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.