Malaria in Pregnancy: Nutrition and Immunologic Effects (MAL2)

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.

Study Overview

• Status: Completed
• Conditions: Anemia; Low Birth Weight; Malaria; Perinatal Mortality
• Intervention / Treatment: Other: Placebo; Dietary supplement: Vitamin A; Dietary supplement: Zinc

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 2500
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Tanzania
  • Dar es Salaam, Tanzania, PO BOX 65001
    • Muhimbili University of Health and Allied Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Daily oral dose from enrollment until delivery
Active Comparator: Vitamin A	Dietary supplement: Vitamin A; Daily oral dose of 2500 IU from enrollment until delivery
Active Comparator: Zinc	Dietary supplement: Zinc; Daily oral dose of 25 mg from enrollment until delivery
Active Comparator: Vitamin A + Zinc	Dietary supplement: Vitamin A; Daily oral dose of 2500 IU from enrollment until delivery; Dietary supplement: Zinc; Daily oral dose of 25 mg from enrollment until delivery

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Harvard School of Public Health (HSPH)
• Collaborators: Muhimbili University of Health and Allied Sciences
• Investigators: Principal Investigator: Ferdinand Mugusi, MD, MMed, Muhimbili University of Health and Allied Sciences

Publications and helpful links

General Publications

• Yang J, Wang D, Darling AM, Liu E, Perumal N, Fawzi WW, Wang M. Methodological approaches to imputing early-pregnancy weight based on weight measures collected during pregnancy. BMC Med Res Methodol. 2021 Feb 5;21(1):24. doi: 10.1186/s12874-021-01210-3.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: April 30, 2010
• First Submitted That Met QC Criteria: April 30, 2010
• First Posted (Estimate): May 4, 2010

Study Record Updates

• Last Update Posted (Estimate): April 24, 2015
• Last Update Submitted That Met QC Criteria: April 22, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Malaria; Anemia; Zinc; Perinatal mortality; Low birth weight; Vitamin A
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Body Weight; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Pregnancy Complications; Death; Birth Weight; Malaria; Perinatal Death; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin A
• Other Study ID Numbers: HD57941-01A2