Multiple Micronutrient Supplementation vs Iron and Folic Acid Among Pregnant Women in Cambodia

Antenatal multiple micronutrient supplementation (MMS) is a potentially cost-effective, scalable approach that can contribute to addressing the persistent challenge of maternal undernutrition, reducing low birth weight, reducing small-for-gestational age births, and potentially reducing preterm birth. A 2019 independent patient (IDP) meta-analysis indicates MMS decreased mortality for female neonates and provided greater reductions in the risk of low birthweight and preterm birth for infants born to undernourished and anemic women. The 2019 Cochrane Review compared the effects of MMS to iron folic acid (IFA) supplementation in another review and meta-analysis and found MMS supplementation was associated with reduced small-for-gestational age births. Operationalizing MMS interventions in different country contexts is urgently needed to improve the health of mothers and children. However, guidelines on antenatal MMS supplementation have yet to be widely adopted into national policies, in part because the WHO guidelines do not reflect recent evidence.

Helen Keller Intl, with support from Vitamin Angels, conducted a landscape analysis of antenatal MMS supplementation in Cambodia to supportive or potentially supportive stakeholders to accelerate MMS uptake and use in Cambodia. During a stakeholder consultation help in September 2021, workshop participants concluded it is an appropriate time to consider the transition from iron folic acid supplementation (IFA) to MMS supplementation. Following this consultation, a multi-stakeholder Steering Committee was formed, consisting of technical and government representatives from a range of disciplines, to oversee and support this transition.

The landscape analysis revealed that key Cambodian stakeholders are open to exploring the feasibility of a transition from IFA to MMS supplementation for pregnant women and identified key operational and implementation research priorities to inform the transition process. One of those questions relates to the acceptability by pregnant women of MMS in terms of packaging, color, ease of consumption, taste, and overall liking.

The landscape analysis also highlighted the need to assess the adherence of MMS vs. IFA supplementation. WHO recommends that all pregnant women receive a standard dose of 30-60 mg iron and 400 µg folic acid beginning as soon as possible during pregnancy. Ideally, women should receive IFA no later than the first trimester of pregnancy, which means taking 180 tablets before delivery. It is important to note that many countries (including Cambodia) aim for women to receive 90 or more tablets during pregnancy. Currently, in Cambodia the government is distributing 90 tablets of IFA to pregnant women attending public antenatal care services. Thus, to transition from 90 tablets of IFA to 180 tablets is not as easy as a pill switch. To ensure pregnant women can receive the full benefits from MMS supplementation, transitioning from IFA to MMS will require pregnant women to come into ANC during their first trimester and adhere to the recommended 180 tablets of MMS throughout their pregnancy.

To date there are no published studies or documentation from Cambodia on pregnant women's acceptability of MMS supplements or adherence to a 180-dosage regimen of MMS. A 2011 study in two provinces in Cambodia found access to antenatal care (ANC), the number of supplements provided, and ANC attendance were the strongest determinants for adherence to IFA supplementation. Another analysis in Cambodia found the primary reasons for not taking the WHO recommended number of 180 IFA doses (WHO, 2012) were starting ANC after the 1st trimester and not attending all recommended ANC visits. In Nepal, researchers have found knowledge about preventable conditions and benefits, perceived barriers, social support, and perceived severity of not taking the supplement predicted IFA compliance while other also found forgetting to take the supplements was a barrier. In a study from Vietnam, determinants of adherence to either folic acid, IFA, or MMS supplementation were socioeconomic status, ethnicity, occupation, and parity, as well as increased contact with health workers. Acceptability studies which included MMS supplementation have identified organoleptic properties perceived benefits, and fears or perceived negative effects as influential factors on acceptance and utilization.

Following the landscape analysis, Vitamin Angels and Helen Keller co-hosted with the Ministry of Health (MoH) a Consensus Building Stakeholder Workshop. Workshop participants recommended conducting a pilot test to engage with the pregnant women who are going to be consuming the product, as well as with the health care actors who will be involved in product delivery. Following the workshop, the MoH formed an MMS Steering Committee comprised of many key stakeholders within the MoH, United Nations, and civil society. The MMS Steering Committee will review the implementation research protocol, provide guidance, and, also, meet quarterly to review implementation progress and feedback on development of health provider counseling materials and other strategic behavioral change materials.

Assessment of the acceptability and feasibility of a new intervention should be done with end users prior to implementation, especially when the strategy requires possible changes in care processes. Determining the acceptability of MMS supplements with pregnant women will enhance understanding of barriers to implementation and help to develop an MMS supplementation scale-up strategy that is feasible and cost-effective. Implementation strategies will need to consider a host of drivers that influence acceptability and adherence, including MMS product availability, affordability, and acceptability as well as improvements to health seeking behaviors during pregnancy. Determining non-inferiority of adherence is also critical when introducing a new supplement. Given the dearth of studies and knowledge around MMS supplementation in Cambodia, Helen Keller and Vitamin Angels propose formative and implementation research to identify factors influencing adherence to antenatal supplementation to effectively inform an MMS supplementation strategy and ANC service delivery.

Rationale for the Study MMS supplements are a new product for pregnant women and health providers in Cambodia. As it is intended to replace IFA, MMS supplementation uptake requires careful introduction and transition to ensure optimal supplement acceptability and compliance, without which improving maternal nutrition may remain a challenge. As others have suggested that transitioning to MMS therefore requires a formative research phase to inform programming and service delivery. Specifically, testing product acceptability, labeling, packaging, health worker capacity building strategies, and behavioral change messaging to promote daily use among Cambodian pregnant women is important before fully transitioning to and scaling up MMS supplementation. Furthermore, concerns expressed by host-country stakeholders question the impact on ANC use (ensuring at least four visits) if MMS is provided in a large quantity (i.e., 90 or 180 tablets) to pregnant women need to be explored.

Aim and Objectives The aim of this study is to assess factors that influence optimal MMS consumption, defined as 180 tablets during pregnancy, and provide recommendations to the MoH MMS Steering Committee to effectively transition to distribution of 180 tablets of MMS supplements as part of routine ANC services. Specific recommendations generated by this study will be related to product acceptability, packaging, labeling, training needs, behavioral change messaging, adherence, and best ways to integrate MMS within ANC services. Results of this adherence research are intended to be used by the MoH and the MMS Steering Committee.

This study has the following objectives:

1. Assess acceptability of IFA and MMS supplements.
2. Assess adherence to recommended IFA and MMS supplementation.
3. Assess non-inferiority of MMS compared to IFA supplementation.
4. Assess impact of pill quantity provided at one time on ANC attendance.
5. Evaluate factors that influence adherence behavior.
6. Develop recommendations for product marketing and service delivery to encourage adherence to MMS supplementation.