Maternal Hyperoxygenation for Congenital Heart Disease

Overseen By Liqun Sun, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: The Hospital for Sick Children

Disqualifiers: Unusual CHDs, Complex cardiac condition, 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

Duration: 30-45 minutes per session

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether providing extra oxygen to pregnant mothers can benefit babies with certain heart defects before birth. The researchers aim to determine if this additional oxygen can enhance the baby's brain development and support better growth after birth. The trial involves mothers whose unborn babies have specific congenital heart diseases, such as hypoplastic left heart syndrome or tetralogy of Fallot. Pregnant women informed that their baby has one of these heart conditions and who plan to continue their pregnancy may be suitable candidates for this trial. As an unphased trial, it offers a unique opportunity for mothers to contribute to groundbreaking research that could improve outcomes for babies with heart defects.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that maternal hyperoxygenation is safe for fetuses with congenital heart disease?

Research has shown that oxygen therapy is generally safe and well-tolerated. A small initial study found that low-dose oxygen therapy was safe for pregnant women with certain fetal conditions. Other studies on adults with heart problems have found that oxygen therapy usually does not cause harm. However, traditional oxygen therapies can occasionally lead to complications, though these are rare. Overall, evidence suggests oxygen therapy is likely safe in this context. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using maternal hyperoxygenation as a treatment for congenital heart disease (CHD) in fetuses because it offers a non-invasive approach that could potentially improve fetal heart function. Unlike current treatments that often involve post-birth surgical interventions, this method uses oxygen gas to enhance oxygen delivery to the fetus during pregnancy. The idea is that by increasing oxygen levels while the mother undergoes imaging scans, it may help in better developing the fetal heart without the need for immediate surgery after birth, offering a proactive rather than reactive solution to managing severe CHD.

What evidence suggests that maternal hyperoxygenation might be an effective treatment for congenital heart disease?

Research has shown that oxygen therapy can benefit individuals with congenital heart disease (CHD). For those with cyanotic CHD, oxygen therapy improves exercise abilities, such as endurance and work rate. One study found it useful for calming children during medical procedures. This suggests that oxygen can enhance the cooperation between the heart and lungs. Although results may vary depending on the type of CHD, these findings offer hope that oxygen therapy, which participants in this trial will receive, might support brain growth and development in unborn babies when used during pregnancy. ^{2 4 6 7 8}

Who Is on the Research Team?

Mike Seed, MD

Principal Investigator

The Hospital for Sick Children

Edgar Jaeggi, MD

Principal Investigator

The Hospital for Sick Children

Are You a Good Fit for This Trial?

This trial is for pregnant mothers aged 18 or older with a fetus diagnosed with certain congenital heart defects (CHDs) and planning active post-birth treatment. It excludes those considering pregnancy termination, fetuses with unusual CHDs, major non-cardiac/genetic issues affecting brain development, complex cardiac conditions, significant maternal health problems that prevent MRI scans, or multiple pregnancies.

Inclusion Criteria

My unborn baby has been diagnosed with a heart defect and will receive treatment after birth.

Written maternal informed consent

Exclusion Criteria

You have certain complex heart defects, such as abnormal connections between the heart's chambers or obstructions in blood vessels.

You have a serious heart problem, or the baby's heart is not working well.

The mother has health conditions that make it difficult to do a fetal MRI, like being very overweight or feeling very uncomfortable in small spaces.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Pregnant mothers with fetuses diagnosed with CHD receive acute maternal hyperoxygenation (MH) during echocardiography and MRI

30-45 minutes per session

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Until birth

Regular monitoring until birth

What Are the Treatments Tested in This Trial?

Interventions

• Oxygen gas

Trial Overview The study tests if breathing extra oxygen (maternal hyperoxygenation) can increase the unborn baby's brain oxygen levels in cases of CHD. The goal is to see if this could help the baby's brain grow better before birth and improve their learning abilities after they're born. It also seeks to find which types of CHD might benefit most from this treatment.

How Is the Trial Designed?

Group I: Severe fetal congenital heart disease (CHD) Experimental Treatment 1 Intervention

Mothers whose fetuses have a diagnosis of CHD will be exposed to 10-15 L/minute of oxygen while undergoing echocardiogaphy and MRI scanning

Oxygen gas is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Oxygen gas for:

• Respiratory distress syndrome
• Chronic obstructive pulmonary disease (COPD)
• Congenital heart disease (CHD)

Approved in United States as Oxygen gas for:

• Respiratory distress syndrome
• Chronic obstructive pulmonary disease (COPD)
• Congenital heart disease (CHD)

Approved in Canada as Oxygen gas for:

• Respiratory distress syndrome
• Chronic obstructive pulmonary disease (COPD)
• Congenital heart disease (CHD)

Approved in Japan as Oxygen gas for:

• Respiratory distress syndrome
• Chronic obstructive pulmonary disease (COPD)
• Congenital heart disease (CHD)

Approved in China as Oxygen gas for:

• Respiratory distress syndrome
• Chronic obstructive pulmonary disease (COPD)
• Congenital heart disease (CHD)

Approved in Switzerland as Oxygen gas for:

• Respiratory distress syndrome
• Chronic obstructive pulmonary disease (COPD)
• Congenital heart disease (CHD)

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

Maternal hyperoxygenation has been explored since the 1960s as a potential treatment for various obstetric conditions, but there is still no clear evidence supporting its benefits, particularly for fetal growth restriction.

Research on maternal oxygen therapy for fetal congenital cardiac disease has shown mixed results and raised concerns about possible adverse effects, highlighting the need for careful consideration before conducting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calling into question the future of hyperoxygenation in pregnancy. McHugh, A., El-Khuffash, A., Franklin, O., et al.[2021]

Maternal hyperoxygenation (MHO) involves administering high levels of oxygen (60% to 100%) to pregnant women, which is monitored using ultrasound to assess its effects on fetal cardiovascular circulation.

The review highlights the potential benefits of both acute and chronic MHO in managing various fetal diseases, suggesting it may be a useful intervention in prenatal care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maternal hyperoxygenation during pregnancy as a tool in fetal disease diagnosis and treatment. Zalinska, A., Respondek-Liberska, M., Slodki, M.[2023]

Chronic maternal hyperoxygenation (CMH) therapy has shown promise in improving fetal pulmonary blood flow and enhancing the growth of the left heart in fetuses with left-sided cardiac defects, potentially leading to better heart structure development as gestation progresses.

Despite its benefits, there are concerns regarding potential fetal complications, such as growth restriction and impacts on brain development, which need to be carefully considered when using CMH therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful prenatal treatment with continuous chronic maternal hyperoxygenation therapy in hypoplastic left heart in two pregnancies: Case report. Bolluk, G., Oztarhan, A., Vural, C., et al.[2023]

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]

Hyperbaric oxygenation (HBO) has been shown to effectively reduce cardiologic, obstetric, and perinatal complications in pregnant patients with both acquired and congenital heart diseases, based on a study of 150 patients.

The use of HBO as an adjunct intervention significantly decreased maternal and perinatal mortality rates in these patients, highlighting its potential as a beneficial treatment during pregnancy and delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of hyperbaric oxygenation in the treatment of patients with heart defects and during labor]. Barg, AA.[2016]

In a study of 99 laboring patients, prolonged exposure to supplemental oxygen during labor did not increase umbilical cord oxygen levels; in fact, it was associated with lower oxygen levels in the umbilical vein, indicating potential harm.

The findings suggest that longer durations of oxygen supplementation may impair placental oxygen transfer, raising concerns about the safety and efficacy of this common resuscitation technique during labor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The duration of intrapartum supplemental oxygen administration and umbilical cord oxygen content. Watkins, VY., Martin, S., Macones, GA., et al.[2021]

In fetuses with intrauterine growth restriction, maternal hyperoxygenation significantly increased the pulsatility index in the middle cerebral artery, indicating a disruption of the brain-sparing effect, which is crucial for fetal development.

In contrast, fetuses with normal growth did not show significant changes in the middle cerebral artery, but both groups experienced a significant decrease in pulsatility indices in the pulmonary arteries after hyperoxygenation, suggesting altered blood flow dynamics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of maternal hyperoxygenation on fetal circulatory system in normal growth and IUGR fetuses. What we can learn from this impact. Khatib, N., Thaler, I., Beloosesky, R., et al.[2018]

Hyperbaric oxygen therapy (HBO) is safe for use during pregnancy and can help reduce the severity of fetal injuries caused by carbon monoxide (CO) poisoning.

There is ongoing discussion about the specific carboxyhemoglobin (COHb) levels that should prompt the use of HBO therapy in pregnant patients, highlighting the need for clear protocols in medical organizations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open issues in management of carbon monoxide poisoning in pregnancy: practical suggestions. Eleftheriou, G., Butera, R., Lonati, D., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0167527321019562

Effect of oxygen therapy on exercise performance in ... Patients with cyanotic CHD significantly improved their exercise performance, in terms of maximal work-rate and endurance time along with an improved arterial ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33934982/

Effect of High-Flow Nasal Cannula Oxygen Therapy on ... It is effective for pediatric patients with non-cyanotic congenital heart disease who require procedural sedation.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10908418/

Presurgical Use of Hypoxic Mixture for Systemic Perfusion ... The primary outcome was improved systemic circulation and decreased pulmonary over-circulation measured directly with Qp/Qs and indirectly with ...

4. publications.ersnet.org publications.ersnet.org/content/errev/19/118/300

Therapeutic approaches in adults with congenital heart ... Nocturnal oxygen therapy has been shown to be of no benefit in patients with Eisenmenger syndrome [17], whilst in other patients with CHD-PAH data are lacking.

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1714855

A Randomized Trial of High-Flow Oxygen Therapy in ... Observational and physiological studies suggest that decreased work of breathing, improved oxygenation, and reduced rates of intubation are ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1768426/

Acute effects of 40% oxygen supplementation in adults with ... This study examined the acute effects of 40% oxygen supplementation in adults with cyanotic congenital heart disease (CCHD).

7. 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.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0147956323001103

Cardiopulmonary outcomes following high flow nasal ... However, some studies reported a complication rate concurrent with traditional oxygen therapies, and a suggested HFNC failure rate of 50% was observed. •.