Enhancing Nutrition and Antenatal Infection Treatment for Maternal and Child Health in Ethiopia

Phase 4

Withdrawn

• Conditions: Maternal; Malnutrition, Affecting Fetus; Sexually Transmitted Diseases; Low Birthweight; Urinary Tract Infections; Pregnancy and Infectious Disease; Preterm Birth
• Interventions: Drug: Placebo oral tablet 500 mg; Other: Enhanced Infection Management Package (EIMP); Dietary Supplement: Multiple Micronutrient or Fortified Balanced Energy Protein Supplement; Drug: Azithromycin 500 mg

• Registration Number: NCT04171388
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

The ENAT study will test the impact of packages of antenatal interventions to enhance maternal nutrition and manage pregnancy infections on the outcomes of infant birth size, gestational length, and infant growth in the first 6 months of life. Approximately 5,280 pregnant women will be enrolled into the study from 12 health centers in the Amhara region of Ethiopia. Routine antenatal care will be strengthened in all health centers, and six health centers will be randomized to additionally provide a nutritional intervention including daily multiple-micronutrient or a fortified balanced-energy protein supplement for malnourished women. Women across all 12 health centers will be individually randomized to receive one of three infection management interventions in pregnancy: 1) enhanced infection management package (screening-treatment for urinary tract infections and sexually transmitted infections, presumptive deworming); 2) presumptive azithromycin (2g at \<24 wks and a second dose at least 4 weeks later); or 3) placebo. The women and their infants will be followed until 6 months postpartum. Outcomes of interest include birth size (weight, length), gestational age, maternal weight gain in pregnancy, maternal anemia, antimicrobial resistance, and infant size at 6 months.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-10-09
• Study First Submitted QC: 2019-11-19
• Study First Posted: 2019-11-20
• Study Start: 2020-03-01
• Status Verified: 2020-08
• Last Update Submitted: 2020-08-13
• Last Update Posted: 2020-08-17
• Primary Completion: 2021-05-28
• Study Completion: 2021-11-30

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

• Pregnant women <=24 weeks gestation with a viable pregnancy based on a best clinical algorithm (LMP and/or symphysis fundal height)

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Exclusion Criteria

• Pregnant women presenting at enrollment >24 weeks
• Pregnant women presenting with non-viable fetus
• Women who do not intend to deliver in the study catchment area
• Known allergy to Azithromycin or macrolide antibiotic
• Women who refuse to provide consent

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Routine care: Placebo	Placebo oral tablet 500 mg	In all pregnancies presenting at all centers, routine antenatal care will be strengthened: * Provision of iron-folic acid and tetanus toxoid vaccine * Screening for anemia and blood pressure * Screening/treatment of HIV, syphilis, malaria, tuberculosis Placebo tablets will be administered twice in pregnancy: at enrollment (\<=24 weeks) and a follow up ANC visit at least 4 weeks later.
Routine care: Enhanced Infection Management Package (EIMP)	Enhanced Infection Management Package (EIMP)	At the study enrollment visit, pregnant women will receive presumptive deworming (albendazole) and screening for urinary tract infection and sexually transmitted infections (chlamydia and gonorrhea). Women with identified infections will be treated with appropriate antibiotics. A second dose of albendazole will be given at a follow up ANC visit at least 4 weeks after enrollment.
Enhanced Nutrition Package (ENP): Placebo	Multiple Micronutrient or Fortified Balanced Energy Protein Supplement	Pregnant women will receive a daily multiple micronutrient. Women with undernutrition, identified with mid-upper arm circumference \<23 cm, will receive a daily fortified balanced energy protein supplement. Placebo tablets will be administered twice in pregnancy: at enrollment (\<=24 weeks) and a follow up ANC visit at least 4 weeks later.
Enhanced Nutrition Package (ENP): Placebo	Placebo oral tablet 500 mg	Pregnant women will receive a daily multiple micronutrient. Women with undernutrition, identified with mid-upper arm circumference \<23 cm, will receive a daily fortified balanced energy protein supplement. Placebo tablets will be administered twice in pregnancy: at enrollment (\<=24 weeks) and a follow up ANC visit at least 4 weeks later.
ENP: Azithromycin	Multiple Micronutrient or Fortified Balanced Energy Protein Supplement	Pregnant women will receive a daily multiple micronutrient. Women with undernutrition, identified with mid-upper arm circumference \<23 cm, will receive a daily fortified balanced energy protein supplement. Azithromycin will be provided twice in pregnancy: at enrollment (\<=24 weeks) and a follow up ANC visit at least 4 weeks later.
ENP: EIMP	Multiple Micronutrient or Fortified Balanced Energy Protein Supplement	Pregnant women will receive a daily multiple micronutrient. Women with undernutrition, identified with mid-upper arm circumference \<23 cm, will receive a daily fortified balanced energy protein supplement. At the study enrollment visit, pregnant women will receive presumptive deworming (albendazole) and screening for urinary tract infection and sexually transmitted infections (chlamydia and gonorrohea). Women with identified infections will be treated with appropriate antibiotics. A second dose of albendazole will be given at a follow up ANC visit at least 4 weeks after enrollment.
ENP: EIMP	Enhanced Infection Management Package (EIMP)	Pregnant women will receive a daily multiple micronutrient. Women with undernutrition, identified with mid-upper arm circumference \<23 cm, will receive a daily fortified balanced energy protein supplement. At the study enrollment visit, pregnant women will receive presumptive deworming (albendazole) and screening for urinary tract infection and sexually transmitted infections (chlamydia and gonorrohea). Women with identified infections will be treated with appropriate antibiotics. A second dose of albendazole will be given at a follow up ANC visit at least 4 weeks after enrollment.
Routine care: Azithromycin	Azithromycin 500 mg	Azithromycin will be provided twice in pregnancy: at enrollment (\<=24 weeks) and a follow up ANC visit at least 4 weeks later.
ENP: Azithromycin	Azithromycin 500 mg	Pregnant women will receive a daily multiple micronutrient. Women with undernutrition, identified with mid-upper arm circumference \<23 cm, will receive a daily fortified balanced energy protein supplement. Azithromycin will be provided twice in pregnancy: at enrollment (\<=24 weeks) and a follow up ANC visit at least 4 weeks later.

Primary Outcome Measures

Name	Time	Method
Birth weight	Within 72 hours of birth	Mean infant weight (g) among live born infants measured \<72 hour of delivery
Birth length	Within 72 hours of birth	Mean infant length (cm) among live born infants measured \<72 hours of delivery

Secondary Outcome Measures

Name	Time	Method
Gestational age	Birth	Mean gestational age at delivery
Preterm birth	Birth	Proportion of pregnancies resulting in spontaneous birth \<37 weeks gestation among all births
Small-for-gestational age (SGA)	within 72 hours of birth	Proportions of newborns born SGA (\<10% birthweight for gestational age and sex) among live born infants whose birthweight if measured within 72 hours of delivery.
Low birthweight	within 72 hours of birth	Proportion of newborns born with weight \<2500 g among liveborn infants whose weight is measured within 72 hours of delivery
Length-for-age	Birth, 6 months	Mean Length-for-age Z scores at birth and 6 months of age among live born infants based on the WHO growth reference standards (WHO 2006)
Weight-for-age	Birth, 6 months	Mean Weight-for-age Z scores at birth and 6 months of age among live born infants based on the WHO growth reference standards (WHO 2006)
Prevalence of nasopharyngeal macrolide resistance in mothers-infants	1 and 6 months post-partum	Prevalence of nasopharyngeal macrolide resistance among S. pneumoniae isolates in mothers-infants at 1 and 6 months postpartum
Rate of weight gain in pregnancy	From date of first 2nd trimester antenatal care (ANC) visit until date of last ANC visit before birth, assessed up to 6 months	Maternal weight gain (kg) per week gestation in the 2nd and 3rd trimester
Maternal anemia	Third trimester antenatal care visit (28-40 weeks gestation)	Mean hemoglobin concentration
Stillbirth	Birth	Rate of stillbirths per 1000 births