Nutritional and Anti-infective Interventions for Malnutrition in Pregnancy (Beleuman Welbodi)

Study Overview
=================
Brief Summary
-----------------
Acute malnutrition in pregnancy is a risk factor for adverse outcomes in mothers and their unborn children. Undernutrition during pregnancy can result in maternal complications such as life-threatening hemorrhage and hypertensive disorders of pregnancy and infant complications such as intrauterine growth retardation, low birth weight, pre-term delivery and poor cognitive development. Poor women in the developing world are at heightened risk of malnutrition due to inadequate dietary intake and are subject to transmission of a number of infections including malaria, intestinal helminths, and genitourinary infections. Food interventions for malnutrition may be less effective under conditions with excessive inflammation and infection, and especially so during pregnancy. Without specifically addressing treatment for infections, undernourished mothers may be less responsive to nutritional interventions. The benefits of treating both malnutrition and common infections simultaneously remain largely unstudied. This study tests the hypothesis that malnourished pregnant women receiving 100 grams per day of a specially formulated ready-to-use supplementary food in addition to a combination of 5 anti-infective interventions will have greater weight gain in pregnancy and deliver larger, longer infants than women receiving the standard of care. The outcome of the pregnancy and maternal nutritional status will be followed until 6 months after delivery.

Official Title
-----------------
Randomized Control Trial of the Use of Supplementary Food and Measures to Control Inflammation in Malnourished Pregnant Women to Improve Birth Outcomes

Conditions
-----------------
Pregnancy, Malnutrition in Pregnancy, Nutrition Disorders, Stunting

Intervention / Treatment
-----------------
* Dietary Supplement: Ready-to-use-supplementary food
* Dietary Supplement: Corn-soy-blend
* Drug: Monthly intermittent preventive treatment of malaria during pregnancy (IPTp)
* Drug: Standard intermittent preventive treatment of malaria during pregnancy (IPTp)
* Other: Insecticide-treated mosquito net
* Drug: Azithromycin
* Drug: Albendazole
* Combination Product: Bacterial vaginosis testing and treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pregnant women and consenting to study participation Fundal height not greater than 32 cm Mid-upper arm circumference ≤23 cm Planning to reside in the study area during pregnancy and 6 months post partum Attending 1 of the 40 antenatal clinic sites Exclusion Criteria: < 16 years of age without adult willing to consent Known pregnancy complications such as gestational diabetes, pre-eclampsia, hypertension

Ages Eligible for Study
-----------------
Minimum Age: 14 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ready-to-use supplementary food + anti-infective bundle<br>The women randomized to this arm will receive a ready-to-use-supplementary food (RUSF) designed specifically for pregnancy. The RUSF will provide a total of 520 kcal, 18 g protein, and 200% of recommended daily allowance (RDA) for most micronutrients during pregnancy. The supplement is also optimized to provide excellent protein quality and optimal polyunsaturated fatty acid composition. These women will receive 5 anti-infective interventions: 1) insecticide-treated mosquito net, 2) monthly intermittent preventive treatment of malaria during pregnancy (IPTp) 3) azithromycin at the second and third trimester 4) albendazole given in second trimester, and 5) bacterial vaginosis testing and treatment at enrollment and again at weeks 28-34 | Dietary Supplement: Ready-to-use-supplementary food<br>* Specially formulated supplementary food for pregnancy<br>Drug: Monthly intermittent preventive treatment of malaria during pregnancy (IPTp)<br>* Sulfadoxine-pyrimethamine (500 mg / 25 mg) given every 4 weeks, beginning at enrollment or at 13 weeks' gestation, whichever is later.<br>* Other names: Sulfadoxine-pyrimethamine;Other: Insecticide-treated mosquito net<br>* An insecticide-treated mosquito net at the time of enrollment into the study.<br>Drug: Azithromycin<br>* Azithromycin 1 gram given once in second trimester and again during weeks 28-34 of gestation.<br>Drug: Albendazole<br>* Single dose albendazole 400mg given in the second trimester.<br>Combination Product: Bacterial vaginosis testing and treatment<br>* Testing for bacterial vaginosis at enrollment and again at weeks 28-34 using a rapid diagnostic test for sialidase. Those with positive tests will receive extended release metronidazole 750mg daily for 7 days.<br>|
| Active Comparator: Corn-soy-blend<br>The women randomized to this arm will receive the standard of care for Sierra Leone. The treatment provided to women in this group includes 3.5 kg super cereal with 350 g vegetable oil every two weeks. This provides 250 mg portion/day of the super cereal and 25g oil/day for the mother. Women will receive the food for the duration of their pregnancy. These women will receive the current recommendations of the government of Sierra Leone, which includes standard intermittent preventive treatment of malaria during pregnancy (IPTp) of 2 doses of sulfadoxine/ pyrimethamine, iron and folic acid supplement with a goal of 90 pills/pregnancy, an insecticide-treated mosquito net, and albendazole for deworming in the second trimester. | Dietary Supplement: Corn-soy-blend<br>* Standard of care for malnutrition in pregnancy in Sierra Leone<br>Drug: Standard intermittent preventive treatment of malaria during pregnancy (IPTp)<br>* Standard of care for Sierra Leone is 2 doses of sulfadoxine/ pyrimethamine (500mg/ 25mg).<br>* Other names: Sulfadoxine-pyrimethamine;Other: Insecticide-treated mosquito net<br>* An insecticide-treated mosquito net at the time of enrollment into the study.<br>Drug: Albendazole<br>* Single dose albendazole 400mg given in the second trimester.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infant birth length | mean birth length of infants born to mothers in the study | up to 40 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal weight gain | Average weekly weight gain of women in the study | up to 40 weeks | 
| Proportion recovered from maternal malnutrition | proportion of women who reach mid-upper-arm circumference (MUAC) > 23 cm | up to 40 weeks | 
| Premature delivery | proportion of infants born prematurely | up to 36 weeks | 
| Newborn head circumference | mean head circumference of infants born to women in the study | up to 40 weeks | 
| Infant birth weight | mean birth weights of infants born to mothers in the study | up to 40 weeks | 
| Infant weight at 6 weeks, 3 and 6 months | infant ponderal growth | up to 6 months | 
| Infant length at 6 weeks, 3 and 6 months | infant linear growth | up to 6 months | 
| Infant survival at 3 and 6 months | survival of infants in the study | up to 6 months |