Hypertension and Preeclampsia Intervention Trial At Term: The HYPITAT-trial

1. Hypertension and Preeclampsia Intervention Trial At Term:The HYPITAT-trial Corine M Koopmans, Ben W J Mol, Jan G Aarnoudse, Paul P Van Den Berg Henk Groen, Christine Willekes, Anneke Kwee, Kitty WM Bloemenkamp, Joris AM Van Der Post, Hubertina CJ Scheepers and Maria MG Van Pampus, On behalf of the HYPITAT study group

2. BackgroundPIH & PE In The Netherlands the most important causes of maternal mortality and morbidity 10-15% of all pregnancies are complicated by PIH or PE Maternal mortality 4.0 per 100.000 pregnancies1,2 The majority declare after 32 weeks The only causal treatment is termination of pregnancy 1 Schuitemaker, et al 2 Schutte, et al

3. BackgroundPIH & PE In pre-term pregnancies conservative expectant management is advocated in order to improve fetal maturity, as long as the risk for the mother is acceptable3,4 3 Sibai, et al 4 Odendaal, et al

4. BackgroundPIH & PE In term pregnancies there is no evidence which treatment would be the best...

5. Induction of Labour or Expectant Management?

6. BackgroundInduction of labour Decrease of severe maternal and neonatal complications Increase the risk of instrumental vaginal delivery and caesarean section5 5Data of Dutch national perinatal registration

7. Aim To investigate whether in women with PIH or mild PE induction of labour at term will reduce severe maternal morbidity compared with expectant management.

8. Methods Randomized controlled clinical trial 38 Dutch hospitals Inclusion period: October 2005 to March 2008

9. MethodsInclusion criteria Singleton pregnancy (N=720) Child in cephalic presentation PIH or mild PE PIH: DBP ≥ 95 mmHg PE: DBP ≥ 90 mmHg and proteinuria GA: 36+0 to 41+0 weeks

10. MethodsExclusion criteria Previous caesarean section Pre-existing diseases, as hypertension, diabetes and renal disease Severe hypertension Proteinuria ≥ 5 gram/ 24 hours Intravenous anti-hypertensive medication HELLP-syndrome Oliguria < 500 ml in 24 hours Small for gestational age fetus

11. Interventions Induction of labour Labour was induced within 24 hours after randomization. Expectant management Monitoring of mother and child until the onset of spontaneous delivery.

12. MethodsPrimary Outcome Composite adverse maternal outcome: Maternal mortality Severe hypertension Severe proteinuria Eclampsia HELLP-syndrome Major postpartum hemorrhage Thromboembolic disease Pulmonary edema Placental abruption

13. MethodsSecondary Outcomes Neonatal mortality & morbidity Mode of delivery spontaneously vaginal instrumental delivery caesarean section Quality of life Costs

14. MethodsPower Analysis The maternal complication rate in the expectant management group was thought to be 12% based on data from the Dutch national delivery registries. In total, 720 patients had to be randomized to show a reduction from 12% to 6% in adverse maternal outcome (two-sided test, alpha .05; beta .80)

15. MethodsAnalysis Intention-to-treat Relative risk and 95% confidence intervals Chi-square statistics

16. 1154 women were eligible 397 refused randomization: 73 induction of labour 324 expectant management 756 randomly assigned 377 were assigned to induction of labour 379 were assigned to expectant management 11 delivered spontaneously 1 primary caesarean section 365 induction of labour 199 delivered spontaneously 7 primary caesarean section 172 induction of labour 0 were lost to follow-up 1 was lost to follow-up 377 women were analyzed 378 women were analyzed

17. Baseline Characteristics Values expressed in n(%) or mean ± SD

18. Expectant Management (n=378)Reasons for induction Values expressed in n(%)

19. Results Values expressed in n(%) or mean ± SD

20. Primary OutcomeSevere maternal complications Values expressed in n(%)

21. Primary OutcomeSevere maternal complications Values expressed in n(%)

22. Primary OutcomeSevere maternal complications Values expressed in n(%)

23. Secondary OutcomeNeonatal Outcome Values expressed in n(%)

24. Secondary Outcome Mode of delivery Values expressed in n(%)

25. Secondary Outcome Mode of delivery Values expressed in n(%)

26. Induction better Expectant management better

27. Expectant management better Induction better

28. Summary Induction of labour gives a lower maternal complication rate than expectant management a reduction in caesarean section rate a trend towards a better neonatal outcome

29. Conclusion Hypitat trial Induction of labour in pregnancies complicated by PIH or mild PE at term is better than expectant management.

30. University Medical Centre Groningen Maria G van Pampus, Jan G Aarnoudse, Paul P van den Berg, Henk Groen. Academic Medical Centre Amsterdam Ben WJ Mol, Sylvia Vijgen, Denise Bijlenga, Joris AM van der Post. Onze Lieve Vrouwen Gasthuis Amsterdam Dick J Bekedam Hospital Rijnstate Arnhem Karin de Boer Scheper Hospital Emmen Jan M Burggraaff Leiden University Medical Centre Kitty WM Bloemenkamp Twee Steden Hospital Tilburg Addi P Drogtrop Sint Elisabeth Hospital Tilburg Arie Franx Medical Centre Haaglanden Den Haag Christianne JM de Groot Gelre Hospital Apeldoorn Anjoke JM Huisjes University Medical Centre Utrecht Anneke Kwee Martini Hospital Groningen Aren J van Loon Spaarne Hospital Hoofddorp Annemiek Lub Amphia Hospital Breda Dimitri NM Papatsonis Atrium Medical Centre Heerlen Frans JME Roumen University Medical Centre Nijmegen Hubertina CJ Scheepers University Hospital Maastricht Christine Willekes

31. Research nurses…

32. Relation between maternal complications and mode of delivery- Expectant management group - Values expressed in n(%)

33. Relation between maternal complications and mode of delivery- Induction of labour group- Values expressed in n(%)

34. Baseline Characteristics Values expressed in n(%) or mean ± SD

35. Primary and secondary Outcomes Values expressed in n(%)

36. Expectant managementPrimary outcome Values expressed in n(%)

37. Expectant managementMode of delivery Values expressed in n(%) or mean ± SD

38. Quality of life: SF-36 Physical Component Baseline p= .897 6 Weeks PP p= .088 6 Months PP p= .349

39. Quality of life: SF-36 Mental Component Baseline p= .968 6 Weeks PP p= .438 6 Months PP p= .478

40. ConclusionQuality of life In women with PIH or mild PE at term, maternal QoL on the physical plane is slightly better after induction of labour than after expectant management.

41. Costs per patient

42. Mean costs per patient

43. ConclusionCosts Induction of labour results in a considerable cost saving compared to expectant management. Mainly due to differences in the ante partum period.