Healthy Mums, Healthy Babies: Multiple Micronutrient Supplementation in Ethiopia

Birth Weight Clinical Trial

Official title:

Healthy Mums, Healthy Babies in Ethiopia: a Cluster-randomized Trial to Evaluate the Programme Effectiveness of a Multiple Micronutrient Supplement Delivered to Pregnant Women Through Routine Antenatal Care to Improve Newborn Birthweight

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05708183
• Other study ID #: 101534IC
• Status: Active, not recruiting
• Start date: January 15, 2023
• Est. completion date: February 28, 2025

Study information

• Verified date: September 2022
• Source: London School of Hygiene and Tropical Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background: This programme effectiveness study responds to the need for evidence on the effect on birthweight of switching from iron-folic acid supplementation (IFA) to multiple micronutrient supplementation (MMS) as part of routine antenatal care in Ethiopia. A 2019 meta-analysis of trial data reported a mean improvement of 35g in newborn birthweight amongst newborns born to women who took MMS in pregnancy compared to those who took IFA. Responding to this evidence, in 2020 the World Health Organisation updated its global guideline on MMS from 'not recommended' to 'recommended in the context of rigorous research'. The guideline identifies priority research being 'to establish the impact of switching routine antenatal IFA to MMS on important health outcomes, equity, acceptability, feasibility, sustainability and health-care resources in different country settings.' In 2022 the Ministry of Health of Ethiopia (MoH), will change from MMS to IFA in a set of pilot districts. EPHI and LSHTM have been asked to evaluate the effect of this change on mean birthweight and propose the current trial for this purpose.

The overall aim is to evaluate the programme effectiveness on mean birthweight of providing MMS as part of routine antenatal care, compared to providing IFA.

Findings will support the MoH to make evidence-informed decisions about the large-scale implementation of MMS in Ethiopia and also contribute to the global evidence base on the effectiveness of MMS in a programmatic setting.

Methods: A two-arm cluster randomized trial will be used to estimate the effect of the programme change on mean birthweight, with cost-effectiveness and process evaluations embedded in the trial design.

Women aged 15-49 who deliver a live born child in a study district health facility (mother/infant dyads) will be eligible for enrolment in the study.

The primary outcome measure will be birthweight, recorded in facilities at the time of birth as part of the routine maternity care.

Secondary objectives include costs of providing MMS, acceptability of MMS, adherence to antenatal micronutrient supplementation and implementation challenges.

Description:

AIM: The overall aim of the MMS evaluation is to evaluate the programme effectiveness on birthweight of providing MMS as part of routine antenatal care, relative to providing IFA.

STUDY DESIGN: This program effectiveness study includes a cluster randomized trial to estimate the effect of MMS on the primary outcome, birthweight, with embedded cost and process evaluations to measure the secondary objectives.

The overall study design is built around a two-arm, facility-based, cluster randomized trial with district as the unit of randomization (the cluster), whereby districts are randomized to a comparison arm that continues to deliver iron-folic acid supplementation (IFA) as part of the standard antenatal care package, or to an intervention arm where IFA is removed from the standard antenatal care package and replaced with multi-micronutrient supplementation (MMS).

STUDY PERIOD: The entire MMS evaluation will continue for 36 months, starting in March 2022. During 2022, permissions will be obtained and protocols written. At the start of 2023, a baseline facility survey will be implemented to collect the primary outcome birthweight data plus data for the secondary objectives. An endline facility survey will be approximately 24 months after baseline.

LOCATION: The evaluation will be done in 42 districts in five regions of Ethiopia. The districts were selected by the Ethiopian Ministry of Health as a pilot area to implement the switch from MMS to IFA as part of routine care, with the intention of also permitting the RCT evaluation of that switch.

42 Districts in detail: Gambella Region (2 districts): Itang especial woreda; Godere;

Somali Region (4 districts): Kebribaya; Ararso; Awbare; Aware;

Oromia Region (20 districts): Gursum; Deder; Goba Koricha; Bele Gesgar; Rayitu; Dodola; Wondo; Kersa; Ejere; Gimbichu; Gemechis; Adami Tulu Jido; Sire; Guna; Medawelabu; Dire; Arero; Becho; Jimma Arjo; Ejersa Lafoo;

Southern Nations Nationalities, and People's Region (12 districts): Sodo; Enemor; Shahsego; Chencha Zuria; Atote Ulo; South Ari; Duguna Fango; Kachabira Bira; Silti; Wonago; Zala; Karat Zuria;

Sidama Region (4 districts): Shebedino; Dara; Aleta chuko; Bona Zuria;

PRIMARY OBJECTIVE: The primary objective is to estimate the effect of MMS implementation on the mean birthweight of babies born in government health facilities to women living in areas where MMS is implemented, relative to the mean birthweight of babies born in government health facilities to women living in areas where standard antenatal IFA supplementation is implemented.

PRIMARY OUTCOME: Birthweight measured as part of routine maternity care in enrolled facilities will be measured during baseline and endline facilty surveys in intervention and comparison areas.

The facility survey protocol for recording the primary outcome, birthweight, will align with routine practices in health facility maternity wards whereby midwives routinely document birthweight. Digital scales will be provided to facilities for this purpose, replacing manual scales. The study team will work with midwives to ensure training in appropriate use of digital scales, accurate recording of birthweight in grammes to four digits, and continuous quality control measures including scale calibration.

SECONDARY OBJECTIVES:

• To estimate the cost and cost-effectiveness of the MMS intervention

• To investigate the processes of MMS implementation including addressing questions about how delivery is achieved and what is actually delivered (fidelity, dose, adaptations, reach and context) and the mechanisms of impact (how providers and clients respond to MMS and any unanticipated pathways or consequences)

• To assess the acceptability and adherence of MMS

SECONDARY ANALYSES AND OBJECTIVES: During the baseline and endline facility surveys additional data collection tools will be used including: (i) a structured tool to capture information about the characteristics of and antenatal care received by women who are included in the primary outcome analysis; (ii) a structured tool to collect data on costs of implementing MMS; (iii) a structured facility readiness assessment to collect data on availability of services, supplies and trained staff (iv) semi-structured interviews with facility staff on their experience of providing antenatal care services; (v) semi-structured exit interviews with facility users on their experience of using antenatal care services.

In addition, during the interval between baseline and endline, a system that aligns with routine reporting will be developed to capture monitoring data on implementation processes, births, and birthweights. The need for additional qualitative interviews with health care users and health care providers to explore emerging topics regarding adherence and acceptability will be reviewed together with the implementation team when implementation has begun and after analysis of baseline data collection.

STUDY POPULATION: For the primary outcome, the study population are mother/infant dyads who are resident in study districts and who access childbirth care in the health centres of those districts. For the secondary objectives there are two study populations: (i) the health staff providing antenatal care services in health centres and (ii) currently pregnant women accessing antenatal care there.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 25620
• Est. completion date: February 28, 2025
• Est. primary completion date: April 15, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 15 Years to 49 Years

Eligibility

Inclusion Criteria:

• For the primary outcome, mothers who deliver a liveborn child in enrolled health facilities and who are willing/consent to participate in the study.

• For the secondary objectives, all antenatal care staff and pregnant women attending for routine antenatal care during the survey periods will be included.

Exclusion Criteria:

• For the primary outcome, stillbirths will be excluded. Data for any newborn who subsequently dies while still in the facility will be excluded from all secondary analyses.

Related Conditions & MeSH terms

• Birth Weight

Intervention

Dietary Supplement:
• Multiple micronutrient supplementation (MMS)
Ethiopia will distribute the UNIMMAP (United Nations International Multiple Micronutrient Antenatal Preparation) formulation that includes 30mg iron. The supplement contains 15 essential vitamins and minerals including: Retinol (Vitamin A-acetate) 800 µg; Vitamin E (as vitamin E-acetate) 10 mg; Vitamin D (as Cholecalciferol) 200 IU; Vitamin B1 (Thiamine mononitrate) 1.4 mg; Vitamin B2 (As Riboflavin) 1.4 mg; Vitamin B3 (As Nicotinamide) 18 mg; Vitamin B6 (as Pyridoxine 1.9 mg; Vitamin B12 (as Cyanocobalamin) 2.6 mg; Folic Acid 400 µg; Vitamin C (As Ascorbic Acid) 70 mg; Iron (As ferrous sulphate) 30 mg; Zinc (As zinc sulphate) 15 mg; Copper (as Copper Sulphate) 2 mg; Selenium (as Sodium selenite) 65 µg; Iodine (as Potassium Iodate) 150 µg.
• Iron folate supplementation (IFA)
IFA delivered as part of routine antenatal care, according to current policy

Locations

Country	Name	City	State
Ethiopia	Ethiopia Public Health Institute	Addis Ababa

Sponsors (2)

Lead Sponsor	Collaborator
London School of Hygiene and Tropical Medicine	Ethiopian Public Health Institute

Country where clinical trial is conducted

Ethiopia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Birthweight	The primary objective is to estimate the effect of MMS implementation on the mean birthweight of babies born in government health facilities to women living in areas where MMS is implemented, relative to the mean birthweight of babies born in government health facilities to women living in areas where standard antenatal IFA supplementation is implemented.	Cross-sectional baseline birthweight in Feb 2023, reflecting use of nutrition interventions in the 9 months leading to the birth, Jun 2022 - Feb 2023. Cross-sectional endline b/w measured 2 years later, Feb 2025, ie, pregnancies Jun 2024 - Feb 2025.