Acute Maternal Hyperoxygenation in CHD

Congenital Heart Disease (CHD): Hemodynamic Effects of Acute Maternal Hyperoxygenation in the Fetus

Congenital heart disease (CHD) is predominantly detected before birth. Using echocardiography and MRI, this study will determine whether acute exposure to maternal hyperoxygenation (MH) leads to measurable increases in fetal cerebral oxygenation from baseline in fetuses with CHD. The study aims to determine whether MH could be used as a chronic in-utero treatment strategy to promote brain growth/maturation to birth and to improve postnatal neurodevelopmental outcomes, and identify the types of CHD most likely to benefit from chronic MH.

This study determines the impact of administering oxygen to mother during the later part of pregnancy on cerebral oxygen delivery in fetuses who were identified with severe forms of Congenital Heart disease (CHD) including the following groups:

• Group 1: Single ventricular (SV) lesions, including hypoplastic left heart syndrome (HLHS); pulmonary atresia with intact ventricular septum (PA/IVS); tricuspid atresia (TA); unbalanced AV septal defect (AVSD); double inlet ventricle (DILV); and severe form of Ebstein's anomaly (EA with pulmonary atresia) of the tricuspid valve; and
• Group 2: Tetralogy of Fallot (TOF),including TOF-like double outlet right ventricle (DORV), pulmonary atresia with ventricular septal defect (PA/VSD)
• Group 3: Bi-ventricular lesions with transposition of the great arteries (TGA), including DORV with TGA

Children with severe CHD experience challenges in multiple developmental domains, impacting executive function, memory, language, and other aspects of cognitive and motor function. It is now well established that brain growth and development are adversely affected by CHD and it is increasingly clear that central nervous system changes that occur in the third trimester play a particularly important role in the pathogenesis of adverse neurodevelopmental outcomes.

Supplemental maternal oxygen will used in the last trimester for a short period of time (acute MH) in pregnant mothers carrying babies with CHD to briefly increase fetal oxygen levels to those reached in the newborn with spontaneous breathing. This study will examine whether and to what degree acute MH will improve the cerebrovascular oxygenation. The rate and duration of MH (10 to 15L/min by mask for up to 30-45 minutes/test) is considered to be safe to the mother and her fetus. Both fetal echocardiography and fetal MRI will be used to determine the effects of acute MH on the fetal-placental circulation and will determine in fetuses with CHD whether acute exposure to MH leads to measurable increases in fetal cerebral oxygenation from baseline. Thus it could potentially become useful as a chronic in-utero treatment strategy to promote brain growth/maturation to birth and to improve postnatal neurodevelopmental outcomes.

Inclusion Criteria:

• Pregnant mothers ≥18 years of age

• Written maternal informed consent

• Fetal diagnosis of one of the CHDs (1-3) as listed below and intention of active treatment after birth:

  1. Single ventricular (SV) lesions: hypoplastic left heart syndrome (HLHS); pulmonary atresia with intact ventricular septum (PA/IVS); tricuspid atresia (TA); unbalanced AV septal defect (AVSD); double inlet ventricle (DILV); and severe form of Ebstein's anomaly (EA) of the tricuspid valve associated with functional or anatomical right outflow obstruction. HLHS will include aortic stenosis with mitral stenosis, aortic atresia with mitral stenosis or mitral atresia. Pulmonary or aortic obstruction is defined as a condition with minimal or absent antegrade flow across the respective valve. Severe forms of EA is defined as lesion without anterograde pulmonary flow in the setting of severe tricuspid regurgitation.
  2. Bi-ventricular lesions with right ventricular outflow tract obstruction (BV/RVOTO); tetralogy of Fallot (TOF), TOF-like double outlet right ventricle (DORV), and pulmonary atresia with ventricular septal defect (PA/VSD).
  3. Bi-ventricular lesions with transposed great arteries (TGA w/ VSD; TGA w/o VSD; DORV with TGA)

Exclusion Criteria:

• Termination of pregnancy
• Unusual CHDs (e.g. EA with circular shunt, TOF with AVSD, and TOF with absent pulmonary valve syndrome, TGA associated with moderate- severe outflow tract obstruction
• Complex cardiac condition (e.g poor fetal cardiac function and/or fetal hydrops, fetal arrhythmia such as frequent premature atrial beats, abnormal baseline heart rate (<110 bpm; > 160 bpm) in the third trimester)
• Major non-cardiac lesions and major genetic abnormalities affecting brain size and development
• Significant maternal co-morbidities that precludes a fetal MRI (e.g. significant obesity, claustrophobia)
• Multiple pregnancy