Oxygen for Intrauterine Resuscitation of Category II Fetal Heart Tracings

Fetal Hypoxia Clinical Trial

— O2C2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02741284
• Other study ID #: 201602164
• Status: Completed
• Phase: N/A
• Start date: June 2016
• Est. completion date: December 2020

Study information

• Verified date: November 2021
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: December 2020
• Est. primary completion date: June 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Electronic Fetal Monitoring
• Fetal Hypoxia
• Fetal-Placental Circulation
• Hypoxia

Intervention

Drug:
• Room air

• 10L Oxygen by nonrebreather mask

Locations

Country	Name	City	State
United States	Barnes Jewish Hospital	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (16)

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. — View Citation

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. — View Citation

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. Epub 2006 Feb 16. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Lorente L, Martín MM, Abreu-González P, Domínguez-Rodriguez A, Labarta L, Díaz C, Solé-Violán J, Ferreres J, Cabrera J, Igeño JC, Jiménez 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. — View Citation

Lorente L, Martín MM, Abreu-González P, Ramos L, Argueso M, Cáceres JJ, Solé-Violán J, Lorenzo JM, Molina I, Jiménez 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Westgren M, Divon M, Horal M, Ingemarsson I, Kublickas M, Shimojo N, Nordström L. Routine measurements of umbilical artery lactate levels in the prediction of perinatal outcome. Am J Obstet Gynecol. 1995 Nov;173(5):1416-22. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Patients With Resolved Recurrent Decelerations	Number of patients with resolution of recurrent variable or recurrent late decelerations within 60 minutes of randomization	60 minutes after randomization
Primary	Mean Umbilical Artery Lactate 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	Umbilical Artery pH	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
Secondary	Mode of Delivery	Delivery via Cesarean section, operative vaginal delivery (forceps or vacuum), or spontaneous vaginal delivery	At delivery
Secondary	Umbilical Artery pCO2	Partial pressure of carbon dioxide as collected on cord gases at time of delivery	At time of delivery
Secondary	Umbilical Artery pO2	Partial pressure of oxygen as collected on cord gases at time of delivery	Time of delivery
Secondary	Umbilical Artery Base Deficit	As determined by cord gas collection at time of delivery	At time of delivery