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

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

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.

Study Overview

• Status: Withdrawn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

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

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

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Routine care: Placebo; 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.	Drug: Placebo oral tablet 500 mg; Placebo 500mg (Idifarma): 2g (4 tablets) at 2 time points during pregnancy; enrollment (<24 weeks gestation), and follow up ANC at least 4 weeks later
Experimental: Routine care: Azithromycin; Azithromycin will be provided twice in pregnancy: at enrollment (<=24 weeks) and a follow up ANC visit at least 4 weeks later.	Drug: Azithromycin 500 mg; Azithromycin 500mg (Kern Pharma): 2g (4 tablets) at 2 time points during pregnancy: enrollment (<=24 weeks gestation), and follow-up ANC at least 4 weeks later
Experimental: Routine care: 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.	Other: Enhanced Infection Management Package (EIMP); ENROLLMENT VISIT: Screening for bacteriuria with urine culture, and antimicrobial susceptibility testing; Screening for chlamydia and gonorrhea with Cepheid GeneXpert; Presumptive deworming with albendazole 500mg. FOLLOWUP TREATMENT VISIT: For women with identified urinary tract infection or asymptomatic bacteriuria, treatment with antibiotics based on antimicrobial susceptibility patterns. For women with identified chlamydia or gonorrhea, treatment of woman (and partner) with appropriate antibiotics. Test of cure sample and retreatment of infection. Second deworming with albendazole at least 4 weeks after enrollment ANC visit.
Experimental: Enhanced Nutrition Package (ENP): Placebo; 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.	Drug: Placebo oral tablet 500 mg; Placebo 500mg (Idifarma): 2g (4 tablets) at 2 time points during pregnancy; enrollment (<24 weeks gestation), and follow up ANC at least 4 weeks later; Dietary supplement: Multiple Micronutrient or Fortified Balanced Energy Protein Supplement; Daily multiple micronutrient (MMN) tablet (Contract Pharmacal Corp) for women with mid-upper arm circumference (MUAC) >=23 cm, OR Daily fortified balanced energy protein (BEP) supplement (DSM South Africa; Faffa Food Products): Fortified corn-soy blend (784 kcal/day) for women with MUAC <23 cm
Experimental: ENP: Azithromycin; 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.	Drug: Azithromycin 500 mg; Azithromycin 500mg (Kern Pharma): 2g (4 tablets) at 2 time points during pregnancy: enrollment (<=24 weeks gestation), and follow-up ANC at least 4 weeks later; Dietary supplement: Multiple Micronutrient or Fortified Balanced Energy Protein Supplement; Daily multiple micronutrient (MMN) tablet (Contract Pharmacal Corp) for women with mid-upper arm circumference (MUAC) >=23 cm, OR Daily fortified balanced energy protein (BEP) supplement (DSM South Africa; Faffa Food Products): Fortified corn-soy blend (784 kcal/day) for women with MUAC <23 cm
Experimental: ENP: 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.	Other: Enhanced Infection Management Package (EIMP); ENROLLMENT VISIT: Screening for bacteriuria with urine culture, and antimicrobial susceptibility testing; Screening for chlamydia and gonorrhea with Cepheid GeneXpert; Presumptive deworming with albendazole 500mg. FOLLOWUP TREATMENT VISIT: For women with identified urinary tract infection or asymptomatic bacteriuria, treatment with antibiotics based on antimicrobial susceptibility patterns. For women with identified chlamydia or gonorrhea, treatment of woman (and partner) with appropriate antibiotics. Test of cure sample and retreatment of infection. Second deworming with albendazole at least 4 weeks after enrollment ANC visit.; Dietary supplement: Multiple Micronutrient or Fortified Balanced Energy Protein Supplement; Daily multiple micronutrient (MMN) tablet (Contract Pharmacal Corp) for women with mid-upper arm circumference (MUAC) >=23 cm, OR Daily fortified balanced energy protein (BEP) supplement (DSM South Africa; Faffa Food Products): Fortified corn-soy blend (784 kcal/day) for women with MUAC <23 cm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Birth weight	Mean infant weight (g) among live born infants measured <72 hour of delivery	Within 72 hours of birth
Birth length	Mean infant length (cm) among live born infants measured <72 hours of delivery	Within 72 hours of birth

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Beth Israel Deaconess Medical Center; Johns Hopkins Bloomberg School of Public Health; Boston Children's Hospital; Harvard School of Public Health (HSPH); Jhpiego; Addis Continental Institute of Public Health; Amhara Public Health Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2020
• Primary Completion (Anticipated): May 28, 2021
• Study Completion (Anticipated): November 30, 2021

Study Registration Dates

• First Submitted: October 9, 2019
• First Submitted That Met QC Criteria: November 19, 2019
• First Posted (Actual): November 20, 2019

Study Record Updates

• Last Update Posted (Actual): August 17, 2020
• Last Update Submitted That Met QC Criteria: August 13, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Chlamydia; Gonorrhea; Urinary tract infection; Preterm birth; Small for gestational age; Maternal nutrition; Low birthweight; Presumptive antibiotics
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Nutrition Disorders; Body Weight; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Infections; Communicable Diseases; Premature Birth; Birth Weight; Urinary Tract Infections; Malnutrition; Sexually Transmitted Diseases; Physiological Effects of Drugs; Anti-Infective Agents; Anti-Bacterial Agents; Micronutrients; Trace Elements; Azithromycin
• Other Study ID Numbers: 2018P002479

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No