Malaria in Pregnancy: Nutrition and Immunologic Effects

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy of zinc and/or vitamin A supplementation in reducing the risk of placental malaria and its associated adverse pregnancy outcomes.

Detailed Description
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Malaria accounts for a major proportion of the disease burden in Tanzania with 14 to 18 million new malaria cases being reported each year resulting in 100,000-125,000 deaths. Malaria results in impaired productivity for those between 15-55 years and lost learning opportunities in the 5-25 year age group. Dar es Salaam is characterized as an area with endemic and perennial malaria, with transmission occurring during the entire year. P. falciparum accounts for more than 95% of malaria infections. A number of interventions have contributed to reducing the burden of the disease in some settings in Tanzania and beyond, including vector control measures, bed nets, and prophylaxis and treatment of malaria. However, malaria remains a serious problem among pregnant women and children. We will examine the efficacy of micronutrient supplements as a means of enhancing immune response to malaria in pregnancy and reducing the risks of associated adverse clinical outcomes. If successful, such a low-cost intervention would be added to the armamentarium against this disease. NOTE: The time frames listed for the maternal malaria and hemoglobin outcomes were updated on 4/22/15. This record initially indicated that maternal malaria anemia and hemoglobin would be measured at several specific time points throughout the study. Instead, maternal malaria was measured throughout pregnancy and hemoglobin was measured only at delivery. Due to an oversight, we did not update this record when this protocol change took effect at the start of the study.

Official Title
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Malaria in Pregnancy: Nutrition and Immunologic Effects

Conditions
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Malaria, Low Birth Weight, Anemia, Perinatal Mortality

Intervention / Treatment
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* Dietary Supplement: Vitamin A
* Dietary Supplement: Zinc
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primigravida or secundigravidae At or before 13 weeks of gestation HIV-negative Intend to stay in Dar es Salaam until delivery and for at least 6 weeks thereafter Exclusion Criteria: Not primigravida or secundigravidae After 13 weeks of gestation HIV-positive Do not intend to stay in Dar es Salaam until delivery and for at least 6 weeks thereafter

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: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin A<br> | Dietary Supplement: Vitamin A<br>* Daily oral dose of 2500 IU from enrollment until delivery<br>|
| Active Comparator: Zinc<br> | Dietary Supplement: Zinc<br>* Daily oral dose of 25 mg from enrollment until delivery<br>|
| Active Comparator: Vitamin A + Zinc<br> | Dietary Supplement: Vitamin A<br>* Daily oral dose of 2500 IU from enrollment until delivery<br>Dietary Supplement: Zinc<br>* Daily oral dose of 25 mg from enrollment until delivery<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Daily oral dose from enrollment until delivery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of placental malaria | Placental infection status will be categorized as infected if there are asexual parasites in the placenta blood; not infected if the placental blood smear is negative; or status unknown if no placental smear is available. | Delivery | 
| Low birth weight | Low birth weight will be defined as birth weight less than 2500 grams. | Delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal anemia | Anemia is defined as hemoglobin less than 11 g/dl. Severe anemia is less than 8.5 g/dl. | Delivery | 
| Perinatal death |  | at or after 28 weeks of gestation and in the first 7 days of life | 
| Maternal malaria | Maternal malaria will be defined as fever within the last 72 hours with any parasitemia on a peripheral blood smear. | During pregnancy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malaria, Low birth weight, Anemia, Perinatal mortality, Vitamin A, Zinc