Association between intrapartum fetal pulse oximetry and adverse perinatal and long-term outcomes: a systematic review and meta-analysis protocol

Introduction

Intrapartum fetal monitoring aims to improve perinatal outcome while avoiding unnecessary operative interventions¹. The gold standard for assessment of fetal well-being continues to be the auscultation of the fetal heart, along with the interpretation of alterations in the fetal heart rate pattern, as demonstrated through cardiotocography (CTG) to try to predict babies at risk of hypoxic brain injury and adverse perinatal outcomes. Despite its status as the established benchmark in care, employed in approximately 90% of births in the United States (US) and on a global scale, there is a pervasive consensus that current fetal monitoring devices based on heart rate, do not prevent or accurately detect fetal hypoxic brain injury^2–7. The current use of cardiotocography (CTG) as a method of monitoring intrapartum fetal well‐being during labour is associated with an increased caesarean section rate, compared with intermittent auscultation of the fetal heart rate, resulting in a reduction in neonatal seizures, although no differences in other neonatal outcomes⁸. CTG is complicated by significant inter- and intra-observer variation^2,9,10. Furthermore, CTG demonstrates a low positive predictive value for fetal hypoxia, meaning that among those fetuses that CTG indicates are at risk for hypoxia, a smaller proportion will truly be hypoxic^2,9,10. This can lead to an increased frequency of false-positive results, thus potentially prompting unnecessary interventions based on an overestimated risk of fetal hypoxia. Consequently, such misinterpretations could contribute to the escalating rates of caesarean deliveries observed worldwide. For instance, in the US, the caesarean delivery rate has surged, increasing from 20.7% in 1996 to 32.1% in 2021¹¹. Similarly in the United Kingdom, the caesarean delivery rate has increased from 14.7% from 1990 to 1999 to 35.21% in 2021–2022^12,13.

Fetal blood sampling (FBS) is widely used as a complementary tool to improve the specificity and sensitivity of CTG¹⁴. FBS has been shown to reduce operative vaginal delivery rates without affecting neonatal outcomes but it is a complex, invasive procedure². There is a need for more accurate methods of intrapartum fetal surveillance that will decrease the incidence of adverse neonatal and long-term neurodevelopmental outcomes while maintaining the lowest possible rate of obstetric intervention.

Fetal pulse oximetry (FPO) is a technology that may contribute to improved intrapartum fetal wellbeing evaluation by providing a non-invasive measurement of fetal oxygenation status^15–18. FPO offers a potential dual advantage over traditional fetal heart rate monitoring. It quantifies the percentage of oxygenated haemoglobin directly, thereby assessing fetal oxygenation, which is pivotal in mediating the harmful consequences of hypoxia/ischaemia. Additionally, it utilises a well-established, non-invasive technology, regarded as safe and broadly implemented in all modern intensive care units and operating theatres⁸. Based on data from both human and animal studies, average intrapartum fetal oxygen saturation (FSp02) range from 35% to 65%^19–21. FSpO2 levels of 30% or higher are generally considered reassuring for the human fetus. However, if FSpO2 levels are less than 30% for a duration of 10 minutes or more, additional evaluation or intervention is warranted^{17,19,22–24} A study by McNamara et al. (n=100) demonstrated that babies born in poor condition had abnormal fetal oximetry values²⁵. FPO is advantageous over FBS in that it is a non-invasive and continuous monitoring technique.

A Cochrane Review published in 2014 compared fetal intrapartum pulse oximetry with other fetal surveillance techniques⁸. This review included seven trials reporting on a total of 8013 pregnancies. The primary outcomes were caesarean section, hypoxic‐ischaemic encephalopathy, neonatal seizures and long‐term neurodevelopmental outcomes. The authors found no significant differences in the overall caesarean delivery rate between those monitored with FPO and those not monitored with FPO or for whom the FPO results were not displayed to the clinician or woman (four studies, n = 4008, risk ratio (RR) 0.99, 95% confidence intervals (CI) 0.86 to 1.13, I² = 45). The authors noted a reduction in the number of caesarean sections performed for cases of non-reassuring fetal status in the FPO plus CTG group compared to the CTG only group in two of the four analyses: firstly when considering pregnancies at or beyond 34 weeks where fetal FBS was not required prior to study entry (comprising four studies with 4008 participants, RR 0.65, 95% CI 0.46 to 0.90, I² = 63) Secondly, in situations where FBS was a prerequisite before study participation (one study involving 146 participants), the RR was notably low at 0.03, with a 95% confidence interval spanning from 0.00 to 0.44. Additionally, the review reported a reduction in operative births (comprising caesarean sections or operative vaginal births) for non-reassuring fetal status when FPO was combined with CTG monitoring, compared to CTG monitoring alone. This finding was consistent across two studies involving 1610 participants, with a RR of 0.74 (95% confidence interval: 0.62 to 0.89). However, no statistically significant differences were observed in several other outcome measures, including Apgar scores less than four at five minutes or less than seven at five minutes, umbilical arterial pH less than 7.10, neonatal intensive care unit (NICU) admissions, length of hospital stays, mortality, or fetal skin trauma, when comparing the use of FPO in conjunction with CTG to fetal electrocardiography combined with CTG. The results of this review may have been influenced by a large randomised control trial (RCT) by Bloom et al.²⁶ which had several limitations. Namely, that they did not describe the number of caesarean births indicated by the FPO results, nor did they describe counter-measures, including posture change according to the fetal oxygen saturation values, administration of tocolytic agents, and expedited delivery. Furthermore, observational studies were not included in the previous systematic review. In contrast, our planned review will take a more comprehensive approach, incorporating evidence not just from RCTs, but also from cohort studies, case-control studies, and observational studies.

Uchida et al. conducted a narrative review on FPO as a measure of intrapartum fetal condition. They concluded that FPO with fetal heart rate monitoring in selected cases of non-reassuring fetal status may reduce the caesarean section rate²⁷. While Uchida and colleagues discussed 31 studies and seven RCTs in their review of previous literature, they did not conduct a systematic review of previous literature. Therefore, we aimed to synthesise the previous literature examining the association between intrapartum fetal oxygen saturation and perinatal and long-term outcomes in the offspring in the form of a systematic review and meta-analysis.

This review has been registered with PROSPERO (CRD42023457368) on 4^th September 2023 and follows the PRISMA-P guidelines²⁸.

Methods

Conclusions

The systematic review and meta-analysis will summarise the existing literature investigating the association between intrapartum fetal oxygen saturation and adverse perinatal and long term outcomes in offspring. This review is of considerable importance as it explores the potential utility of fetal pulse oximetry as a method for intrapartum fetal monitoring. There is a pressing need for innovative and reliable approaches to monitor fetal well-being during labour, and this review could provide pivotal insights in this regard.

Potential strengths and limitations of this study

The robustness of this review is bolstered by the implementation of a thorough search strategy, a prospectively registered protocol, and strict compliance with PRISMA guidelines. Additionally, the engagement of three reviewers in the process of eligibility screening and two reviewers in the process of data extraction, and quality assessment of the included studies serves to substantially mitigate the potential for reviewer-based bias in the systematic review. Furthermore, this review will not have language restrictions, reducing the risk that relevant indexed studies be overlooked. In the scope of this review, we will only incorporate studies that have been formally published. this may render our review susceptible to publication bias, as studies with significant or positive results are often likely to be published³². If possible, a funnel plot will be used to assess the presence of publication bias. Moreover, the existence of confounding variables poses a significant challenge in observational research. Possible confounders might encompass the age of the mother, parity, maternal body mass index, heterogenous clinical approaches, different methods of monitoring FSp02 and pregnancy complications such as intrauterine growth restriction, pre-eclampsia and gestational diabetes mellitus. As noted previously, our meta-analyses will present both unadjusted and adjusted outcomes, whenever feasible, using the generic inverse variance approach. This adjustment will be based on the definitions provided in each of the studies we've reviewed.

Dissemination

It is anticipated that findings of this review will be disseminated through publication in a peer-reviewed journal and presented at scientific conferences.

Study status

Not commenced yet.