Preventing Maternal Deaths due to Pre-Eclampsia/Eclampsia (PE/E)

Objectives Present PE/E as a public health priority Define interventions available for PE/E prevention, detection and management Share country experiences and expected results

PE/E: Pregnancy-Induced Hypertension 18% of all maternal deaths worldwide Highest in Latin America Estimated in 2002: 4,152,000 PE/E cases 63,000 deaths …and the lives of many babies Sources: Countdown to 2015 Decade Report (2000–2010) WHO and UNICEF 2010; Balancing the Scales, Engender Health, 2007; Khan et al., 2006

Pre-Eclampsia/Eclampsia (PE/E) As MMR declines in Indonesia, a higher proportion of maternal deaths are now due to eclampsia. Second to hemorrhage as a specific direct cause of maternal mortality ↓MMR, ↑ % eclampsia 7–15% pregnant women will develop PE 1–3% progress to eclampsia Increases risk of perinatal mortality Sources: Khan et al., 2006; WHO 1994; Lain, K et al 2002; Dolea, C., and AbouZahr, C. 2003; Indonesia Maternal Health Assessment, 2010

7 times more likely to develop PE, Bearing the Burden A woman in a developing country is 7 times more likely to develop PE, 3 times more likely to progress to eclampsia, and 14 times more likely to die of eclampsia. Source: Balancing the Scales, Engender Health, 2007 Photo credit: Stephjanie Suhowatsky

Why Do Women Die from PE/E? Infrequent ANC means infrequent screening Poor detection during ANC of high BP, proteinuria <50% of women deliver with a SBA Reluctance to treat: Concern over the management of severe PE cases Reluctance to give the loading dose of MgSO4 before referral/transfer Limited access to emergency obstetric and newborn care (EmONC) The primary cause of PPH is uterine atony and this can be addressed with active management of the third stage of labor. We cannot predict who will experience PPH on the basis of risk factors. Globally, only about half of deliveries are attended by a person with midwifery skills. Those who receive skilled care tend to be residents of urban areas and more well-to-do. How can we reach everyone else? Referral and transport to facilities for skilled care is not always the answer when PPH occurs in the community because death from hemorrhage can occur in 2 hours. A very famous man very recently said and I quote: “Women are not dying because of diseases we cannot treat…They are dying because societies have yet to make the decision that their lives are worth saving.” Many of you in this room know this great man. That was Mahmoud Fathalla and what he said is so true for Post partum hemorrhage. Women are not dying of postpartum hemorrhage because we know very well how to prevent most of PPH. Women are not dying of PPH because we know very well how to treat postpartum hemorrhage. Women are dying because we have not taken to scale simple prevention measures and treatments, we have not worked out how to take care to the most vulnerable and needy and we have failed to empower our communities and most peripheral health workers to prevent and treat PPH.   And in Mahmoud Fathalla’s words, they are dying because societies have yet to make the decision that their lives are worth saving Source: Make Every Mother and Child Count: The Case for Preventing Postpartum Hemorrhage, H Sanghvi ppt, June 2005 Source: Countdown to 2015 Decade Report (2000–2010) WHO and UNICEF 2010

Hypertension in Pregnancy Source: Wagner, LK. First Choice Community Healthcare. American Family Physician;70(12):2317-2324. 15 December 2004.

Typical Signs and Symptoms What is PE/E? Probable Diagnosis Typical Signs and Symptoms Mild PE Two readings of diastolic BP 90 mm Hg or more but below 110 mm Hg 4 hours apart Proteinuria up to 2+ Severe PE Diastolic BP 110 mm Hg or more Proteinuria 3+ or more Hyperreflexes (patellar or bicep) Headache (↑ frequency, unrelieved by regular analgesics) Blurred vision Oliguria (<400 mL urine in 24 hours) Upper abdominal pain (epigastric pain; pain in right upper quadrant) Pulmonary edema Eclampsia Convulsions and coma (unconscious) Diastolic blood pressure 90 mm Hg or more Proteinuria 2+ or more Coma (unconscious) Other symptoms and signs of severe PE 5 main causes of MD Hemorrhage:the leading cause of maternal death; Sepsis – systemic infection Induced abortion is presented separately (13%) – though actual COD is Hem or Sepsis Eclampsia is condition of high blood pressure during pregnancy – is responsible for 13% Obstructed labor – 7% Indirect causes – not 4 big COD - are pre-existing conditions that are exacerbated by pregnancy – In areas of high HIV prev, such as S. A., is leading cause of maternal death Want to draw your attention to distribution of causes because policy implications vary by cause For ex: ~60% of all maternal deaths occur + - 48 hours of delivery – within concentrated period of time, but can’t be predicted Ob Labor – you may have 24-48 hours to access care Hem: least forgiving – on average, in 2 hours woman can exsanguinate Source: Making childbirth safer: Promoting Evidence-based Care ppt, POPPHI Source: Prevention and management of pre-eclampsia and eclampsia Reference Manual for Healthcare Providers, MCHIP, 2011

Who is at Risk for PE? All pregnant women are potentially at risk. A family history of PE or prior PE/E Pre-existing condition: obesity, chronic hypertension and diabetes Age: Adolescents, women >35 years Primigravida Poor outcome of previous pregnancy (IUGR, abruptio placentae, fetal death) First pregnancy with a new partner Photo credit: Sheena Currie Risk factors not very useful: Primigravida are now about 50% of obstetric population A significant proportion of PE occurs postpartum No effective or affordable biochemical or biophysical predictor available All pregnant women are potentially at risk. All need prevention and early detection of PE.

What Can Be Done? Prevention Detection Management Seeking simple, inexpensive and effective solutions that reach all pregnant women. Prevention Detection Management Photo credit: Stephanie Suhowatsky Photo credit: Sheena Currie Photo credit: Anita Khemka

Almost 100 interventions tested in randomized trials Prevention Almost 100 interventions tested in randomized trials x x x

Primary Prevention Intervention Pregnancy outcome Recommended? Prevention of IUGR Theoretically contributes to primary prevention of PE (and IUGR) in the next generation Yes Family planning Potential to reduce pregnancies at risk for PE Pre-conceptual prevention and/or treatment of obesity Potential to reduce PE Calcium supplementation Reduces PE in those at high risk and with low baseline dietary calcium intake; No effect on perinatal outcome High risk of gestational hypertension; low dietary calcium intake Low-dose aspirin Reduces PE; Reduces fetal or neonatal deaths Populations at increased risk Magnesium or zinc supplementation No PE reduction Insufficient evidence to recommend* Fish oil supplementation and other sources of fatty acids No effect on low- or high-risk populations s/a* Heparin or low-molecular weight heparin Reduces PE in women with renal disease and thrombophilia Anti-oxidant vitamins (C, E) Reduced PE in one trial Protein or salt restriction No effect No Source: Prevention and management of pre-eclampsia and eclampsia reference manual, MCHIP, 2011

Potential Impact of Calcium Calcium reduces PE by 50% High-risk women Low calcium intake Universal calcium supplementation could: Prevent 21,500 maternal deaths Reduce DALYs by 620,000 Table taken from the Lancet trial 2008 about interventions for maternal and child under-nutrition What works? Interventions for maternal and child undernutrition and survival, Bhutta et al, Lancet, 2008 Source: Bhutta et al., Lancet, 2008

Daily Calcium Intake Minimum daily calcium intake, Adult WRA (1000−1200 mg/day) Minimum daily calcium intake, Pregnant Women (1300−1500 mg/day) Source: Calcium and Prevention of Pre-eclampsia: Summary of Current Evidence, Monitoring, Evaluation and Research Task Force of the PE/E working group 2010

Potential Impact of Aspirin 17% reduction in the risk of PE >75 mg of aspirin per day 14% reduction in the risk of fetal, neonatal and infant deaths Daily low-dose aspirin before 16 weeks of gestation among women at risk for PE = significant decrease in: PE Severe PE IUGR Preterm birth Garlic, exercise , acupunture Source: Bujold et al., 2010; Knight M, Duley L, Henderson-Smart DJ, King JF. (Cochrane Review) 2007

Benefits of PE Prevention Infants of women with PE are 5 times more likely to die than those born to mothers without PE Photo credit: Geeta Sharma

Detecting PE/E: ANC Coverage Source: Mandel B, Evidence Base for PE/E Strategy, 2009

Detecting PE: High BP, Proteinuria Measuring BP: Significant training needed Robust, maintained equipment Only 50% women receive ANC Not all who attend have BP taken Measuring urine protein: Tests not available in low-resource settings Boiling not feasible in high volume sites Photo credit: Daniel Antonaccio Describe why tests are pricey Source: Mandel B, Evidence Base for PE/E Strategy, 2009

ANC in Africa: BP Measurement and Urine Analysis Source: DHS (as noted on the slide)

Detecting PE: Point of Care Diagnostics Protein Test This is an example of point of care diagnostic test: Low cost Easy to use: ANC, community level Immediate results Jhpiego—JHU-BME: Patent Pending Photo credit: Daniel Antonaccio

Managing PE/E and Preventing Eclampsia Severe PE and eclampsia management: Anti-convulsants: Magnesium sulfate can reduce the occurrence of eclamptic seizures by more than 50% and maternal deaths by 46%. Anti-hypertensives: Indicated for maternal benefit and may prolong pregnancy/improve fetal maturity. Induction of labor: In severe PE, within 24 hours of the onset of symptoms; eclampsia within 12 hours of the onset of convulsions/fits. Source: L, Gulmezoglu A, Henderson-Smart D. 2006. The Cochrane Library. Magpie Trial Collaborative Group: Lancet 2002.

Magnesium Sulfate: Evidence Treat severe PE Magpie Trial, 2002, 10,000 women, 33 countries Reduced the occurrence of eclampsia by 58% Reduced maternal deaths by 46% Treat eclampsia Collaborative Eclampsia Trial (1995) compared 3 most popular treatments (magnesium sulfate, diazepam, and phenytoin) Magnesium sulfate had a 52% and 67% lower recurrence of convulsions than diazepam and phenytoin, respectively Sources: Duley L, Gulmezoglu A, Henderson-Smart D. 2006; Duley L, Henderson-Smart D. 2003; Beguma R et al., 2001

Magnesium Sulfate and the Neonate Better outcomes than diazepam or phenytoin Fewer neonatal deaths Greater vigor of babies (5 minutes after birth) Decreased need for care: Lower chances of long hospital stay in intensive care unit; Shorter duration of stay in neonatal care unit; and Fewer neonatal admissions to a special care unit. Source: Duley et al., 2003a

by treating approximately Preventing Eclampsia 1 case of eclampsia can be prevented by treating approximately 7women with severe PE This woman, Hema Gharti Magar, was suffering from backache, vomiting and lower abdominal pain. Her husband brought her by rickshaw to Dhanghadi in Kailali district in Nepal in November 2009. They diagnosed, tested and treated her for severe pre-eclampsia. Although at many health facilities in Nepal, nurses are hesitant to diagnose severe pre-eclampsia and immediately give magnesium sulphate. Fortunately for Hema, staff here were prepared and proactive. The nurse administered magnesium sulphate and monitored Hema continuously. Source: Sibai, 2005 Photo credit: Geeta Sharma

Immediate Treatment: Magnesium Sulfate Severe PE/E patients who received a loading dose before referral have: Reduced number of convulsions Controlled convulsions Shortened time to full consciousness Reduced maternal mortality and stillbirths Loading dose useful at home births and peripheral facilities Seizure to Treatment Interval Source: Rashida et al., 2004

Magnesium Sulfate: Challenges Not uniformly recommended in national service delivery guidelines Limited availability: Only included in half of the world’s national essential drugs list Perceived need for close monitoring Requires updated, empowered and skilled providers to administer Because eclampsia is rare experience with use of MgSO4 is minimal Inexpensive: Little incentive for companies to commercialize Inconvenient in packs of 500–1000 mL (need 250 mL) Source: Reducing eclampsia-related deaths—a call to action, the Lancet, 2008

Benefits of Magnesium Sulfate Use A 50% increase in the use of magnesium sulfate would prevent 10—15 maternal deaths per 100,000 live births Source: Fernando Althabe presentation at CIHR, WHO and NIH Workshop Ottawa, September 24—25, 2009 Photo credit:Daniel Antonaccio

Expected Results Reduced PE incidence among calcium-deficient populations Increased detection of PE Improved severe PE case management Increased awareness about danger signs Decreased eclampsia cases Reduced maternal and perinatal mortality

Results: Improved Management of Severe PE/E in Nepal, 2009 22 facilities: Average score on 3 standards increased from 22%–60%

Results: Reduced Case Fatality Rate from PE/E Magnesium Sulfate Use in Purulia, West Bengal, India, 2002–2006

On the Horizon: 2003…2011? “The technologies identified 5 years ago continue to be the key issues” Nutritional supplements to prevent PE/E Antiplatelets to prevent PE/E Methods for early detection of PE/E or elevated risk for PE/E Scaling up use of magnesium sulfate for both prevention and treatment of eclampsia Source: Tsu and Coffey, BJOG, 2009

Conclusion Eclampsia is a major contributor to maternal and neonatal mortality. Calcium and aspirin can reduce PE risk among some groups of pregnant women. Improved PE detection is needed: during ANC and to reach those not using ANC. Eclampsia can be prevented through early diagnosis and prompt PE treatment. Magnesium sulfate is effective and needs to be scaled up.