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.