INTRODUCTION
Investigators have observed a fetal cardiovascular response to maternal
hyperoxygenation (MH) therapy,
which leads to an improvement in fetal pulmonary blood flow and an
enhanced venous return to the left heart as gestational age increases
(1). Investigators have therefore studied chronic maternal
hyperoxygenation (CMH) therapy as a fetal initial and/or corrective
treatment opportunity, especially for left-sided obstructed congenital
heart diseases and hypoplastic left heart lesions (2-7).
The principle of MH is based on the oxygen-induced decrease in fetal
pulmonary vascular resistance. The response of the fetal pulmonary
vasculature to additional oxygen has been shown to occur by the
completion of 26 gestational weeks (8). The reduction in fetal pulmonary
resistance should increase pulmonary arterial blood flow and pulmonary
venous return. In addition, the improved left atrial volume should
stimulate growth of the following cardiac structures growth: mitral
valve; left ventricle; and aortic valve.
There have been concerns, however, about CMH therapy with respect to
fetal complications (growth restriction) and fetal brain and placental
development (9).
We present herein two patients diagnosed antenatally, one with mitral
valve and aortic hypoplasia (AH), and another with isthmic hypoplasia.
Both patients developed hypoplastic left heart syndrome (HLHS), and were
successfully treated with CMH therapy in the third trimester without
requiring any further surgical procedures.
CASE REPORT
Case 1
A 28-year-old gravida 1 para 0 at 27 weeks gestation was referred for
evaluation of antenatally-diagnosed AH + HLHS. Fetal echocardiography
was performed by AG (Voluson E8, GE Healthcare Ultrasound, Milwaukee,
WI, USA), and confirmed the diagnosis of left ventricular hypoplasia due
to mitral valve hypoplasia, left ventricular outflow tract obstruction,
a small peri-membranous ventricular septal defect (VSD), and reverse
flow at the aortic isthmus and duct without other extracardiac
pathologic findings. The family had been informed of the prognosis at
two other maternal-fetal clinics; however, she declined karyotyping
and/or termination of the pregnancy (TOP). Following information on MH
therapy, the family accepted this management option.
At
28 + 0 gestational weeks, CMH therapy was initiated in accordance with
previously described protocols (2, 5).
The fetus was monitored biweekly
via echocardiography to assess ductus arteriosus constriction and
cardiovascular status, and daily cardiotocography in the outpatient
clinic during subsequent therapy days. Additionally, fetal growth,
cranial measurements, and umbilical and middle cerebral artery (MCA)
Doppler measurements were determined during follow-up evaluations.
Left ventricle length and width z-scores progressively increased during
CMH therapy, especially during the first 3 weeks. Left cardiac
measurements were near normal levels at the end of therapy (Figures 1
and 2; Videos 1 and 2). The bidirectional Doppler flow pattern in the
aortic isthmus, in which the retrograde flow portion was greater,
changed at the end of therapy and antegrade flow was established during
fetal therapy. Similarly, reverse flow in the foramen ovale from
left-to-right also changed during therapy with appropriate intracardiac
flow from right-to-left.
CMH therapy was continued for 46 days, but due to spontaneous rupture of
membranes at 35 + 4 gestational weeks, a cesarean section was performed
and a 2,980 g male newborn with Apgar scores of 6 and 9 at 1 and 5 min,
respectively, was delivered. The left ventricle measurements were within
normal limits, but a restrictive peri-membranous ventricular septal
defect, mild mitral stenosis, and mild aortic stenosis were diagnosed
postnatally (by KO). The newborn
was followed in the NICU during the first week of life and was
discharged home without surgery on day 10. No ocular, respiratory,
neurologic, glucose metabolism, or growth anomalies were detected during
the neonatology examination. Postnatal karyotyping and chromosomal
microarray were normal.
During the first year of life, a subaortic ridge with minimal aortic
regurgitation developed in addition to the initial diagnoses.
Routine follow-up evaluations
continue at 2 years of age.
Case 2
A 35-year-old gravida 2 para 0 at 25 weeks gestation underwent fetal
echocardiography as a second opinion for an isthmic hypoplasia + HLHS
diagnosis. The family had been informed about the prognosis based on a
normal karyotype and chromosomal microarray results in her country of
residence, and declined a TOP. The family was offered and accepted CMH
therapy after all questions were answered.
At 28 + 0 gestational weeks, CMH therapy was initiated and performed as
described above and below. Because the patient resided in a neighboring
country, subsequent antenatal examinations could only performed at 30
and 34 gestational weeks after the first week of therapy. Although
isthmic hypoplasia persisted and was visible during the entire duration
of pregnancy with aliasing Doppler flow (2.7 mm at 28 weeks, z-score
-2.04; 3.1 mm at 30 weeks, z-score -1.69; 3.8 mm at 34 weeks, z-score
-1.29) (10), the left ventricle length and width z-scores increased
throughout CMH therapy (Figures 1 and 2, Video 3).
After 51 days of CMH therapy, a Cesarean section was performed at 36+2
weeks gestation and a 3,800 g male newborn with Apgar scores of 7 and 9
at 1 and 5 min, respectively, was delivered in own country of residence.
The newborn was followed in the NICU during the first week and the
initial cardiac examinations were unremarkable, according to reports.
Discharge to home occurred without intervention on day 7. The baseline
postnatal examination was performed in the first month (by KO) and
showed normal left ventricle and aortic arch sizes during the first
postnatal month [isthmus, 4.9 mm (z-score -0.70)]. No ocular,
respiratory, neurologic, glucose metabolism, or growth defects were
detected during examination at the 6th and
12th months (Figure 3). Routine follow-up evaluations
continue at 16 months of age.