ZAHARA II

Zwangerschap bij vrouwen met een Aangeboren HARtAfwijking-II

(Pregnancy in women with congenital heart disease II)

Objective
The hemodynamic burden of pregnancy has a significant impact on the maternal heart and vascular system. Our recent retrospective analyses of 1802 pregnancies (ZAHARA-I study) have shown that women with CHD are not only more susceptible to cardiac complications (arrhythmias, deterioration of exercise tolerance, heart failure) but also to obstetric/peri-/neonatal/infant  complications (miscarriages, hypertension related disorders, preterm labour/delivery, small for gestational age children, foetal/peri-/neonatal/infant  mortality). An important common denominator in the obstetric/neonatal pathophysiology is an inadequate utero-placental circulation, but the relation between hemodynamic parameters, uteroplacental flow parameters and peri-/neonatal/infant /obstetric complications has not been investigated in CHD patients.

Primary Objectives

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.

Secondary Objectives

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.

Study design

The ZAHARA-II study is an international prospective multi-centre cohort study.

Study population

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.

Pregnant women with congenital heart disease presenting after the 20th week of pregnancy should be included in the EuroHeartSurvey; contact j.roos@erasmusmc.nl).

Outcome measures

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).

Power/data analysis

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.

Time schedule

Start inclusion: March 2008. Inclusion at 20 weeks gestation ends November 2010.  Follow-up until March 2012.

Project leaders
Dr. P.G. Pieper PhD, cardiology, UMCG Groningen

Prof. Dr. JG Aarnoudse MD, PhD, obstetrics & gynaecology UMCG Groningen

Contact

Ali Balci, Arts-onderzoeker UMCG

Departement of Cardiology

University Medical Center Groningen

Tel: 050-361 52 88

Mobile: 06 212 82 099

E-mail: a.balci@thorax.umcg.nl