Calcium supplementation to prevent pre-eclampsia in Low- and Middle-Income Countries: IPD meta-analysis, network meta-analysis and economic evaluation

WHAT IS THE PROBLEM?

Pre-eclampsia, a condition in pregnancy associated with high blood pressure and protein in the urine, is a major cause of avoidable deaths in mothers and babies, particularly in low and middle-income countries. Calcium supplements in pregnancy could prevent pre-eclampsia and potentially save 21,500 mothers every year from dying in these countries. Although calcium is on the national essential medicines list of these countries, and the World Health Organization (WHO) recommends high-dose calcium (>1.5g/day) to prevent pre-eclampsia, calcium deficiency in pregnancy continues to be a major preventable public health challenge.

We can attribute this to the reluctance of mothers to take large, unpalatable high-dose calcium tablets 3-times a day that is often associated with side effects such as vomiting and constipation. Furthermore, large numbers of bulky tablets pose logistical difficulties with transport and storage, limiting their availability in rural areas. The healthcare professionals also have concerns about the large calcium doses affecting the absorption of iron needed to treat anaemia.

WHAT NEEDS TO BE DONE?

There is an urgent need for us to identify a) the group of women who will benefit the most from calcium supplementation (based on individual characteristics) b) the most effective and acceptable minimal dose of calcium, and c) the best time to start the supplement to prevent pre-eclampsia and complications. Policymakers and healthcare professionals also need information on the barriers to the uptake of calcium and its implementation, and the cost implications of supplementation within limited healthcare resources.

WHAT HAS BEEN DONE SO FAR?

To-date, despite over 30,000 women participating in numerous studies on calcium supplementation to prevent pre-eclampsia, we were able to answer the above questions due to differences in the characteristics of women, the dosage and timing of calcium in these studies. Our international collaborative network (i-CIP) has established a partnership between researchers from low, middle- and high-income countries who conducted the above studies, WHO guideline developers, and experts on calcium supplementation in pregnancy to answer the gaps in research.

WHAT DO WE PLAN TO DO?

In this proposal, we plan to combine the data from individuals who participated in studies on calcium supplementation by a technique called 'IPD meta-analysis' to determine if the effects of calcium differed between different groups of women, and if it varied according to the dose and duration of calcium use. We will obtain the views of mothers and healthcare professionals through surveys and interviews on what they consider may hinder the uptake and use of the calcium supplementation strategy that we find to be most effective.

We will study the costs of calcium supplementation against the costs saved in low- and middle-income countries by avoiding pre-eclampsia and its complications. This economic model will be provided in a format that can be used by experts in other countries to determine the relevant economic impact. Research capacity strengthening of our partners is the key to the long-term sustainability of the project.

WHAT DO WE EXPECT WILL HAPPEN?

We expect our findings to lead to an update of the existing WHO guidelines on calcium supplementation in pregnancy, inform policymakers on optimal strategies and costs to promote calcium supplementation, reduce calcium deficiency in pregnant women, and improve outcomes for mother and baby by preventing pre-eclampsia. We planned this proposal in partnership with the patient and public involvement groups so that women are involved in the co-development of the study and dissemination.

Our collaboration with WHO (Reproductive health, Nutrition, Human Reproduction Programme HRP Alliance) is key to the development and dissemination of our work through guidelines and existing networks.