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Following the release of the 2016 WHO Guidelines for Antenatal Care, The New York Academy of Sciences assembled a scientific task force comprised of international experts in micronutrient deficiencies, public health, nutrition, pediatrics and health economics to:

• Compile the evidence on the prevalence of micronutrient deficiencies in pregnant women or women of reproductive age
• Review the evidence on the benefits and risks of multiple micronutrient supplements on maternal and perinatal outcomes
• Create a roadmap to guide decisions in countries considering the implementation of such programs.

The findings from the first phase of this initiative show that substantial benefits may be expected, in terms of mortality reduction and poor birth outcome, by shifting from IFA to MMS in Antenatal Care programs.

Promoting MMS in Low and Middle-Income Countries

The Multiple Micronutrient Supplementation Technical Advisory Group (TAG) assists countries considering the use of multiple micronutrient supplements in their antenatal care programs. The New York Academy of Sciences and the TAG have collaborated with UNICEF, with funding from the Bill & Melinda Gates Foundation, to promote the uptake of MMS by pregnant women in a number of pilot low and middle-income countries (LMICs). These promotional efforts encompass the following activities:

• Recruitment and coordination of a Technical Advisory Group (TAG) to provide evidence and materials to governments in LMICs so that they can tailor the use of MMS to their specific conditions
• Facilitation of global MMS efforts, via the creation of a communications hub to advise and document the pilot phase throughout the planned implementation
• Provision of technical support to UNICEF as it rolls out MMS in four pilot countries (Bangladesh, Madagascar, Burkina Faso and Tanzania), as well as other locations considering making the switch from iron and folic acid to MMS

For this initiative, UNICEF assisted with the rollout and implementation of MMS in pilot LMIC countries. Vitamin Angels supplied the product and provision of MMS. The Healthy Mother’s Healthy Babies Consortium brought together stakeholders, including country representatives, research and knowledge institutions, non-governmental organization (NGOs), technical organizations, UN agencies, private sector stakeholders, and funders to work together to raise awareness, trigger policy change and accelerate adoption of MMS.

Review of Evidence

Why MMS?

Multiple-micronutrient deficiencies often coexist among women of reproductive age (WRA) in low- and middle-income countries (LMICs). This may put their health and that of their offspring at risk, especially during pregnancy when micronutrients requirements increase. Multiple micronutrient supplements (MMS) may fill those gaps but in 2016 the WHO Guidelines for Antenatal Care reaffirmed their recommendation of IFA for routine use in pregnancy. WHO’s recommendation was based on “…some evidence of risk, and some important gaps in the evidence”. The WHO Guideline however, commented that “policy-makers in populations with a high prevalence of nutritional deficiencies might consider the benefits of MMS on maternal health to outweigh the disadvantages, and may choose to give MMS”.

Since the release of the 2016 ANC Guidelines, two important reviews were carried out that provided high quality evidence on the potential benefits to be gained in terms of various antenatal and maternal outcomes by switching from IFA to MMS. Specifically, the IDP meta-analysis found that, when compared to IFA alone, MMS would:

• Reduce the risk of stillbirth
  • by 8% in the overall population of pregnant women
  • by 21% in the group of anemic pregnant women
• Reduce the risk of mortality among 6-month infants
  • by 29% in the group of anemic pregnant women
  • by 15% in female infants
• Reduce the risk of low birth weight (<2500g)
  • by 12% in the overall population of pregnant women
  • by 19% in the group of anemic pregnant women
• Reduce the risk of preterm (<37 weeks) birth
  • by 8% in the overall population of pregnant women
  • by 16% in the group of underweight women
• Reduce the risk of being born small-for-gestational age
  • by 3% in the overall population of pregnant women
  • by 8% in the group of anemic pregnant women

In 2020, WHO reviewed the new evidence that became available since the publication of the 2016 ANC Guidelines and updated the recommendations for MMS during pregnancy. These updated Guidelines now state that antenatal MMS that include IFA are recommended in the context of rigorous research.

Reference: Smith ER, Shankar AH, Wu LS-F, et al. 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 randomized trials in low-income and middle-income countries. Lancet Glob Heal. 2017;5(11):e1090-e1100.

MMS and COVID-19

• Preventing and controlling micronutrient deficiencies in populations affected by an emergency​
• Use of MMS for maternal nutrition and birth outcomes during COVID
• Protecting Maternal Diets and Nutrition Services in the Context of COVID-19

Key Scientific Papers

• 2016 WHO Guidelines for Antenatal Care
• 2020 update on MMS – WHO Guidelines for Antenatal Care
• WHO recommendations on antenatal nutrition: an update on multiple micronutrient supplements
• 2019 Cochrane Review
• 2017 Lancet GH Review
• Review of the evidence regarding the use of MMS in low‐ and middle‐income countries
• Replacing IFA with MMS among pregnant women in Bangladesh and Burkina Faso: costs, impacts, and cost‐effectiveness
• The upper level: examining the risk of excess micronutrient intake in pregnancy from antenatal supplements
• Benefits of MMS supplementation in pregnancy
• Expert consensus on an open-access UNIMMAP–MMS product specification
• Setting research priorities on multiple micronutrient supplementation in pregnancy
• Interventions to increase adherence to micronutrient supplementation during pregnancy: a protocol for a systematic review
• Antenatal multiple micronutrient supplementation: call to action for change in recommendation (letter to the editor)
• Multiple micronutrient supplementation during pregnancy: a decade of collaboration in action
• Interventions to Increase Adherence to Micronutrient Supplementation During Pregnancy: A Systematic Review
• Multiple micronutrient supplements versus iron-folic acid supplements and maternal anemia outcomes: an iron dose analysis
• Effect of multiple micronutrient supplements v. iron and folic acid supplements on neonatal mortality: a reanalysis by iron dose
• Micronutrient supplements in pregnancy: an urgent priority
• Antenatal multiple micronutrient supplements versus iron-folic acid supplements and birth outcomes: Analysis by gestational age assessment method

Reports

• Meeting 1 Report
• Meeting 2 Report
• eBriefing: Improving Birth Outcomes with Multiple Micronutrient Supplementation
• MMS Implementation Meeting Report
• Decision-maker Guidance
• Decision-maker Guidance (French)
• Decision-maker Guidance (Spanish)
• MMS Iron Dose Summary

Technical Reference Materials

• TRM I: Technical Brief for Policy Makers
• TRM II: Training Materials
• TRM III: Logistics of Implementation
• FAQ

Background Materials

Torheim, L.E., Ferguson, E.L., Penrose, K., Arimond, M. (2010). Women in Resource-Poor Settings Are at Risk of Inadequate Intakes of Multiple Micronutrients. J Nutr, 140(11): 2051S-2058S

Pathak, P., Kapil, U., Yajnik, C. S, Kapoor, S. K., Dwivedi, S. N., & Singh, R. (2007). Iron, Folate, and Vitamin B12 Stores among Pregnant Women in a Rural Area of Haryana State, India. Food and Nutrition Bulletin, 28(4): 435–438.

Lee, S., Talegawkar, S., Merialdi, M., & Caulfield, L. (2013). Dietary intakes of women during pregnancy in low- and middle-income countries. Public Health Nutrition, 16(8): 1340-1353.

Kulkarni, B., Christian, P., LeClerq, S., & Khatry, S. (2010). Determinants of compliance to antenatal micronutrient supplementation and women’s perceptions of supplement use in rural Nepal. Public Health Nutrition, 13(1), 82-90.

Gernand, A. D., Schulze, K. J., Stewart, C. P., West, K. P., & Christian, P. (2016). Micronutrient deficiencies in pregnancy worldwide: health effects and prevention. Nature reviews. Endocrinology, 12(5), 274-89.

Lu, C., Black, M. M., & Richter, L. M. (2016). Risk of poor development in young children in low-income and middle-income countries: an estimation and analysis at the global, regional, and country level. The Lancet. Global health, 4(12), e916-e922.

Jiang, T., Christian, P., Khatry, S.K., Wu, L., West, K.P. (2005). Micronutrient Deficiencies in Early Pregnancy Are Common, Concurrent, and Vary by Season among Rural Nepali Pregnant Women. J Nutr, 135(5), 1106-1112.

Project Outcomes

This initiative, supported by a grant from the Bill & Melinda Gates Foundation, is a collaboration between UNICEF, the MMS Technical Advisory Group, and the New York Academy of Sciences. Activities carried out through this effort include:

• The development of a Communications Hub to link the various stakeholders (scientists, implementers, multilateral organizations, policy makers and the private sector) involved in MMS programs
• The coordination of technical support to adopting countries, including the preparation of technical reference materials to explain and organize MMS programs and to train the health workforce in their implementation
• UNICEF implementation of a MMS rollout in 4 pilot countries (Bangladesh, Madagascar, Burkina Faso and Tanzania)
• Promote and support MMS programs in additional countries as needed
• A webinar to disseminate the findings of the scientific task force
• A systematic review on interventions to increase adherence to micronutrient supplementation during pregnancy

MMS Meeting Workshops

Core Product Specification Workshop, November 11-12, 2019

On November 11th and 12th, 2019, the Academy and the Micronutrient Forum (MNF) co-hosted a workshop in Washington DC to develop a Core Product Specification for multiple micronutrient supplement in pregnancy.

Technical Report

Task Force on Multiple Micronutrient Supplementation (MMNS) in Pregnancy, April 17-18, 2018

Second of two closed door technical consultation at the Academy. While the first meeting examined the benefits and potential risks of multiple micronutrient supplementation, the second consultation focused primarily on considerations for the development of a roadmap to guide countries considering multiple micronutrient supplement implementation

Meeting Report

Task Force on Multiple Micronutrient Supplementation in Pregnancy, November 15-16, 2017

First of two closed-door technical consultations at the Academy to review recent evidence on the benefits and risks of multiple micronutrient supplementation, identify research gaps, and determine which populations may benefit most from supplementation.

Meeting Report

Sponsors

Funding Support

Organized By

Thiamine deficiency remains a pressing public health issue. Infantile beriberi, a disease caused by thiamine deficiency, presents during the exclusive breastfeeding period and without treatment commonly results in death within hours of clinical presentation. There is also growing evidence suggesting sub-clinical thiamine deficiency may have a measurable, lasting impact on cognitive development and psychomotor functions.

However, addressing the spectrum of thiamine deficiency disorders (TDD) is impeded by several gaps in knowledge. This initiative seeks to address the key gaps in our knowledge of TDD and to develop a model for control of TDD in the most affected countries. The Academy is engaged in research to reduce the global burden of thiamine deficiency. With funding from the Bill & Melinda Gates Foundation, this project includes a number of research partners around the world and aims to fill several research gaps.

Key Knowledge Gaps

1. Limitations in assessing status.

2. Lack of knowledge about prevalence, particularly in sub-Saharan Africa

3. Lack of strategy to address deficiencies, particularly during lactation

4. No standard approach to surveillance and prevention

5. No standard case definition

Research

In 2017, the Academy convened an expert panel to estimate the global burden of thiamine deficiency and related disease risks and to review possible intervention strategies to reduce the associated burden of disease. The panel concluded that there is a surprising lack of information on this condition, despite its likely importance as a cause of infant mortality in South Asia and possibly in other LMIC, and its known effects on child development. Following the panel’s recommendations, this initiative aimed to address the key knowledge gaps that were identified through the following projects.

Supplementation

Determine the appropriate level of thiamine supplementation during lactation to provide adequate thiamine status for mothers and their infants. A dose response trial of lactating women in Cambodia measured thiamine content in breast milk, as well as in the blood of mother and infants.

Resulting publication:

– Gallant et al (2021) Low-dose thiamine supplementation of lactating Cambodian mothers improves human milk thiamine concentrations: a randomized controlled trial. The American Journal of Clinical Nutrition. 114 (1): 90–100.

Cognitive Outcomes

There is evidence that even asymptomatic thiamine deficiency can cause long-lasting cognitive deficits. The infants enrolled in the supplementation trial underwent neurological testing to look for cognitive differences between supplementation and placebo groups.

Resulting publication:

– Measelle et al (2021) Thiamine supplementation holds neurocognitive benefits for breastfed infants during the first year of life. Ann. N.Y. Acad. Sci., 1498: 116-132.

Fortification

Salt has been identified a good vehicle for thiamine fortification in South-East Asia. This project measured salt consumption in Cambodia to inform the level of thiamine required to adequately fortify salt.

Resulting publications:

– Chan et al (2021) Assessment of salt intake to consider salt as a fortification vehicle for thiamine in Cambodia. Ann. N.Y. Acad. Sci., 1498: 85-95.

– Green et al (2021) Modeling thiamine fortification: a case study from Kuria atoll, Republic of Kiribati. Ann. N.Y. Acad. Sci., 1498: 108-115.

– Whitfield et al (2021) Thiamine fortification strategies in low- and middle-income settings: a review. Ann. N.Y. Acad. Sci., 1498: 29-45.

Biomarkers

The relationship between the two thiamine biomarkers, thiamine diphosphate and the erythrocyte transketolase assay, is being studied to assess which biomarker is best suited to identify thiamine deficiency.

Resulting publication:

– Jones et al (2021) Erythrocyte transketolase activity coefficient (ETKAC) assay protocol for the assessment of thiamine status. Ann. N.Y. Acad. Sci., 1498: 77-84.

African Surveys

Some neurological disorders found in Sub-Saharan Africa have similar symptoms to thiamine deficiency disorders and the increase in rice consumption has raised concern that thiamine deficiency may also be present in Africa. A study was conducted to assess thiamine status in Gambian women of reproductive age.

Resulting publication:

– Bourassa et al (2021) Thiamine deficiency in Gambian women of reproductive age. Ann. N.Y. Acad. Sci.

Surveillance and Control Programs

Thiamine deficiency is most well known in South Asia and despite the efforts in the region, it remains a pervasive problem. We supported countries to develop surveillance and control programs to reduce the burden thiamine deficiency through fortification, supplementation, education, behavior change and surveillance programs. Technical Reference Materials have been developed for his purpose.

Thiamine Deficiency Disorder Case Definition

A clear case definition for TDD has not been established and creates challenges in efficiently diagnosing TDD. A case control study is being carried to establish a case definition based on cohorts of infants and children in Laos.

Resulting publications:

– Hess et al (2020) Establishing a case definition of thiamine responsive disorders among infants and young children in Lao PDR: protocol for a prospective cohort study. BMJ Open. 2020 Feb 13;10(2):e036539.

– Smith et al (2021) Traditional postpartum food restrictions among women in northern Laos: Preliminary analysis of an ongoing prospective cohort study. Proceedings of the Nutrition Society, 80(OCE1), E30.

– Smith et al (2021) Thiamine deficiency disorders: a clinical perspective. Ann. N.Y. Acad. Sci., 1498: 9-28.

– Koshy et al (2021) The rediscovery of thiamine deficiency disorders at a secondary level mission hospital in Northeast India. Ann. N.Y. Acad. Sci., 1498: 96-107.

Thiamine Deficiency in High-Income Countries

Thiamine deficiency has been typically associated with alcoholism in high-income countries, or as a prevalent problem in low- and middle-income countries whose populations rely on staple foods with a low content of thiamine. Several literature reviews and retrospective studies suggested that, in high resource settings, non-alcoholic thiamine deficiency can be prevalent when associated with certain health conditions or lifestyles.

Resulting publications:

– Gomes et al (2021) Thiamine deficiency unrelated to alcohol consumption in high-income countries: a literature review. Ann. N.Y. Acad. Sci., 1498: 46-56.

– Rakotoambinina et al (2021) Pediatric thiamine deficiency disorders in high-income countries between 2000 and 2020: a clinical reappraisal. Ann. N.Y. Acad. Sci., 1498: 57-76.

– Mates et al (2021) A Retrospective Case Series of Thiamine Deficiency in Non-Alcoholic Hospitalized Veterans: An Important Cause of Delirium and Falling?. Journal of clinical medicine, 10(7), 1449.

– Gibson et al (2020) Benfotiamine and Cognitive Decline in Alzheimer’s Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial . J Alzheimers Dis. 78(3):989-1010.

Resources

Recent publications

2021 Thiamine Special Issue

Useful Documents

Technical Reference Materials 

Thiamine Workshop 1 Report

Thiamine Workshop 2 Report

Thiamine content of foods in key countries 

Cambodia 

Laos

Thiamine availability based on food balance sheets (2011)

Thiamine availability below 1.2 mg/capita/day

High % of energy from low-thiamine staple crops

Analysis of thiamine biomarkers

Guidance to assess thiamine biomarkers

Analytical requirements of ThDP and ETKA

Large-scale survey on thiamine status

Women of reproductive age

Infants 

Food fortification with thiamine

Countries with existing thiamine fortification programs

Educational materials 

For healthcare professionals: “Thiamine deficiency disorders: identification and treatment”

For healthcare professionals: “Infantile beriberi: clinical symptoms and case studies”

For healthcare professionals: “A guide to increase thiamine intake and prevent thiamine deficiency”.

For pregnant women and lactating mothers: “The importance of thiamine during pregnancy, breastfeeding and infancy”

Relevant websites

Global Fortification Data Exchange

Food Fortification Initiative

OpeN-Global

Key scientific publications

Whitfield, K.C., Bourassa, M.W., Adamolekun, B., et al. (2018). Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs. Annals of the New York Academy of Sciences, 1430(1), 3-43.

Hiffler, L., Adamolekun, B., Fischer, P.R., Fattal-Vavleski, A. (2017). Thiamine content of F‐75 therapeutic milk for complicated severe acute malnutrition: time for a change? Annals of the New York Academy of Sciences, 1404(1), 20-26.

Adamolekun, B., Hiffler, L. (2017). A diagnosis and treatment gap for thiamine deficiency disorders in sub-Saharan Africa? Annals of the New York Academy of Sciences, 1408(1), 15-19.

Whitfield, K.C., Karakochuk, C.D., Kroeun, H., et al. (2017). Household consumption of thiamin-fortified fish sauce increases erythrocyte thiamin concentrations among rural Cambodian women and their children younger than 5 years of age: a randomized controlled efficacy trial. The Journal of Pediatrics, 181, 242-247.

Johnson, C. R., Fischer, P. R., Thacher, T. D., et al. (2019). Thiamin deficiency in low- and middle-income countries: Disorders, prevalences, previous interventions and current recommendations. Nutrition and Health. 

Workshops

Two technical workshops are planned in order to support the development of surveillance and control programs in countries where thiamine deficiency is a public health problem. While the first workshop was held in November 2019, both workshops aim to discuss steps to be taken by each country to roll out a TDD control and prevention program in their specific context; and provide necessary knowledge and training to establish their program. 

Workshop 1, November 19-21, 2019, Luang Prabang

The first regional workshop was held in Luang Prabang, Lao PDR, with participation from several other countries in the region where thiamine deficiency is a public health problem. Participating countries included, Lao PDR, Myanmar, Cambodia, Bhutan, Thailand, Vietnam and India (Assam and Kashmir). The aims of this workshop were: to bring experts and the most current knowledge about prevalence, assessment, and possibly interventions for thiamine deficiency; assess individual country situation and need; and to introduce the Technical Reference Materials (TRMs). Discussions focused on the inputs and activities needed to enable country officials to begin planning their TDD control program.

Workshop 2, March 9 and 11, 2021

The second meeting of the Global Thiamine Alliance was hosted virtually. The first day of the workshop was held as a public webinar, where recent developments in thiamine research were widely disseminated. On the second day of the workshop, which was limited to the participants of the first workshop, we discussed the progress and barriers that individual countries had on their proposed action plan and the future needs of the Global Thiamine Alliance.

Through a grant provided by the Bill & Melinda Gates Foundation, The New York Academy of Sciences created a consortium for nutrition modeling aimed at improving the usability of tools for nutrition policy making and at increasing their uptake by low middle income countries (LMIC). In April 2017, the Institute partnered with the Micronutrient Forum to convene a two-day technical consultation to review seven tools designed to help decision makers in LMICs develop and streamline their nutrition programs and interventions.

These tools were selected on the basis of their ability to elaborate nutrition policy scenarios adapted to national priorities and contexts, whether through the use of mathematical optimization routines or other evidence-based analytical approaches. Services provided by those tools range from advocacy to allocative efficiency to budget planning. The meeting highlighted the deep capabilities of those tools, and several examples were presented of successful use that confirmed their potential utility to nutrition policy making.

What is Nutrition Modeling?

Nutrition Modeling refers to computer assisted optimization routines that seek to select a best solution with regard to a nutrition objective among a set of available policy or program alternatives. Some tools on the Consortium follow mathematical optimization algorithms, some use spreadsheet formula, some use qualitative methods to drill down on nutrition data. Regardless of design, they all share the intent of improving the use of available knowledge and data in designing nutrition policies and programs.

The mandate of the Nutrition Modeling Consortium is to:

• Increase end-users’ input in the specification of services to be provided by these tools.
• Help end-users understand better how those tool can serve their nutrition programming needs.
• Advance the joint utility and effectiveness of the modeling tools through a collective effort by nutrition modelers in order to enhance their technical inter-operability, and improve their usability to end-users.

How the Consortium Works

The Consortium of Nutrition Modelers aims to improve the use of the evidence base in policy and program decision making through the use of mathematical modeling of nutrition activities. It is led by a Scientific Organizing committee composed of nutrition modelers and end-users. The Secretariat has the responsibility of linking the SOC to the modeling community and to end-users, to coordinate the work of the Consortium and to organize and convene meetings of the Consortium.