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Commentary from Dr. Anna Tsirka (Hartford, CT, USA), section editor of Pediatric and Fetal Cardiology Journal Watch
Take Home Message
Based on this small, phase 1 pilot study, low dose long term oxygen administration in the second and third trimester to mothers of fetuses with single ventricle physiology (SVP) was well tolerated, safe, and did not cause any perinatal maternal or offspring complications. It however did not appear to have any positive or negative effect on postnatal morbidity, mortality or neurodevelopment up to 18 months after birth.
Introduction
Neurodevelopmental deficits are more common in the setting of SVP than in other forms of congenital heart disease (CHD) and represent an important comorbidity for patients with these complex congenital malformations. Previous studies have found associations between fetal brain volume and cerebral oxygenation. It has been postulated that maternal supplemental oxygen (MSO) could represent an early interventional strategy to augment brain growth in utero.
Methods
This was a pilot phase-1, open-label, single-center, non- randomized clinical trial conducted at The Hospital for Sick Children and Sinai Health System in Toronto, Canada, from February 2018 to May 2023. MSO was started between 20-32 weeks gestation up to delivery. Participants self-administered MSO using portable and home ambulatory oxygenators providing 3–4L/min of supplemental oxygen via nasal prongs to achieve an estimated 40% fraction of inspired oxygen (FiO2) for up to 24 h per day. A fetal MRI was performed at 36 weeks gestation that included assessment of fetal blood flow. The participants were given a study diary. A preoperative brain MRI was also performed postnatally, and a neurodevelopment evaluation was performed at 18 months of age. The primary outcome measures were safety and feasibility. A secondary analysis involved comparing fetal and post-natal data from diagnosis until 18 months of age between MSO and SOC groups.
Results
25 mother-baby dyads participated in the MSO group and were compared to 217 dyads who received standard of care (SOC). Table 1 describes the demographic characteristics.
The mothers who enrolled in the study were older. They received MSO for about 16 hours/day for a median of 63 days.
There were no significant complications from MSO as depicted in table 2. The most common maternal complications were epistaxis and local irritation.
Fetal growth was no different between MSO and standard of care. There were no differences in doppler measurements by fetal echocardiogram in the two groups, and there were no differences in flow patterns by late fetal MRI.
At delivery, there were no differences between the two groups in birthweight, gestational age, Apgar scores. The preoperative brain MRI did not reveal any significant differences in brain size, cerebral hemorrhage or white matter injury.
By 18months of age, no significant differences in mortality rates (16% vs 19%; P = 0.79) were observed between those who received MSO and those who received SOC during gestation Additionally, Bayley developmental assessment at 18months of age revealed no significant differences in cognitive, language and motor composite scores between patients who received MSO and those who received SOC during gestation
Discussion:
This pilot phase-1 study indicates that continuous low-dose MSO in pregnancies affected by fetal
SVP is safe for both the mother and fetus and demonstrates that continuous self-administration of MSO in the second half of gestation is feasible. However, the preliminary findings suggest that this protocol did not improve fetal cerebral oxygen delivery or result in improvements in early outcomes, such as perinatal brain growth or injury, or 18-month neurodevelopmental outcomes. This may be the result of the dose of oxygen (40% by nasal cannula). It may also reflect that the sample size was small (only 25 dyads).
Further studies of different methods of O2 administration with larger samples size may be indicated in the future.