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

O'Neill, Sinéad M.; Agerbo, Esben; Kenny, Louise C.; Henriksen, Tine B.; Kearney, Patricia M.; Greene, Richard A.; Mortensen, Preben Bo; Khashan, Ali S.

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

dc.contributor.author	O'Neill, Sinéad M.
dc.contributor.author	Agerbo, Esben
dc.contributor.author	Kenny, Louise C.
dc.contributor.author	Henriksen, Tine B.
dc.contributor.author	Kearney, Patricia M.
dc.contributor.author	Greene, Richard A.
dc.contributor.author	Mortensen, Preben Bo
dc.contributor.author	Khashan, Ali S.
dc.contributor.editor	Fisk, Nicholas M.
dc.contributor.funder	Health Research Board	en
dc.contributor.funder	Science Foundation Ireland	en
dc.contributor.funder	National Perinatal Epidemiology Centre, College of Medicine and Health, University College Cork
dc.date.accessioned	2014-09-30T16:33:22Z
dc.date.available	2014-09-30T16:33:22Z
dc.date.issued	2014-07-01
dc.date.updated	2014-08-28T13:55:00Z
dc.description.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. 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.	en
dc.description.sponsorship	Health Research Board (PhD Scholars programme in Health Services Research, Grant No. PHD/2007/16) ; Science Foundation Ireland (08/IN.1/B2083, 12/RC/2272)	en
dc.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	O'NEILL, S. M., AGERBO, E., KENNY, L. C., HENRIKSEN, T. B., KEARNEY, P. M., GREENE, R. A., MORTENSEN, P. B. & KHASHAN, A. S. 2014. Cesarean Section and Rate of Subsequent Stillbirth, Miscarriage, and Ectopic Pregnancy: A Danish Register-Based Cohort Study. PLoS Med, 11, e1001670. http://dx.doi.org/10.1371%2Fjournal.pmed.1001670	en
dc.identifier.doi	10.1371/journal.pmed.1001670
dc.identifier.issued	7	en
dc.identifier.journaltitle	Plos Medicine	en
dc.identifier.startpage	e1001670	en
dc.identifier.uri	https://hdl.handle.net/10468/1676
dc.identifier.volume	11	en
dc.language.iso	en	en
dc.publisher	Public Library of Science	en
dc.rights	© 2014 O'Neill et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.	en
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	en
dc.subject	Caesarean section	en
dc.subject	Pregnancy	en
dc.subject	Population based cohort-study	en
dc.subject	Cesarean section
dc.title	Cesarean section and rate of subsequent stillbirth, miscarriage and ectopic pregnancy: a Danish register-based cohort study	en
dc.type	Article (peer-reviewed)	en

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