Epidural analgesia during labour and severe maternal morbidity: population based study

Data sources and study population

We linked six Scotland-wide administrative databases: the Scottish Morbidity Record-2 (SMR02), the Scottish Morbidity Record-1 (SMR01), the Scottish Birth Record, the National Records of Scotland, the Scottish Stillbirth Infant Death Survey, and the Scottish Intensive Care Society Audit Group. The SMR02 documents all obstetric inpatient and day case admissions during pregnancy and the postnatal period and includes maternal and infant characteristics. The SMR02 is subject to regular quality assurance checks, with data more than 99% complete since the late 1970s.1819 The SMR01 records all non-obstetric inpatient and day case admissions according to ICD-9 and ICD-10 (international classification of diseases, ninth revision and 10th revision, respectively) codes and UK NHS OPCS-4 (Office of Population Censuses and Surveys classification of interventions and procedures).2021 All neonatal care is recorded in the Scottish Birth Record. The National Records of Scotland registers all births, stillbirths, and infant deaths, and the Scottish Stillbirth Infant Death Survey collects additional information from the relevant coordinator of the survey (obstetrician, paediatrician, or midwife) at each hospital. The database of the Scottish Intensive Care Society Audit Group records admission data for all Scottish intensive care and high dependency units, with regular data validation.22

Inclusion and exclusion criteria

We analysed all women in labour in Scotland between 1 January 2007 and 31 December 2019 with gestation between 24+0 and 42+6 weeks. Births were excluded after this period to remove any potential confounding influence of the covid-19 pandemic. We also excluded births when mode of delivery, child identity, or data for analgesia during labour were not recorded (n=38 705, 5.5% of all 697 981 pregnancies considered); see supplementary eFigure 1), as well as births by elective caesarean section as these women knew their mode of delivery in advance and would not experience labour, and therefore by definition could not have chosen to have epidural analgesia (n=92 060, 13.2%; see supplementary eFigure 1).

Epidural analgesia

We defined epidural analgesia during labour as conventional lumbar epidural sited at any time during labour. This definition is consistent with standard medical practices in the UK, where epidural drugs are generally administered only after labour has commenced. We were unable to identify use of combined spinal epidural (spinal injection plus insertion of an epidural catheter), as SMR02 classifies the procedure as spinal anaesthesia. Combined spinal epidural is used infrequently in Scotland, representing only 1% of epidural use during labour.23 Women recorded as having no epidural could have delivered without additional analgesia or anaesthesia or have required spinal or general anaesthesia for operative delivery, reflecting the unpredictability of labour outcomes and the resultant different potential pathways care may take. Since recording of anaesthetic intervention is hierarchical, we could not identify if women who had a spinal or general anaesthetic also had epidural analgesia at an earlier point. Conversion of epidural analgesia to spinal or general anaesthesia occurs in around 5% of women.24

Outcomes

The primary outcome was SMM, defined as a composite outcome of ≥1 of 21 conditions according to the US CDC criteria for SMM or a critical care admission, with either occurring at any point from the date of delivery to 42 days post partum (described as SMM). In keeping with other published data, we incorporated critical care admission as an SMM indicator because the CDC’s definition does not cover all SMM events (eg, asthma attack, status epilepticus).4 We identified conditions using ICD-9, ICD-10, and OPCS codes from SMR01, SMR02, and Scottish Intensive Care Society Audit Group datasets (see supplementary eTable 1 for table of codes).3 The CDC’s definition of SMM has a sensitivity of 77% and specificity of 99% in identifying SMM compared with medical records.25

Secondary outcomes aimed to capture more severe morbidity and included ≥1 of the 21 CDC conditions when that condition resulted in admission for critical care (described as SMM plus critical care), and respiratory morbidity (ventilation, tracheostomy, acute respiratory distress syndrome, or respiratory complications of anaesthesia), as diagnosed from the date of delivery to 42 days post partum (see supplementary eTable 1).

Minor modifications were made to the CDC SMM criteria to accommodate data recording practices in Scotland (see supplementary eTable 1). In line with other UK studies,426 we found that the UK definition for postpartum haemorrhage (≥500 mL blood loss) resulted in over-reporting of major obstetric haemorrhage (ICD-10 code O72), and therefore we included postpartum haemorrhage only if it occurred in association with a critical care admission, indicating a clinically significant haemorrhage event. Alternative metrics such as volume of blood loss and blood transfusion are not reliably recorded in SMR02. Similar to a previous Scottish study, we found the incidence of sepsis had increased exponentially from 2012 (see supplementary eFigure 2).4 This might reflect different coding practices and changes in guidance with the publication of the 2012 Surviving Sepsis recommendations resulting in increased awareness of the condition.2728 Because sepsis is defined as the presence of an infection and evidence of acute organ dysfunction, we included it only if associated with admission to a critical care unit.

Given that in our analyses, as in any risk analyses, we censored at the first SMM condition, the difference between the primary outcome and the first secondary outcome is illustrated by considering a mother with eclampsia diagnosed on the day of delivery and acute heart failure diagnosed on postnatal day 22. In the primary analysis, that woman would be censored on the day of delivery. In contrast, a woman with eclampsia diagnosed on the day of delivery who experienced heart failure resulting in critical care admission at 22 days postnatally when heart failure was diagnosed, would be censored at postnatal day 22. Conversely, a woman with the same conditions at the same time points but who was not admitted to critical care for either would not be considered at risk for the secondary outcome of SMM plus critical care admission (and would contribute to the comparator group—no SMM plus critical care).

Confounders and other variables used in analyses

To determine confounding variables before analyses, we used the established definition of a confounder—something that is a known or plausible reason for having both epidural analgesia during labour and SMM, and we considered all potential plausible pathways between these variables.29 We included these confounders (irrespective of whether they were available in our data) in directed acyclic graphs drawn using the R package “DAGGitty,”30 to highlight sources of unmeasured confounding and how these might be captured by other measured confounders on the same confounding path (see supplementary eFigures 3a and 3b). We included socioeconomic status and ethnicity as these factors are increasingly recognised as influencing poor maternal outcomes and epidural analgesia use during labour.131415 Ethnicity was defined using NHS Scotland 2011 census categories.31 As we did not have information on individual socioeconomic status, we used residential area deprivation according to the Scottish index for multiple deprivation as a proxy; the first 10% of deprivation denoting the most deprived areas and the last 10% the least deprived.32 Pre-existing comorbidities that plausibly influence the use of epidural analgesia and SMM were defined for each mother by calculating a Bateman index score, an extensively validated, weighted, risk prediction tool including 20 conditions plus maternal age that is specific to obstetric patients and more accurately predicts SMM than other generic comorbidity indices (see supplementary eTable 2)33 To avoid conflating comorbid conditions with the outcome of SMM, we applied strict criteria, restricting these diagnoses to the period between 180 days before the estimated date of conception (as described in the original paper by Bateman et al)33 and the day before delivery. This approach ensured the validity of our findings by accurately reflecting the impact of comorbidities on risk of SMM. Using ICD-9 and ICD-10 codes from SMR02, we obtained information on maternal height, weight, and smoking status plus obstetric indices of previous caesarean section, parity, and induction of labour. Gestational age at birth was based on ultrasound assessment in the first half of pregnancy. Smoking status at booking was defined as current, former, or never. Birth location was categorised into obstetric unit, freestanding midwifery unit, or home birth. Obstetric units were defined as hospitals with on-site obstetric and anaesthetic services, inclusive of epidural analgesia provision, or midwifery led units co-located with an obstetric unit. Freestanding midwifery units were defined as midwifery led units without direct access to obstetric or anaesthetic services.34

In exploratory analyses we assessed whether associations differed by the presence of a medical indication for epidural analgesia and by gestational age. We classified births as preterm if they occurred before 37 weeks’ gestation and as term or post term if they occurred at ≥37+0 weeks. Births were further classified using World Health Organization (WHO) criteria as extremely preterm (<28 weeks), very preterm (28 to <32 weeks), and moderate to late preterm (≥32 to 36+6 weeks), and by whether labour occurred spontaneously or was commenced iatrogenically.35

We defined medical indications for epidural analgesia as any of serious cardiovascular or respiratory disease (congestive heart failure, congenital heart disease, pulmonary hypertension, ischaemic heart disease, asthma); pre-eclampsia; previous caesarean section; breech presentation; multiple pregnancy; and morbid obesity (BMI ≥40), diagnosed before the date of delivery and with no contraindication to epidural insertion (see supplementary eTable 3).6363738394041 These indications are easily identified by obstetric, anaesthesia, and midwifery staff, reflect criteria that drive common decision making processes, and are in widespread use in clinical practice. These conditions were included if recorded up to the day pre-delivery to ensure they occurred before the decision to have an epidural and any episodes of SMM.

Statistical analysis

As this was a whole population study, we did not perform sample size calculations. We report baseline characteristics by epidural status. Continuous variables are expressed as medians with interquartile range (IQR), and categorical variables as counts and percentages. For group comparison, we used standardised differences.

To adjust for confounders, we used multivariable Poisson regression models with cluster robust sandwich estimators under the generalised estimation equation framework (see supplementary eFigures 3a and 3b). These models were chosen in place of log-binomial models to avoid problems with convergence. The robust estimator was used to correct the inflated variance found from the standard Poisson model, and to account for more than one birth in some women.42 We also assessed a zero inflated Poisson model using a single zero inflation parameter applied to all observations to account for any excess of zeros in the model. This indicated no excess of zeros (P>0.9), further supporting the use of a multivariable Poisson regression model with cluster robust errors. In the modelling of risk analyses, we censored at the first SMM condition (ie, a mother with two SMM conditions was only counted once in the analysis). These models were used to determine adjusted relative risks and absolute risks. As we a priori assumed that outcomes might differ depending on gestational age, we included this as an interaction and adjusted for all of the other previously defined confounders. To explore potential residual confounding from confounders that we did not consider because evidence was lacking to suggest they would affect epidural use and SMM, we calculated an E-value.43 The E-value was defined as the minimum strength of association that one confounder or several unmeasured confounders would need to have with both epidural analgesia and SMM, conditional on the confounders we adjusted for, to fully explain a specific exposure-outcome association. This was calculated using the EValue package (version 4.1.3).

Patient and public involvement

This study used anonymised data from national registries, focusing on the analysis of existing information without necessitating new direct contact with participants. Despite the inherent limitations of our approach, including the lack of allocated funding for direct patient involvement, we recognised the importance of incorporating public perspectives into our research. While direct involvement in designing the research question, the outcome measures, and study implementation was not feasible, our motivation was strongly influenced by discussions with members of the public and specific concerns highlighted by patients about maternal morbidity rates. These conversations, along with a priority setting exercise by the James Lind Alliance on the impact of epidural analgesia during labour, shaped our research focus.16 Although formal patient and public involvement was not integrated into the study’s design, we engaged with the public by inviting a patient to review our manuscript, whose insights contributed to refining our presentation and interpretation of findings.