Zwangerschap bij vrouwen met een Aangeboren HARtAfwijking-II
(Pregnancy in women with congenital heart disease II)
a) To prospectively investigate the changes in cardiac parameters (echocardiography, NT-pro-BNP) and uteroplacental flow (biometry, pulsatility index, diastolic notching) during/after pregnancy in women with CHD and compare these changes with age/parity-matched healthy controls.
b) To relate the cardiac parameters (pre-pregnancy and during pregnancy) with the occurrence of cardiovascular, obstetric and peri-/neonatal/infant complications.
c) To relate the cardiac parameters (pre-pregnancy and during pregnancy) and uteroplacental flow measurements with the occurrence of obstetric complications and peri-/neonatal/infant complications.
d) To elucidate the mechanisms behind the increased incidence of obstetric and peri-/neonatal/infant complications in CHD patients by focusing on changes in utero-placental perfusion.
e) To evaluate the incidence of permanent (1 year) decline of exercise tolerance in women with CHD and compare this with healthy women.
f) To evaluate the risks scores for cardiac and peri-/neonatal/infant complications in pregnant women developed by Siu et al and by the ZAHARA-I investigators prospectively in women with CHD.
g) To continue the (worlds largest) registration (ZAHARA registration) of pregnancy outcome in CHD women, primarily to facilitate the future assessment of long-term effects of pregnancy on survival and morbidity in CHD patients.
The ZAHARA-II study is an international prospective multi-centre cohort study.
At least 160 pregnant women with a congenital heart anomaly presenting before 20 weeks of gestation in one of the participating medical centres will be included. In addition 60 parity and age matched healthy controls will be included by the midwifery in Groningen.
Main outcome will be:
Change in cardiac parameters: Among others significant deterioration in size/function of subpulmonary or systemic ventricle; aggravation of valve regurgitation at least 1 grade; persistent (1 year) significant aggravation of valve stenosis, etc.; significant elevation of NT-pro-BNP, compared to healthy controls- Difference of uteroplacental flow parameters between healthy controls and CHD patients (pulsatility index, % persistent diastolic notching)
Composite endpoint of cardiac complications
Composite endpoint of obstetric complications
Composite endpoint of offspring complications
Composite endpoint of uteroplacental flow related complications (PIH, pre-eclampsia, eclampsia, intrauterine growth retardation, small for gestational age birth weight, premature delivery, offspring mortality within the first year after birth).
Primary endpoint A (pulsatility index, patients vs. controls):
In a cohort study, sample sizes of 160 (patients) and 60 (controls), the means of pulsatility indices are to be compared. The total sample of 240 subjects achieves 80% power to detect a difference of 0.05 in pulsatility index (25% of the expected standard deviation) among the means versus the alternative of equal means using an independent samples T test with a 0.05 significance level. The common standard deviation within a group is assumed to be 0.20.
Start inclusion: March 2008. Inclusion at 20 weeks gestation ends November 2010. Follow-up until March 2012.
Prof. Dr. JG Aarnoudse MD, PhD, obstetrics & gynaecology UMCG Groningen
Dept. Of cardiology: PG Pieper, Dept. of Cardiology, UMCG, Groningen; BJM Mulder, AMC, Amsterdam; JW Roos-Hesselink, Erasmus mc, Rotterdam; APJ van Dijk, UMCN St. Radboud, Nijmegen; HW Vliegen, LUMC, Leiden; E Wajon, MST, Enschede; JLM Stappers, AZM, Maastricht; GJ Sieswerda, UMCU, Utrecht; G Veen, VUMC, Amsterdam
Dept. of Obstetrics & Gynaecology: JG Aarnoudse, UMCG, Groningen, The Netherlands; KM Sollie, UMCG, Groningen, The Netherlands
Dept. of Obstetrics & Gynaecology: M. Hanssens, UZL, Leuven, Belgium
And by the Interuniversity Cardiology Institute of the Netherlands - ICIN - http://www.icin.nl/
Ali Balci, Arts-onderzoeker UMCG
Departement of Cardiology
University Medical Center Groningen
Tel: 050-361 52 88
Mobile: 06 212 82 099