Multiple Micronutrient Supplementation for Maternal Anemia Prevention in Tanzania

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pregnancy Related

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Attending first ANC visit at study clinics Pregnant women < 20 weeks gestation (up to 19 weeks and 6 days) 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 Concurrently enrolled in another nutritional clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MMS with 30 mg iron<br>MMS with standard UNIMMAP formulation of 15 micronutrients, including 30 mg of iron | Dietary Supplement: Multiple Micronutrient Supplements with 30 mg of elemental iron<br>* 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.<br>|
| Experimental: MMS with 45 mg iron<br>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<br>* 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.<br>|
| Experimental: MMS with 60 mg iron<br>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<br>* 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.<br>|

What is the study measuring?
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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 27-42 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 | 3rd trimester (weeks 27-42 of pregnancy) | 
| Maternal hemoglobin concentration | Continuous hemoglobin concentration measured from venous blood by complete blood count | 6 weeks postpartum | 
| Proportion of pregnant women with anemia | Hb concentration < 11 g/dL | 3rd trimester (weeks 27-42 of pregnancy) | 
| Proportion of postpartum women with anemia | Hb concentration < 12 g/dL | 6 weeks postpartum | 
| Maternal serum ferritin | Continuous Inflammation-adjusted serum ferritin | 3rd trimester (weeks 27-42 of pregnancy) | 
| Proportion of pregnant women with iron deficiency | Inflammation-adjusted serum ferritin < 15 ug/L | 3rd trimester (weeks 27-42 of pregnancy) | 
| Proportion of pregnant women with iron deficiency anemia | Anemia (Hb < 10 g/dL) and iron deficiency (inflammation-adjusted serum ferritin < 15 ug/L) | 3rd trimester (weeks 27-42 of pregnancy) | 
| 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 42 days post delivery | 
| 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 | 
| Proportion of women with postpartum hemorrhage | Clinical diagnosis of postpartum hemorrhage or use of critical interventions to treat postpartum hemorrhage | From 24 weeks gestation through 42 days post delivery | 
| Proportion of women with peripartum infection | Infection in the peripartum period | 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 | During pregnancy through 42 days after pregnancy end | 
| Proportion of women with symptoms consistent with depression | Patient Health Questionnaire-9 (PHQ-9) score ranging from 0 to 27, with higher number is consistent with depression and anxiety | 3rd trimester (weeks 27-42 of pregnancy) | 
| Proportion of women with symptoms consistent with depression | Patient Health Questionnaire-9 (PHQ-9) score ranging from 0 to 27, with higher number is consistent with depression and anxiety | 6 weeks postpartum | 
| Proportion of women with malaria infection | Based on HRP2 biomarker and 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 1-40 of pregnancy) | 
| Proportion of stillbirths | Fetal death ≥ 28 weeks gestation | At pregnancy termination (weeks 1-40 of pregnancy) | 
| Birthweight | Continuous birthweight among live births | At birth | 
| Proportion of live birth with low birthweight | Live birth with birthweight < 2500 g | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pregnancy, Multiple Micronutrient Supplementation, Iron, Anemia, Tanzania