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

Trial Summary

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 data supports the effectiveness of the treatment Oxygen therapy for Congenital Heart Disease?

Some studies suggest that using oxygen therapy during pregnancy may help reduce complications in mothers and babies with heart conditions, although results vary and there are concerns about potential side effects. ^{1 2 3 4 5}

Is maternal hyperoxygenation safe for use in pregnancy?

Maternal hyperoxygenation has been used in various pregnancy scenarios, but studies have shown mixed results regarding its safety, with some reporting potentially concerning side effects. Hyperbaric oxygen therapy, a related treatment, is considered safe during pregnancy and can reduce complications in certain conditions. ^{1 2 3 6 7}

How is maternal hyperoxygenation treatment different from other treatments for congenital heart disease in fetuses?

Maternal hyperoxygenation involves giving pregnant women high levels of oxygen through a facemask to improve blood flow and heart growth in fetuses with congenital heart disease. This approach is unique because it directly targets fetal heart development by enhancing blood circulation, unlike other treatments that may not focus on prenatal intervention. ^{1 2 4 6 8}

What is the purpose of this trial?

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.

Research Team

Mike Seed, MD

Principal Investigator

The Hospital for Sick Children

Edgar Jaeggi, MD

Principal Investigator

The Hospital for Sick Children

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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]

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]

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]

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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Calling into question the future of hyperoxygenation in pregnancy. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Maternal hyperoxygenation: A potential therapy for congenital heart disease in the fetuses? A systematic review of the current literature. [2020]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Maternal hyperoxygenation during pregnancy as a tool in fetal disease diagnosis and treatment. [2023]

5. England 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. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Open issues in management of carbon monoxide poisoning in pregnancy: practical suggestions. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

The duration of intrapartum supplemental oxygen administration and umbilical cord oxygen content. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Successful prenatal treatment with continuous chronic maternal hyperoxygenation therapy in hypoplastic left heart in two pregnancies: Case report. [2023]