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

Addis Continental Institute of Public Health, Johns Hopkins Bloomberg School of Public Health, Boston Children's Hospital, Beth Israel Deaconess Medical Center, Harvard School of Public Health (HSPH), Amhara Public Health Institute, Jhpiego

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.

Low Birthweight, Preterm Birth, Maternal; Malnutrition, Affecting Fetus, Sexually Transmitted Diseases, Urinary Tract Infections, Pregnancy and Infectious Disease

Low birthweight, Preterm birth, Maternal nutrition, Small for gestational age, Chlamydia, Gonorrhea, Urinary tract infection, Presumptive antibiotics

2x3 factorial randomized controlled trial, with cluster randomization of nutrition interventions and individually randomized infection management interventions

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.

Azithromycin will be provided twice in pregnancy: at enrollment (<=24 weeks) and a follow up ANC visit at least 4 weeks later.

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.

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.

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.

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.

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

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

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

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.

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.

Proportion of newborns born with weight <2500 g among liveborn infants whose weight is measured within 72 hours of delivery

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)

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)

From date of first 2nd trimester antenatal care (ANC) visit until date of last ANC visit before birth, assessed up to 6 months

Prevalence of nasopharyngeal macrolide resistance among S. pneumoniae isolates in mothers-infants at 1 and 6 months postpartum

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