- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02741284
Oxygen for Intrauterine Resuscitation of Category II Fetal Heart Tracings (O2C2)
Oxygen for Category II Intrauterine Fetal Resuscitation: A Randomized, Noninferiority Trial
Study Overview
Status
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- Barnes Jewish Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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
Publications and helpful links
General Publications
- Thorp JA, Trobough T, Evans R, Hedrick J, Yeast JD. The effect of maternal oxygen administration during the second stage of labor on umbilical cord blood gas values: a randomized controlled prospective trial. Am J Obstet Gynecol. 1995 Feb;172(2 Pt 1):465-74. doi: 10.1016/0002-9378(95)90558-8.
- Robinson B, Nelson L. A Review of the Proceedings from the 2008 NICHD Workshop on Standardized Nomenclature for Cardiotocography: Update on Definitions, Interpretative Systems With Management Strategies, and Research Priorities in Relation to Intrapartum Electronic Fetal Monitoring. Rev Obstet Gynecol. 2008 Fall;1(4):186-92.
- Khazin AF, Hon EH, Hehre FW. Effects of maternal hyperoxia on the fetus. I. Oxygen tension. Am J Obstet Gynecol. 1971 Feb 15;109(4):628-37. doi: 10.1016/0002-9378(71)90639-9. No abstract available.
- Althabe O Jr, Schwarcz RL, Pose SV, Escarcena L, Caldeyro-Barcia R. Effects on fetal heart rate and fetal pO2 of oxygen administration to the mother. Am J Obstet Gynecol. 1967 Jul 15;98(6):858-70. doi: 10.1016/0002-9378(67)90205-0. No abstract available.
- Nesterenko TH, Acun C, Mohamed MA, Mohamed AN, Karcher D, Larsen J Jr, Aly H. Is it a safe practice to administer oxygen during uncomplicated delivery: a randomized controlled trial? Early Hum Dev. 2012 Aug;88(8):677-81. doi: 10.1016/j.earlhumdev.2012.02.007. Epub 2012 Mar 23.
- Khaw KS, Wang CC, Ngan Kee WD, Pang CP, Rogers MS. Effects of high inspired oxygen fraction during elective caesarean section under spinal anaesthesia on maternal and fetal oxygenation and lipid peroxidation. Br J Anaesth. 2002 Jan;88(1):18-23. doi: 10.1093/bja/88.1.18.
- Tuuli MG, Stout MJ, Shanks A, Odibo AO, Macones GA, Cahill AG. Umbilical cord arterial lactate compared with pH for predicting neonatal morbidity at term. Obstet Gynecol. 2014 Oct;124(4):756-761. doi: 10.1097/AOG.0000000000000466.
- Westgren M, Divon M, Horal M, Ingemarsson I, Kublickas M, Shimojo N, Nordstrom L. Routine measurements of umbilical artery lactate levels in the prediction of perinatal outcome. Am J Obstet Gynecol. 1995 Nov;173(5):1416-22. doi: 10.1016/0002-9378(95)90627-4.
- Cahill AG, Roehl KA, Odibo AO, Macones GA. Association and prediction of neonatal acidemia. Am J Obstet Gynecol. 2012 Sep;207(3):206.e1-8. doi: 10.1016/j.ajog.2012.06.046.
- Frey HA, Tuuli MG, Shanks AL, Macones GA, Cahill AG. Interpreting category II fetal heart rate tracings: does meconium matter? Am J Obstet Gynecol. 2014 Dec;211(6):644.e1-8. doi: 10.1016/j.ajog.2014.06.033. Epub 2014 Jun 17.
- Dalle-Donne I, Rossi R, Colombo R, Giustarini D, Milzani A. Biomarkers of oxidative damage in human disease. Clin Chem. 2006 Apr;52(4):601-23. doi: 10.1373/clinchem.2005.061408. Epub 2006 Feb 16.
- Ilhan N, Ilhan N, Simsek M. The changes of trace elements, malondialdehyde levels and superoxide dismutase activities in pregnancy with or without preeclampsia. Clin Biochem. 2002 Jul;35(5):393-7. doi: 10.1016/s0009-9120(02)00336-3.
- Pryor WA, Stanley JP. Letter: A suggested mechanism for the production of malonaldehyde during the autoxidation of polyunsaturated fatty acids. Nonenzymatic production of prostaglandin endoperoxides during autoxidation. J Org Chem. 1975 Nov 28;40(24):3615-7. doi: 10.1021/jo00912a038. No abstract available.
- Suhail M, Suhail S, Gupta BK, Bharat V. Malondialdehyde and Antioxidant Enzymes in Maternal and Cord Blood, and their Correlation in Normotensive and Preeclamptic Women. J Clin Med Res. 2009 Aug;1(3):150-7. doi: 10.4021/jocmr2009.07.1252. Epub 2009 Aug 12.
- Lorente L, Martin MM, Abreu-Gonzalez P, Dominguez-Rodriguez A, Labarta L, Diaz C, Sole-Violan J, Ferreres J, Cabrera J, Igeno JC, Jimenez A. Sustained high serum malondialdehyde levels are associated with severity and mortality in septic patients. Crit Care. 2013 Dec 11;17(6):R290. doi: 10.1186/cc13155.
- Lorente L, Martin MM, Abreu-Gonzalez P, Ramos L, Argueso M, Caceres JJ, Sole-Violan J, Lorenzo JM, Molina I, Jimenez A. Association between serum malondialdehyde levels and mortality in patients with severe brain trauma injury. J Neurotrauma. 2015 Jan 1;32(1):1-6. doi: 10.1089/neu.2014.3456.
- Raghuraman N, Wan L, Temming LA, Woolfolk C, Macones GA, Tuuli MG, Cahill AG. Effect of Oxygen vs Room Air on Intrauterine Fetal Resuscitation: A Randomized Noninferiority Clinical Trial. JAMA Pediatr. 2018 Sep 1;172(9):818-823. doi: 10.1001/jamapediatrics.2018.1208.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 201602164
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