Management Protocol
Fetal therapy was approved by the Institutional Review Board (reference number: 2020/377). Written informed consent was obtained from both families.
At 28 + 0 weeks gestation, CMH therapy was initiated in accordance with previously described protocols (2, 5). On the first day, oxygen was provided for 6 h, One hour after administration of oxygen, the pulmonary circulation response and improved venous return loading effect to the left ventricle was demonstrated by Doppler sonography. Fetal pulmonary venous blood flow velocity and quantitative changes in color Doppler of lung vessels were compared to document pulmonary vasodilation, as described by Kohl (3). From the second day forward, the patient received daily MH therapy for 8 h (50% FiO2 at 6 L/min via face mask until delivery) in a continuous fashion. The fetus was monitored with biweekly echocardiography to monitor ductus arteriosus constriction and cardiovascular status, and daily cardiotocography in the outpatient clinic. Doppler evaluation of the umbilical artery (UA) and MCA was performed. All Doppler values, including the MCA pulsatility index (PI), UA PI, and UA systolic-to-diastolic (S:D) ratio, were measured using the average values of three consecutive cycles. The cerebroplacental ratio (CPR) was calculated as the MCA PI-to-UA PI.
Measurements of the long and short ventricular axes, and the mitral (MV) and tricuspid valves (TV) were obtained from the four-chamber view from the inner edge-to-the inner edge at end-diastole. The aortic valve (AV), ascending aorta (AAo), descending aorta (DAo), pulmonary valve (PV), and main pulmonary artery (MPA) measurements were obtained during ventricular ejection in the longitudinal view. The aortic isthmus was closely measured proximal to the insertion of the arterial duct with ductal diameter measurement in the three-vessel trachea (3VT) section. Additionally, the flow pattern at the isthmus was followed on the 3VT or sagittal view with a Doppler angle < 10°. Evaluation of fetal cardiovascular structures was carried out several times. The first two measurements were obtained immediately before treatment and in the first week of MH therapy. Moreover, documentation was performed in a 2- or 4-week period during pregnancy follow-up.
Postnatal cardiac evaluation and follow-up was performed by our pediatric cardiologist (KO) blinded to prenatal measurements several times in the 1st week, and at 6 and 20 months of age in the first case, and in the 1st month (because she delivered in her country of residence), in the 6th and 12th months in the second case (Figures 1 and 2).
Each measurement was used to obtain antenatal and postnatal z-scores using previously published normative data. The data were expressed as gestational age–related and postnatal z-scores-based data (Detroit data) provided by a Web site calculator available at http://www.parameterz.com (10-14).
Maternal arterial PO2 was measured via maternal femoral artery puncture on the first and final days of MH therapy. A postnatal ocular examination of the neonate and a chest x-ray of the mother were performed. Additionally, neurologic examinations were performed and routine glucose and biochemical laboratory results were obtained during every visit in the first year of life.