Condition category
Pregnancy and Childbirth
Date applied
17/07/2020
Date assigned
29/07/2020
Last edited
29/07/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Maternal undernutrition and infections in pregnancy are important causes of poor birth outcomes, including low birth weight (less than 2,500 grams at birth) and preterm birth (less than 37 weeks). In Ethiopia, one in three mothers are malnourished and infections in pregnancy are common, but screening and treatment for such conditions are limited. Each year, an estimated 635,000 (20%) babies are born with a low birth weight, and 320,000 (10%) are born prematurely.

The ENAT Study (Enhancing Nutrition and Antenatal infection Treatment for maternal and child health) aims to determine the effectiveness of a program to enhance the delivery of antenatal interventions that improve maternal nutritional status and management of infections in pregnancy. The ENAT study will assess the impact of this program on maternal and infant health outcomes in West Gojjam and South Gondar Zones of the Amhara regional state of Ethiopia.

Who can participate?
Pregnant women presenting for antenatal care in 12 health facilities who are <= 24 weeks pregnant.

What does the study involve?
Health centers will be randomly assigned either to routine care or to a strengthened capacity care model. The health centers assigned to the strengthened capacity model will provide Ethiopian FMOH and WHO recommended nutritional interventions to pregnant women, including adequately iodized salt and a balanced energy protein supplement (local corn soya blend) for undernourished women. Pregnant women presenting for antenatal care at all health centers will be randomly assigned to receive routine management of pregnancy infections or an enhanced program to test and treat for genitourinary tract infections. Women, and their infants, will be assessed at several time points during antenatal care, birth, and up to 6 months postpartum.

What are the possible benefits and risks of participating?
All women will have an ultrasound at enrollment that will date the pregnancy and help identify any major problems. Some women will receive iodized salt and a corn soya blend, which may improve the nutritional status of the mother and the growth and development of the baby.
For women who receive infection screening and treatment, the treatment of infections in pregnancy may prevent maternal and newborn infections. Additionally, treatment of these infections may reduce risk of inflammation, which may help prevent the baby being born too small (low birth weight) or too soon (premature).

Where is the study run from?
This study is being run by the Addis Continental Institute of Public Health (Addis Ababa, Ethiopia) and the Brigham and Women’s Hospital (Boston, MA, USA).

When is the study starting and how long is it expected to run for?
January 2018 to June 2022.

Who is funding the study?
The Bill and Melinda Gates Foundation (USA)

Who is the main contact?
In Ethiopia:
Professor Yemane Berhane: Addis Continental Institute of Public Health, yemaneberhane@addiscontinental.edu.et
In the US:
Dr. Anne (CC) Lee; Brigham and Women's Hospital, alee6@bwh.harvard.edu

Trial website

Contact information

Type

Public

Primary contact

Ms Michelle Eglovitch

ORCID ID

Contact details

Brigham and Women's Hospital
15 Francis St.
Boston
02115
United States of America
617-525-7579
meglovitch@bwh.harvard.edu

Type

Scientific

Additional contact

Prof Yemane Berhane

ORCID ID

http://orcid.org/0000-0002-2527-1339

Contact details

Addis Continental Institute of Public Health
Ayat Zone 8
Addis Ababa
-
Ethiopia
+251 116 390 039
yemaneberhane@addiscontinental.edu.et

Type

Scientific

Additional contact

Dr Anne Lee

ORCID ID

http://orcid.org/0000-0001-9737-3476

Contact details

Brigham and Women's Hospital
15 Francis St.
Boston
02115
United States of America
+1-617-732-8343
alee6@bwh.harvard.edu

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

2018P002479

Study information

Scientific title

Effect of antentatal interventions to improve maternal nutritional status and infection control on birth outcomes and infant growth in rural Ethiopia

Acronym

ENAT

Study hypothesis

1. Increasing coverage of a package of WHO-recommended interventions to enhance antenatal screening and treatment of genitourinary tract infections during pregnancy (urinary tract infections/asymptomatic bacteriuria, sexually/reproductive transmitted infections) will increase birth weight by at least 58 grams and birth length by at least 3.0 mm, compared to newborns of pregnant women receiving routine care
2. Increasing coverage of a package of WHO-recommended interventions to enhance maternal nutritional status (iron-folate in pregnancy/lactation, use of adequately iodized salt, and balanced energy protein supplement to women with MUAC <23 cm) will increase birth weight by at least 80.3 gm and birth length by 7.8 mm
3. Increasing coverage of BOTH packages of interventions to enhance maternal nutrition AND antenatal infection management will increase birth weight by at least 78.9 grams and birth length by at least 4.2 mm, compared to newborns of women receiving routine care (neither of these packages).

Ethics approval

1. Approved 04/03/2019, Partners Human Research Committee/IRB (Partners Healthcare, 399 Revolution Drive, Suite # 710, Somerville MA, 02145, USA; +1-857-282-1900; no email provided), ref: none provided
2. Approved 18/02/2019, Addis Continental Institute of Public Health (ACIPH) IRB (ACIPH Head Office, Ayat Zone 8, Addis Ababa, Ethiopia; +251 116 390 039; aciph@addiscontinental.edu.et), ref: none provided

Study design

Open-label pragmatic comparative study cluster-randomized and individually randomized

Primary study design

Interventional

Secondary study design

Pragmatic comparative effectiveness study

Trial setting

GP practices

Trial type

Prevention

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet.

Condition

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

Intervention

RANDOMIZATION
After a participant has consented, a study nurse will open a sequential, numbered sealed opaque envelope containing the allocation, and the participant will be assigned to that study arm.

STUDY ARMS
Arm 1: Enhanced Nutrition Package (ENP) health center, Enhanced Infection Management Package (EIMP) participant.
The health center will be strengthened to provide WHO/FMOH-recommended nutrition interventions in pregnancy. Pregnant women will receive a supply of adequately iodized salt for household use and iron-folate tablets from enrollment to 6 months postpartum. Women with undernutrition (mid-upper arm circumference <23 cm), will also receive a daily balanced energy protein supplement (SuperCereal, local corn soya blend, Faffa Food Products).
At the study enrollment visit, pregnant women will receive screening for bacteriuria with urine culture, and antimicrobial susceptibility testing; screening for chlamydia and gonorrhea (Cepheid GeneXpert); and presumptive deworming with mebendazole 500mg. Symptomatic women will also be tested for bacterial vaginosis and trichomonas.

At a follow-up visit, women with identified urinary tract infection or asymptomatic bacteriuria will be treated with antibiotics based on antimicrobial susceptibility patterns. For women with chlamydia or gonorrhea, the participant (and partner) will be treated per FMOH guidelines with recommended antibiotics. Test of cure samples will be obtained, and persistent infection will be retreated. A second deworming dose will be provided in the 3rd trimester ANC visit.

Arm 2: ENP health center, standard care infection management participant.
The health center will be strengthened to provide WHO/FMOH-recommended nutrition interventions in pregnancy. Pregnant women will receive a supply of adequately iodized salt for household use and iron-folate tablets from enrollment to 6 months postpartum. Women with undernutrition (mid-upper arm circumference <23 cm), will also receive a daily balanced energy protein supplement (SuperCereal, local corn soya blend, Faffa Food Products).
Maternal genitourinary tract infections will be managed as per standard FMOH health center guidelines that utilize a syndromic management approach.

Arm 3: Standard nutrition care health center, EIMP participant.
At the study enrollment visit, pregnant women will receive screening for bacteriuria with urine culture, and antimicrobial susceptibility testing; screening for chlamydia and gonorrhea (Cepheid GeneXpert); and presumptive deworming with mebendazole 500mg. Symptomatic women will also be tested for bacterial vaginosis and trichomonas.

At a follow-up visit, women with identified urinary tract infection or asymptomatic bacteriuria will be treated with antibiotics based on antimicrobial susceptibility patterns. For women with chlamydia or gonorrhea, the participant (and partner) will be treated per FMOH guidelines with recommended antibiotics. Test of cure samples will be obtained, and persistent infection will be retreated. A second deworming dose will be provided in the 3rd trimester ANC visit.

Arm 4: Standard of care nutrition and infection management.
Pregnant women will receive routine antenatal care services at the health center per Ethiopian Federal Ministry of Health (FMoH) guidelines. Maternal genitourinary tract infections will be managed as per standard FMOH health center guidelines that utilize a syndromic management approach.

FOLLOW UP:
All pregnant women and infants will be followed up until 6 months post-partum in all four study arms.

Intervention type

Mixed

Phase

Drug names

Primary outcome measure

1. Birth weight: Mean infant weight (g) among live born infants measured <72 hour of delivery
2. Birth length: Mean infant length (cm) among live born infants measured <72 hours of delivery

Secondary outcome measures

1. Gestational age: Mean gestational age, measured using ultrasound, at delivery
2. Preterm birth: Proportion of pregnancies resulting in spontaneous birth <37 weeks’ gestation among all births, measured using birth assessment, at birth
3. 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, measured using digital infant scales, at birth
4. Low birthweight: Proportion of newborns born with weight <2500 g among liveborn infants whose weight is measured within 72 hours of delivery, measured using digital infant scales, at birth
5. 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, measured using infant length boards, at birth
6. 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, measured using digital infant scales, at birth
7. Rate of weight gain in pregnancy: Maternal weight gain (kg) per week gestation in the 2nd and 3rd trimester, measured using digital maternal scales, from date of first 2nd trimester antenatal care (ANC) visit until date of last ANC visit before birth, assessed up to 6 months
8. Maternal anemia: Mean hemoglobin concentration, using Mission Hb or similar hemoglobin devices, at the third trimester antenatal care visit (28-40 weeks’ gestation)
9. Stillbirth: Rate of stillbirths per 1000 births, measured using maternal assessment, throughout the study period
10. UTI: Maternal clinically diagnosed urinary tract infection (cystitis, pyelonephritis) reported in medical records in 3rd trimester
11. Maternal endometritis or puerperal sepsis measured by clinical diagnosis in medical records at or within 42 days after birth

Overall trial start date

01/01/2018

Overall trial end date

01/06/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

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

Participant type

Healthy volunteer

Age group

All

Gender

Female

Target number of participants

3,600 participants in 12 clusters (health centers) across 4 study arms (300 per health center)

Participant exclusion criteria

1. Pregnant women presenting with non-viable fetus
2. Women who do not intend to deliver in the study catchment area
3. Women who refuse to provide consent

Recruitment start date

01/08/2020

Recruitment end date

01/08/2021

Locations

Countries of recruitment

Ethiopia

Trial participating centre

Addis Continental Institute of Public Health
Ayat Zone 8
Addis Ababa
-
Ethiopia

Sponsor information

Organisation

Brigham and Women's Hospital

Sponsor details

75 Francis St.
Boston
02115
United States of America
+1-617-732-5500
bwhmediarelations@partners.org

Sponsor type

Research organisation

Website

http://www.brighamandwomens.org/

Funders

Funder type

Charity

Funder name

Bill and Melinda Gates Foundation

Alternative name(s)

Bill & Melinda Gates Foundation, Gates Foundation, 比尔及梅琳达·盖茨基金会, बिल एंड मिलिंडा गेट्स फाउंडेशन, BMGF, B&MGF

Funding Body Type

private sector organisation

Funding Body Subtype

Trusts, charities, foundations (both publically funded and privately funded)

Location

United States of America

Results and Publications

Publication and dissemination plan

Study findings will be disseminated to stakeholders and publications planned for peer-reviewed journals.

IPD sharing statement:
The current data sharing plans for this study are unknown and will be available at a later date

Intention to publish date

01/06/2023

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

23/07/2020: Trial’s existence confirmed by Partners Healthcare.