Trials. 2025 Jun 14;26(1):206. doi: 10.1186/s13063-025-08906-7.
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.
PMID:40517226 | DOI:10.1186/s13063-025-08906-7
