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Korb and colleagues(1) investigated the important and complex issue of cesarean delivery and subsequent severe acute maternal morbidity (SAMM). Observational studies comparing maternal and perinatal outcomes following vaginal and cesarean delivery have been criticized for inappropriate comparison groups and the inability to address confounding by indication. Despite efforts to overcome these challenges, the study by Korb and colleagues(1) is compromised by these same issues and consequently the results need to be interpreted with caution.
Firstly, comparing outcomes following successful vaginal and cesarean deliveries is misleading with respect to causal inference. Risks of an outcome across two interventions can be meaningfully contrasted only if those who received one intervention were candidates for receiving the other intervention. This is known as the principle of exchangeability,(2) which dictates that both groups should be exchangeable with respect to an outcome had they been subjected to the identical exposure.(3) However, a successful vaginal delivery is an impossibility for a substantial fraction of women who deliver by cesarean. To address this limitation, in 2006 the NIH State-of-the-Science expert panel on cesarean delivery recommended that all future research comparing maternal and neonatal outcomes following vaginal and cesarean delivery be based on planned vaginal versus planned cesarean delivery.(4) Korb and colleagues(1) applied this approach in a sensitivity analysis (Appendix 7); however, the absence of a significant association between cesarean delivery and SAMM among the three subgroups of women aged <25, 25-29, and 30-34 years (80% of the study population) was not discussed. Instead, the authors emphasized the finding of increased SAMM following planned cesarean delivery among older women (≥35 years). Nevertheless, there was no information describing the subgroups of women with respect to key demographic and clinical characteristics (e.g. parity, BMI) or whether women may have had a specific reason for planning a cesarean vs. vaginal delivery, and this makes the validity and generalisability of the subgroup analysis unclear.
Secondly, although this study attempted to address confounding by indication with propensity score analysis, the indications for intervention were not quantified and hence not included in the propensity score. For instance, no distinction was made for emergency cesarean delivery, which is invariably unplanned and therefore indicated due to fetal or maternal reasons. In fact, all intrapartum cesarean deliveries are unplanned and indeed indicated. Further, it is plausible that this unmeasured confounding by indication increased with maternal age and manifested more prominently in older women.
From the research standpoint, a clearly formulated research question and a sound understanding of confounding and the temporal sequence between exposure, outcome, and factors in the causal pathway are crucial for assessing causal associations. Unfortunately, since the study by Korb and colleagues(1) did not satisfy these research imperatives, the clinical relevance of their results is questionable. Maternity care providers should inform women about the maternal and perinatal risks associated with both cesarean and vaginal delivery, and ultimately, the balance between these risks will dictate the use of obstetric interventions.
Giulia M. Muraca, PhD
Postdoctoral Fellow
Clinical Epidemiology Unit
Department of Medicine, Solna
Karolinska Institutet
Stockholm, Sweden
Neda Razaz, PhD
Postdoctoral Fellow
Clinical Epidemiology Unit
Department of Medicine, Solna
Karolinska Institutet
Stockholm, Sweden
References
1. Korb D, Goffinet F, Seco A, Chevret S, Deneux-Tharaux C. Risk of severe maternal morbidity associated with cesarean delivery and the role of maternal age: a population-based propensity score analysis. CMAJ 2019;191:E352-60.
2. Greenland S, Robins JM. Identifiability, exchangeability and confounding revisited. Epidemiol Perspect Innov 2009;6:4.
3. Hernán MA. A definition of causal effect for epidemiological research. J Epidemiol Community Health 2004;58:265-71.
4. NIH State-of-the-Science Conference Statement: Cesarean delivery on maternal request. Obstet Gynecol 2006;107:1386-97.