Updated June 1: A new RCT has been published regarding the use of oxygen therapy in labour. I have added it to the section on “other RCTs” below.
When the fetal heart rate pattern seen on CTG monitoring during labour is considered abnormal, clinicians typically use measures that aim at restoring the pattern to normal. This is often called intrauterine resuscitation. Some of the commonly used approaches are to change the birthing woman’s position, give intravenous fluids, or to administer oxygen. This post is part two of a five-part series looking at the evidence for intrauterine resuscitation. You can read part one (recent research about how often intrauterine resuscitation is used) here.
It is important to set out some expectations for the kind of evidence I am looking for in this series. I don’t believe that it is enough for intrauterine resuscitation attempts to simply restore the wiggles on the CTG to a pattern considered to be normal. Recalling that the aim of intrapartum fetal monitoring is to prevent fetal damage from hypoxia, we should be looking for evidence that these practices improve perinatal outcomes. Or at the very least, resuscitation efforts should reduce the use of other interventions, such as fetal blood sampling, instrumental birth, and caesarean section.
For each of these posts, I start by setting out the assumptions about how the therapy is proposed to work, and how that lines up with what we know about physiology. I will then share the existing research and summarise key findings. There’s heavy science content in here for those who (like me) delight in such things. You are also welcome to skip to the “too long, didn’t read” (TL;DR) summary at the end of this post (and each of the ones to come) for an answer to the question – does intrauterine resuscitation (in this case giving oxygen) when the CTG is abnormal make things better for the fetus and the birthing woman?
Why give oxygen?
At first glance, administering oxygen seems logical. In theory, low levels of oxygen cause changes in the fetal heart rate pattern. Giving more oxygen to the birthing woman so that the oxygen levels in the fetus increase could reasonably be expected to be a sensible fix to the problem. Let’s start by reviewing the physiological journey an oxygen molecule takes. This will bring to light reasons why the issue is much more complex than it first seems.
It is also important to remember that the false positive rate of abnormal CTG patterns is high (Ekengård, Cardell, & Herbst, 2021). That is, many fetuses with an abnormal CTG pattern have normal oxygen levels. There is no way that additional oxygen will benefit a fetus with already normal oxygen levels.
Physiology is more complex that you think
Women are not giant balloons with a fetus floating inside. Plugging the woman into an oxygen supply and turning it on to fill her up and surround the fetus inside our balloon woman isn’t how oxygen transfer works. With very few exceptions, birthing women have normal levels of blood oxygen. These exceptions are typically clinical obvious (like severe viral pneumonia from COVID-19 infection causing the woman to be hypoxic).
Women shift air (or supplementary oxygen if this is being given) in and out of their lungs by breathing. Oxygen molecules diffuses from the lungs into the blood stream through a thin layer of cells in the alveoli, while carbon dioxide moves in the other direction. Conditions that impact on movement of air in and out of the lungs (e.g. asthma), movement of oxygen through the wall of the alveoli (e.g. pneumonia), or the movement of blood through the lungs (e.g. pulmonary embolism) can prevent inspired oxygen from getting into the blood stream.
A small proportion of oxygen is transported through the body by being dissolved in in blood. Most oxygen is bound to haemoglobin – the stuff in red blood cells that makes them red. The capacity of blood to capture oxygen from the lungs and transport it to the placenta is most definitely finite. Putting more oxygen into the lungs doesn’t automatically equate to more oxygen reaching the vital structures of the fetus that rely on good oxygen levels for normal functioning. Delivering adequate levels of oxygen to the fetus depends on:
- How many maternal haemoglobin molecules there are (Hb concentration). Anaemia has an impact on the total oxygen carrying capacity of blood. If all red blood cells were maximally saturated with oxygen, but the haemoglobin concentration was half of the normal level, then oxygen carrying capacity would be reduced by half.
- How many times per minute blood is passing by the alveoli (cardiac output). Cardiac output is the volume of blood leaving the heart per minute and is determined by the woman’s heart rate and the volume of blood pumped with each heartbeat. Conditions that alter cardiac output include reduced blood volume (e.g secondary to heavy bleeding), or damage to the heart (e.g. cardiomyopathy).
- How many haemoglobin molecules have oxygen molecules attached to them (oxygen saturation or SpO2). Optimal oxygen transfer requires that haemoglobin molecules are very efficient at grabbing any passing oxygen and binding it. This is called high oxygen affinity. Disorders of haemoglobin structure (e.g. thalassaemia) can reduce this. Adding more oxygen to inspired air won’t add more oxygen to the blood if every haemoglobin molecule has already reached its capacity to hold oxygen. Most healthy adults have levels of 98 or 99% saturation breathing regular air, so there is not much room to increase oxygen saturation.
- How easy it is for haemoglobin molecules to let go of oxygen when blood reaches the placenta. This needs low oxygen affinity. As tissues use oxygen they produce carbon dioxide. As carbon dioxide levels rise and blood becomes more acidic, the haemoglobin molecule has less affinity for oxygen and releases the oxygen where it is needed most. Breathing 100% oxygen reduces carbon dioxide levels and increases the oxygen affinity of haemoglobin. That makes it easier for oxygen to hop onto any empty spots on haemoglobin molecules, but harder for it to get off and into the fetal blood stream (Tomimatsu, et al., 2013).
- How much blood is delivered to the placenta. This depends on uterine blood flow. Factors that modify blood flow through the uterine arteries include uterine contractions, maternal blood pressure, and constriction of the uterine arteries. There is some evidence suggesting that high oxygen levels can reduce uterine blood flow by causing uterine artery constriction (Simchen, et al., 2005).
- How easy it is for oxygen to pass from maternal blood to fetal blood across the placenta. Factors that impact on the ability of the placenta to transfer oxygen from the maternal circulation include the health of the placenta itself, and blood flow in the umbilical vessels. Cord compression and low fetal blood pressure reduce placental blood flow. Many of the causes of low oxygen levels in the fetus will limit the effectiveness of giving maternal oxygen to increase fetal oxygen levels, because they were already making placental oxygen transfer difficult.
- How many fetal haemoglobin molecules there are and their oxygen affinity. During fetal life, haemoglobin is a different shaped molecule (HbF or fetal haemoglobin). It has a higher oxygen affinity than adult haemoglobin. This makes it very effective at sucking up oxygen molecules, therefore creating a concentration gradient that favours the movement of oxygen from the maternal into the fetal circulation. Genetic disorders affecting the shape of the haemoglobin molecule (e.g. sickle cell disease) alter oxygen affinity. Fetal anaemia has a significant impact on the total oxygen carrying capacity of fetal blood.
- How well blood flows to vital structures within the fetal body. Delivering oxygen to tissues with high oxygen demand, like the brain, requires hat blood must flow freely to those tissues. Low maternal carbon dioxide levels (a consequence of breathing oxygen enriched air) causes a fall in fetal carbon dioxide levels. This in turn leads to vasoconstriction in the arteries supplying the fetal brain, reducing oxygen delivery to the brain (Tomimatsu, et al., 2013).
Anything that disrupts the movement of oxygen between the alveoli and the oxygen requiring tissues of the fetus reduces oxygen delivery and can lead to hypoxic damage in those tissues. Giving additional inspired oxygen can not overcome these barriers to oxygen transfer.
Too much oxygen is not harmless
Evidence of the harms of oxygen use has been demonstrated in both adult and neonatal medicine (Martin & Grocott, 2013). High levels of oxygen can cause irreversible tissue damage, particularly to tissues already injured by previously low levels of oxygen. Additional oxygen delivered to the fetus is therefore not necessarily a good thing. Carefully titrated oxygen is a useful therapy for people with low oxygen levels, but it is not a magic cure-all.
How would you study the use of oxygen to improve an abnormal CTG?
The best research approach to answer the question about whether giving oxygen to birthing women when the CTG is abnormal is beneficial would be a randomised controlled trial (RCT). To do this you would identify a group of women with an abnormal CTG pattern. Half would be given additional oxygen to breathe through a mask while the other half would be given unenriched room air to breathe through the same sort of mask. Clinicians and the women would not know which gas mixture they were given. Outcome measures would include the CTG pattern, oxygen and pH status of the baby at birth, operative birth rates, and other outcomes like Apgar scores and neonatal seizures that would be useful clinical information to know.
What does the RCT evidence look like?
Someone has conducted an RCT that looks sort of like this, but it took until 2020 for researchers to get around to it (Moors, et al., 2020a, 2020b). 117 women in the second stage of labour were included. All had intermediate or abnormal CTG recordings as determined by the FIGO guideline. Those randomised to the intervention group were given 100% oxygen via a rebreathing mask until birth, while those in the control group had routine care (note that this means that clinicians knew who did and who did not get oxygen, introducing a possible risk for bias). The primary outcome measure was the CTG pattern, where the depth and duration of decelerations was measured by computer interpretation of the CTG. Neonatal outcomes and mode of birth were also analysed. 46 women gave birth within 15 minutes of being randomised and they were excluded from analysis as it was considered too soon after treatment to note a significant effect.
No significant difference in the depth or duration of decelerations was found between women given oxygen and those that were not. Re-analysis of the overall CTG pattern by a group of obstetricians who did not know which study group women were in showed that women given oxygen were more likely to have a CTG that improved (14%), compared with women in the routine care group (3%). Note that the rate of improvement was still low in the group given oxygen. No differences in neonatal outcomes (Apgar scores, cord blood gases, intensive care nursery admissions) were found. There were also no differences in mode of birth.
Other randomised controlled trials
A systematic review and meta-analysis addressing the question of oxygen use was published in 2021 (it includes the Moors et al. papers described above). Raghuraman and colleagues also examined other research where oxygen was administered to women preventatively during scheduled caesarean section or labour. Oxygen was given whether fetal monitoring was abnormal or not. They included 16 trials in total. Only studies with cord blood gas results were included. Giving oxygen was not associated with improvements in the pH of blood from the umbilical artery at birth, nor with changes in Apgar scores, or admission to neonatal intensive care.
There has been one further RCT conducted since this systematic review (Chuia, et al., 2022). Women who were admitted to hospital in early labour and who had a normal CTG pattern were randomised to either receive 10 L of oxygen per minute via a face mask for the duration of labour, or to breathe room air. 140 women were enrolled and cord blood gas results were available for 135 of these. The mean duration of oxygen use was 322 minutes.
There were no differences between the two groups for the mode of birth, the duration of labour (in total or by each stage), Apgar scores, use of resuscitation, or admission to the neonatal nursery. Umbilical artery oxygen levels (pO2 and oxygen saturation) were no different. Umbilical artery pH levels were marginally lower when oxygen was used (7.23 vs 7.27) and this reduction was evident across all labour durations. Retrospective reanalysis of the CTG (by clinicians blinded to the group the women were in) showed no differences in the incidence of abnormal CTG patterns.
What happens when you stop using oxygen?
Burd and colleagues (2021) examined what happened when a guideline was introduced in an American hospital to decrease the use of oxygen supplementation for abnormal CTG patterns. Outcomes from 474 women prior to introduction of the guideline and 859 women after were examined. Introduction of the guideline reduced oxygen use from 23% of birthing women to under 1%. No changes in the mode of birth or neonatal outcomes occurred (Apgar scores, intensive care nursery admission, neonatal death).
What do I need to know as a clinician?
Here’s the TL;DR summary for those of you who didn’t want the details. There is no research evidence showing that administering additional oxygen to birthing women who have an abnormal CTG fixes anything in a clinically meaningful way. Limiting the use of oxygen therapy to women with low oxygen levels is not harmful to perinatal outcomes.
As I have explored the world of CTG monitoring, I have seen time and time again how maternity clinicians have become seduced by the lure of simple approaches to fix dreadful problems. We so desperately want to make things better that we fail to collect evidence, or when it is presented to us, we ignore it. It is less threatening to believe that putting the CTG on will prevent stillbirth in labour, or that providing education, or using a new CTG monitoring guideline will improve outcomes related to CTG use, or that collecting a fetal blood sample will prevent unnecessary caesarean sections. To this list we can now add putting oxygen on birthing women with an abnormal CTG. There is a real risk is that while we carry on pretending these things work, we miss opportunities to find an alternative that works.
References
Burd, J. , Anderson, K. , Berghella, V. , Duncan, D. , Baxter, J. & Quist-Nelson, J. (2021). Evaluation of an initiative to decrease the use of oxygen supplementation for Category II fetal heart rate tracings. Obstetrics & Gynecology, 138(4), 627-632. doi: 10.1097/AOG.0000000000004544.
Chuai, Y., Jiang, W., Zhang, L., Chuai, F., Sun, X., Peng, K., Gao, J., Dong, T., Chen, L., & Yao, Y. (2022). Effect of long-duration oxygen vs room air during labor on umbilical cord venous partial pressure of oxygen: a randomized controlled trial. American Journal of Obstetrics and Gynecology, in press. https://doi.org/10.1016/j.ajog.2022.05.028
Ekengård, F., Cardell, M., & Herbst, A. (2021). Impaired validity of the new FIGO and Swedish CTG classification templates to identify fetal acidosis in the first stage of labor. Journal of Maternal-Fetal & Neonatal Medicine, in press, 1-8. https://doi.org/10.1080/14767058.2020.1869931
Fawole, B. & Hofmeyr, GJ. (2012). Maternal oxygen administration for fetal distress. Cochrane Database of Systematic Reviews, 12, CD000136. DOI: 10.1002/14651858.CD000136.pub2.
Martin, D., & Grocott, M. (2013). Oxygen therapy in anaesthesia: the yin and yang of O2. British Journal of Anaesthesia, 111(6), 867–871. https://doi.org/10.1093/bja/aet291
Moors, S., Bullens, L., van Runnard Heimel, P., Dieleman, J., Kulik, W., Bakkeren, D., van den Heuvel, E., van der Hout-van der Jagt, M., & Oei, S. (2020a). The effect of intrauterine resuscitation by maternal hyperoxygenation on perinatal and maternal outcome; a randomized controlled trial. American Journal of Obstetrics and Gynecology MFM, 2(2), 100102. https://doi.org/10.1016/j.ajogmf.2020.100102
Moors, S., Joshi, R., Bullens, L., van Oostrum, N., Regis, M., van den Heuvel, E., Oei, S., van Laar, J., & van der Hout-van der Jagt, M. (2020b). A randomized controlled trial studying the effect of maternal hyperoxygenation of fetal heart rate in suspected fetal distress. Physiological Measurement, 41, 115002. https://doi.org/10.1088/1361-6579/abc0b6
Raghuraman, N., Temming, L., Doering, M., Stoll, C., Palanisamy, A., Stout, M., Colditgz, G., Cahill, A., & Tuuli, M. (2021). Maternal oxygen supplementation compared with room air for intrauterine resuscitation: a systematic review and meta-analysis. Journal of the American Medical Association Pediatrics, 175(4), 368–76. doi: 10.1001/jamapediatrics.2020.5351
Simchen, M., Tesler, J., Azami, T., Preiss, D., Fedorko, L., Goldszmidz, E., Fisher, J., Kingdom, J., Slorach, L., & Hornberger, K. (2005). Effects of maternal hyperoxia with and without normocapnia in uteroplacental and fetal Doppler studies. Ultrasound in Obstetrics and Gynecology, 26(5), 495-499. https://doi.org/10.1002/uog.1995
Tomimatsu, T., Kakigano, A., Mimura, K., Kanayama, T., Koyama, S., Fujita, S., Taniguchi, Y., Kanagawa, T., & Kimura, T. (2013). Maternal carbon dioxide level during labor and its possible effect on fetal cerebral oxygenation: mini review. Journal of Obstetrics and Gynaecology Research, 39(1), 1–6. https://doi.org/10.1111/j.1447-0756.2012.01944.x
Tags: intrauterine resuscitation, oxygen, Physiology
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