{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T03:29:16Z","timestamp":1780370956057,"version":"3.54.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T00:00:00Z","timestamp":1749859200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T00:00:00Z","timestamp":1749859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-044514"],"award-info":[{"award-number":["INV-044514"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>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\u00a0mg of iron may be less effective in reducing maternal anemia compared to IFA supplements containing 60\u00a0mg of iron. This poses a clinical and programmatic dilemma for countries with a high burden of maternal anemia (&gt;\u200940% prevalence) where the World Health Organization (WHO) recommends using IFA with 60\u00a0mg of iron.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\/design<\/jats:title>\n            <jats:p>We will conduct an individually randomized, quadruple-blind superiority trial of daily antenatal MMS in Dar es Salaam, Tanzania (<jats:italic>n<\/jats:italic>\u2009=\u20096381 pregnant women). Participants will be randomized to receive a daily MMS regimen during pregnancy containing 60\u00a0mg iron, 45\u00a0mg iron, or 30\u00a0mg 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\u00a0weeks of gestation and will receive the randomized MMS regimen from enrollment until the time of pregnancy outcome\/delivery.<\/jats:p>\n            <jats:p>The primary outcome is maternal third-trimester moderate or severe anemia (Hb\u2009&lt;\u200910.0\u00a0g\/dL). The proportion of women who have moderate or severe anemia at 32\u00a0weeks of gestation will be compared between MMS containing 60\u00a0mg iron versus MMS containing 30\u00a0mg iron, as well as MMS containing 45\u00a0mg iron versus MMS containing 30\u00a0mg iron. Secondary outcomes include maternal hemoglobin concentration, anemia, maternal iron deficiency, and maternal iron deficiency anemia at 32\u00a0weeks gestation and 6\u00a0weeks postpartum; preeclampsia, antepartum bleeding, postpartum hemorrhage, maternal peripartum infection, pregnancy-related death, symptoms consistent with depression, fatigue, and maternal malaria during pregnancy and 42\u00a0days 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\u00a0weeks 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Discussion<\/jats:title>\n            <jats:p>This study will produce causal evidence on whether MMS containing 60 or 45\u00a0mg of iron is superior to MMS containing 30\u00a0mg 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Trial registration<\/jats:title>\n            <jats:p>ClinicalTrials.gov NCT06079918. Registered on 2023\u201310-06.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Trial status<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13063-025-08906-7","type":"journal-article","created":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T03:58:25Z","timestamp":1749873505000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"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"],"prefix":"10.1186","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5715-9459","authenticated-orcid":false,"given":"Emily R.","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfa","family":"Muhihi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blair J.","family":"Wylie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Mugusi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Said","family":"Aboud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Bakari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafaie","family":"Fawzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabani","family":"Kinyogoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin M.","family":"Oakley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Sando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria S.","family":"Brownlee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea B.","family":"Pembe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Sudfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honorati","family":"Masanja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,14]]},"reference":[{"key":"8906_CR1","unstructured":"World Health Organization. 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H. Chan School of Public Health Institutional Review Board (Ref. No. IRB22-1581), Columbia University Medical Center (IRB-AAAU7271), the Ifakara Health Institute Institutional Review Board (IHI\/IRB\/No: 45\u20132023), the Muhimbili University of Health and Allied Sciences Institutional Review Board (MUHAS-REC-07\u20132023-1801), the National Health Research Ethics Committee (NatHREC) (Ref. No. NIMR\/HQ\/R.8a\/Vol. IX\/4448), Tanzania Commission for Science and Technology (COSTECH) (Permit No. CST00000303-2024\u20132024-00342) and the Tanzania Medicine and Medical Device Authority (TMDA) (Ref No. BC.69\/96\/98\/01). All participants will provide written informed consent before enrollment into the trial and will have the right to withdraw at any time.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"No competing interests to report for any authors or trial staff members.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"206"}}