Maternal hyperoxygenation in the fetus with heart disease

Children with complex congenital heart disease (CHD) disease show altered brain maturation and neurodevelopmental outcome. One cause might be a disturbed blood and oxygen supply of the brain of the unborn. Within the frame of the research fellowship at the Hospital for Sick Children, University of Toronto, we aim to investigate prenatal therapy options on increasing blood and oxygen supply of the brain of fetuses with complex CHD. Using echocardiography and magnetic resonance imaging we will assess fetal brain blood and oxygen supply while for some minutes the mother is inhaling 100% oxygen (maternal hyperoxygenation). We assume that maternal oxygen application as described will increase the oxygen blood content especially in the fetal brain thus preventing fetal cerebral maldevelopment.

Originally we aimed to assess variables influencing brain maturation and neurodevelopmental outcome of patients with complex congenital heart disease (CHD), with the focus on the variable of having the fetus' mother inhale pure oxygen for some minutes ('acute maternal hyperoxygenation'). Federal and universitary restrictions due to the Covid-19 pandemic forced us to shift our focus on two other forms of fetal intervention: (1) medication against abnormal heart frequency and rhythm (antiarrhythmics); (2) catheter opening/dilation of a vessel valve (valvuloplasty). First we examined the course of an abnormal and too fast fetal heart rhythm (tachyarrhythmia), a potentially life-threatening condition. By ultrasound and electrophysiologic examinations we could show that fetal tachyarrhythmia is untreatable in 10% of patients, recurs during the first days of life in an additional 30% of patients, and that advanced fetal arrhythmia characteristics predict treatment success and recurrence within the first days of life. For patients successfully treated in utero with a normal rhythm after birth, prenatal predictors of tachyarrhythmia recurrence were missing; However, a specific early postnatal electrophysiologic examination may help decide if antiarrhythmics can be safely avoided. Then we focused on outcome prediction based on ultrasound-assessment of fetal cardiac form and function in complex CHD where the lung valve is small or absent and the ventricular septum is intact (pulmonary atresia with an intact ventricular septum (PAIVS)). Outcome depends on whether the right-sided structures are good-size allowing catheter or surgical intervention to a two chamber (biventricular, BV) heart (opening or dilating the lung valve may promote growth of right-sided structures and improve the outcome; particularly patients who naturally have good chances of a BV outcome benefit from such intervention), or whether they are too small forcing the patient to follow a SV pathway with its several surgeries bearing a high risk of long-term complications. 60% of our patients were eligible to specific surgery achieving a BV heart with a 100% compared to 60% 1-year survival of patients with a SV. We found that in the fetus with PAIVS it is difficult to predict whether the underlying lesion is suitable for a BV circulation: published predictive scores performed worse than claimed. We succeeded to develop an optimized score for BV vs. SV prediction. All in all I got important insight into outcome prediction and the decision making process for fetal intervention. Apart from the scientific achievements, I established close contacts to the world's leading experts in the field and learned a lot of large-scale scientific and clinical management.