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Prevention of child wasting in Asia: Possible role for multiple micronutrient supplementation in pregnancy

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By Kristen M. Hurley, Endang L Achadi, Clayton Ajello, Sufia Askari, Madhavika Bajoria, Kalpana Beesabathuni, Quinn Harvey, Toslim Uddin Khan, Shannon King, Klaus Kraemer, Otte Santika, Sri Sumarmi, Abdul Razak Thaha and Robert E Black.

Kristen M. Hurley PhD, MPH is Associate Professor of Human Nutrition at John Hopkins Bloomberg School of Public Health (JHSPH) and Senior Vice President for Nutrition at Vitamin Angels.

Endang L Achadi MD, DrPH, MPH is Professor of Nutrition at the Public Health University of Indonesia, Vice Chairman of the Indonesian Institute of Nutrition (IGI) and Member of Expert Task Force, National Food and Nutrition Board (DKP).

Clayton Ajello Dr.PH, MPH is Senior Technical Advisor to Vitamin Angels and serves on the boards of the Micronutrient Forum and Vitamin Angels.

Sufia Askari M.B.B.S., MPH is Director of Child Health and Development at the Children’s Investment Fund Foundation.

Madhavika Bajoria MPA is Manager for Nutrition Integration at Sight and Life.

Kalpana Beesabathuni MBA, MS is Global Lead for Technology and Entrepreneurship at Sight and Life.

Quinn Harvey MA is a Senior Program Manager at Vitamin Angels.

Shannon King MSPH is a PhD candidate at JHSPH Program for Human Nutrition.

Klaus Kraemer PhD is Managing Director of Sight and Life and Adjunct Associate Professor of International Health at JHSPH.

Toslim Uddin Khan MBA, MA is Chief of Programs at Social Marketing Company, Bangladesh.

Otte Santika MSc is Senior Program Advisor for Indonesia at Vitamin Angels.

Sri Sumarmi M.Si, DR is Professor of Nutrition at the Faculty of Public Health, University of Airlangga.

Abdul Razak Thaha MD, M.Sc is Professor of Nutrition at the Faculty of Public Health, University of Hasanudin and Chairman of the IGI.

Robert E Black MD is Professor of International Health and Director of the Institute for International Programs at JHSPH.

Background

South Asia has the highest prevalence of wasting¹ in children under five years old of all world regions at 14.8%. Prevalence in East Asia and the Pacific is 3.7%. Countries in South and East Asia and the Pacific have two thirds (65.5%) of the 47 million children with wasting globally (UNICEF, WHO & World Bank, 2020). The highest prevalence of wasting in South Asia is at birth (Mertens et al, 2020), indicating the importance of foetal growth restriction, commonly assessed by the newborn being small for gestational age (SGA) compared with an international foetal growth standard (Lee et al, 2017). Babies who are born SGA have an elevated risk of being wasted in early childhood compared to those who are appropriate for gestational age (odds ratio (OR) 2.46, 95% confidence interval (CI) 2.15, 2.81) (Christian et al, 2013).

With the high prevalence of wasting at birth and in early infancy, interventions during pregnancy have a role in the prevention of wasting, especially in South Asian countries. An antenatal intervention with promise for improving foetal growth is multiple micronutrient supplementation (MMS) (Box 1). A Cochrane Collaboration meta-analysis of 15 randomised controlled trials of MMS vs. iron and folic acid (IFA) supplementation during pregnancy in low- and middle-income countries (LMICs) found a significant reduction of SGA (relative risk 0.92, 95% CI 0.88, 0.97) (Keats et al, 2019). Even greater benefits have been demonstrated in populations with a high prevalence of anaemia in pregnant women (Smith et al, 2017). In addition, on the continuum of antenatal care interventions, MMS is among the most cost-effective, including being more cost-effective than IFA supplementation (Kashi et al, 2019).

Based on this evidence, there is a growing consensus among leading experts in the field of public health nutrition to provide MMS to pregnant women in LMICs as a replacement for IFA supplementation during antenatal care services. Many national health services interested in MMS have started to explore ways to accelerate and then sustain national MMS coverage, adherence and measurable health impact.

Box 1: MMS formulation

Introduction and scaling of MMS for pregnant women

A generic model (or roadmap) for exploring introduction and eventually large-scale use of any innovation in healthcare is shown in Figure 1. This approach was informed by past efforts to introduce and scale public health interventions (e.g., the introduction and scaling of oral rehydration salts for the treatment of diarrhoea (Ruxin, 1994) and the introduction and scaling of several methods of contraception). This serves as a tool for identifying an ‘entry point’ for accelerating the use of MMS and includes the following three phases:

Phase I: Preparatory and advisory phase: To ensure long-term success of efforts to incorporate MMS into healthcare systems, Phase I initiatives and activities are often focused on creating an enabling environment for policy recommendations and the creation of an implementation plan. Local stakeholders are identified and engaged to: i) raise awareness and advocate for use of MMS; ii) facilitate an understanding of the evidence as it relates to the benefits of MMS over IFA; and iii) develop a consensus on the need to introduce MMS and the feasibility thereof.

In addition to awareness-raising and advocacy activities, highly motivated local influencers often seek first-hand experience with MMS use in operating health-systems settings. Such exploratory activities should be encouraged because they can help local influencers better understand how to integrate MMS into antenatal care services and even to understand how to use MMS as a vehicle for strengthening antenatal care services. In this regard, exploratory use of MMS by local influencers can inform policy formation and the subsequent design of more formal introductory initiatives (see Phase II below). Finally, because MMS may not be widely available at country level and significant lead time may be needed to produce or import the supplements, Phase I also must focus attention (if needed) on the question of how to access MMS supplies, including the capacity and potential for local production.

Phase II: Introduction: As stakeholders arrive at a consensus to adopt use of MMS, they often generate questions about the most effective and efficient ways to organise and introduce its delivery. Phase II allows stakeholders the opportunity to conduct implementation research to answer these questions and to learn how to incorporate the intervention under real-world conditions before making a national commitment. Additionally, local authorities may use Phase II as an opportunity to solidify plans for eventual procurement (or long-term product donation in fragile contexts) for Phase III scaling.

Phase III: Scaling: Once initial introduction is complete, attention turns to building capacity for large-scale deployment of MMS nationally. For local authorities, this means scaling the workforce capacities developed during the introduction phase to achieve coverage across the entire country. Apart from continuing education for healthcare providers and adjustments to ongoing monitoring and evaluation, there will also be a need to develop a healthy marketplace for ongoing procurement of MMS, whether from local or global suppliers.  

When is it appropriate to begin to examine introduction and scaling of MMS and decide on an entry point for action?

While there is strong evidence to support a transition from IFA to MMS, the World Health Organization (WHO) has not provided clear guidance on how to determine under what circumstances the introduction and use of MMS is justifiable, beyond stating in its 2016 Antenatal Care Guidelines that, “policy-makers in populations with a high prevalence of nutritional deficiencies might consider the benefits of MMS supplements to maternal health to outweigh the disadvantages, and may choose to give MMS supplements that include iron and folic acid.” (WHO, 2016). To address this gap in guidance, the Task Force for Multiple Micronutrient Supplementation for Pregnant Women (Bourassa et al, 2019) recently specified overall conditions on how to determine readiness of a national health system to begin to explore a transition from IFA to MMS. Its principal recommendations are that exploring the transition is justifiable when:

• Documentation exists of high levels of nutritional deficiency in the population at large;
• The health system has an existing platform, such as antenatal care services, to deliver MMS; and
• Steps have or are being taken to understand the cost-related implications of using MMS, focused primarily on cost-effectiveness.

It should be noted that just before publication of this article, WHO released new antenatal care guidelines to update its previous “no recommendation” on MMS to a “yes recommendation — context specific” in which WHO recommends use of MMS in the context of continuing research. Of note is that WHO appears to recommend implementation research of the type that is presented in the case studies below as a possible entry point of introduction of MMS (WHO, 2020). The new antenatal care guidelines which recommend that MMS be explored in a research context are consistent with the interpretive guidance provided by the MMS - TAG that MMS be explored in populations that are experiencing a high prevalence of micronutrient deficiencies, where there is an existing antenatal care service delivery platform, and that cost-effectiveness be considered in the exploration of MMS introduction. The full implications of the release of the new 2020 WHO Antenatal Care Guidelines is yet to be fully digested, and inevitably, there will be a lot of public discussion about the implications of those guidelines.

With overall conditions fulfilled, there is still an important need to decide on the ‘entry point’ for activities that can lead to a meaningful conversation about potential use of MMS. Identifying an entry point requires undertaking a careful examination of the national landscape either before or as a part of the activities of Phase I identified above, but before embarking on introduction and eventual large-scale implementation. Examples of how two countries (Indonesia and Bangladesh) have begun to implement MMS are presented in the case studies below, with the Indonesia experience highlighting activities and progress related to policy development and Bangladesh focusing on the creation of a market-based model.

Case Study 1: Indonesia

Decision to explore MMS use for pregnant women in Indonesia

In Indonesia there are more than 5.3 million pregnancies each year and an estimated 95.6% of women attend at least one antenatal care visit during their pregnancy (MoH, 2019). The prevalence of anaemia among pregnant women is high (48.9%) and wasting (<-2 z-scores weight-for-length) in children under two years of age is 11.7% (National Institute of Health and Research and Development, 2019).

The Government of Indonesia currently recommends and procures IFA with 60 mg of elemental iron and 400 µg of folic acid for pregnant women (MoH Indonesia, 2015). The majority (73.2%) of pregnant women receive IFA tablets during antenatal care (National Institute of Health and Research and Development, 2019). However, only 6.9% of them consumed 90 tablets as currently recommended in Indonesia (National Institute of Health and Research and Development, 2019). Plans for research into low adherence to IFA in Indonesia are currently underway to try to understand and address this problem.

In terms of cost-effectiveness, transitioning from IFA to MMS is considered “very cost-effective” in Indonesia according to the World Health Organization (WHO) threshold and has a high return on investment. The transition is expected to avert 925,250 disability-adjusted life years (DALYs) over a 10-year period, prevent the deaths of an additional 8,616 children and yield benefits that are 483 times greater than the costs (Nutrition International, 2019a).

Having considered the conditions laid out by the Task Force, Indonesia made the decision to explore the use of MMS as part of routine antenatal care services and is currently focused on Phase I (preparatory and advisory phase) to create an enabling environment that supports an MMS policy recommendation and the creation of an implementation plan.

Phase I MMS exploratory initiatives

A key activity in Phase I was undertaking exploratory research initiatives to implement MMS programmes with several district health offices, including Banggai district in central Sulawesi and Probolinggo district in East Java. In Banggai and Probolinggo districts, an international non-governmental organisation (NGO), Vitamin Angels (VA), is providing a supply of MMS to support a joint partnership between Indonesian universities and the district health office (Hasanuddin University in Banggai district and Airlangga University in Probolinggo) to integrate MMS into its antenatal platform as a replacement for IFA (Steets et al, 2020; Sumarmi et al, 2014). In addition, the University of Hasanuddin is planning to expand these activities into three new districts and one city in 2020. Engaging in these exploratory initiatives not only supported efforts to raise awareness of MMS among key influencers in Indonesia, but also served to generate local evidence to inform a future policy.

Phase I MMS awareness-raising and advocacy

Based on national interest and MMS implementation experiences, Hasanuddin University, Airlangga University and VA partnered to co-sponsor a symposium at the Asian Congress of Nutrition (ACN) in Bali, Indonesia in August 2019. The objective of the symposium was to update participants on global MMS policy and the most recent evidence of the benefits of MMS use compared to IFA supplementation. Following the symposium, a two-part technical consultation was conducted to provide participants with an opportunity to: i) seek guidance from international and national experts on maternal health and nutrition strategy to inform Ministry of Health strategy and policy pertaining to MMS use; and ii) explore issues, challenges and opportunities related to immediate access to a standardised United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) MMS product while local capacity is created to meet long-term demand.

Phase I MMS policy adoption

To build on the momentum generated during the ACN conference and technical consultations, VA sponsored the Indonesian Institute of Nutrition (IGI) to convene a group of experts in Indonesia in January 2020. The meeting included participants from government, local universities, international and local non-governmental organisations and other key stakeholders. The primary objective of the meeting was to generate consensus regarding the efficacy of MMS that would lead to a recommendation to adopt an MMS policy. Key outputs included consensus regarding the efficacy, safety, cost-effectiveness and affordability of MMS use in Indonesia (Keats et al, 2019; Smith et al, 2017, Bourassa et al, 2019). In addition, it was agreed that there was a need for a formal recommendation that leads to the formation of an MMS policy and that the formation of an Indonesian MMS Task Force was necessary to pursue this effort.

Phase I progress to date in Indonesia includes: i) the creation of an Indonesian MMS Task Force working towards MMS policy formation; ii) the provision of resources to conduct implementation research; and iii) efforts to ensure both a short-term (procured internationally and imported) and long-term (manufactured and procured locally) supply of MMS in Indonesia.

In addition, given the emerging consensus among stakeholders regarding the need to effectively introduce and scale MMS, implementation research strategies that include a preparatory, introduction and scaling phase are being planned for Phase II (Introduction).

Case Study 2: Bangladesh

Decision to explore MMS use for pregnant women in Bangladesh

In Bangladesh there are three million pregnancies (UN DESA, 2019) each year and widespread micronutrient deficiencies, with over 40% of women of reproductive age suffering from anaemia and 57% suffering from zinc deficiency (Ara et al, 2019). As a result, Bangladeshi women give birth to small babies; the country has the highest prevalence (28%) of low birth weight children in the world and the under-five wasting prevalence (8.4%) equals the average in low- and middle-income countries (LMICs) (UNICEF & WHO, 2019).

The use of key maternal and newborn health services remains critically low in Bangladesh, with only 37% of all pregnant women attending four antenatal care visits (NIPORT, 2017). On the other hand, compared with many other LMICs, Bangladesh has a dense network of retail pharmacies across the country, which are the preferred first point of contact for most of the population and a familiar entity in community life (Ahmed et al, 2017). Furthermore, at the base of the pyramid, those from the poorest segments together account for a staggering 75% of all pregnant women in Bangladesh. With a per capita daily household income between USD 0.50 and USD 2.50, these women purchase medicines and supplements from neighbourhood pharmacies. It is therefore important to ensure that a powerful and comprehensive solution such as MMS is available in these stores through a market-based model.

A transition from IFA to MMS is considered to be very cost-effective in Bangladesh, averting 1,268,067 disability-adjusted life years (DALYs) over a 10-year period, preventing the deaths of an additional 12,640 children and yielding benefits that are 294 times greater than the costs (Nutrition International, 2019b).

Based on these factors, the Government of Bangladesh made the decision to undergo an effort to strengthen its antenatal care system, including exploring the distribution of MMS to ultra-poor women through a demonstration pilot supported by the United Nations Children’s Fund (UNICEF), the Bill and Melinda Gates Foundation, Sight and Life, and local partners such as International Centre for Diarrhoeal Disease Research, Bangladesh. To complement this systems-strengthening approach, stakeholders in Bangladesh are also supporting a market-based model to ensure sustainable demand and supply of MMS, described in more detail below.

Phase I: Stakeholder alignment and policy adoption

The Children’s Investment Fund Foundation (CIFF), a philanthropic organisation that focuses on improving children’s lives, has assembled a consortium of stakeholders to sustainably shape the market for affordable and accessible MMS in Bangladesh. This consortium includes a social enterprise partner, Social Marketing Company (SMC), which has a large nationwide network of franchisee pharmacies catering predominantly to base-of-the-pyramid consumers; Sight and Life, a global nutrition knowledge organisation with expertise building social business models; and the Global Alliance for Improved Nutrition (GAIN), an international non-governmental organisation.

To facilitate the exchange of information and experience on the use of MMS in these two ongoing programmes (demonstration pilot and market-based model), a national-level technical advisory group (TAG) has been set up. The TAG, convened by the Institute of Public Health Nutrition under the Ministry of Health and Family Welfare, is aligning the efforts of all key stakeholders and will play an important role in harmonising standards and facilitating the inclusion of MMS in Bangladesh’s essential medicines list and national standard treatment guidelines.

Phase II: Ensuring sustainable demand and supply of MMS using a market-based model

The consortium assembled by CIFF will help shape the market for MMS in Bangladesh. The goal of the market-based model is to get high-quality MMS (product) to pregnant women in Bangladesh at the right price, with effective promotion and the correct place or channel of distribution, while creating the right policy environment.

Product: Bangladesh has a vibrant pharmaceutical market and several brands of prenatal multiple micronutrients are already available in the market. However, none of them match the UNIMMAP formulation and most have a lower number or lower dosage of critical micronutrients. The consortium successfully enlisted a local pharmaceutical company to develop the UNIMMAP formulation of MMS; a first batch has been manufactured, undergone lab and stability testing, and is currently going through independent quality checks. Based on market surveys and assessment of consumer preferences conducted by SMC and Sight and Life, the product will be packaged in blister packs of 10 tablets per strip and 5 strips per box.

Price: Based on the market analysis and product benchmarking conducted by Sight and Life, the price of current MMS brands (not UNIMMAP-conformant) in Bangladesh ranges from USD 1.80 to USD 2.10 for a pack of 30-50 tablets. The consortium has successfully negotiated a lower price than the current market price for the same pack size, while adhering to the UNIMMAP formulation and ensuring that no actor in the value chain will incur a loss. Moreover, Bangladesh has a favourable regulatory environment for local companies to produce MMS affordably. The Bangladesh Drug Administration has set a price ceiling on finished supplements, a low import duty of 5% on the ingredients, and a prohibitively high import duty on finished supplements from foreign companies. Thus, the local pharmaceutical sector is well positioned to bring high-quality MMS directly to consumers.

Place: There are more than 200,000 pharmacies in Bangladesh, 81% of which are in rural areas. They are so common that two or three pharmacies can be found in every village market, more than 70 in major urban centres, and often thousands in a big city such as Dhaka. SMC operates a 12,000-strong social franchising network of community-level private medical practitioners and pharmacists who offer affordable public health products and services, including medicines. During stage one (2020-2021) of the market-based model, MMS will be available in all 12,000 pharmacies. During stage two (2022-2025), distribution will be expanded to cover the entire 200,000-strong pharmacy network in the country.

Promotion: To create awareness and demand for MMS, an intensive and integrated social marketing campaign will be implemented which will include: i) demand-creation for consumers and their key influencers; ii) demand-creation with health providers; and iii) creation of a digital interface with consumers to monitor adherence and uptake. 

Phase III: Scaling and impact

The market-based model will be fully operational in 2021 and it is envisioned that a total of 3.5 million pregnant women in Bangladesh will have accessed an affordable and high-quality MMS product by 2025. With the forecasted sales through a sustainable and locally owned, market-based model and the consequent reduction in low birth weight, an estimated 77,000 Bangladeshi children will be born healthy every year and have the opportunity to reach their full potential.

Conclusion

Given recent evidence, the use of MMS in pregnancy should be seriously considered, especially in regions of the world where the prevalence of wasting is high at birth and micronutrient deficiencies are common among women of reproductive age. In the context of the COVID-19 pandemic and its associated negative impacts on the economy, food access and health services, the risk of maternal and child mortality is sharply increasing due to conditions such as maternal micronutrient deficiency and early child wasting (Fore et al, 2020; Headey et al, 2020­; Headey & Ruel, 2020; Roberton et al, 2020;). MMS is a potential solution for mitigating these risks, as acknowledged by the international nutrition community (UNICEF et al, 2020; Multiple Micronutrient Supplementation in Pregnancy: Technical Advisory Group, 2020). Indonesia and Bangladesh provide examples of how to initiate and accelerate the use of MMS in two different contexts in Asia.

For more information please contact Kristen M. Hurley. 

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¹ Defined as <-2 z-scores weight-for-length/height.

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Figure 1: Model (roadmap) to national multiple micronutrient supplementation introduction and scaling

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Kristen Hurley, Endang L Achadi, Clayton Ajello, Sufia Askari, Madhavika Bajoria, Kalpana Beesabathuni, Quinn Harvey, Toslim Uddin Khan, Shannon King, Klaus Kraemer, Otte Santika, Sri Sumarmi, Abdul Razak Thaha and Robert E Black (). Prevention of child wasting in Asia: Possible role for multiple micronutrient supplementation in pregnancy. Field Exchange 63, October 2020. p76. www.ennonline.net/fex/63/childwastingpreventionasia

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