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

2. 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

3. 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

4. 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

5. 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

6. 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

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

8. 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 hours of delivery – within concentrated period of time, but can’t be predicted
Ob Labor – you may have 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

9. 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.

10. 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

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

12. 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

13. 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

14. 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

15. 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

16. 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

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

18. 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

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

20. 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

21. 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 The Cochrane Library. Magpie Trial Collaborative Group: Lancet 2002.

22. 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

23. 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

24. 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 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

25. 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

26. 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

27. 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

28. 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

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

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

31. 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

32. 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.