Oxygen Therapy for Fetal Heart Defects

Overseen By Mike Seed, MBBS

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: The Hospital for Sick Children

Disqualifiers: Complex TGA, Arrhythmia, Non-cardiac lesions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether giving extra oxygen to pregnant women can help doctors better understand heart defects in unborn babies, specifically Transposition of the Great Arteries (TGA), where the heart's main arteries are switched. By observing the baby's heart response to oxygen, researchers aim to identify which babies might need immediate care after birth. During certain tests, the mother breathes oxygen through a mask. Ideal candidates for this trial are those carrying a baby with a straightforward version of TGA and planning active treatment for the baby after birth. As an unphased trial, this study allows participants to contribute to groundbreaking research that could enhance future care for babies with heart defects.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What prior data suggests that this oxygen therapy is safe for fetal heart defects?

Research has shown that oxygen therapy is generally safe during pregnancy. One study found that when pregnant women briefly inhaled oxygen, it altered the baby's blood flow, but these changes did not appear harmful. Another study examined low-dose oxygen therapy for pregnancies with certain fetal conditions and found it safe and well-tolerated.

Overall, these findings suggest that using oxygen in short sessions, such as the 30 to 45-minute ones in this trial, is likely safe for both mother and baby. While research has not shown any major side effects, participation in a trial like this should still involve careful monitoring by doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for fetal heart defects, which often involve surgical interventions or medications to manage symptoms, oxygen therapy offers a non-invasive option. Researchers are excited about this approach because it involves delivering oxygen gas directly via a face mask, potentially enhancing the clarity of MRI and echocardiogram images. This method could improve diagnostic accuracy without the need for more invasive procedures, providing a safer and more comfortable experience for both the mother and the fetus.

What evidence suggests that oxygen therapy is effective for fetal heart defects?

Research has shown that oxygen therapy, which participants in this trial will receive, might improve health outcomes for unborn babies with heart defects. Studies have found that higher oxygen levels can aid the development of fetuses with heart issues. For example, when mothers inhale more oxygen, it has been linked to better growth of the aortic annulus, a part of the baby's heart. Oxygen therapy could benefit fetuses by enhancing blood flow and oxygen delivery, crucial for healthy development. Although more research is needed, early results suggest this treatment could be helpful for certain heart defects in unborn babies. ^{2 4 5 6 7}

Who Is on the Research Team?

Edgar Jaeggi, MD

Principal Investigator

The Hospital for Sick Children, Toronto

Mike Seed, MD

Principal Investigator

The Hospital for Sick Children, Toronto

Are You a Good Fit for This Trial?

This trial is for pregnant individuals whose fetus has been diagnosed with a heart condition known as Transposition of the Great Arteries (TGA), with or without a small hole in the heart (VSD). Participants should be planning on active management after the baby's birth.

Inclusion Criteria

My unborn baby has been diagnosed with a heart condition involving the transposition of the great arteries, possibly with a small hole in the heart.

Intention of active postnatal management after birth

Exclusion Criteria

I have significant health issues not related to my heart.

My unborn baby has a complex heart condition called TGA.

I cannot have a fetal MRI due to health reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Maternal Hyperoxygenation

Participants undergo transient maternal hyperoxygenation to assess fetal intracardiac and pulmonary blood flow using echocardiography and MRI

1 day

1 visit (in-person)

Follow-up

Participants are monitored for neonatal outcomes from intrauterine demise to hospital discharge, or up to 1 year of age if pulmonary hypertension exists

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Oxygen gas

Trial Overview The study is testing if breathing extra oxygen (hyperoxygenation) can help doctors better predict which babies with TGA will have good or poor mixing of blood in their hearts before they are born.

How Is the Trial Designed?

Group I: Oxygen gas Experimental Treatment 1 Intervention

10-15 L/min of oxygen by face mask for up to 45 minutes for the MRI and up to 30 minutes for the echocardiogram.

Who Is Running the Clinical Trial?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

Published Research Related to This Trial

Oxygen therapy is crucial for infants with respiratory failure, aiming to reduce hypoxemia, prevent pulmonary hypertension, and decrease respiratory and cardiac strain, but there is a lack of consensus on its use across different medical centers.

The Spanish Society of Pediatric Pneumology has developed recommendations based on a review of existing literature to standardize oxygen therapy practices, addressing its indications, benefits, risks, and cost-effectiveness, particularly for home oxygen therapy management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oxygen therapy in acute and chronic conditions: Indications, oxygen systems, assessement and follow-up]. Luna Paredes, MC., Asensio de la Cruz, O., Cortell Aznar, I., et al.[2016]

Oxygen therapy is crucial for the care of premature infants in the NICU, but it poses risks of oxidant injury due to their limited antioxidant defenses, which can lead to serious complications like retinopathy and chronic lung disease.

The article emphasizes the importance of proper oxygen therapy practices for NICU nurses to minimize oxygen-related complications and improve the health outcomes of premature infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rethinking oxygen therapy for premature infants in terms of oxidative stress]. Yuan, CJ., Hua, YM., Lee, TY.[2013]

The most common side effects of hyperbaric oxygen (HBO2) therapy are middle ear barotrauma, affecting up to 2% of patients, which can be managed through techniques like autoinflation or tympanostomy tubes.

While rare, more severe side effects from HBO2 therapy can include oxygen toxicity leading to issues like progressive myopia and pulmonary dyspnea, with serious complications like seizures occurring at higher oxygen pressures, particularly in patients with acidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of hyperbaric oxygen therapy. Camporesi, EM.[2014]

Oxygen therapy is crucial for treating hypoxia by increasing the oxygen concentration in the air a patient breathes, which helps improve cellular metabolism.

Helium-oxygen mixtures (heliox) can effectively reduce respiratory effort and enhance gas exchange in patients with airway obstructions, and they do so with minimal adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Medicinal gases: oxygen and heliox]. Rodríguez Núñez, A., Martinón Sánchez, JM., Martinón Torres, F.[2019]

Maternal oxygen therapy in cases of suspected impaired fetal growth was associated with a lower perinatal mortality rate, showing a relative risk reduction of 50%, based on three studies involving 94 women.

However, the observed benefits may be influenced by the higher gestational age of the mothers receiving oxygen, indicating that more research is needed to fully understand the safety and efficacy of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maternal oxygen administration for suspected impaired fetal growth. Say, L., Gülmezoglu, AM., Hofmeyr, GJ.[2022]

Hypoxic gas ventilation therapy using a nitrogen gas mixture safely improves cerebral blood supply in patients with congenital heart diseases, as indicated by increased cerebral oxygen saturation and improved middle cerebral artery blood flow.

In a study of 8 patients, cerebral oxygen saturation increased from an average of 67.3% to 70.7% within 24 hours of treatment, demonstrating that this therapy does not compromise oxygen delivery to the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in cerebral oxygen saturation and blood flow during hypoxic gas ventilation therapy in HLHS and CoA/IAA complex with markedly increased pulmonary blood flow. Toiyama, K., Hamaoka, K., Oka, T., et al.[2019]

Maternal oxygen inhalation during pregnancy and labor may provide benefits to the fetus, suggesting a potential therapeutic role for oxygen therapy in these situations.

The review highlights the ongoing debate about the advantages and disadvantages of oxygen administration, indicating that more research is needed to fully understand its effects on both mother and fetus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of maternal oxygen administration on the fetus. Bartnicki, J., Saling, E.[2019]

Maternal hyperoxygenation (MH) therapy in fetuses with congenital heart disease (CHD) showed promising results, with 270 fetuses treated and evidence of increased size in hypoplastic cardiac structures and improved blood flow metrics, indicating potential therapeutic benefits.

No significant adverse events were reported during the therapy, suggesting that MH is a safe intervention; however, further randomized controlled trials are necessary to confirm its efficacy and outcomes for specific types of CHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maternal hyperoxygenation: A potential therapy for congenital heart disease in the fetuses? A systematic review of the current literature. Co-Vu, J., Lopez-Colon, D., Vyas, HV., et al.[2020]

In a review of over 1.5 million hyperbaric oxygen therapy treatments, only 0.68% were linked to adverse events, indicating that serious complications are rare.

The most common issues reported were barotrauma and confinement anxiety, while severe events like oxygen toxicity occurred in less than 0.05 per 1000 treatments, suggesting that HBO therapy is a safe and low-risk treatment when following proper protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Analysis of Adverse Events in Hyperbaric Oxygen Therapy (2012-2015): Lessons Learned From 1.5 Million Treatments. Jokinen-Gordon, H., Barry, RC., Watson, B., et al.[2022]

In a study of 1,308 patients receiving hyperbaric oxygen (HBO2) therapy, five seizure episodes were reported during 10,425 treatments, indicating a low but notable risk of seizures, particularly in patients with carbon monoxide poisoning and arterial gas embolism.

Despite the occurrence of seizures, none of the patients experienced lasting effects, suggesting that while seizures can happen during HBO2 therapy, the overall safety profile remains high, and clinicians should be prepared to manage such events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seizure during hyperbaric oxygen therapy: experience at a single academic hospital in Korea. Lee, CH., Choi, JG., Lee, JS., et al.[2021]

Oxygen therapy is effective in increasing survival rates for patients with chronic obstructive pulmonary disease (COPD) and respiratory failure, but it has not been proven beneficial for patients with moderate hypoxaemia or other chronic respiratory conditions.

The choice of oxygen source and flow rate should be tailored to individual patient needs, considering factors like comfort, adaptability, and cost, to ensure proper oxygen saturation levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous home oxygen therapy. Ortega Ruiz, F., Díaz Lobato, S., Galdiz Iturri, JB., et al.[2016]

Oxygen therapy is crucial for hospitalized children to prevent or treat tissue hypoxia, but it must be prescribed carefully like any medication to avoid inappropriate use.

The article emphasizes the importance of understanding the indications, administration, monitoring, and potential risks of oxygen therapy to maximize its benefits and minimize toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pediatric Oxygen Therapy: A Clinical Update. Haque, A., Rizvi, M., Arif, F.[2018]

In a review of 41,273 hyperbaric oxygen therapy sessions involving 3,737 patients over 20 years, the incidence of oxygen toxicity seizures (OTS) was found to be low at 0.06%, indicating that while OTS is a risk, it is relatively rare.

The study revealed that the rate of OTS increases significantly with higher pressures, particularly above 203 kPa, suggesting that pressure levels during treatment should be carefully monitored to minimize the risk of seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen toxicity seizures: 20 years' experience from a single hyperbaric unit. Banham, ND.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8429855/

Maternal hyperoxygenation in congenital heart disease - PMC The authors found that oxygen intake over 9 hours per day was associated with improved aortic annular growth whereas the number of days on MH was not associated ...

2. withpower.com withpower.com/trial/phase-transposition-of-great-vessels-8-2018-9edbb

Oxygen Therapy for Fetal Heart Defects Yes, the treatment is promising because it may help fetuses with heart defects by improving their oxygen levels, which can support better development and health ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02965638

Trial of Maternal Oxygen for Fetal Left Heart Hypoplasia The purpose of this study is to determine if maternal hyperoxygenation is an effective treatment for fetal left heart hypoplasia versus room air (placebo).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6514285/

Acute therapy of newborns with critical congenital heart disease In general, administration of oxygen should be avoided or only be administrated with the objective of an arterial oxygen saturation of around 80 ...

5. ahajournals.org ahajournals.org/doi/10.1161/JAHA.120.018777

Fetal Cerebral Oxygenation Is Impaired in Congenital ... Cerebral oxygenation is lower in fetuses with congenital heart disease compared with controls with similarities noted across physiologic ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38629477/

Safety and feasibility pilot study of continuous low-dose ... This pilot phase-1 clinical trial indicates that low-dose MSO therapy is safe and well tolerated in pregnancies diagnosed with fetal SVP.

7. eurjmedres.biomedcentral.com eurjmedres.biomedcentral.com/articles/10.1186/s40001-025-02456-z

Maternal oxygen inhalation affects the fetal hemodynamic in ... Our study found that brief maternal oxygen inhalation in the third trimester was associated with significant changes in fetal hemodynamics, specifically higher ...