Background: With caesarean 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 caesarean
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 caesarean sections, sub-group analyses by type of
caesarean, 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 caesarean (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 caesarean 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
caesarean, with maternally requested caesarean 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 caesarean section, as well as lack of data on antepartum/intrapartum stillbirth and
gestational age for stillbirth and miscarriage.
Conclusions: This study found that caesarean 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 caesarean
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.