screening and early detection of preeclampsia harshad sanghvi vice-president & medical director...
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Screening and early detection of Preeclampsia
Harshad SanghviVice-President & Medical Director
Jhpiego
Africa meeting: Interventions For Impact in EONCAddis 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
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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
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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
69 (60 - 77)
0 20 40 60 80 100
Doppler combinations of FVWDoppler resistance indexDoppler pulsatility indexDoppler other ratiosDoppler bilateral notchingDoppler any/unilateral notchingSDS Page proteinuria 100 (88 - 100)KallikreinuriaMicroalbumin/creatinine ratioMicroalbuminuriaTotal albuminuriaTotal proteinuriaUrinary calcium/creatinine ratioUrinary calcium excretionSerum uric acidOestriolHCGFoetal DNAFibronectin totalFibronectin cellularAFPBMI<19.8BMI>24.2BMI>29
0 20 40 60 80 100
BMI>34
2529882119111224645316332127982
2289679821469726192933114345153307142219088
22281345705514
2681172732351373135
13709715272044021441082316200
11 (8 - 16)41 (29 - 53)23 (15 - 33)18 (15 - 21)
64 (54 - 74)66 (54 - 76)48 (29 - 69)55 (37 - 72)48 (34 - 62)63 (51 - 74)
19 (12 - 28)62 (23 - 90)70 (45 - 87)35 (13 - 68)50 (36 - 64)57 (24 - 84)36 (22 - 53)26 (9 - 56)24 (16 - 35)50 (31 - 69)65 (42 - 83)50 (30 - 70)9 (5 - 16)
83 (52 - 98)
80 (73 - 86) 75 (62 - 84)88 (80 - 93)93 (87 - 97)
86 (82 - 90)80 (74 - 85)87 (75 - 94)80 (73 - 86)92 (87 - 95)82 (74 - 87)
75 (73 - 77)68 (57 - 77)89 (79 - 94)89 (79 - 94)80 (66 - 89)74 (69 - 79)83 (73 - 90)82 (61 - 93)89 (86 - 92)88 (80 - 93)94 (86 - 98)96 (79 - 99)96 (94 - 98)
98 (98 - 100)
Sensitivity Specificity
Sn (95% CI)Test No of studies No of women Sp (95% CI)
Prediction of preeclampsiaMethods of prediction and prevention of pre-eclampsia: systematic reviews ofaccuracy and effectiveness literature with economic modelling CA Meads, et al 2008
0.01 0.1 0.2 0.5 1 2 5 10
Progesterone 0.21 (0.03, 1.77)
Nitric oxide donors and precursors 0.83 (0.49, 1.41)
Diuretics 0.68 (0.45, 1.03)
Antiplatelets 0.81 (0.75, 0.88)
Antihypertensives v none 0.99 (0.84, 1.18)
Marine oils 0.86 (0.59, 1.27)
Magnesium 0.87 (0.57, 1.32)
Garlic 0.78 (0.31, 1.93)
Energy/protein restriction 1.13 (0.59, 2.18)
Isocaloric balanced protein supplementation 1.00 (0.57, 1.75)
Balanced protein/energy intake 1.20 (0.77, 1.89)
Nutritional advice 0.98 (0.42, 1.88)
Calcium 0.48 (0.33, 0.69)
Antioxidants 0.61 (0.50, 0.75)
Altered dietary salt 1.11 (0.46, 2.66)
Rest alone for normal BP 0.05 (0.00, 0.83)
Exercise 0.31 (0.01, 7.09)
Bed rest for high BP 0.98 (0.80, 1.20)
Ambulatory BP
1
4
4
43
19
4
2
1
2
1
3
1
12
7
2
1
2
1
0
128
170
1391
33439
2402
1683
474
100
284
782
512
136
15206
6082
631
32
45
228
0
Relative Risk (95% Confidence Interval)
RR (95% CI)Intervention No of RCTs No of women
Primary Prevention Of PE
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0 50
100 150 200 250 300 350 400 450 500
0.94 0.95 0.96 0.97 0.98 0.99
Effectiveness (proportion free of pre-eclampsia)
Co
st p
er w
om
an(
UK
£ 2
005)
No test, calcium to all
Comparing Cost and Effectiveness of Interventions for Preventing PE
Good Question: Are calcium supplements out of reach for low resource settings
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 (2005-06) 94 71
Malawi (2004) 95 58
Nigeria (2008) 55 45
Ethiopia (2005) 28 12
Mozambique (2003) 84 53
Ghana (2008) 94 78
Rwanda (2007-08) 96 24
Senegal (2005) 91 40
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*Macro International, 2011. Measure DHS. Data representative of women who gave birth in the 5 years prior to the survey.
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%
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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
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
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Sanghvi, Lee, Jayaram, Trachtenberg, Acharya
Current Prototype
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Secondary Prevention: Detecting Pre-eclampsia
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
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Extremely Affordable Point of Care Diagnostics:Prototype Protein Test
Sanghvi, Crocker, Mongale
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
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Sanghvi, Crocker, Mongale
Performance standards: Severe PE/E
Performance standard Verification n criteria
The provider correctly describes signs and symptoms of Severe PE and E
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The provider describes correct management of Severe PE and E
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The provider correctly describes follow up actions 12
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Example of Verification criteria: Administer 4 gm of Magnesium Sulphate IV over 5 minutes ( 20 ml of 20% Magnesium Sulphate)
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
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Baseline
2 months
4 months
% facilities meeting standards
14% 36% 59%
% facilities where no standard met
27% 0% 0%
Average score 26% 60% 63%
facility % reaching standard
SBA training sites
87%
Govt Hosp
50%
Private hospitals
17%
Med school
38%
PHCC 33%
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, AntihypertensivesUrgent delivery 21