Multiple Micronutrient Supplementation for Maternal Anemia Prevention in Tanzania (MMS-MAP)

Individually Randomized Trial of Higher-dose Iron (60 mg, 45 mg) Compared to Low-dose Iron (30 mg) in Multiple Micronutrient Supplements in Pregnancy on Moderate and Severe Maternal Anemia

This is an individually randomized controlled trial to assess the effect of multiple micronutrient supplements (MMS) containing 60 and 45 mg iron as compared to MMS containing 30 mg of iron (standard UNIMMAP formulation) on maternal moderate or severe anemia. This study will help inform countries like Tanzania that currently use IFA containing 60 mg of iron regarding the dose of iron to use in MMS.

Study Overview

• Status: Recruiting
• Conditions: Pregnancy Related
• Intervention / Treatment: Dietary supplement: Multiple Micronutrient Supplements with 30 mg of elemental iron; Dietary supplement: Multiple Micronutrient Supplements with 45 mg of elemental iron; Dietary supplement: Multiple Micronutrient Supplements with 60 mg of elemental iron

• Study Type: Interventional
• Enrollment (Estimated): 6381
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Christopher R Sudfeld, ScD, ScM; Email: csudfeld@hsph.harvard.edu
• Study Contact Backup: Name: Emily R Smith, ScD, MPH; Phone Number: 202-994-3589; Email: emilysmith@gwu.edu

Study Locations

• Tanzania
  • Dar es Salaam, Tanzania
    • Recruiting
    • Muhimbili University of Health and Allied Sciences
    • Contact: Andrea Pembe, MD; Phone Number: 255-754-262-483; Email: bpembe@muhas.ac.tz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Attending first ANC visit at study clinics
• Pregnant women < 20 weeks gestation by last menstrual period (LMP)
• Aged ≥ 18 years old
• Intending to stay in Dar es Salaam until 6 weeks post delivery
• Provides informed consent

Exclusion Criteria:

• Severe anemia (defined as hemoglobin < 8.5 g/dL per Tanzania standard of care)
• Sickle cell disease (SS and SC) and hemoglobin C disease (CC) as tested by HemoTypeSC
• Concurrently enrolled in another nutritional clinical trial
• Pregnant women with disability or condition which would impair their ability to provide informed consent and complete study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MMS with 30 mg iron; MMS with standard UNIMMAP formulation of 15 micronutrients, including 30 mg of iron	Dietary supplement: Multiple Micronutrient Supplements with 30 mg of elemental iron; MMS with 30 mg iron is the active comparator group. The standard UNIMMAP MMS formulation includes 30 mg of iron which will be taken orally once daily from the time of randomization until delivery.
Experimental: MMS with 45 mg iron; MMS with 45 mg of iron plus standard UNIMMAP formulation for other 14 micronutrients	Dietary supplement: Multiple Micronutrient Supplements with 45 mg of elemental iron; MMS with 45 mg iron is an intervention group. MMS with 45 mg of iron plus standard UNIMMAP formulation for other 14 micronutrients will be taken orally once daily from the time of randomization until delivery.
Experimental: MMS with 60 mg iron; MMS with 60 mg of iron plus standard UNIMMAP formulation for other 14 micronutrients	Dietary supplement: Multiple Micronutrient Supplements with 60 mg of elemental iron; MMS with 60 mg iron is an intervention group. MMS with 60 mg of iron plus standard UNIMMAP formulation for other 14 micronutrients will be taken orally once daily from the time of randomization until delivery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of pregnant women with third-trimester moderate or severe anemia	Defined as a hemoglobin concentration <10 g/dL.	3rd trimester (weeks 28-42 of pregnancy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal hemoglobin concentration	Continuous hemoglobin concentration measured from venous blood by complete blood count	6 weeks postpartum
Proportion of postpartum women with anemia	Hb concentration < 12 g/dL	6 weeks postpartum
Proportion of women with antepartum bleeding	Self-reported or clinical diagnosis of bleeding from or into the genital tract	From 24 weeks gestation through delivery
Birthweight	Continuous birthweight among live births	At birth
Gestational age at birth	Duration of gestation in weeks as a continuous measure among live births based on best obstetric estimate among live births	At birth
Proportion of preterm live births	Live birth <37 weeks gestation (based on best obstetric estimate)	At birth
Birthweight for gestational age	Continuous centile based on INTERGROWTH-21st standard birth centile among live births	At birth
Proportion of small-for-gestational age live births (<10th percentile)	Size-for-gestational age <10th on the INTERGROWTH-21st standard among live births	At birth
Proportion of small-for-gestational age live births (<3rd percentile)	Size-for-gestational age <3rd percentile on the INTERGROWTH-21st standard among live births	At birth
Infant hemoglobin concentration	Continuous Hb concentration measured from capillary blood by complete blood count	At 6 weeks of age
Infant serum ferritin	Continuous inflammation adjusted serum ferritin	At 6 weeks of age
Proportion of neonatal deaths	Death of liveborn infant during the first 28 completed days of life	From birth to 28 days of age
Proportion of infant deaths < 42 days	Death of a live born infant during the first 42 completed days of life	From birth to 42 days of age
Proportion of women with preeclampsia	Gestational hypertension and gestational proteinuria among participants without chronic hypertension or gestational proteinuria among participants with chronic hypertension (superimposed preeclampsia) or clinical diagnosis of preeclampsia by managing clinical team or development of severe features of preeclampsia even in the absence of proteinuria	From 20 weeks gestation through delivery
Proportion of live births with low birthweight	Live birth with birthweight < 2500 g	At birth
Proportion of infants with iron deficiency	Inflammation-adjusted serum ferritin < 20 ug/L	At 6 weeks of age
Maternal hemoglobin concentration	Continuous hemoglobin concentration measured from venous blood by complete blood count	3rd trimester (weeks 28-42 of pregnancy)
Proportion of pregnant women with anemia	Hb concentration < 11 g/dL	3rd trimester (weeks 28-42 of pregnancy)
Maternal serum ferritin	Inflammation-adjusted serum ferritin	3rd trimester (weeks 28-42 of pregnancy)
Proportion of pregnant women with iron deficiency	Inflammation-adjusted serum ferritin < 15 ug/L	3rd trimester (weeks 28-42 of pregnancy)
Proportion of pregnant women with iron deficiency anemia	Anemia (Hb < 11 g/dL) and iron deficiency (inflammation-adjusted serum ferritin < 15 ug/L)	3rd trimester (weeks 28-42 of pregnancy)
Proportion of women with postpartum hemorrhage	Clinical diagnosis of postpartum hemorrhage or use of critical interventions to treat postpartum hemorrhage	From delivery through 42 days post delivery
Proportion of women with infection-related severe maternal outcomes	Severe infection-related such as hospitalization for infection, women presenting with WHO near-miss criteria to define organ system dysfunction, invasive procedure to treat the source of infection (vacuum aspiration, dilatation and curettage, wound debridement, drainage, laparotomy and lavage, other surgery), or maternal death from infection.	During pregnancy through 42 days postpartum
Proportion of women with pregnancy-related death	Death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the cause of death	Pregnancy through 42 days of pregnancy termination
Proportion of women with symptoms consistent with depression	Patient Health Questionnaire-9 (PHQ-9) score ranging from 0 to 27, with higher scores consistent with depression and anxiety	3rd trimester (weeks 28-42 of pregnancy)
Proportion of women with symptoms consistent with depression	Patient Health Questionnaire-9 (PHQ-9) score ranging from 0 to 27, with higher scores consistent with depression and anxiety	6 weeks postpartum
Proportion of women with symptoms consistent with fatigue	FACIT assessment score ranging from 0 to 52, with lower scores consistent with fatigue.	3rd trimester (weeks 28-42 of pregnancy)
Proportion of women with symptoms consistent with fatigue	FACIT assessment score ranging from 0 to 52, with lower scores consistent with fatigue.	6 weeks postpartum
Proportion of women with malaria infection	Based on HRP2 biomarker or rapid-diagnostic tests (RDTs)	Pregnancy through 42 days postpartum
Proportion of fetal deaths	A product of human conception, irrespective of the duration of the pregnancy, which, after expulsion or extraction, does not breath or show any other evidence of life such as beating of the heart, pulsation of the umbilical cord, or definite movement of voluntary muscles, whether or not the umbilical cord has been cut or the placenta is attached	At pregnancy termination (weeks 1-42 of pregnancy)
Proportion of stillbirths	Fetal death ≥ 28 weeks gestation	At pregnancy termination (weeks 1-42 of pregnancy)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent adherence	The percentage of days a pregnant woman takes a MMS pill out of the total number of days from randomization to delivery	During pregnancy (up to week 42)
Diarrhea	Self-reported any diarrhea symptoms during the intervention period	During pregnancy (up to week 42)
Heartburn	Self-reported any heartburn symptoms during the intervention period	During pregnancy (up to week 42)
Constipation	Self-reported any constipation symptoms during the intervention period	During pregnancy (up to week 42)
Vomiting	Self-reported any vomiting symptoms during the intervention period	During pregnancy (up to week 42)
Nausea	Self-reported any nausea symptoms during the intervention period	During pregnancy (up to week 42)
Leg Cramps	Self-reported any leg cramps during the intervention period	During pregnancy (up to week 42)
Low back/pelvic pain	Self-reported any low back/pelvic pain during the intervention period	During pregnancy (up to week 42)
Maternal blood lead concentration	Continuous blood lead concentration measured from whole blood	3rd trimester (weeks 28-42 of pregnancy)
Maternal plasma zinc concentration	Continuous zinc concentration measured from plasma	3rd trimester (weeks 28-42 of pregnancy)

Collaborators and Investigators

• Sponsor: George Washington University
• Collaborators: Columbia University; Harvard School of Public Health (HSPH); Ifakara Health Institute; Muhimbili University of Health and Allied Sciences; Africa Academy for Public Health
• Investigators: Principal Investigator: Honorati Masanja, PhD, Ifakara Health Institute; Principal Investigator: Blair Wylie, MD, MPH, Columbia University; Principal Investigator: Andrea Pembe, MD, MMed, PhD, FCOG, Muhimbili University of Health and Allied Sciences; Principal Investigator: Christopher R Sudfeld, ScD, ScM, Harvard University; Principal Investigator: Emily R Smith, ScD, MPH, The Goerge Washington University; Principal Investigator: Alfa Muhihi, MD, MPH, Africa Academy for Public Health

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: July 25, 2023
• First Submitted That Met QC Criteria: October 6, 2023
• First Posted (Actual): October 12, 2023

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 27, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Pregnancy; Anemia; Iron; Tanzania; Multiple Micronutrient Supplementation
• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia; Physiological Effects of Drugs; Iron; Micronutrients; Trace Elements
• Other Study ID Numbers: MMS-MAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No