP): an individually randomized trial of higher-dose iron (60 mg, 45 mg) compared to low-dose iron (30 mg) in multiple micronutrient supplements in pregnancy |
| title_full_unstemmed | Multiple micronutrient supplementation for maternal anemia prevention (MMS-MAP): an individually randomized trial of higher-dose iron (60 mg, 45 mg) compared to low-dose iron (30 mg) in multiple micronutrient supplements in pregnancy |
| title_short | Multiple micronutrient supplementation for maternal anemia prevention (MMS-MAP): an individually randomized trial of higher-dose iron (60 mg, 45 mg) compared to low-dose iron (30 mg) in multiple micronutrient supplements in pregnancy |
| title_sort | multiple micronutrient supplementation for maternal anemia prevention mms map an individually randomized trial of higher dose iron 60 mg 45 mg compared to low dose iron 30 mg in multiple micronutrient supplements in pregnancy |
| topic | Multiple micronutrient supplements Dietary supplements Pregnancy Pregnancy complications Anemia Iron |
| url | https://doi.org/10.1186/s13063-025-08906-7 |
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