Introduction This programme effectiveness study responds to the need for evidence of the effect on birth weight of switching from iron-folic acid supplementation to multiple micronutrient supplementation as part of routine antenatal care in Ethiopia. A 2019 meta-analysis reported a mean increase of 35 grammes in birth weight amongst newborns of women who took multiple micronutrient supplements in pregnancy compared to those who took iron-folic acid. Responding to that evidence, the government of Ethiopia decided to implement a 21 district pilot of the use of multiple micronutrient supplementation in routine antenatal care and requested an evaluation of implementation outcomes, including on birth weight.

Methods and analysis A pragmatic, facility-based, randomised trial is being conducted in 42 districts over 5 regions of Ethiopia between January 2023 and December 2024. Districts have been randomised to one of two arms, either to retain iron-folic acid supplementation as part of routine antenatal care or switch to multiple micronutrient supplementation. During the study period the birth weights of all eligible babies born in enrolled health facilities in these 42 districts are continuously recorded alongside data on maternal receipt and use of either multiple micronutrient or iron-folic acid supplementation. We hypothesise that newborns of women resident in the 21 multiple micronutrient supplementation districts will have higher mean birthweight than newborns of women resident in the 21 iron-folic acid supplementation districts. Facility surveys involving pregnant women and health care workers at baseline, midline, and endline contribute to a process evaluation and cost and cost-effectiveness evaluation.

Discussion Results from this pragmatic trial will be used by the government of Ethiopia in assessing success of the MMS pilot and for decision making about subsequent scale-up. The findings will also inform global decision making, particularly in settings where a transition from iron-folic acid to multiple micronutrient supplementation is being contemplated at scale.

Strengths and limitations of this study

- This pragmatic cluster-randomised trial evaluates implementation outcomes, processes and costs of a large-scale policy change to prenatal care piloted in Ethiopia, generating evidence that is actionable for country decision making and relevant to other settings.

- Continuous data collection, capturing information on all births in enrolled health facilities, makes use of and strengthens routine health management information systems.

- The design permits a dose-response analysis considering the changes in birth weight for different levels of coverage, and permits adjustment for seasonality.

- Interpretation of trial outcome findings must be made in the context of coverage of and adherence to prenatal MMS and IFA in the pilot areas.

The authors have declared no competing interest.

ClinicalTrials.gov Identifier: NCT05708183; protocol version 2

This study was funded by a grant to the London School of Hygiene & Tropical Medicine by the Children's Investment Fund Foundation.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Approval granted by the Ethiopian Public Health Institute [EPHI-IRB-455-2022] and the London School of Hygiene and Tropical Medicine [LSHTM ref 28021].

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Senait Alemayehu Senaitalbgmail.com

Elias Asfaw Eliasasfawegmail.com

Alemneh Kabeta Daba Alemneh33gmail.com

Atkure Defar Atkure.deghebolshtm.ac.uk

Charles Opondo Charles.Opondolshtm.ac.uk

Lars Åke Persson Lars.Perssonlshtm.ac.uk

Joanna Schellenberg Joanna.Schellenberglshtm.ac.uk

Girum Taye girumt2000yahoo.com

Anene Tesfa Anenetesfagmail.com

Bedasa Tessema Bedasatessemagmail.com

Kalkidan Zenebe Kallzkidangmail.com

Masresha Tessema Dr.masresha.tessemagmail.com

This is a protocol manuscript. All data produced in the work described here will be available upon reasonable request to the authors.