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HYPERTENSIVE DISORDERS OF PREGNANCY

HYPERTENSIVE DISORDERS OF PREGNANCY. A/Prof Sandra Lowe. What’ s old What’ s new What does it mean to your practise?. What’s old?. Incidence of hypertensive disorders. In Australia: Any HT disorder 9.8% Chronic HT 0.6% Preeclampsia 4.2% Eclampsia 0.1% Gestational HT 4.3%

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HYPERTENSIVE DISORDERS OF PREGNANCY

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  1. HYPERTENSIVE DISORDERS OF PREGNANCY A/Prof Sandra Lowe

  2. What’ s old What’ s new What does it mean to your practise?

  3. What’s old?

  4. Incidence of hypertensive disorders • In Australia: • Any HT disorder 9.8% • Chronic HT 0.6% • Preeclampsia 4.2% • Eclampsia 0.1% • Gestational HT 4.3% • Chronic HT + preeclampsia 0.3% MJA, 2005:182(7):332-335 Am J Obstet Gynecol 2013

  5. Major maternal and neonatal morbidityChronic Chronic PE GH No HT + PE % % % % % APH 0.9 1.4 1.5 0.9 0.8 Severe PPH 0.8 1.0 1.6 0.9 0.7 ARF/ALF/I 0.1 0.4 0.5 0.2 0.1 ICU 0.3 2.2 2.0 0.3 0.1 Major M&M 1.8 4.8 6.4 2.1 1.6 Major neonatal morbidity or mortality 6.1 14.1 9.2 3.1 3.3 Roberts CL, MJA, 2005:182(7):332-335

  6. Maternal mortality • RR for women with preeclampsia/ eclampsia dying in the first 12 months following birth when compared with normotensive women of 5.1 (95% CI, 3.07- 8.60). • All cause maternal deaths within 12 months: 17/97 =18% had experienced preeclampsia. • Deaths within 42 days of birth: 5/30=17% had experienced preeclampsia.

  7. Definition of hypertension in pregnancy • Systolic ≥ 140 mmHg and/or diastolic ≥ 90 mmHg (K5) • Which is more important: systolic or diastolic ? • In the 24 patients being treated immediately before stroke, systolic pressure was 160 mm Hg or greater in 23 (95.8%) and more than 155 mm Hg in 100%. In contrast, only 3 of 24 patients (12.5%) exhibited prestroke diastolic pressures of 110 mm Hg or greater, only 5 of 28 reached 105 mm Hg, and only 6 (25%) exceeded a mean arterial pressure of 130 mm Hg before stroke. O & G 2005,105(2):246-54 • Renal function in women with severe preeclampsia was significantly impaired and highly correlated with systolic or diastolic blood pressure. Hypertension in Pregnancy. 24(3):247-57, 2005.

  8. Does a rise of 30/15mmHg predict preeclampsia? AM J OG 1989,160(2):419-23. • Does warrant closer observation

  9. Severe hypertension requiring urgent treatment • ≥170 or /110 mmHg • level of blood pressure above which cerebral autoregulation is overcome in normotensive individuals. • associated with a risk of cerebral haemorrhage and hypertensive encephalopathy HT. 2007 Jul;50(1):14-24.

  10. Serial brain MRI of a patient with eclampsia 1 2 3 1 and 2 Increasing cerebral oedema posterior cerebral cortex 3 After IV gadolinium contrast demonstrating disruption of the blood-brain barrier.

  11. Classification Preeclampsia Gestational Hypertension Chronic Hypertension Chronic Hypertension with superimposed preeclampsia

  12. Classification • Preeclampsia • HT after 20 weeks gestation plus involvement of one or more of the following systems • Renal-proteinuria, raised creatinine, oliguria • Haematological- thrombcytopenia, hemolysis, DIC • Liver: raised AST,ALT, upper abdominal pain • Neurological: eclampsia, hypereflexia with clonus, severe headache, visua; disturbance, stroke • Pulmonary edema • Fetal growth restriction • Placental abruption

  13. Dipstick proteinuria needs to be confirmed by spot urine  30mg/mmol or 24 hr urine 300mg/day Hyperuricemia is not diagnostic

  14. Pathophysiology • Phase 1: • failure of trophoblast invasion into spiral arteries prior to 20 weeks • hypoxic & dysfunctional placenta • Phase 2: • Placenta releases factor(s) into maternal circulation endothelial inflammatory response with endothelial dysfunction, increased oxidative stress • Phenotype: • Mixture of maternal and fetal syndrome

  15. Whats new?

  16. Search for the preeclampsia circulating factor Current putative factors: Imbalance between angiogenic growth factors VEGF and PlGF and soluble placental derived anti-angiogenic factors such as sFlt-1 and endoglin VEGF vascular endothelial growth factor PlGF placental growth factor sFlt-1 soluble fms-like tyrosine kinase 1: VEGF and PlGF receptor Endoglin: TGF (transforming growth factor) b1 and b3 co-receptor

  17. In women with preeclampsia, excess sFlt 1 binds VEGF and PlGF : • Antiangiogenic • Blocks VEGF-mediated vasodilation • The antagonism of both PlGF and VEGF is necessary to create the maternal syndrome of preeclampsia Excess SFlt1 explains hypertension and proteinuria in preeclampsia

  18. Mean Concentrations of Soluble fms-like Tyrosine Kinase 1 (sFlt-1) and Placental Growth Factor (PlGF) According to Preeclampsia Status and Severity Levine, R. et al. N Engl J Med 2004;350:672-683

  19. Fetal growth restriction and angiogenic factors Early onset <34 weeks Am J OG 2006; 195,1 Crispi et al Late onset >34 weeks Am J OG 2006; 195,1 Crispi et al

  20. “isolated IUGR with no maternal disease is also associated with changes in placental angiogenic factors and subclinical endothelial dysfunction. “ • Stresses the importance of maternal predisposition for manifestation of maternal syndrome

  21. Management of hypertensive disorders of pregnancy THE MANAGEMENT OF HYPERTENSIVE DISORDERS OF PREGNANCY 2014 • Prev version : ANZJOG 2009; 49: 242–246

  22. Investigation of new onset HT • Assess clinically • Admit: • Preeclampsia • Severe HT or other symptoms • Concerns re fetal well-being • Investigations: • Spot urine PCR • Full blood count • Creatinine, electrolytes, urate • Liver function tests • Ultrasound assessment of fetal growth, amniotic fluid volume and umbilical artery Doppler assessment.

  23. Further assessment depending on diagnosis • Normal: reassess 3-7 days

  24. Clinical role of measuring angiogenic factors • Potential role: • Prediction-T1 • Diagnosis: • Differentiating CKD, CHT, other conditions • Management: • Predicting the need for delivery

  25. Prediction of preeclampsia • Best for early onset disease, but this only comprises 10% of hypertensive disorders of pregnancy • Must be relevant for the full spectrum of women with preeclampsia, including not only those presenting with hypertension and proteinuria but the 26% manifesting primarily as hypertension with another multisystem complication • Local normal ranges for parameters such as PlGF

  26. Diagnosis of HDP • Analogous to troponin for MI • Indicator of adverse outcome • Early data suggests outperforms current indicators eg BP, proteinuria, plat count etc ; esp in early onset disease Circulation.2012; 125: 911-919 • May be useful to discriminate CKD, thrombocytopenia, ??SLE from superimposed preeclampsia

  27. Management of women who present with suspected pre-eclampsia • PELICAN: • Prospective multicenter study of plasma PlGF in women presenting with suspected preeclampsia between 20 and 35 weeks' gestation (and up to 41 weeks' gestation as a secondary analysis). • Outcome was predicting delivery for confirmed preeclampsia within 14 days • N=625 • 55% developed confirmed preeclampsia • In 287 women, PlGF <5th centile had high sensitivity (0.96; 95% confidence interval, 0.89-0.99) and negative predictive value (0.98; 0.93-0.995) • specificity was lower (0.55; 0.48-0.61). • Better for predicting preeclampsia than all other commonly used tests, singly or in combination Circulation, 2013: 18(19):2121-31

  28. Prognostic performance

  29. Other studies • Rana et al: • N= 616 women • sFlt1 and PLGF, sFlt1/PlGF ratio • sFlt1/PlGF ratio at presentation was elevated in participants who experienced any adverse outcome compared with those who did not (47.0 [25th–75th percentile, 15.5–112.2] versus 10.8 [4.1–28.6]; P<0.0001. • <34 weeks (n=167) • any adverse outcome 226.6 [50.4–547.3] versus 4.5 [2.0–13.5]; P<0.0001 • addition of sFlt1/PlGF ratio to hypertension and proteinuria significantly improved the prediction for subsequent adverse outcomes (area under the curve, 0.93 for hypertension, proteinuria, and sFlt1/PlGF versus 0.84 for hypertension and proteinuria alone; P=0.001). • Delivery occurred within 2 weeks of presentation in 86.0% of women with an sFlt1/PlGF ratio ≥85 compared with 15.8% of women with an sFlt1/PlGF ratio <85 (HR, 15.2; [8.0–28.7]) Circulation , 2012: 125(7): 911-919.

  30. Subgroup analysis for diagnosis of PE or superimposed PE • Area under ROC for low PLGF • CHT alone or CKD±CHT: 0.89 SE(0.07) • Serum creat didn’t affect PLGF • PPV : 88% • NPV: 91% • Sens 47% Bramham et al, Abstract

  31. Management of preeclampsia and gestational hypertension • Before 34 weeks: • Delivery is the definitive management • Prolongation of pregnancy is desirable at least to administer corticosteroids for fetal lung maturation • Continuation of pregnancy carries risks • Management should be in a Unit with appropriate expertise

  32. Preeclampsia before 34 weeks Churchill D: Cochrane Database of Systematic Reviews. 7:CD003106, 2013

  33. Management between 34 and 36+6 weeks • Uncertain • Hypitat II: • Severe GH, mild PE, deteriorating CH Awaiting: PHOENIX : Similar UK trial early stages of recruitment

  34. Management between 36-41 weeks • HYPITAT I: • Multi-centred randomised trial • Singleton pregnancy, PIH or mild preeclampsia between 360 and 410 weeks • IOL or expectant monitoring until onset of labour • n=756 • Netherlands The Lancet, 2009, 374 [9694]: 979 – 988.

  35. No maternal deaths or eclampsia Most of benefit was reduced incidence of severe HT No significant difference in neonatal outcomes

  36. Impact of Hypitat • Induction of labour increased from 58.3 to 67.1% (P < 0.001) • Prevalence of eclampsia decreased from 0.85 to 0.19% (P < 0.001) • Risk of caesarean delivery after labour induction between women with favourable and unfavourable cervices was equal in IOL group • Women with an unfavourable cervix benefited more from labour induction than other women. • Women who were managed expectantly, the longer the cervix the higher the rate of LSCS and the greater the risk of developing maternal high-risk situations

  37. Timing of delivery and gestation of presentation of preeclampsia

  38. Management principles • Team approach to management • Determine clear “endpoints” for delivery for each patient • Control HT and other maternal derangements before delivery

  39. Treatment of hypertension • What blood pressure target do you aim for ? • Recommend treatment for all women ≥160 systolic or 100 diastolic • Treat BP ≥170mm Hg systolic or 110mmHg diastolic urgently • Consider treatment 140-159 or /90-99 mm Hg

  40. Antihypertensive treatment Severe HT: treat urgently

  41. Give long acting agents concurrently All Units should have protocols for management of severe hypertension

  42. Controversy regarding treatment of mild-moderate hypertension • In favour: • blood pressure may be extremely labile in preeclampsia and treatment at lower blood pressure levels will prevent or attenuate acute and severe rises in blood pressure • in addition, it is possible that pharmacologic arteriolar vasodilation may help improve organ perfusion • Against: • little risk to the mother in having relatively mild hypertension for a short time • fetal perfusion is dependent upon adequate maternal blood pressure • lowering blood pressure suppresses an important sign of the severity or progression of preeclampsia.

  43. CHIPS • Randomised trial of less tight v tight control of BP • GA at randomisation: 4-33 weeks • Chronic or gestational HT • N=987 • Target diastolic 100 v 85 mmHg • Actual BP achieved- • 138.8 v 133 systolic • 89.9 v 85.3 diastolic • Results: • No difference in pregnancy loss, serious maternal complications, BW or SGA, admission to Neonatal nursery >48 hrs • Incidence of severe HT >160/110mHg : • Tight control 27.5% v less-tight 40.6%**

  44. Ongoing treatment for hypertension

  45. Other aspects of management • Thromboprophylaxis • Intravenous fluids • Cautious, carefully monitored • Women with severe preeclampsia immediately prior to parenteral hydalazine, regional anaesthesia or immediate delivery • Initial management in women with oliguria where there is a suspected or confirmed deficit in intravascular volume • Crystalloid or colloid

  46. Haematologic and hepatic manifestations • Platelet transfusion for severe thrombocytopenia at the time of Caesarean delivery, PPH, wound or vulval hematoma or other bleeding • FFP &/or cryoprecipitate for management of coagulopathy indicated by active bleeding and a prolonged APTT and INR • Steroid therapy is not indicated for management of thrombocytopenia or hepatic involvement  

  47. Eclampsia • Eclampsia 4.2% of preeclamptics • Antenatally 25.1% • During labor 44.1% • Postnatally 26.3% • Not specified 4.5% • . • Comprehensive protocols required in each Unit • Resuscitation • Prevention with Mg Sulfate • Control HT • Plan delivery • Prevention: local policy re Mg sulphate • In Aust and NZ: low morbidity from eclampsia • High NNT

  48. Fetal Surveillance

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