Low Birthweight, Preterm Birth, Maternal; Malnutrition, Affecting Fetus, Sexually Transmitted Diseases, Urinary Tract Infections, Pregnancy and Infectious Disease
Conditions
Keywords
Low birthweight, Preterm birth, Maternal nutrition, Small for gestational age, Chlamydia, Gonorrhea, Urinary tract infection, Presumptive antibiotics
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.
Interventions
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_SUPPLEMENTMultiple 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
DRUGPlacebo 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
OTHEREnhanced 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.
Sponsors
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
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Masking of Azithro vs. Placebo arm only
Intervention model description
2x3 factorial randomized controlled trial, with cluster randomization of nutrition interventions and individually randomized infection management interventions
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| Gestational age | Birth | Mean gestational age at delivery |
| Maternal anemia | Third trimester antenatal care visit (28-40 weeks gestation) | Mean hemoglobin concentration |
| Stillbirth | Birth | Rate of stillbirths per 1000 births |
| 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 |
| Preterm birth | Birth | Proportion of pregnancies resulting in spontaneous birth \<37 weeks gestation among all births |
Outcome results
None listed