Oxygen for Intrauterine Resuscitation of Category II Fetal Heart Tracings

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.

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