Introduction of MMS to Antenatal Care in Bamako, Mali (MAMAN)

Introduction of Multiple Micronutrient Supplementation to Antenatal Care in Bamako, Mali

The aim of this implementation research is to compare how different implementation strategies influence the acceptability and adherence to antenatal supplement use in pregnancy.

Study Overview

• Status: Completed
• Conditions: Adherence, Medication
• Intervention / Treatment: Dietary supplement: Iron Folic Acid Supplement; Dietary supplement: United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) MMS

Detailed Description

In the past several decades, the République du Mali (Mali) has achieved reductions in both maternal mortality ratio and neonatal mortality rate. However, with an estimated 562 maternal deaths per 100,000 live births and 65.8 infant deaths per 1,000 births, substantial changes to maternal child health services will likely need to be implemented to realize the benefits of universal healthcare for mothers and children and recover from the damaging impacts of colonialism and conflict. The prevalence of low birth weight (<2.5 kg) among children whose birth weights are known is estimated to be approximately 16%, but is likely underestimated. The Malian decentralized health system places antenatal care (ANC) at Centre de Santé Communautaire (CSCOM), a type of community-based health center. Approximately 36% of women in Mali access ANC in the first trimester. Within the context of ANC, the current national policy in Mali recommends that pregnant women take daily IFA supplements that contain 60 mg of iron and 400 μg of folic acid starting at the first ANC contact and ending three months after delivery. However, recent DHS data indicates that coverage of iron for pregnant women for at least 90 days has remained sub-optimal, and may be decreasing, with only 28% of women taking iron tablets for at least 90 days during their last pregnancy.

While IFA supplements have been a component of the "gold standard" of antenatal nutritional care for decades, there is clear and consistent evidence from clinical trials that MMS provide additional benefits over IFA in reducing adverse pregnancy outcomes. As compared to IFA, MMS performs better in reducing the occurrence of small for gestational age (SGA), low birth weight (LBW), preterm birth, and stillbirth. MMS performs even better than IFA with respect to pregnancy outcomes and infant survival when used by pregnant women who are anemic or underweight. Further, MMS has been demonstrated to be safe, cost-effective, and possible to produce at price parity with IFA. In 2020, the WHO released updated ANC guidelines recommending the use of MMS containing iron and folic acid in the context of rigorous research, including implementation research (IR) to establish the impact of switching from IFA supplements to MMS, including evaluation of uptake, acceptability, adherence, and cost-effectiveness.

This implementation research study design will facilitate answering the following questions, all of which were deemed to be of importance when considering the potential switch from supplementation with iron and folic acid (IFA) to multiple micronutrient supplementation (MMS) in the Malian context:

1. How does adherence to antenatal supplement use compare across study arms?
2. How does acceptability of antenatal supplements compare across study arms for both ANC clients and midwives?
3. What level of acceptability is associated with a novel counseling package for MMS?
4. What is the cost-effectiveness of switching from IFA to MMS in the Malian context?

• Study Type: Interventional
• Enrollment (Actual): 486
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mali
  • Bamako, Mali
    • JPIEGO Mali

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

INCLUSION CRITERIA:

Sample Group 1: Pregnant Women

Potential supplementation trial participants must meet all the following criteria to be eligible for inclusion in the study:

1. Age 18 years or older at screening.
2. At time of enrollment, able and willing to comply with all study requirements and complete all study procedures.
3. Able and willing to provide verbal informed consent to be screened for and to take part in the study.
4. Intention to stay within study catchment area for study duration and willingness to give adequate locator information, as defined in site standard operating procedures (SOPs).
5. Presenting for first ANC visit.

6. Pregnant, as confirmed by at least one of the following:

   1. Uterine examination
   2. Urine human chorionic gonadotropin (HCG)
   3. Ultrasound

Sample Group 2: Midwives

Midwives who participated in delivery of the intervention will be recruited from the six health center study sites. Inclusion criteria includes the provision of verbal informed consent.

Sample Group 3: Pharmacists

Pharmacists who participated in delivery of the intervention will be recruited from the six health center study sites. Inclusion criteria includes the provision of verbal informed consent.

Sample Group 4: Family Members

Family members (e.g., male partners and mothers/mothers-in-law) will be recruited based on participation of their female family member in the study protocol. Inclusion criteria includes the provision of verbal informed consent.

EXCLUSION CRITERIA:

Sample Group 1: Pregnant Women

Potential supplementation trial participants who meet any of the following criteria will be excluded from the study:

1. At time of enrollment, evidence of gestational age greater than 26 0/7 weeks, using one or more of the following methods: a) Uterine examination, b) First day of last normal menstrual period, and c) Ultrasound
2. As determined by the site investigator, any significant uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder, or infectious disease. Note: examples of uncontrolled conditions include but are not limited to the following: HIV not virally suppressed, COVID-19 infection, symptomatic malaria infection.
3. Has any other condition that, in the opinion of the site investigator, would preclude verbal informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
4. At time of enrollment, any known condition requiring routine antenatal care to take place at a location other than the study site CSCOM, e.g., Rh- negative status.
5. At enrollment, reports either of the following: a) Participation in any research study involving drugs, vaccines, or medical devices during the current pregnancy, b) Expected to participate in other research studies involving drugs, vaccines, or medical devices for the duration of study participation

Sample Group 2: Midwives

Potential participants who do not provide verbal informed consent will not be included.

Sample Group 3: Pharmacists

Potential participants who do not provide verbal informed consent will not be included.

Sample Group 4: Family Members

Potential participants who do not provide verbal informed consent will not be included.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: IFA + Standard of Care; Iron and Folic Acid (IFA) tablets dispensed 30 tablets at a time + standard of care [Represents standard of care comparison]	Dietary supplement: Iron Folic Acid Supplement; Standard of Care Intervention
Experimental: MMS 30 + novel counseling; MMS dispensed 30 tablets at a time (MMS 30) with novel counseling	Dietary supplement: United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) MMS; Introduction of UNIMMAP MMS along with novel counseling strategies to increase acceptability and adherence to prenatal supplementation; Other Names: novel counseling strategies
Experimental: MMS 180 + novel counseling; MMS dispensed 180 tablets at a time (MMS 30) with novel counseling	Dietary supplement: United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) MMS; Introduction of UNIMMAP MMS along with novel counseling strategies to increase acceptability and adherence to prenatal supplementation; Other Names: novel counseling strategies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to the Antenatal Supplement Intervention (pill count)	Adherence assessment (pill count report)	4 weeks post-enrollment (ANC-2)
Adherence to the Antenatal Supplement Intervention (pill count)	Adherence assessment (pill count report)	ANC follow-up visit (ANC-3) - approximately 4-6 weeks after ANC-2
Adherence to the Antenatal Supplement Intervention (pill count)	Adherence assessment (pill count report)	ANC follow-up visit (ANC-4) - approximately 4-6 weeks after ANC-3
Adherence to the Antenatal Supplement Intervention (pill count)	Adherence assessment (pill count report)	ANC follow-up visit (ANC-5) - approximately 4-6 weeks after ANC-4
Adherence to the Antenatal Supplement Intervention (pill count)	Adherence assessment (pill count report)	ANC follow-up visit (ANC-6) - approximately 4-6 weeks after ANC-5
Adherence to the Antenatal Supplement Intervention (pill count)	Adherence assessment (pill count report)	ANC follow-up visit (ANC-7) - approximately 4-6 weeks after ANC-6
Adherence to the Antenatal Supplement Intervention (pill count)	Adherence assessment (pill count report)	ANC follow-up visit (ANC-8) - approximately 4-6 weeks after ANC-7
Adherence to the Antenatal Supplement Intervention (pill count)	Adherence assessment (pill count report)	Postnatal visit (6 weeks after delivery of infant)
Adherence to Antenatal Supplement Intervention (self report)	Interviewer administered retrospective self report	4 weeks post-enrollment (ANC-2)
Adherence to Antenatal Supplement Intervention (self report)	Interviewer administered retrospective self report	ANC follow-up visit (ANC-3) - approximately 4-6 weeks after ANC-2
Adherence to Antenatal Supplement Intervention (self report)	Interviewer administered retrospective self report	ANC follow-up visit (ANC-4) - approximately 4-6 weeks after ANC-3
Adherence to Antenatal Supplement Intervention (self report)	Interviewer administered retrospective self report	ANC follow-up visit (ANC-5) - approximately 4-6 weeks after ANC-4
Adherence to Antenatal Supplement Intervention (self report)	Interviewer administered retrospective self report	ANC follow-up visit (ANC-6) - approximately 4-6 weeks after ANC-5
Adherence to Antenatal Supplement Intervention (self report)	Interviewer administered retrospective self report	ANC follow-up visit (ANC-7) - approximately 4-6 weeks after ANC-6
Adherence to Antenatal Supplement Intervention (self report)	Interviewer administered retrospective self report	ANC follow-up visit (ANC-8) - approximately 4-6 weeks after ANC-7
Adherence to Antenatal Supplement Intervention (self report)	Interviewer administered retrospective self report	Postnatal visit (6 weeks after delivery of infant)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acceptability of Antenatal Supplement (i.e., pregnant women)	Proportion of ANC clients (i.e., pregnant women) who find the antenatal supplement to be acceptable.	At 4 weeks post-enrollment (ANC-2)
Acceptability of Antenatal Supplement (i.e., pregnant women)	Proportion of ANC clients (i.e., pregnant women) who find the antenatal supplement to be acceptable.	ANC follow-up visit (ANC-3) - approximately 4-6 weeks after ANC-2
Acceptability of Antenatal Supplement (i.e., pregnant women)	Proportion of ANC clients (i.e., pregnant women) who find the antenatal supplement to be acceptable.	ANC follow-up visit (ANC-4) - approximately 4-6 weeks after ANC-3
Acceptability of Antenatal Supplement (i.e., pregnant women)	Proportion of ANC clients (i.e., pregnant women) who find the antenatal supplement to be acceptable.	ANC follow-up visit (ANC-5) - approximately 4-6 weeks after ANC-4
Acceptability of Antenatal Supplement (i.e., pregnant women)	Proportion of ANC clients (i.e., pregnant women) who find the antenatal supplement to be acceptable.	ANC follow-up visit (ANC-6) - approximately 4-6 weeks after ANC-5
Acceptability of Antenatal Supplement (i.e., pregnant women)	Proportion of ANC clients (i.e., pregnant women) who find the antenatal supplement to be acceptable.	ANC follow-up visit (ANC-7) - approximately 4-6 weeks after ANC-6
Acceptability of Antenatal Supplement (i.e., pregnant women)	Proportion of ANC clients (i.e., pregnant women) who find the antenatal supplement to be acceptable.	ANC follow-up visit (ANC-8) - approximately 4-6 weeks after ANC-7
Acceptability of Antenatal Supplement (i.e., pregnant women)	Proportion of ANC clients (i.e., pregnant women) who find the antenatal supplement to be acceptable.	Postnatal visit (6 weeks after delivery of infant)
Acceptability of Antenatal Counseling (i.e., pregnant women)	Proportion of ANC clients (i.e., pregnant women) who find the antenatal counseling to be acceptable.	At 4 weeks post-enrollment (ANC-2)
Acceptability of Antenatal Counseling (i.e., pregnant women)	Proportion of ANC clients (i.e., pregnant women) who find the antenatal counseling to be acceptable. Perceptions of midwives, pharmacists, and family members on counseling acceptability.	ANC follow-up visit (ANC-3) - approximately 4-6 weeks after ANC-2
Acceptability of Antenatal Counseling (i.e., pregnant women)	Proportion of ANC clients (i.e., pregnant women) who find the antenatal counseling to be acceptable. Perceptions of midwives, pharmacists, and family members on counseling acceptability.	ANC follow-up visit (ANC-4) - approximately 4-6 weeks after ANC-3
Acceptability of Antenatal Counseling (i.e., pregnant women)	Proportion of ANC clients (i.e., pregnant women) who find the antenatal counseling to be acceptable. Perceptions of midwives, pharmacists, and family members on counseling acceptability.	ANC follow-up visit (ANC-5) - approximately 4-6 weeks after ANC-4
Acceptability of Antenatal Counseling (i.e., pregnant women)	Proportion of ANC clients (i.e., pregnant women) who find the antenatal counseling to be acceptable. Perceptions of midwives, pharmacists, and family members on counseling acceptability.	ANC follow-up visit (ANC-6) - approximately 4-6 weeks after ANC-5
Acceptability of Antenatal Counseling (i.e., pregnant women)	Proportion of ANC clients (i.e., pregnant women) who find the antenatal counseling to be acceptable. Perceptions of midwives, pharmacists, and family members on counseling acceptability.	ANC follow-up visit (ANC-7) - approximately 4-6 weeks after ANC-6
Acceptability of Antenatal Counseling (i.e., pregnant women)	Proportion of ANC clients (i.e., pregnant women) who find the antenatal counseling to be acceptable. Perceptions of midwives, pharmacists, and family members on counseling acceptability.	ANC follow-up visit (ANC-8) - approximately 4-6 weeks after ANC-7
Acceptability of Antenatal Counseling (i.e., pregnant women)	Proportion of ANC clients (i.e., pregnant women) who find the antenatal counseling to be acceptable.	Postnatal visit (6 weeks after delivery of infant)
Acceptability of Antenatal Supplement (i.e., midwives) - Global Acceptability Assessment Form (supplement) and Focus Group Discussion Guide	Proportion of midwives who find the antenatal supplement to be acceptable.	Within 2 months of study completion
Acceptability of Antenatal Supplement (i.e., pharmacists) - Global Acceptability Assessment Form (supplement) and Focus Group Discussion Guide	Proportion of pharmacists who find the antenatal supplement to be acceptable.	Within 2 months of study completion
Acceptability of Antenatal Supplement (i.e., family members) - Global Acceptability Assessment Form (supplement) and Focus Group Discussion Guide	Proportion of family members of ANC clients who find the antenatal supplement to be acceptable.	Within 2 months of study completion
Acceptability of Antenatal Counseling (i.e., midwives) - Global Acceptability Assessment Form (counseling) and Focus Group Discussion Guide	Proportion of midwives who find the antenatal counseling to be acceptable.	Within 2 months of study completion
Acceptability of Antenatal Counseling (i.e., pharmacists) - Global Acceptability Assessment Form (counseling) and Focus Group Discussion Guide	Proportion of pharmacists who find the antenatal counseling to be acceptable.	Within 2 months of study completion
Acceptability of Antenatal Counseling (i.e., family members) - Global Acceptability Assessment Form (counseling) and Focus Group Discussion Guide	Proportion of family members of ANC clients who find the antenatal counseling to be acceptable.	Within 2 months of study completion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy Outcome - Maternal Hemoglobin (Exploratory outcomes)	Maternal hemoglobin collected at delivery admission as reported on health record.	Collected at delivery via health record review
Pregnancy Outcome - Gestational Age (Exploratory outcomes)	Gestational age collected at delivery as reported on health record (best obstetric estimate)	Collected at delivery via health record review
Birth outcome (Exploratory outcomes)	Birthweight as reported on health record.	Collected at delivery via health record review

Collaborators and Investigators

• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborators: Bill and Melinda Gates Foundation; Jhpiego; Center for Vaccine Development - Mali

Publications and helpful links

General Publications

• Alkema L, Chou D, Hogan D, Zhang S, Moller AB, Gemmill A, Fat DM, Boerma T, Temmerman M, Mathers C, Say L; United Nations Maternal Mortality Estimation Inter-Agency Group collaborators and technical advisory group. Global, regional, and national levels and trends in maternal mortality between 1990 and 2015, with scenario-based projections to 2030: a systematic analysis by the UN Maternal Mortality Estimation Inter-Agency Group. Lancet. 2016 Jan 30;387(10017):462-74. doi: 10.1016/S0140-6736(15)00838-7. Epub 2015 Nov 13.
• Bourassa MW, Osendarp SJM, Adu-Afarwuah S, Ahmed S, Ajello C, Bergeron G, Black R, Christian P, Cousens S, de Pee S, Dewey KG, Arifeen SE, Engle-Stone R, Fleet A, Gernand AD, Hoddinott J, Klemm R, Kraemer K, Kupka R, McLean E, Moore SE, Neufeld LM, Persson LA, Rasmussen KM, Shankar AH, Smith E, Sudfeld CR, Udomkesmalee E, Vosti SA. Review of the evidence regarding the use of antenatal multiple micronutrient supplementation in low- and middle-income countries. Ann N Y Acad Sci. 2019 May;1444(1):6-21. doi: 10.1111/nyas.14121. Epub 2019 May 27.
• Engle-Stone R, Kumordzie SM, Meinzen-Dick L, Vosti SA. Replacing iron-folic acid with multiple micronutrient supplements among pregnant women in Bangladesh and Burkina Faso: costs, impacts, and cost-effectiveness. Ann N Y Acad Sci. 2019 May;1444(1):35-51. doi: 10.1111/nyas.14132. Epub 2019 May 27.
• Demographic Health Survey Mali 2018. https://link.edgepilot.com/s/58ae5387/4L1KP3pdmU6VyyFqGxSdsQ?u=https://dhsprogram.com/methodology/survey/survey-display-517.cfm
• Institut National de la Statistique - INSTAT, Cellule de Planification et de Statistique Secteur Santé-Développement Social et Promotion de la Famille CPS/SS-DS-PF et ICF. 2019. Enquête Démographique et de Santé au Mali 2018.Bamako, Mali et Rockville, Maryland, USA : INSTAT, CPS/SS-DS-PF et ICF.
• Keats EC, Haider BA, Tam E, Bhutta ZA. Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database Syst Rev. 2019 Mar 14;3(3):CD004905. doi: 10.1002/14651858.CD004905.pub6.
• Smith ER, Shankar AH, Wu LS, Aboud S, Adu-Afarwuah S, Ali H, Agustina R, Arifeen S, Ashorn P, Bhutta ZA, Christian P, Devakumar D, Dewey KG, Friis H, Gomo E, Gupta P, Kaestel P, Kolsteren P, Lanou H, Maleta K, Mamadoultaibou A, Msamanga G, Osrin D, Persson LA, Ramakrishnan U, Rivera JA, Rizvi A, Sachdev HPS, Urassa W, West KP Jr, Zagre N, Zeng L, Zhu Z, Fawzi WW, Sudfeld CR. Modifiers of the effect of maternal multiple micronutrient supplementation on stillbirth, birth outcomes, and infant mortality: a meta-analysis of individual patient data from 17 randomised trials in low-income and middle-income countries. Lancet Glob Health. 2017 Nov;5(11):e1090-e1100. doi: 10.1016/S2214-109X(17)30371-6.
• WHO antenatal care recommendations for a positive pregnancy experience: Nutritional interventions update: Multiple micronutrient supplements during pregnancy [Internet]. Geneva: World Health Organization; 2020. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK560384/
• United Nations Interagency Group for Child Mortality Estimation. Level and trend in child mortality report. 2017

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2022
• Primary Completion (Actual): April 15, 2023
• Study Completion (Actual): April 15, 2023

Study Registration Dates

• First Submitted: January 27, 2022
• First Submitted That Met QC Criteria: March 25, 2022
• First Posted (Actual): April 5, 2022

Study Record Updates

• Last Update Posted (Actual): May 1, 2023
• Last Update Submitted That Met QC Criteria: April 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Adherence; Acceptability; Implementation Research; Antenatal Care; Multiple Micronutrient Supplements (MMS)
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Vitamins; Vitamin B Complex; Hematinics; Micronutrients; Trace Elements; Folic Acid
• Other Study ID Numbers: IRB00017475

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After data collection and analysis, Johns Hopkins Biostatistics Center (JHBC) and Johns Hopkins University (JHU) investigators will de-identify the data. The de-identified data will be shared with Research Triangle Institute (RTI) who is responsible for managing access to the shared data from all partners across the Gates ANC-PNC research collaborative, of which Jhpiego is a partner. This data will be collected and stored through the Synapse platform. The data will not be individually identifiable. The investigators will also adhere to JHBC's data sharing policies.
• IPD Sharing Time Frame: After data collection and analysis. The individual personal data (IPD) will be share after the data analysis for the described research questions (see above) is complete
• IPD Sharing Access Criteria: The data will be collected and stored through the Synapse platform. The data will not be individually identifiable. Investigators will also adhere to JHBC's data sharing policies.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No