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

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

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.

Study Overview

• Status: Completed
• Conditions: Nutrition Disorders; Pregnancy; Stunting; Malnutrition in Pregnancy
• Intervention / Treatment: Dietary supplement: Ready-to-use-supplementary food; Drug: Monthly intermittent preventive treatment of malaria during pregnancy (IPTp); Other: Insecticide-treated mosquito net; Drug: Azithromycin; Drug: Albendazole; Combination product: Bacterial vaginosis testing and treatment; Dietary supplement: Corn-soy-blend; Drug: Standard intermittent preventive treatment of malaria during pregnancy (IPTp)

• Study Type: Interventional
• Enrollment (Actual): 1489
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sierra Leone
  • Pujehun District
    • Pujehun, Pujehun District, Sierra Leone
      • 1 Moriba Street

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ready-to-use supplementary food + anti-infective bundle; 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; Specially formulated supplementary food for pregnancy; Drug: Monthly intermittent preventive treatment of malaria during pregnancy (IPTp); Sulfadoxine-pyrimethamine (500 mg / 25 mg) given every 4 weeks, beginning at enrollment or at 13 weeks' gestation, whichever is later.; Other Names: Sulfadoxine-pyrimethamine; Other: Insecticide-treated mosquito net; An insecticide-treated mosquito net at the time of enrollment into the study.; Drug: Azithromycin; Azithromycin 1 gram given once in second trimester and again during weeks 28-34 of gestation.; Drug: Albendazole; Single dose albendazole 400mg given in the second trimester.; Combination product: Bacterial vaginosis testing and treatment; 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.
ACTIVE_COMPARATOR: Corn-soy-blend; 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.	Other: Insecticide-treated mosquito net; An insecticide-treated mosquito net at the time of enrollment into the study.; Drug: Albendazole; Single dose albendazole 400mg given in the second trimester.; Dietary supplement: Corn-soy-blend; Standard of care for malnutrition in pregnancy in Sierra Leone; Drug: Standard intermittent preventive treatment of malaria during pregnancy (IPTp); Standard of care for Sierra Leone is 2 doses of sulfadoxine/ pyrimethamine (500mg/ 25mg).; Other Names: Sulfadoxine-pyrimethamine

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: The Children's Investment Fund Foundation
• Investigators: Study Chair: Mark J Manary, MD, Washington University School of Medicine

Publications and helpful links

General Publications

• Hendrixson DT, Smith K, Lasowski P, Callaghan-Gillespie M, Weber J, Papathakis P, Iversen PO, Koroma AS, Manary MJ. A novel intervention combining supplementary food and infection control measures to improve birth outcomes in undernourished pregnant women in Sierra Leone: A randomized, controlled clinical effectiveness trial. PLoS Med. 2021 Sep 28;18(9):e1003618. doi: 10.1371/journal.pmed.1003618. eCollection 2021 Sep.
• Hendrixson DT, Koroma AS, Callaghan-Gillespie M, Weber J, Papathakis P, Manary MJ. Use of a novel supplementary food and measures to control inflammation in malnourished pregnant women in Sierra Leone to improve birth outcomes: study protocol for a prospective, randomized, controlled clinical effectiveness trial. BMC Nutr. 2018 Apr 2;4:15. doi: 10.1186/s40795-018-0218-y. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 27, 2017
• Primary Completion (ACTUAL): September 24, 2019
• Study Completion (ACTUAL): February 24, 2020

Study Registration Dates

• First Submitted: March 5, 2017
• First Submitted That Met QC Criteria: March 8, 2017
• First Posted (ACTUAL): March 14, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 7, 2021
• Last Update Submitted That Met QC Criteria: January 5, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Malnutrition; Nutrition Disorders; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Folic Acid Antagonists; Antiplatyhelmintic Agents; Anti-Infective Agents, Urinary; Renal Agents; Anticestodal Agents; Pyrimethamine; Azithromycin; Sulfadoxine; Fanasil, pyrimethamine drug combination; Albendazole
• Other Study ID Numbers: 201611119

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No