Oxygen for Intrauterine Resuscitation of Category II Fetal Heart Tracings (O2C2)

November 23, 2021 updated by: Washington University School of Medicine

Oxygen for Category II Intrauterine Fetal Resuscitation: A Randomized, Noninferiority Trial

Maternal oxygen administration for concerning fetal heart rate tracing (FHT) patterns is common practice on Labor and Delivery units in the United States. Despite the broad use of oxygen, it is unclear if this practice is beneficial for the fetus. The purpose of this study is to compare oxygen to room air in patients with Category II fetal heart tracings with regard to neonatal acid-base status, subsequent tracings, and production of reactive oxygen species

Study Overview

Detailed Description

Maternal oxygen administration for concerning fetal heart rate tracing (FHT) patterns is common practice on Labor and Delivery units in the United States. Despite the broad use of oxygen, it is unclear if this practice is beneficial for the fetus. Category II FHT, as defined by the National Institute of Child Health and Human Development (NICHD) (Robinson), is a broad class of FHT patterns that may suggest cord compression and/or placental insufficiency for which oxygen is most commonly administered. Although some animal and human studies (Khazin, Althabe) have demonstrated that maternal hyperoxygenation can alleviate such fetal heart rate decelerations, this purported benefit has not been shown to translate into improved fetal outcomes, particularly in relation to acid-base status. In fact, some studies suggest harm with oxygen use due to lower umbilical artery pH and increased delivery room resuscitation (Nesterenko, Thorp) or increased free radical activity (Khaw). Given the indeterminate evidence for this ubiquitously employed resuscitation technique, there is an urgent need to further study the utility of maternal oxygen administration in labor for fetal benefit.

We propose a randomized controlled non-inferiority trial comparing oxygen to room air in patients with Category II FHT. Our central hypothesis is that room air alone is not inferior to oxygen administration with regard to neonatal acid-base status and FHT and may in fact, be a safer option for resuscitation due to less production of reactive oxygen species.

Primary Aim: Determine the effect of maternal oxygen administration for Category II FHT on arterial umbilical cord lactate.

Hypothesis: Room air, as a substitute for oxygen supplementation, is no different than oxygen in altering the acid-base status of the neonate as reflected in umbilical arterial (UA) lactate.

Fetal hypo-oxygenation, as reflected by decelerations in the FHT, results in metabolic acidosis due to a shift from aerobic to anaerobic metabolism in which lactate and hydrogen ion production significantly increase causing a decrease in pH (Tuuli). Elevated umbilical cord lactate has been shown to be a surrogate for fetal metabolic acidosis and resultant neonatal morbidity (Tuuli, Westgren). The theorized benefit of maternal oxygen administration is increased oxygen delivery to the fetus resulting in reversal of anaerobic metabolism/ metabolic acidosis. This, however, has not been substantiated by evidence thus far. Women with persistent Category II FHT tracing will be randomly assigned to supplemental oxygen or room air. The primary outcome will be umbilical arterial lactate level, and secondary outcomes will be other umbilical cord gas parameters including UA pH, UV oxygen saturation, and UA base deficit.

Secondary Aim #1: Characterize the effect of oxygen administration on fetal heart tracing patterns Hypothesis: Oxygen administration will be associated with a rate of persistent Category II FHT that is not different from those exposed to room air.

Oxygen is typically administered as a response to FHT interpretation. Evidence thus far shows that Category II FHT are associated with a wide spectrum of neonatal outcomes and therefore do not uniformly reflect fetal acid-base status (Cahill, Frey). Hence, evaluating the effect of oxygen on subsequent FHT categorization is pivotal to labor management. The outcome that will be investigated is rate of persistent Category II FHT after intervention.

Secondary Aim #2: Evaluate the safety of oxygen administration by measuring reactive oxygen species (ROS) in maternal and neonatal blood.

Hypothesis: Oxygen administration will be associated with increased oxidative stress in maternal and neonatal cord blood as represented by malondialdehyde (MDA).

Over-oxygenation can result in free radical or ROS formation that have detrimental downstream effects. The presence of reactive oxygen species results in degradation of lipids in the cell membrane and resultant formation of malondialdehyde (MDA) (Dalle-Donne), which has been studied as a surrogate for oxidative stress (Ilhan, Pryor, Suhail, Lorente).

This study will be a prospective, randomized non inferiority trial to be conducted a single center. This study will include term, singleton patients admitted to Labor& Delivery for spontaneous labor or labor induction. Multiples, significant fetal anomalies, Category III FHT, umbilical artery doppler abnormalities and preterm pregnancies will be excluded. Additionally, women will be excluded if oxygen is required for maternal indications such as hypooxygenation or cardiopulmonary disease. Our primary objective will be umbilical cord lactate. Secondary objectives include additional cord gas parameters including umbilical artery pH, umbilical artery base deficit, and umbilical vein oxygen saturation; FHT categorization and deceleration patterns; maternal and umbilical cord blood measurement of malondialdehyde. Women will be consented at time of admission for labor and randomized when at least 6cm dilated with Category II FHT necessitating provider intervention.

Study Type

Interventional

Enrollment (Actual)

114

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Barnes Jewish Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Term, singleton patients admitted to Labor& Delivery for spontaneous labor or labor induction

Exclusion Criteria:

  • Multiple pregnancy
  • Significant fetal anomalies
  • Category III FHT
  • Umbilical artery doppler abnormalities
  • Maternal hypooxygenation or need for oxygen

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: No Oxygen
Room air
Active Comparator: Oxygen
10L oxygen by nonrebreather mask

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Umbilical Artery Lactate at Delivery
Time Frame: At delivery
Determined by umbilical artery cord gas collected at time of delivery and only in patients with paired (umbilical artery and umbilical vein) cord gases.
At delivery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Umbilical Artery pH
Time Frame: At time of delivery
Determined by umbilical artery cord gas collected at time of delivery and only in patients with paired (umbilical artery and umbilical vein) cord gases.
At time of delivery
Mode of Delivery
Time Frame: At delivery
Delivery via Cesarean section, operative vaginal delivery (forceps or vacuum), or spontaneous vaginal delivery
At delivery
Umbilical Artery pCO2
Time Frame: At time of delivery
Partial pressure of carbon dioxide as collected on cord gases at time of delivery
At time of delivery
Umbilical Artery pO2
Time Frame: Time of delivery
Partial pressure of oxygen as collected on cord gases at time of delivery
Time of delivery
Umbilical Artery Base Deficit
Time Frame: At time of delivery
As determined by cord gas collection at time of delivery
At time of delivery

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With Resolved Recurrent Decelerations
Time Frame: 60 minutes after randomization
Number of patients with resolution of recurrent variable or recurrent late decelerations within 60 minutes of randomization
60 minutes after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

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General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2016

Primary Completion (Actual)

June 1, 2017

Study Completion (Actual)

December 1, 2020

Study Registration Dates

First Submitted

April 10, 2016

First Submitted That Met QC Criteria

April 12, 2016

First Posted (Estimate)

April 18, 2016

Study Record Updates

Last Update Posted (Actual)

November 26, 2021

Last Update Submitted That Met QC Criteria

November 23, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Other Study ID Numbers

  • 201602164

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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