Perinatal DeathNCT03996317
Maternal Hyperoxygenation for Intrapartum Fetal Heart Rate Tracing Abnormalities
A study testing Room air in people with Perinatal Death and Respiratory Distress Syndrome, Newborn, run by Loma Linda University at 1 site in United States.
Trial summary
Hyperoxygenation for resuscitation of abnormal fetal heart rate tracings has been routine obstetric practice. However, there have not been any studies to support this practice. Recent literature have either found no associated benefit to intrapartum maternal oxygen administration, or in a number of studies… Read more about this study
- Who is it for?
- Ages 18 to 55 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Perinatal Death, Respiratory Distress Syndrome, Newborn, Hypoxic-Ischemic Encephalopathy
- What is being tested?
- Room air
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2021to 30 Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Singleton pregnancy
- Gestational age between 37and0 weeks and 41and6 weeks
- Admitted for induction of labor or in active labor
- No known fetal anomalies
Who cannot join
- History of 2 or more cesarean delivery
- Maternal contraindications to labor
- Fetal contraindications to labor
- Maternal hemoglobin <8 on admission
- Maternal medical conditions requiring oxygen supplement at baseline (including but not limited to: severe cardiac conditions, uncontrolled asthma, pulmonary embolism, pulmonary fibrosis, pulmonary edema, pneumonia, sepsis etc.)
Trial locations and contacts
1 site in 1 country.
United States1 site
Loma Linda University Children's Hospital
Loma Linda, California, 92354
About this study
Official title: Maternal Hyperoxygenation for Intrapartum Fetal Heart Rate Tracing Abnormalities: a Randomized Clinical Trial
Hyperoxygenation for resuscitation of abnormal fetal heart rate tracings has been routine obstetric practice. However, there have not been any studies to support this practice. Recent literature have either found no associated benefit to intrapartum maternal oxygen administration, or in a number of studies demonstrated higher risk of neonatal complications. Despite these studies, the evidences have not been adequate to change the clinical practice because the majority of these studies either focused on biological differences rather than clinical outcomes data or were retrospective rather than randomized trials. Therefore, the investigators propose a large single center randomized clinical trial to determine the effects of maternal hyperoxygenation therapy for the treatment of fetal heart rate tracing abnormalities.
Read the detailed description
Continuous fetal heart rate tracing is part of the standard practice during intrapartum obstetric management. The goal of fetal heart rate monitoring is to identify early signs of fetal distress during labor, initiate effective interventions to improve fetal outcomes and reduce the risk of cesarean and operative vaginal delivery, and when interventions fail to improve the fetal status, to help guide the decision to proceed with operative delivery in order to minimize fetal/neonatal morbidity as a result of fetal intolerance to labor.
There are four major components to fetal heart tracing that guide obstetric management: baseline, variability, acceleration, and deceleration (uterine contraction pattern is also assessed to guide management). When one or more of these components are outside of normal values, it may be associated with fetal hypoxemia/acidemia. The typical management of these abnormal findings include maternal reposition, IV fluid bolus, increase maternal blood pressure, stopping uterine contractions, amnioinfusion, and maternal oxygen. The goal of therapy is to increase maternal blood flow to the uterus and therefore improve maternal-placental perfusion, increase oxygen delivery to and carbon dioxide removal from the fetus.
Maternal oxygenation is part of the standard management of fetal tracing abnormalities nationwide, and is part of the American College of Obstetricians and Gynecologists (ACOG) guideline for this specific indication. Its use intuitively make sense, as one of the major concerns with fetal tracing abnormalities is the development of fetal hypoxemia leading to anaerobic metabolism and the ensuing development of metabolic acidosis. However, clinical evidence to support its use is lacking. This is partly due to the long-ingrained culture of routine oxygen delivery on Labor and Delivery across the country, therefore no clinical trails were considered until recently. More importantly, from a physiologic standpoint, the fetal hemoglobin has significantly higher oxygen affinity compared to adult hemoglobin. Therefore, increasing maternal oxygen saturation does not lead to significant change in fetal oxygen saturation in general. In addition, some of the reasons for the development of fetal hypoxemia and acidemia are due to placental insufficiency or umbilical cord compression. In these circumstances, there is limited oxygen delivery in the fetal circulation at the maternal-fetal interface and therefore maternal oxygen therapy will have limited effects on fetal oxygenation.
Furthermore, there is growing concern regarding the potential risks associated with supraphysiologic oxygen levels. At a cellular level, hyperoxygenation increased the production of oxygen free radicals, which results in cell damage. This is reflected in the neonatal literature regarding hyperoxygenation during neonatal resuscitation, including higher risk for respiratory and neurologic complications, the American Academy of Pediatrics (AAP) no longer recommend initial neonatal hyperoxygenation during resuscitation. There are similar concerns in oxygen use during obstetric management in recent literature. A number of studies have demonstrated higher risk of neonatal complications associated with maternal intrapartum hyperoxygenation (3-6). However, the evidences have not been adequate to change the clinical practice because the majority of these studies either focused on biological differences rather than clinical outcomes data or were retrospective rather than randomized trials.
Given the ingrained nature of maternal oxygen therapy, the lack of clinical evidence in favor of its use, and concerns regarding potential harm, large scale clinical trials are needed to assess the risks and benefits of the current standard practice. Therefore, the investigators propose a large single center randomized clinical trial to determine the effects of maternal hyperoxygenation therapy for the treatment of fetal heart rate tracing abnormalities.
Trial interventions include the following:
Fetal heart rate abnormalities include one or more of the following:
Recurrent decelerations: more than 2 in a 20 minute period Minimal or absent variability Fetal bradycardia Fetal tachycardia
Routine fetal resuscitation measures will be taken for fetal heart rate abnormalities at the discretion of the obstetric team. These may include:
Maternal repositioning IV fluid bolus Anesthesiology management of hypotension Stopping oxytocin infusion Administering Terbutalin Amnioinfusion Operative vaginal delivery Cesarean delivery In addition to above management options, patient will be assigned to one of two treatment arms through computerized randomization Treatment arm 1 Routine labor management at the discretion of the obstetric team Maternal oxygenation with 10L non-rebreather mask will be given with any above fetal heart rate abnormalities.
Maternal oxygenation is discontinued at the resolution of fetal tracing abnormality or after delivery.
Treatment arm 2 Routine labor management at the discretion of the obstetric team Maternal oxygenation is withheld unless indicated for maternal pulse oximetry is less than 92%
- Conditions
- Perinatal Death, Respiratory Distress Syndrome, Newborn, Hypoxic-Ischemic Encephalopathy, Neonatal Seizure, Meconium Aspiration Syndrome, Intracranial Hemorrhages
- Being tested
- Room air
- Medical subject headings
- Perinatal Death, Respiratory Distress Syndrome, Newborn, Hypoxia-Ischemia, Brain, Meconium Aspiration Syndrome, Intracranial Hemorrhages
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Room airOther
Avoidance of hyperoxygenation
| Study group | Role | What they receive |
|---|---|---|
| Standard care | No intervention | Standard practice where 10L/min O2 is delivered to patient by mask when any fetal tracing abnormalities are identified. |
| Room air | Experimental | O2 will be withheld at times when fetal tracing abnormalities are identified. Patient will continue to breath room air. Receives: Other: Room air |
What is being measured
The primary outcome is the main question the study is designed to answer.
Perinatal death
Death during intrapartum or neonatal period
Measured: Delivery through discharge and average of 1 week
Respiratory distress syndrome
Need for respiratory support up to 72 hours of life
Measured: Delivery through 72 hrs of life
Low 5 minute Apgar score
5 minute Apgar score <=3
Measured: At 5 minute of life
Hypoxic-ischemic encephalopathy
Measured: Delivery through discharge and average of 1 week
Neonatal seizure
Seizure or seizure like activity during the neonatal period.
Measured: Delivery through discharge and average of 1 week
Meconium aspiration syndrome
Measured: Delivery through discharge and average of 1 week
Intracranial hemorrhage
Intraventricular hemorrhage grades III or IV, subdural hematoma, subarachnoid hematoma, and subgaleal hematoma
Measured: Delivery through discharge and average of 1 week
Neonatal hypotension
hypotension (low average blood pressure) based on weight requiring vasopressor support (medication to increase blood pressure).
Measured: Delivery through discharge and average of 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2019
- Study startJun 2021 (estimated)
- Primary completion30 Jun 2022 (estimated)
- Study completion30 Dec 2022 (estimated)
Why it stopped: COVID-19
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Perinatal DeathStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Loma Linda University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ruofan Yao, MD MPH, Principal investigator, Loma Linda University Medical Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03996317
- Sponsor's protocol ID
- 5190191
- Status last verified
- Aug 2021
- First submitted
- 18 Jun 2019
- Last updated
- 17 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Maternal Hyperoxygenation for Intrapartum Fetal Heart Rate Tracing Abnormalities: a Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT03996317
- Acronym / sponsor ID
- 5190191
- Conditions
- Perinatal Death, Respiratory Distress Syndrome, Newborn, Hypoxic-Ischemic Encephalopathy, Neonatal Seizure, Meconium Aspiration Syndrome, Intracranial Hemorrhages
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: COVID-19
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Loma Linda UniversityUniversity, hospital or other
- Study start
- Jun 2021 (estimated)
- Primary completion
- 30 Jun 2022 (estimated)
- Study completion
- 30 Dec 2022 (estimated)
- First posted
- 24 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hyperoxygenation for resuscitation of abnormal fetal heart rate tracings has been routine obstetric practice. However, there have not been any studies to support this practice. Recent literature have either found no associated benefit to intrapartum maternal oxygen administration, or in a number of studies demonstrated higher risk of neonatal complications. Despite these studies, the evidences have not been adequate to change the clinical practice because the majority of these studies either focused on biological differences rather than clinical outcomes data or were retrospective rather than randomized trials. Therefore, the investigators propose a large single center randomized clinical trial to determine the effects of maternal hyperoxygenation therapy for the treatment of fetal heart rate tracing abnormalities.
Detailed description
Continuous fetal heart rate tracing is part of the standard practice during intrapartum obstetric management. The goal of fetal heart rate monitoring is to identify early signs of fetal distress during labor, initiate effective interventions to improve fetal outcomes and reduce the risk of cesarean and operative vaginal delivery, and when interventions fail to improve the fetal status, to help guide the decision to proceed with operative delivery in order to minimize fetal/neonatal morbidity as a result of fetal intolerance to labor.
There are four major components to fetal heart tracing that guide obstetric management: baseline, variability, acceleration, and deceleration (uterine contraction pattern is also assessed to guide management). When one or more of these components are outside of normal values, it may be associated with fetal hypoxemia/acidemia. The typical management of these abnormal findings include maternal reposition, IV fluid bolus, increase maternal blood pressure, stopping uterine contractions, amnioinfusion, and maternal oxygen. The goal of therapy is to increase maternal blood flow to the uterus and therefore improve maternal-placental perfusion, increase oxygen delivery to and carbon dioxide removal from the fetus.
Maternal oxygenation is part of the standard management of fetal tracing abnormalities nationwide, and is part of the American College of Obstetricians and Gynecologists (ACOG) guideline for this specific indication. Its use intuitively make sense, as one of the major concerns with fetal tracing abnormalities is the development of fetal hypoxemia leading to anaerobic metabolism and the ensuing development of metabolic acidosis. However, clinical evidence to support its use is lacking. This is partly due to the long-ingrained culture of routine oxygen delivery on Labor and Delivery across the country, therefore no clinical trails were considered until recently. More importantly, from a physiologic standpoint, the fetal hemoglobin has significantly higher oxygen affinity compared to adult hemoglobin. Therefore, increasing maternal oxygen saturation does not lead to significant change in fetal oxygen saturation in general. In addition, some of the reasons for the development of fetal hypoxemia and acidemia are due to placental insufficiency or umbilical cord compression. In these circumstances, there is limited oxygen delivery in the fetal circulation at the maternal-fetal interface and therefore maternal oxygen therapy will have limited effects on fetal oxygenation.
Furthermore, there is growing concern regarding the potential risks associated with supraphysiologic oxygen levels. At a cellular level, hyperoxygenation increased the production of oxygen free radicals, which results in cell damage. This is reflected in the neonatal literature regarding hyperoxygenation during neonatal resuscitation, including higher risk for respiratory and neurologic complications, the American Academy of Pediatrics (AAP) no longer recommend initial neonatal hyperoxygenation during resuscitation. There are similar concerns in oxygen use during obstetric management in recent literature. A number of studies have demonstrated higher risk of neonatal complications associated with maternal intrapartum hyperoxygenation (3-6). However, the evidences have not been adequate to change the clinical practice because the majority of these studies either focused on biological differences rather than clinical outcomes data or were retrospective rather than randomized trials.
Given the ingrained nature of maternal oxygen therapy, the lack of clinical evidence in favor of its use, and concerns regarding potential harm, large scale clinical trials are needed to assess the risks and benefits of the current standard practice. Therefore, the investigators propose a large single center randomized clinical trial to determine the effects of maternal hyperoxygenation therapy for the treatment of fetal heart rate tracing abnormalities.
Trial interventions include the following:
Fetal heart rate abnormalities include one or more of the following:
Recurrent decelerations: more than 2 in a 20 minute period Minimal or absent variability Fetal bradycardia Fetal tachycardia
Routine fetal resuscitation measures will be taken for fetal heart rate abnormalities at the discretion of the obstetric team. These may include:
Maternal repositioning IV fluid bolus Anesthesiology management of hypotension Stopping oxytocin infusion Administering Terbutalin Amnioinfusion Operative vaginal delivery Cesarean delivery In addition to above management options, patient will be assigned to one of two treatment arms through computerized randomization Treatment arm 1 Routine labor management at the discretion of the obstetric team Maternal oxygenation with 10L non-rebreather mask will be given with any above fetal heart rate abnormalities.
Maternal oxygenation is discontinued at the resolution of fetal tracing abnormality or after delivery.
Treatment arm 2 Routine labor management at the discretion of the obstetric team Maternal oxygenation is withheld unless indicated for maternal pulse oximetry is less than 92%
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard care | No intervention | –Standard practice where 10L/min O2 is delivered to patient by mask when any fetal tracing abnormalities are identified. |
| Room air | Experimental | Other: Room airO2 will be withheld at times when fetal tracing abnormalities are identified. Patient will continue to breath room air. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Singleton pregnancy
- Gestational age between 37and0 weeks and 41and6 weeks
- Admitted for induction of labor or in active labor
- No known fetal anomalies
Key exclusion criteria (5 listed)
- History of 2 or more cesarean delivery
- Maternal contraindications to labor
- Fetal contraindications to labor
- Maternal hemoglobin <8 on admission
- Maternal medical conditions requiring oxygen supplement at baseline (including but not limited to: severe cardiac conditions, uncontrolled asthma, pulmonary embolism, pulmonary fibrosis, pulmonary edema, pneumonia, sepsis etc.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Room airAvoidance of hyperoxygenation | Other | Room air |
Primary outcome
Perinatal death
Time frame: Delivery through discharge and average of 1 week
Death during intrapartum or neonatal period
Respiratory distress syndrome
Time frame: Delivery through 72 hrs of life
Need for respiratory support up to 72 hours of life
Low 5 minute Apgar score
Time frame: At 5 minute of life
5 minute Apgar score <=3
Hypoxic-ischemic encephalopathy
Time frame: Delivery through discharge and average of 1 week
Neonatal seizure
Time frame: Delivery through discharge and average of 1 week
Seizure or seizure like activity during the neonatal period.
Meconium aspiration syndrome
Time frame: Delivery through discharge and average of 1 week
Intracranial hemorrhage
Time frame: Delivery through discharge and average of 1 week
Intraventricular hemorrhage grades III or IV, subdural hematoma, subarachnoid hematoma, and subgaleal hematoma
Neonatal hypotension
Time frame: Delivery through discharge and average of 1 week
hypotension (low average blood pressure) based on weight requiring vasopressor support (medication to increase blood pressure).
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ruofan Yao, MD MPH principal investigator
Loma Linda University Medical Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Room air in people with Perinatal Death and Respiratory Distress Syndrome, Newborn, run by Loma Linda University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 17 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Perinatal death (time frame: Delivery through discharge and average of 1 week). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2021.