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

9% 9%

26%

0%

5%

10%

15%

20%

25%

30%

Africa Asia Latin America &the Caribbean

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)

Sources: Khan et al., 2006; WHO 1994; Lain, K et al 2002; Dolea, C., and AbouZahr, C. 2003; Indonesia Maternal Health Assessment, 2010

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

As MMR declines in Indonesia, a higher proportion of maternal deaths are now

due to eclampsia.

Bearing the Burden

Photo credit: Stephjanie SuhowatskySource: Balancing the Scales, Engender Health, 2007

A woman in a developing country is

7 times more likely to develop PE,

3 times more likely to progress toeclampsia, and

14 times more likely to die of eclampsia.

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)

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.

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

Source: Prevention and management of pre-eclampsia and eclampsia Reference Manual for Healthcare Providers, MCHIP, 2011

Who is at Risk for PE?

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

cred

it: Sheena C

urrie

All pregnant women are potentially at risk. All need prevention and early detection of PE.

What Can Be Done?

Prevention

Management

Photo

cred

it: Anita

Khem

ka

DetectionPhoto

cred

it: Sheena C

urrie

Photo

cred

it: Ste

phanie

Suhow

atsk

y

Seeking simple, inexpensive and effective solutions that reach all pregnant women.

Prevention

x x x

Almost 100 interventions tested in randomized trials

Primary Prevention

Source: Prevention and management of pre-eclampsia and eclampsia reference manual, MCHIP, 2011

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 Yes

Pre-conceptual prevention and/or treatment of obesity

Potential to reduce PE Yes

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

s/a*

Anti-oxidant vitamins (C, E) Reduced PE in one trial s/a*

Protein or salt restriction No effect No

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

620,000Source: Bhutta et al., Lancet, 2008

Daily Calcium Intake

472346 363

499 498

352

860

0

500

1000

1500

World DevelopedCountries

Developingcountries

Africa LatinAmerica

Near East Far East

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 birthSource: Bujold et al., 2010; Knight M, Duley L, Henderson-Smart DJ, King JF. (Cochrane

Review) 2007

Benefits of PE Prevention

Photo credit: Geeta Sharma

Infants of women with PE

are 5 timesmore likely to die than those born to mothers without PE

Detecting PE/E: ANC Coverage

16

49

73

28

60

9288

9285

58

36

94 92

78

92 93

79

0

20

40

60

80

100

ANC coverage (at least 1 visit)Afghanistan Bangladesh Burkina Faso Ethiopia Haiti IndiaIndonesia Kenya Malawi Mozambique Nigeria PakistanRwanda South Africa Tanzania Uganda Zambia

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

cred

it: Danie

l A

nto

naccio

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

ANC in Africa: BP Measurement and Urine Analysis

96

79

62

27

968583

50

81

50

78

21

81

6471

8

98

83

66

42

53

12

80

23

93

81

0

20

40

60

80

100

Blood pressure measured Urine sample taken

Burkina Faso-2003 Ethiopia 2005 Ghana 2003 Kenya 2003 Liberia 2007Malawi 2004 Nigeria 2003 Rwanda 2005 Senegal 2005 Tanzania 2004Uganda 2006 Zambia 2007 Egypt 2005

Source: DHS (as noted on the slide)

Detecting PE: Point of Care Diagnostics Protein Test

Jhpiego—JHU-BME: Patent Pending

Photo

cre

dit

: D

anie

l A

nto

nacc

io

This is an example of point of care diagnostic test: Low costEasy to use: ANC, community levelImmediate results

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, respectivelySources: 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

Preventing Eclampsia

Source: Sibai, 2005 Photo credit: Geeta Sharma

1 case of eclampsia

can be prevented

by treating approximately

7women with severe PE

Immediate Treatment: Magnesium Sulfate

5%18%

77%

0

50

100

150

200

<6 hours 6-12 hours >12 hours

# m

ate

rnal death

s

0%

20%

40%

60%

80%

100%

% m

ort

ality

# maternal deaths % mortality

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

Source: Rashida et al., 2004

Seizure to Treatment Interval

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

Source: Fernando Althabe presentation at CIHR, WHO and NIH Workshop Ottawa, September 24—25, 2009

Photo credit:Daniel Antonaccio

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

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

22 facilities: Average score on 3 standards increased from 22%–60%

Results: Improved Management of Severe PE/E in Nepal, 2009

0%

20%

40%

60%

80%

100%

SZH

Cha

um

ala

PH

C

Mala

kheti P

HC

MW

RH

BZH

LZH

AM

DA

UC

MS

BPKIH

S

IDH

Sapta

kosh

i N

H

KZH JH

NM

C

Dh

ulikh

el H

osp

ita

l

Valle

y N

sg H

om

e

Bha

ratp

ur

Hosp

ital

Du

mkauli P

HC

Ash

a H

osp

ita

l

Phew

a C

ity

Hosp

ital

WRH

*Abhiy

an H

osp

ital

Sco

re

Facilities

Baseline % First %

Results: Reduced Case Fatality Rate from PE/E

19%

11%

8%

8% 8%

0%

20%

40%

60%

80%

100%

2002 2003 2004 2005 2006

% o

f M

agnesi

um

Sulfate

Use

d

0%

5%

10%

15%

20%

25%

Case

fata

lity

rate

% MgSO4 use Case fatality rate

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 eclampsiaSource: 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.