Screening and early detection
of Preeclampsia
Harshad Sanghvi
Vice-President & Medical Director
Jhpiego
Africa meeting: Interventions For Impact in EONC
Addis Ababa, 22 February 2011
Definitions
 Preeclampsia: Hypertension, proteinuria in
pregnancy
 Mild: Diastolic 90-100, proteinuria1-2g/l
 Severe: diastolic 110+, proteinuria 3g/l
 Eclampsia: +convulsions
2
Why an additional Focus on PE/E





Mortality associated with PE/E
shows little decline in more than
75% of low resource countries
Between 7-15% of pregnant
women develop preeclampsia
(high BP and proteinuria)
Approximately 1-2% develop
Eclampsia
Contribute between 8-25% of
maternal mortality
Increased risk of perinatal
mortality:
 PE : RR 1.7-3.7
 E : RR 2.9-13.7
Nepal Maternal Mortality Study 1998 & 2009
1998
2009
MMR
539
247
PPH
37%
19%
Eclampsia
14%
21%
Source: Nepal maternal mortality study
2008-9
3
Prediction of Preeclampsia
 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
Implication: All pregnant women potentially at risk
need prevention or early detection of PE
4
Test
No of studies No of women
2
BMI>34
8
BMI>29
9
BMI>24.2
7
BMI<19.8
12
AFP
2
Fibronectin cellular
3
Fibronectin total
3
Foetal DNA
16
HCG
3
Oestriol
5
Serum uric acid
4
Urinary calcium excretion
Urinary calcium/creatinine ratio 6
4
Total proteinuria
2
Total albuminuria
2
Microalbuminuria
1
Microalbumin/creatinine ratio
1
Kallikreinuria
1
SDS Page proteinuria
Doppler any/unilateral notching19
21
Doppler bilateral notching
8
Doppler other ratios
8
Doppler pulsatility index
29
Doppler resistance index
Doppler combinations of FVW 25
16200
410823
440214
152720
137097
135
373
351
72732
26811
514
705
1345
2228
88
190
1422
307
153
14345
29331
2619
14697
7982
22896
Prediction of preeclampsia
0
20
40
60
Sensitivity
80
100
Sn (95% CI)
Sp (95% CI)
18 (15 - 21)
23 (15 - 33)
41 (29 - 53)
11 (8 - 16)
9 (5 - 16)
50 (30 - 70)
65 (42 - 83)
50 (31 - 69)
24 (16 - 35)
26 (9 - 56)
36 (22 - 53)
57 (24 - 84)
50 (36 - 64)
35 (13 - 68)
70 (45 - 87)
62 (23 - 90)
19 (12 - 28)
83 (52 - 98)
100 (88 - 100)
63 (51 - 74)
48 (34 - 62)
55 (37 - 72)
48 (29 - 69)
66 (54 - 76)
64 (54 - 74)
93 (87 - 97)
88 (80 - 93)
75 (62 - 84)
80 (73 - 86)
96 (94 - 98)
96 (79 - 99)
94 (86 - 98)
88 (80 - 93)
89 (86 - 92)
82 (61 - 93)
83 (73 - 90)
74 (69 - 79)
80 (66 - 89)
89 (79 - 94)
89 (79 - 94)
68 (57 - 77)
75 (73 - 77)
98 (98 - 100)
69 (60 - 77)
82 (74 - 87)
92 (87 - 95)
80 (73 - 86)
87 (75 - 94)
80 (74 - 85)
86 (82 - 90)
0
20
40
60
80
Specificity
Methods of prediction and prevention of pre-eclampsia: systematic reviews of
accuracy and effectiveness literature with economic modelling CA Meads, et al 2008
100
Intervention
No of RCTs
No of women
Ambulatory BP
0
0
Bed rest for high BP
1
228
0.98 (0.80, 1.20)
Exercise
2
45
0.31 (0.01, 7.09)
Rest alone for normal BP
1
32
0.05 (0.00, 0.83)
Altered dietary salt
2
631
1.11 (0.46, 2.66)
Antioxidants
7
6082
0.61 (0.50, 0.75)
Calcium
12
15206
0.48 (0.33, 0.69)
Nutritional advice
1
136
0.98 (0.42, 1.88)
Balanced protein/energy intake
3
512
1.20 (0.77, 1.89)
Isocaloric balanced protein supplementation 1
782
1.00 (0.57, 1.75)
Energy/protein restriction
2
284
1.13 (0.59, 2.18)
Garlic
1
100
0.78 (0.31, 1.93)
Magnesium
2
474
0.87 (0.57, 1.32)
Marine oils
4
1683
0.86 (0.59, 1.27)
Antihypertensives v none
19
2402
0.99 (0.84, 1.18)
Antiplatelets
43
33439
0.81 (0.75, 0.88)
Diuretics
4
1391
0.68 (0.45, 1.03)
Nitric oxide donors and precursors
4
170
0.83 (0.49, 1.41)
Progesterone
1
128
0.21 (0.03, 1.77)
Primary Prevention Of PE
RR (95% CI)
0.01
0.1 0.2 0.5 1 2
5 10
Relative Risk (95% Confidence Interval)
Cost per woman
( UK £ 2005)
Comparing Cost and Effectiveness of Interventions
for Preventing PE
500
450
400
350
300
250
200
150
100
50
0
No test, calcium to all
0.94
0.95
0.96
0.97
0.98
0.99
Effectiveness (proportion free of pre-eclampsia)
Good Question: Are calcium supplements out
of reach for low resource settings
7
Coverage of prenatal care: selected
countries*
At least 1 visit (%)
4+ visits (%)
Kenya (2008-09)
91
47
Tanzania (2004-05)
97
62
Uganda (2006)
95
47
Zambia (2007)
97
60
Zimbabwe
94
71
(2004)
95
58
Nigeria (2008)
55
45
Ethiopia (2005)
28
12
Mozambique (2003)
84
53
Ghana (2008)
94
78
Rwanda
96
24
91
40
Malawi
(2005-06)
(2007-08)
Senegal (2005)
*Macro International, 2011. Measure DHS. Data representative of women who gave birth in the 5 years
prior to the survey.
8
Massive unmet need for early
detection of PE Source DHS
Country
% Unmet need for BP
Check
% Unmet need for
Proteinuria Check
Bangladesh
53.1%
70.5%
Bolivia
24.5%
50.9%
DRC
38.8%
57.8%
India
52.5%
56.8%
Indonesia
13.9%
63.0%
Kenya
22.8%
38.9%
Malawi
28.6%
81.3%
Mozambique
48.7%
73.9%
Nepal
43.8%
77.7%
Zimbabwe
14.0%
39.8%
9
Detecting Preeclampsia
Measuring BP:
 Significant training needed to do BP well
 Robust and maintained equipment
• Aneroid BP machines require frequent recalibration
 Currently completely missing about 50% women
who do not receive antenatal care,
 Also missing an additional 15-30% who attend
ANC but do not have BP taken
10
Assessment of BP technology
 The absence of accurate, easily-obtainable, inexpensive devices for
blood pressure measurement;
 The frequent marketing of non-validated blood pressure measuring
devices;
 The relatively high cost of blood pressure devices given the limited
resources available;
 Limited awareness of the problems associated with conventional
blood pressure measurement techniques;
 A general lack of trained manpower and limited training of
personnel.
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How can we detect all the Preeclampsia
before it becomes life threatening
 One approach: Take testing for hypertension and
proteinuria to women in their homes rather than only
depending on them reaching facilities
Seeking simple, inexpensive and effective solutions that reach all
pregnant women
•
•
•
•
•
Reliably detect diastolic BP > 90mmHg
Low cost, low power, easy to manufacture ($5)
For use by semi literate community workers
Culturally compatible e.g. women in deeply conservative societies
will not expose their upper arm for a typical blood pressure
cuff.
Robust in wide temperature ranges and in extreme dry and wet areas.
Solution
Modular Components
• Manual inflatable pressure cuff applied to the wrist to
restrict blood flow.
• Self deflating cuff with digital pressure sensor to provide
feedback to a microcontroller. This automates
hypertension diagnosis set at 90 diastolic for community
use devices
• Hand Cranked generator with a super capacitor for
power as well as batteries.
• Binary LED panel to indicate sufficient power, inflation,
and color codes for semi-literate volunteer to interpret.
Procedure:
Apply Cuff, Crank till Green LED light, inflate till LED
yellow LED, wait as cuff automatically deflates, Red light
and audible signal indicates hypertension
Sanghvi, Lee, Jayaram, Trachtenberg, Acharya
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Current Prototype
Secondary Prevention: Detecting Preeclampsia
Measuring Urine Protein
 Urine dipstick tests quite pricy:
 Test reagent is not what makes it pricy.
 Boiling not feasible in high-volume
sites, not suitable for home testing
 Alternatives e.g.,
 PATHstrips developed for clinic/lab
setting
 dependant on central manufacture of
test strips
15
Extremely Affordable Point of Care Diagnostics:
Prototype Protein Test
Sanghvi, Crocker, Mongale
16
Diagnostic Platform
Reagent Solution
Purpose
Chemical
Protein Indicator
Tetrabromophenol Blue
Acid Buffer
Citric Acid, Sodium Citrate
Liquid Vehicle
Isopropyl Alcohol, DI H2O
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Solution




Reagent modified to yield sharp
color change when there is 0.7g/l
protein:
The test strip prepared by marking
an end of a piece of filter paper with
the reagent.
Use: Pregnant woman who is
instructed to void urine on the test
area of the strip and report if a color
change from yellow to blue occurs.
Blue Color indicates pathological
proteinuria
Sanghvi, Crocker, Mongale
18
Performance standards: Severe PE/E
Performance standard
Verification n
criteria
The provider correctly describes signs and symptoms of
Severe PE and E
7
The provider describes correct management of Severe
PE and E
12
The provider correctly describes follow up actions
12
Example of Verification criteria:
Administer 4 gm of Magnesium Sulphate IV
over 5 minutes
( 20 ml of 20% Magnesium Sulphate)
19
SBMR: Nepal Experience in
improving quality of PEE care
Intervention: 1 day on site whole facility orientation by
NESOG
 Review of standards, practice of skills
 Baseline assessment, gap analysis, action plan
 Re-assess at 2, 4 months
Baseline
% facilities meeting
standards
14%
% facilities where
no standard met
27%
Average score
26%
facility
%
reaching
standard
87%
2
months
4 months
36%
59%
SBA
training
sites
50%
0%
Govt
Hosp
Private
hospitals
17%
Med
school
38%
PHCC
33%
0%
60%
63%
20
Achieving maximum impact of reducing
mortality from PE: From Household to Hospital
Predict preeclampsia
•Risk factors not very useful: Primigravida are now
about 50% of obstetric population and a significant
proportion of PE occurs postpartum
•No effective or affordable biochemical or biophysical
predictor available
Primary prevention √
Calcium, √
Aspirin
Secondary Prevention
•Detect Hypertension
•Detect Proteinuria
•Timely delivery
•BP: Not available for women not reaching prenatal
care (50%) : Missing an additional 15-30% who
attend ANC but do not have BP taken
•Protein test offered to less than 20%( SPA, 6
countries)
Tertiary Prevention√
Magnesium Sulphate, Antihypertensives
Urgent delivery
21