title: Cesarean section and rate of subsequent stillbirth, miscarriage, and ectopic pregnancy: a Danish register-based cohort study.
abstract: 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.
  
  
  RESULTS
  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. Please see later in the article for the Editors' Summary.
authors.affiliation: National Perinatal Epidemiology Centre, Anu Research Centre, Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, Cork, Ireland.
authors.forename: Sinéad M
authors.initials: SM
authors.lastname: O'Neill
authors.affiliation: National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.
authors.forename: Esben
authors.initials: E
authors.lastname: Agerbo
authors.affiliation: Irish Centre for Fetal and Neonatal Translational Research, University College Cork, Cork, Ireland.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Kenny
authors.affiliation: Perinatal Epidemiology Research Unit, Department of Paediatrics, Aarhus University Hospital, Skejby, Denmark.
authors.forename: Tine B
authors.initials: TB
authors.lastname: Henriksen
authors.affiliation: Department of Epidemiology and Public Health, University College Cork, Cork, Ireland.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Kearney
authors.affiliation: National Perinatal Epidemiology Centre, Anu Research Centre, Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, Cork, Ireland.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Greene
authors.affiliation: National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.
authors.forename: Preben Bo
authors.initials: PB
authors.lastname: Mortensen
authors.affiliation: Irish Centre for Fetal and Neonatal Translational Research, University College Cork, Cork, Ireland.
authors.forename: Ali S
authors.initials: AS
authors.lastname: Khashan
mesh_terms: D000022:Abortion, Spontaneous / Q000453:epidemiology* / Q000209:etiology; D000328:Adult; D002585:Cesarean Section; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000453:epidemiology* / Q000209:etiology; D012044:Regression Analysis; D050497:Stillbirth / Q000453:epidemiology*; D055815:Young Adult