1. The evidence for going to scale with Calcium supplementation Harshad Sanghvi Vice-President & Medical Director, Jhpiego Senior Advisor, Accelovate/USAID, MCHIP/USAID Senior Associate, Bloomberg School of Public Health JHU Advocacy meeting for scale-up of calcium supplementation to pregnant woman for prevention of Pre-Eclampsia & Eclampsia Kathmandu, Nepal 10 March 2014

2. Key questions to be answered  Is the problem a major public health concern?  Is there a high demand for a solution?  Is there sufficient evidence of effectiveness of solution?  Will the solution have a significant impact in correcting the problem  Is the solution feasible to implement and will it reach the most vulnerable women early  Are the limitations of the solution acceptable? 2

3. MMR is declining, though still high: 229/100,000 (MMS, 2008/9) SBA deliveries increasing but still low 19% in 2006 to 36% in 2011 2 of 3 women deliver at home with no SBA  Eclampsia is the leading cause of maternal mortality  21% of total maternal deaths  29.8% of hospital maternal deaths 199820092011 MMR 539247 PPH 37%19% Eclampsia14%21% % birth with SBAs 17%19%36% Is the problem a major public health concern in Nepal ?

4. Is there a high demand for a solution?  In discussion since 2007  Potential to impact both MDG 4 &5  Already part of the national strategy including nutrition 4

5. Three prong strategy of MOHP Nepal to address PE/E MOPH NESOG Partnership to improve quality of Eclampsia management using SBMR Strengthen ANC Community detection of PE Calcium pilot ANC Community sprinkles

6. 6 01510 Protective effect Deleterious Effect Is there sufficient evidence of effectiveness of solution? Relative risk

7. Calcium Supplementation versus Placebo 7 01510 Cochrane Review 2012

8. Is there sufficient evidence of effectiveness of solution? P L A I N L A N G U A G E S U M M A R Y:  Calcium supplements help prevent pre-eclampsia, preterm birth and lower the risk of the woman dying or having serious problems related to high blood pressure in pregnancy.  Pre-eclampsia is a major cause of death in pregnant women and newborn babies worldwide. Preterm birth (birth before 37 weeks) is often caused by high blood pressure and is the leading cause of newborn deaths, particularly in low-income countries. The review of 13 trials, involving 15,730 women, found that calcium supplementation during pregnancy is a safe and relatively cheap means of reducing the risk of pre-eclampsia in women at increased risk, and women from communities with low dietary calcium. Women were also less likely to die or have serious problems due to pre-eclampsia. Babies were less likely to be born preterm. No adverse effects have been found but further research is needed into the ideal dosage for supplementation. 8 Hofmeyr GJ, Lawrie TA, Atallah ÁN, Duley L. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database of Systematic Reviews

9. Based on this evidence:  World Health Organization recommends (2011) calcium supplementation with 1.5 to 2g calcium daily to pregnant women with low dietary calcium intake  BUT:  Large dose difficult to implement  May be unnecessarily large, or even harmful

10. Will the solution have a significant impact on correcting the problem 10

11. Dietary modification program in Sydney RHJ Hamlin Lancet 1952

12. Is the solution feasible to implement and will we reach the most vulnerable women early  Difficulty in finding calcium without Vitamin D  Require large storage space: calcium is bulky  Cost for nation-wide scale up  Antenatal distribution feasible but need to get it to women early  Debate regarding dosage coming to closure  Compliance

13. 13 0 50 100 150 200 250 300 350 400 450 500 0.94 0.95 0.96 0.97 0.98 0.99 Effectiveness (proportion free of pre-eclampsia) Cost per woman ( UK £ 2005) No test, calcium to all Comparing Cost and Effectiveness of Interventions for Preventing PE Methods of prediction and prevention of pre-eclampsia: systematic reviews of accuracy and effectiveness literature with economic modeling Meads et al Health Technology Assessment 2008 Vol 12 number 6: United Kingdom

14. Low dose calcium supplementation Results  All trials used 500mg daily  Consistent 60% reduction in pre-eclampsia across all 9 trials (2234 women)  Significant reduction for all high quality trials; and all trials of calcium alone  An unexpected finding in one high quality trial of calcium plus antioxidants commencing at 8-12 weeks of pregnancy was a trend to reduced miscarriage (1/29 versus 8/31, RR 0.06, 95% CI 0.00 to 1.04). Low dose calcium supplementation for preventing pre-eclampsia: a systematic review and commentary, Hofmeyr GJ, Et al, 2014

15. Conclusions  Available evidence supports the probable effectiveness of low-dose calcium supplementation  Low quality of evidence requires further research  If the WHO recommendation of 1.5 to 2g calcium daily is not achievable, it is reasonable to use a lower dosage (eg 500mg daily)

16. Are the limitations of the solution acceptable?  Cost  Lower cost by lowering dose  Sprinkles  Not a silver bullet:  Must continue efforts to detect all PE before it becomes eclampsia  Must improve quality of care for those detected to have PEE 16

17. Final Thought: Unprecedented Commitment Coverage at Scale Quality at Scale Impact at Scale 17