Caesarean section and subsequent pregnancy outcome: a Danish register-based cohort study

Background and Aims: Caesarean section rates have increased in recent decades and the effects on subsequent pregnancy outcome are largely unknown. Prior research has hypothesised that Caesarean section delivery may lead to an increased risk of subsequent stillbirth, miscarriage, ectopic pregnancy and sub-fertility. Structure and Methods: Papers 1-3 are systematic reviews with meta-analyses. Papers 4-6 are findings from this thesis on the rate of subsequent stillbirth, miscarriage, ectopic pregnancy and live birth by mode of delivery. Results Systematic reviews and meta-analyses: A 23% increased odds of subsequent stillbirth; no increase in odds of subsequent ectopic pregnancy and a 10% reduction in the odds of subsequent live birth among women with a previous Caesarean section were found in the various meta-analyses. Danish cohorts: Results from the Danish Civil Registration System (CRS) cohort revealed a small increased rate of subsequent stillbirth and ectopic pregnancy among women with a primary Caesarean section, which remained in the analyses by type of Caesarean. No increased rate of miscarriage was found among women with a primary Caesarean section. In the CRS data, women with a primary Caesarean section had a significantly reduced rate of subsequent live birth particularly among women with primary elective and maternal-requested Caesarean sections. In the Aarhus Birth Cohort, overall the effect of mode of delivery on the rate and time to next live birth was minimal. Conclusions: Primary Caesarean section was associated with a small increased rate of stillbirth and ectopic pregnancy, which may be in part due to underlying medical conditions. No increased rate of miscarriage was found. A reduced rate of subsequent live birth was found among Caesarean section in the CRS data. In the smaller ABC cohort, a small reduction in rate of subsequent live birth was found among women with a primary Caesarean section and is most likely due to maternal choice rather than any ill effects of the Caesarean. The findings of this study, the largest and most comprehensive to date will be of significant interest to health care providers and women globally.

Cesarean section and rate of subsequent stillbirth, miscarriage and ectopic pregnancy: a Danish register-based cohort study

Background: With cesarean section rates increasing worldwide, clarity regarding negative effects is essential. This study aimed to investigate the rate of subsequent stillbirth, miscarriage, and ectopic pregnancy following primary cesarean section, controlling for confounding by indication. Methods and Findings: We performed a population-based cohort study using Danish national registry data linking various registers. The cohort included primiparous women with a live birth between January 1, 1982, and December 31, 2010 (n = 832,996), with follow-up until the next event (stillbirth, miscarriage, or ectopic pregnancy) or censoring by live birth, death, emigration, or study end. Cox regression models for all types of cesarean sections, sub-group analyses by type of cesarean, and competing risks analyses for the causes of stillbirth were performed. An increased rate of stillbirth (hazard ratio [HR] 1.14, 95% CI 1.01, 1.28) was found in women with primary cesarean section compared to spontaneous vaginal delivery, giving a theoretical absolute risk increase (ARI) of 0.03% for stillbirth, and a number needed to harm (NNH) of 3,333 women. Analyses by type of cesarean section showed similarly increased rates for emergency (HR 1.15, 95% CI 1.01, 1.31) and elective cesarean (HR 1.11, 95% CI 0.91, 1.35), although not statistically significant in the latter case. An increased rate of ectopic pregnancy was found among women with primary cesarean overall (HR 1.09, 95% CI 1.04, 1.15) and by type (emergency cesarean, HR 1.09, 95% CI 1.03, 1.15, and elective cesarean, HR 1.12, 95% CI 1.03, 1.21), yielding an ARI of 0.1% and a NNH of 1,000 women for ectopic pregnancy. No increased rate of miscarriage was found among women with primary cesarean, with maternally requested cesarean section associated with a decreased rate of miscarriage (HR 0.72, 95% CI 0.60, 0.85). Limitations include incomplete data on maternal body mass index, maternal smoking, fertility treatment, causes of stillbirth, and maternally requested cesarean section, as well as lack of data on antepartum/intrapartum stillbirth and gestational age for stillbirth and miscarriage. Conclusions: This study found that cesarean section is associated with a small increased rate of subsequent stillbirth and ectopic pregnancy. Underlying medical conditions, however, and confounding by indication for the primary cesarean delivery account for at least part of this increased rate. These findings will assist women and health-care providers to reach more informed decisions regarding mode of delivery.