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.