Clinical trial NCT02741284: Oxygen for Intrauterine Resuscitation of Category II Fetal Heart Tracings
Official title: Oxygen for Category II Intrauterine Fetal Resuscitation: A Randomized, Noninferiority Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Electronic Fetal Monitoring
Fetal Hypoxia
Fetal-Placental Circulation
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2016-04-18
Enrollment: 114
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Umbilical Artery Lactate at Delivery
timeFrame: At delivery
Secondary outcomes:
measure: Umbilical Artery pH
timeFrame: At time of delivery
measure: Mode of Delivery
timeFrame: At delivery
measure: Umbilical Artery pCO2
timeFrame: At time of delivery
measure: Umbilical Artery pO2
timeFrame: Time of delivery
measure: Umbilical Artery Base Deficit
timeFrame: At time of delivery
Other outcomes:
measure: Number of Patients With Resolved Recurrent Decelerations
timeFrame: 60 minutes after randomization
Locations:
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital
state: Missouri
Study officials:
References:
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