prediction of preeclampsia and prevention.pptx

Preeclampsia- Prediction and Prevention

1. PREDICTION OF PRE-ECLAMPSIA - Dr Anakha Pattiyeil

2. ACOG recommends taking a detailed medical history to assess a patient's risks for developing preeclampsia but not using laboratory and imaging screening tests.

3. Good History taking The incidence of preeclampsia - at least 8 percent for pregnant patients with any one of these factors: Previous pregnancy with preeclampsia, especially early onset / adverse outcome. Type 1 or 2 diabetes mellitus. Chronic hypertension. Multifetal gestation. Kidney disease. Autoimmune disease with potential vascular complications (antiphospholipid syndrome, systemic lupus erythematosus). Pre-pregnancy BMI >30 kg/m2 Use of assisted reproductive technology

4. Preeclampsia is diagnosed after 20 weeks of gestation but early measurements - baseline blood pressure. In a systematic review, blood pressure ≥140/90 mmHg before 20 weeks was a good predictor of preeclampsia occurrence , but blood pressures <120/80 mmHg, <130/80 mmHg, and <140/90 mmHg were not predictive of absence of preeclampsia occurrence. In another systematic review, a hypertensive disorder of pregnancy developed in 11.6 percent of patients with blood pressures of 120-139/80-89 mmHg and 5.6 percent of those with blood pressures lower than 120/80 mmHg before 20 weeks of gestation. Routine regular prenatal blood pressure measurement

5. Blood Pressure Elevation Persistent elevation in blood pressure - hallmark. In the pregnant woman the lateral recumbent values are always lower than those in the sitting position. This will delay proper diagnosis and treatment. To avoid these errors, the blood pressure at each pregnant visit should be taken with the patient in the sitting position. The official recommendation of the NHBPEP and the ACOG is to use the Korotkoff V sound, the point of disappearance of the sound, as the marker of diastolic pressure.

6. Screening tests We do not use blood or imaging tests to screen for preeclampsia. Prevalence of preeclampsia in the general obstetric population - low (1 to 7 percent), a test would need very high sensitivity and specificity to accurately predict or exclude the development of the disease. Systematic reviews and expert opinion of studies that evaluated clinically available tests - concluded that tests are not sufficiently accurate and that the overall methodologic quality of available studies was generally poor. Therefore, the ACOG recommends taking a detailed medical history and assessing BP to assess a patient's risks for developing preeclampsia.

7. PROVOCATIVE PRESSOR TESTS Biophysical test such as cold pressure test, the isometric hand grip exercise, and roll over tests also depend on the pathophysiological changes that occur in pre-eclampsia and have poor predictive value . Sensitivity : 55-70% Specificity :85%

8. Angiotensin sensitivity test The abnormal vascular reactivity of patients destined to develop preeclampsia may be detected several weeks before the development of clinical science and symptoms, and the degree of the sensitivity to the angiotensin II may be used as a screening test to identify the patient's address. labor-intensive high incidents of false negative and false positive results. Angiotensin II preparations for human use- not available

9. Roll over test Non-invasive office procedure having an excellent correlation with the angiotensin sensitivity test and serving as an excellent predictor of the development of preeclampsia. It measures the hypertensive response of women in at 28 to 32 weeks who are resting in the Left lateral position and then roll over to supine position. A positive test is an elevation of >/= 20 mmHg. Poor sensitivity and specificity. Isometric Exercise Test (Hand Grip Test) Employs the same principle by squeezing a hand ball.

10. Cold Pressor Test An ice bag was placed on the forehead of the pregnant woman for 3 minutes. BP and heart rate was measured using continuous non-invasive BP measurement device during the stimulus and after the removal of the ice bag. Based on the idea that increased vascular reactivity occurs due to an overactivity of sympathetic nervous systems in women with preeclampsia. A clinical follow up was done to back up the evidence.

11. Mean blood pressure in the second trimester Mean arterial pressure in the second trimester of pregnancy was proposed long time ago as a predictor of preeclampsia. However, it has a low sensitivity and a low positive predictive value. After rest for five minutes, two measurements of MAP should be taken from each arm simultaneously and the average of the four should be considered in the assessment of risk. The MAP is defined as the average arterial pressure during a single cardiac cycle and is calculated from the following formula: MAP = 2/3 diastolic blood pressure + 1/3 systolic blood pressure.

12. The false-positive rate - high, causes excessive patient anxiety and health care costs. Impedance to flow in the uterine arteries normally decreases as pregnancy progresses. Increased impedance for gestational age is an early radiographic feature of preeclampsia and likely reflects high downstream resistance due to defective differentiation of trophoblast, which leads to defective invasion of spiral arteries and failure of these vessels to transform into low resistance vessels.

13. Two types of uterine artery Doppler waveform analysis techniques have emerged for prediction of preeclampsia, as well as other disorders associated with impaired placentation ( eg , fetal growth restriction, pregnancy loss): presence or Absence of diastolic notching (unilateral, bilateral) of the uterine arcuate vessels and Flow waveform ratios ( eg , high resistance or pulsatility index, systolic/diastolic ratio).

14. Normal flow Diastolic notching

15. Biochemical markers that have been proposed to identify women destined to develop pre-eclampsia.

16. Anti Thrombin III Free Fetal DNA Antithrombin plasma levels (AT) have been found decreased in women with preeclampsia (PE), but little is known about the trend of AT during the course of this disease. Since preeclampsia is associated with placental damage, dysfunction or abnormal development, as well as increased trophoblast deportation 6 , it is biologically plausible that  levels of cell-free fetal DNA correlate with the risk for this condition .

17. Fibronectin Patients with pre eclampsia have elevated levels of plasma fibronectin. It has an important role in all cellular adhesions. It is a component of connective tissue and basement membranes. There are studies indicated that increase plasma levels of endothelium originated fibronectin preceed the clinical signs of preclampsia and maybe useful for the prediction of the disease.

18. Proteinuria Proteinuria is a sign of preeclampsia which is defined as > 300 mg of protein in a 24-hour urine collection or a urine protein/creatinine ratio of > 0.3 or persistent >= 30 mg/dl protein in 2 urine samples collected 4 to 6 hours apart, with no evidence of urinary infection or a 1+ reading dipstick in a random urine specimen. Proteinuria is also valuable as a sign of severity and a value = 5 g in 24 hours is one of the criteria to classify preeclampsia as severe. The 24-hour urine collection for protein is the gold standard in the diagnosis

19. Urine dipsticks can be affected by variable excretion, maternal dehydration and bacteriuria. A 1+ dipstick has a 92% positive predictive value to predict > 300 mg of protein. Approximate equivalence is : 1+ = 0.3g/l, 2 + = 1g/l, 3+ = 3g/l. The protein/creatinine ratio that in the nonpregnant state, correlates well with the 24-hour collection. A protein/creatinine ratio of 0.3 has a positive predictive value of 85.5% and a sensitivity of 81.0% for significant proteinuria in the 24-hour collection. A negative result (< 0.3) has a negative predictive value of 47.5%, meaning that about half of the women with a negative result will have significant proteinuria in the 24-hour collection specimen.

20. N ote : T race : 0.15 to 3 mg/dl 1+ : 0.3 mg/dl 2 + : 1 mg/dl 3+ : 3 mg/dl

21. Screening For Inherited Thrombophilias Evidence and studies indicates that inherited thrombophilias (such as Factor V Leiden mutation, prothrombin gene mutation, protein C or S deficiency, and antithrombin deficiency) are not associated with preeclampsia; therefore, screening pregnant individuals for inherited thrombophilias is not useful for predicting those at high risk of developing the disease.

22. Screening For Antiphospholipid Antibodies Antiphospholipid syndrome (APS) is associated with the development of severe early preeclampsia. Prophylaxis with both low-dose aspirin (LDA) and prophylactic-dose heparin starting at the end of the first trimester and continuing throughout pregnancy can decrease the rate of pregnancy complications (including preeclampsia) and improve pregnancy outcome in patients with APS. But screening the general obstetric population for antiphospholipid antibodies is not useful.

23. ASPRE trial The ASPRE trial (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention) was an international multicenter study. Routine screening for preterm PE was carried out at 11-13 weeks’ gestation by maternal factors and biomarkers in about 27,000 singleton pregnancies.

24. Eligible women (n=1,620) with estimated risk for preterm PE of >1 in 100 who agreed to participate in the trial were randomly allocated to aspirin (150 mg/day) or placebo from 11-14 weeks’ gestation until 36 weeks. The participants were recommended to take the tablet at night, rather than during the day, because there is some evidence that treatment at this time may be superior in reducing the rate of PE. Use of aspirin  was associated with a 62% reduction in the incidence of preterm PE and 82% reduction in the incidence of PE at <34 weeks’ gestation.

25. Secondary analysis  of the data of the ASPRE trial showed that: The beneficial effect of aspirin depends on compliance and the reduction in incidence of preterm PE may be about 75% in those with compliance of ≥90% and only 40% in those with compliance of <90%. In chronic hypertension aspirin may not be useful in the prevention of preterm PE. Consequently, if participants with chronic hypertension were excluded from the trial and compliance was ≥90%, aspirin could have potentially reduced the incidence of preterm PE by 95%.

26. Fetal Medicine Foundation Method Of Screening The FMF approach  to screening for PE is to use Bayes theorem to combine the a priori risk from maternal characteristics and medical history with the results of various combinations of biophysical and biochemical measurements made at different times during pregnancy. This approach assumes that if the pregnancy was to continue indefinitely all women would develop PE and whether they do so or not before a specified gestational age depends on competition between delivery before or after development of PE.

27. Primary clinical assessment for screening and prediction of preeclampsia can be objectively performed by ‘easy to use’ HDP- Gestosis score. Process of risk scoring: ✓  This score involves all the existing and emerging risk factors in the pregnant woman. ✓  Score 1, 2 and 3 is allotted to each clinical risk factor as per its severity in development of preeclampsia. ✓  With careful history and assessment of woman a total score is obtained time to time. ✓  When total score is =/> 3; pregnant woman should be marked as ‘At risk for Preeclampsia’. HDP- Gestosis score: Effective and feasible prediction policy

28. PIERS calculator- predicting adverse maternal outcome in preeclampsia

29. This tool is meant to aid caregivers in determining maternal risk in the setting of preeclampsia, in order to guide decisions around triage, transport, and treatment, in combination with an assessment of neonatal risk based on was to evaluate the ability of fullPIERS calculator to predict complications and adverse maternal outcome in preeclampsia.

30. Screening at 11-13 weeks Objective of screening  : to identify the cases that would benefit from prophylactic use of aspiri n. Combined screening  by maternal factors, MAP, UTPI and PLGF predicts about 90% of early PE (<34 weeks), 75% of preterm PE (<37 weeks) and 45% of term PE (≥37 weeks), at screen positive rate of 10%. Inclusion of PAPP-A and sFLT-1 does not improve the performance of screening. NICE guidelines recommend the identification of the high-risk group on the basis of 10 factors from maternal characteristics and medical history; this method identifies only about 40% of cases of preterm PE and 35% of term PE. The ACOG recommends the use of aspirin in women with a history of PE in ≥2 pregnancies or history of PE with delivery <34 weeks; this method identifies 5% of cases of preterm PE and 2% of term PE.

31. Screening at 30-34 weeks The objective of screening  : to estimate the patient-specific risk of developing PE and define the subsequent management of pregnancy, including the timing and content of subsequent visits. In pregnancies that develop PE  the values of MAP, UTPI, and sFLT-1 are increased and PLGF is decreased. For all biomarkers the deviation from normal is inversely related to the gestational age at which delivery becomes necessary for maternal and / or fetal indications and therefore, the performance of screening is better for preterm PE than term PE. Combined screening  by maternal factors, MAP, UTPI, PLGF and sFLT-1 predicts nearly all cases of preterm PE (<37 weeks) but only 55% of term PE (≥37 weeks), at screen positive rate of 5%. The important biomarkers at this gestational age are MAP, PLGF and sFLT-1, with small benefit from inclusion of UTPI.

32. Screening at 35-37 weeks The objective of screening  : estimate the patient-specific risk of developing PE and define the subsequent management. In pregnancies that develop PE  the values of MAP, UTPI and sFLT-1 are increased & PLGF is decreased. Combined screening  by maternal factors, MAP, PLGF and sFLT-1 predicts about 85% of term PE (≥37 weeks), at screen positive rate of 10%. The important biomarkers at this gestational age are MAP, PLGF and sFLT-1, with small benefit from inclusion of UTPI. The detection rate of term PE , at screen positive rate of 10%, improved from about 45% with combined screening at 12 and 22 weeks to about 65% with screening at 32 weeks and 85% with screening at 36 weeks.

33. Stratification of pregnancy management 11-13 weeks’ gestation

34. 20-24 weeks’ gestation

35. 32 weeks’ gestation

36. 36 weeks’ gestation

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