Safety and feasibility pilot study of continuous low‐dose maternal supplemental oxygen in fetal single ventricle heart disease

• Published in: Ultrasound in obstetrics & gynecology Vol. 64; no. 4; pp. 493 - 503
• Main Authors: Lee, F.‐T., Sun, L., Szabo, A., Milligan, N., Saini, A., Chetan, D., Hunt, J.‐L., Macgowan, C. K., Freud, L., Jaeggi, E., Van Mieghem, T., Kingdom, J., Miller, S. P., Seed, M.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-10-2024; Wiley Subscription Services, Inc
• Subjects: Adult; Age; Brain; Brain injury; Cardiovascular diseases; Circumferences; Clinical trials; Concentrators; Dosage; Echocardiography; feasibility; Feasibility Studies; Female; Fetal Development; Fetal Diseases - diagnostic imaging; Fetuses; Gestation; Gestational Age; Gynecology; Head injuries; Heart Defects, Congenital - diagnostic imaging; Heart Defects, Congenital - embryology; Heart diseases; Heart Ventricles - diagnostic imaging; Heart Ventricles - embryology; Humans; Impact analysis; Infant, Newborn; Injury analysis; Magnetic resonance imaging; maternal supplemental oxygen; Medical imaging; Neonates; neurodevelopment; Neurodevelopmental disorders; Neuroimaging; Obstetrics; Oxygen; Oxygen - administration & dosage; Oxygen Inhalation Therapy - methods; Oxygenation; Pilot Projects; pilot study; Pregnancy; Safety; Secondary analysis; single ventricle heart disease; Traumatic brain injury; Ultrasonography, Prenatal; Univentricular Heart - diagnostic imaging; Univentricular Heart - embryology; feasibility; brain injury; neurodevelopment; pilot study; safety; single ventricle heart disease; maternal supplemental oxygen
• ISSN: 0960-7692; 1469-0705; 1469-0705
• DOI: 10.1002/uog.27657

ABSTRACT
Objective
Fetuses with single ventricle physiology (SVP) exhibit reductions in fetal cerebral oxygenation, with associated delays in fetal brain growth and neurodevelopmental outcomes. Maternal supplemental oxygen (MSO) has been proposed to improve fetal brain growth, but current evidence on dosing, candidacy and outcomes is limited. In this pilot study, we evaluated the safety and feasibility of continuous low‐dose MSO in the setting of SVP.
Methods
This single‐center, open‐label, pilot phase‐1 safety and feasibility clinical trial included 25 pregnant individuals with a diagnosis of fetal SVP. Participants self‐administered continuous MSO using medical‐grade oxygen concentrators for up to 24 h per day from the second half of gestation until delivery. The primary aim was the evaluation of the safety profile and feasibility of MSO. A secondary preliminary analysis was performed to assess the impact of MSO on the fetal circulation using echocardiography and late‐gestation cardiovascular magnetic resonance imaging. Early outcomes were assessed, including perinatal growth and preoperative brain injury, and neurodevelopmental outcomes were assessed at 18 months using the Bayley Scales of Infant and Toddler Development 3rd edition, and compared with those of a contemporary fetal SVP cohort (n = 217) that received the normal standard of care (SOC).
Results
Among the 25 participants, the median maternal age at conception was 35 years, and fetal SVP diagnoses included 16 with right ventricle dominant, eight with left ventricle dominant and one with indeterminate ventricular morphology. Participants started the trial at approximately 29 + 2 weeks' gestation and self‐administered MSO for a median of 16.1 h per day for 63 days, accumulating a median of 1029 h of oxygen intake from enrolment until delivery. The only treatment‐associated adverse events were nasal complications that were resolved typically by attaching a humidifier unit to the oxygen concentrator. No premature closure of the ductus arteriosus or unexpected fetal demise was observed. In the secondary analysis, MSO was not associated with any changes in fetal growth, middle cerebral artery pulsatility index, cerebroplacental ratio or head‐circumference‐to‐abdominal‐circumference ratio Z‐scores over gestation compared with SOC. Although MSO was associated with changes in umbilical artery pulsatility index Z‐score over the study period compared with SOC (P = 0.02), this was probably due to initial baseline differences in placental resistance. At late‐gestation cardiovascular magnetic resonance imaging, MSO was not associated with an increase in fetal cerebral oxygen delivery. Similarly, no differences were observed in neonatal outcomes, including preoperative brain weight Z‐score and brain injury, mortality by 18 months of age and neurodevelopmental outcomes at 18 months of age.
Conclusions
This pilot phase‐1 clinical trial indicates that low‐dose MSO therapy is safe and well tolerated in pregnancies diagnosed with fetal SVP. However, our protocol was not associated with an increase in fetal cerebral oxygen delivery or improvements in early neurological or neurodevelopmental outcomes. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.