Maternal Oxygen Supplementation for Fetal Distress

(MOXY Trial)

Overseen By Nandini Raghuraman, MD MSCI

Age: Any Age

Sex: Female

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must not be taking: Nitrous oxide

Disqualifiers: Preterm gestation, Major fetal anomaly, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: During labor

2124 Participants Needed

Trial Summary

What is the purpose of this trial?

More than 80% of the 3 million women who labor and deliver each year in the United States undergo continuous electronic fetal monitoring (EFM) during labor in order to fetal hypoxia and prevent the transition to acidemia, expedited operative delivery, and/or neonatal morbidity. Category II EFM is the most commonly observed group of fetal heart rate features in labor. One common response to Category II EFM is maternal oxygen (O2) supplementation. The theoretic rationale for O2 administration is that it increases O2 transfer to a hypoxic fetus. There are conflicting national guidelines regarding O2 administration - the American College of Obstetricians and Gynecologists suggest O2 is ineffective, whereas the Association of Women's Health, Obstetric, and Neonatal Nurses recommend continued use given lack of definitive data on safety and efficacy. A recent national survey of nearly 600 Labor \& Delivery providers in February 2022 revealed that 49% still use O2 . Thus, there remains equipoise on the topic and high-quality data on the safety of intrapartum O2 is needed. None of the trials to date have studied the effect of intrapartum O2 on important clinical measures of neonatal or maternal morbidity. This safety data is imperative because the field of obstetrics must hold supplemental O2 to the same rigorous standards applied to any drug used in pregnancy. Without data on these definitive outcomes, it will be challenging to implement evidence-based recommendations for supplemental O2 use on Labor \& Delivery. The investigators will conduct a large, multicenter, randomized noninferiority trial of O2 supplementation versus room air in patients with Category II EFM in labor.

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 healthcare provider.

What data supports the effectiveness of the treatment Maternal Oxygen Supplementation for Fetal Distress?

The available research suggests that there is no strong evidence supporting the effectiveness of maternal oxygen supplementation for improving fetal outcomes during labor, and it may even be potentially harmful. Current studies indicate that this treatment should be reserved for cases where the mother has low oxygen levels, rather than as a standard intervention for fetal distress. ^{1 2 3 4 5}

Is maternal oxygen supplementation safe for humans?

Research suggests that while maternal oxygen supplementation is commonly used, it may not be beneficial and could potentially be harmful due to increased free radical activity. Excessive oxygen can have negative effects, and its safety in pregnancy is still uncertain, with some studies reporting adverse effects. ^{2 5 6 7 8}

How is maternal oxygen supplementation different from other treatments for fetal distress?

Maternal oxygen supplementation is unique because it involves giving extra oxygen to the mother to increase the oxygen available to the baby, but current research suggests it may not be beneficial and could even be harmful. Unlike other treatments, it is not yet proven effective in clinical trials and should be used cautiously. ^{1 2 5 9 10}

Eligibility Criteria

This trial is for pregnant women at or beyond 37 weeks of gestation, in spontaneous labor or induction, who speak English or Spanish and are having single babies with planned continuous fetal monitoring. It excludes those scheduled for cesarean delivery, with the most severe fetal heart rate issues (Category III), major fetal anomalies, multiple pregnancies, maternal oxygen levels below 95%, or preterm gestation.

Inclusion Criteria

Planned continuous fetal monitoring

You are pregnant with only one baby.

My pregnancy has reached or passed 37 weeks.

Exclusion Criteria

You were born prematurely.

Planned or scheduled cesarean delivery

You are in the third category of fetal monitoring when you are admitted.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either oxygen supplementation or room air during labor with Category II EFM

During labor

Follow-up

Participants are monitored for neonatal and maternal morbidity outcomes

Up to 28 days

Treatment Details

Interventions

• Maternal Oxygen Supplementation
• Room Air

Trial Overview The study tests whether giving extra oxygen to mothers during labor when there's a concern about the baby's oxygen supply (Category II EFM) is safe and effective compared to just breathing room air. This large study will randomly assign participants to either receive supplemental oxygen or breathe normal air to see which is better.

Participant Groups

Group I: Oxygen Experimental Treatment 1 Intervention

Group II: Room air Active Control 1 Intervention

Maternal Oxygen Supplementation is already approved in United States, European Union for the following indications:

Approved in United States as Oxygen Therapy for:

• Intrauterine resuscitation in cases of indeterminate or abnormal fetal heart rate patterns

Approved in European Union as Oxygen Therapy for:

• Intrauterine resuscitation in cases of indeterminate or abnormal fetal heart rate patterns

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

University of Texas at Austin

Collaborator

Trials

387

Recruited

86,100+

Women and Infants Hospital of Rhode Island

Collaborator

Trials

119

Recruited

59,200+

Dell Children's Medical Center of Central Texas

Collaborator

Trials

7

Recruited

5,004,000+

Brown University

Collaborator

Trials

480

Recruited

724,000+

Findings from Research

There is a lack of strong evidence supporting the use of oxygen therapy for women in labor to improve fetal health, despite its common practice.

Relying on maternal oxygen administration may lead to delays in necessary medical interventions for the fetus, highlighting the need for well-designed clinical trials to determine its actual effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whither oxygen for intrauterine resuscitation? Hamel, MS., Hughes, BL., Rouse, DJ.[2018]

A review found no randomized trials supporting the use of maternal oxygen therapy for fetal distress during labor, indicating a lack of evidence for its effectiveness.

In a single trial involving 85 women, those who received prophylactic oxygen therapy had a higher incidence of low cord blood pH values compared to the control group, suggesting potential harm rather than benefit from this intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maternal oxygen administration for fetal distress. Hofmeyr, GJ.[2018]

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 a study involving 46 pregnant women in their third trimester, brief hyperoxygenation (100% oxygen for 10 minutes) led to a significant decrease in cardiac index and an increase in systemic vascular resistance, indicating potential negative effects on maternal circulation.

Unlike the pregnant group, the nonpregnant group (20 women) showed no significant hemodynamic changes during hyperoxygenation, suggesting that the physiological response to supplemental oxygen differs between pregnant and nonpregnant individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperoxygenation in pregnancy exerts a more profound effect on cardiovascular hemodynamics than is observed in the nonpregnant state. McHugh, A., El-Khuffash, A., Bussmann, N., et al.[2019]

Maternal oxygen supplementation during labor does not appear to benefit fetal health, as indicated by the results of the only two randomized trials conducted on this topic.

There is a potential risk associated with maternal oxygen supplementation, as it may increase free radical activity, suggesting that it should only be used in cases of maternal hypoxia and not for nonreassuring fetal heart rate patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen for intrauterine resuscitation: of unproved benefit and potentially harmful. Hamel, MS., Anderson, BL., Rouse, DJ.[2015]

Oxygen therapy is crucial in treating hypoxemia in acute care, but excessive oxygen supplementation can lead to harmful effects, known as hyperoxemia.

The article emphasizes the importance of following current recommendations for safe oxygen supplementation to avoid the negative consequences associated with too much oxygen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oxygen toxicity in acute care settings]. Lévy, C., Schmit, A., Younossian, AB., et al.[2019]

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]

In a study of 130 healthy women undergoing elective cesarean delivery, the use of supplemental oxygen did not significantly impact neonatal well-being as measured by Apgar scores or umbilical cord blood gases.

While maternal oxygen saturation was higher in the supplemental oxygen group, the differences in neonatal outcomes, including blood gas measurements, were not clinically significant, indicating that oxygen therapy may not be necessary for healthy parturients during cesarean sections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Is oxygen therapy truly useful and necessary during elective cesarean section under spinal anesthesia?]. Palacio, F., Ortiz-Gómez, JR., Fornet, I., et al.[2019]

There is insufficient evidence to support the use of maternal oxygen therapy during labor for fetal distress, as no trials specifically addressed this issue.

In the two trials that examined prophylactic oxygen administration, it was found that abnormal cord blood pH values were significantly more frequent in the oxygen group compared to the control group, suggesting potential harm rather than benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maternal oxygen administration for fetal distress. Fawole, B., Hofmeyr, GJ.[2021]

The review found no evidence supporting the use of maternal oxygen therapy for fetal distress during labor, and two trials on prophylactic oxygen administration showed that it was associated with a significantly higher risk of abnormal cord blood pH values (less than 7.2).

Given the potential risks and lack of efficacy demonstrated, there is an urgent need for further randomized trials to evaluate the effects of oxygen therapy during labor, as current practices may be ineffective or harmful.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maternal oxygen administration for fetal distress. Fawole, B., Hofmeyr, GJ.[2018]

References

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

Whither oxygen for intrauterine resuscitation? [2018]

2. England pubmed.ncbi.nlm.nih.gov

Maternal oxygen administration for fetal distress. [2018]

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

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

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

Hyperoxygenation in pregnancy exerts a more profound effect on cardiovascular hemodynamics than is observed in the nonpregnant state. [2019]

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

Oxygen for intrauterine resuscitation: of unproved benefit and potentially harmful. [2015]

6. Switzerland pubmed.ncbi.nlm.nih.gov

[Oxygen toxicity in acute care settings]. [2019]

7. Ireland pubmed.ncbi.nlm.nih.gov

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

8. Spain pubmed.ncbi.nlm.nih.gov

[Is oxygen therapy truly useful and necessary during elective cesarean section under spinal anesthesia?]. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Maternal oxygen administration for fetal distress. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Maternal oxygen administration for fetal distress. [2018]