Cesarean Section and Rate of Subsequent Stillbirth, Miscarriage, and Ectopic Pregnancy: A Danish Register-Based Cohort Study
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{"title"=>"Cesarean Section and Rate of Subsequent Stillbirth, Miscarriage, and Ectopic Pregnancy: A Danish Register-Based Cohort Study", "type"=>"journal", "authors"=>[{"first_name"=>"Sinéad M.", "last_name"=>"O'Neill", "scopus_author_id"=>"55089863100"}, {"first_name"=>"Esben", "last_name"=>"Agerbo", "scopus_author_id"=>"6603788071"}, {"first_name"=>"Louise C.", "last_name"=>"Kenny", "scopus_author_id"=>"7006011134"}, {"first_name"=>"Tine B.", "last_name"=>"Henriksen", "scopus_author_id"=>"35399074200"}, {"first_name"=>"Patricia M.", "last_name"=>"Kearney", "scopus_author_id"=>"14009447200"}, {"first_name"=>"Richard A.", "last_name"=>"Greene", "scopus_author_id"=>"7401476458"}, {"first_name"=>"Preben Bo", "last_name"=>"Mortensen", "scopus_author_id"=>"7102903327"}, {"first_name"=>"Ali S.", "last_name"=>"Khashan", "scopus_author_id"=>"23488971600"}], "year"=>2014, "source"=>"PLoS Medicine", "identifiers"=>{"pui"=>"373686448", "sgr"=>"84905407775", "issn"=>"15491676", "pmid"=>"24983970", "scopus"=>"2-s2.0-84905407775", "doi"=>"10.1371/journal.pmed.1001670", "isbn"=>"1549-1676 (Electronic) 1549-1277 (Linking)"}, "id"=>"b9bc7153-2bd7-3afe-ac37-11370f6f27c1", "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.\\n\\nMETHODS 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.\\n\\nCONCLUSIONS: 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.", "link"=>"http://www.mendeley.com/research/cesarean-section-rate-subsequent-stillbirth-miscarriage-ectopic-pregnancy-danish-registerbased-cohor", "reader_count"=>53, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Doctoral Student"=>6, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>7, "Other"=>5, "Student > Bachelor"=>8, "Lecturer > Senior Lecturer"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Doctoral Student"=>6, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>7, "Other"=>5, "Student > Bachelor"=>8, "Lecturer > Senior Lecturer"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>1, "Nursing and Health Professions"=>2, "Mathematics"=>2, "Medicine and Dentistry"=>32, "Agricultural and Biological Sciences"=>4, "Business, Management and Accounting"=>1, "Psychology"=>1, "Social Sciences"=>6}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>32}, "Social Sciences"=>{"Social Sciences"=>6}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>2}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Mathematics"=>{"Mathematics"=>2}, "Unspecified"=>{"Unspecified"=>4}}, "reader_count_by_country"=>{"Canada"=>1, "Argentina"=>1, "Norway"=>1, "Denmark"=>1}, "group_count"=>5}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1576860"], "description"=>"<p>Data are <i>n</i> (percent) unless otherwise specified. All pregnancy- and infant-related characteristics are for the first (index) live birth.</p><p>*Maternally requested cesarean data available from 2002–2010 only (cohort <i>n</i> = 258,445).</p>a<p>Smoking data available 1997–2010 only (<i>n</i> = 405,498).</p>b<p>BMI data available 2003–2010 only (<i>n</i> = 230,066).</p>c<p>History of pregnancy loss before the first live birth.</p><p>IQR, interquartile range; SD, standard deviation.</p>", "links"=>[], "tags"=>["epidemiology", "urology", "infertility", "subfertility", "Female subfertility", "women's health", "Maternal health", "birth", "Labor and delivery", "pregnancy", "Miscarriage and stillbirth", "Obstetrics and gynecology", "cohort"], "article_id"=>1090651, "categories"=>["Biological Sciences"], "users"=>["Sinéad M. O'Neill", "Esben Agerbo", "Louise C. Kenny", "Tine B. Henriksen", "Patricia M. Kearney", "Richard A. Greene", "Preben Bo Mortensen", "Ali S. Khashan"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001670.t001", "stats"=>{"downloads"=>7, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Baseline_characteristics_of_the_cohort_for_the_first_live_birth_/1090651", "title"=>"Baseline characteristics of the cohort for the first live birth.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-01 03:41:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1576854"], "description"=>"<p>Flow diagram of study participants.</p>", "links"=>[], "tags"=>["epidemiology", "urology", "infertility", "subfertility", "Female subfertility", "women's health", "Maternal health", "birth", "Labor and delivery", "pregnancy", "Miscarriage and stillbirth", "Obstetrics and gynecology", "diagram"], "article_id"=>1090645, "categories"=>["Biological Sciences"], "users"=>["Sinéad M. O'Neill", "Esben Agerbo", "Louise C. Kenny", "Tine B. Henriksen", "Patricia M. Kearney", "Richard A. Greene", "Preben Bo Mortensen", "Ali S. Khashan"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001670.g001", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Flow_diagram_of_study_participants_/1090645", "title"=>"Flow diagram of study participants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-01 03:41:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1576862"], "description"=>"<p>Data are <i>n</i> (percent). Type of stillbirth was classified as outlined by King-Hele et al. <a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001670#pmed.1001670-KingHele1\" target=\"_blank\">[38]</a>.</p>", "links"=>[], "tags"=>["epidemiology", "urology", "infertility", "subfertility", "Female subfertility", "women's health", "Maternal health", "birth", "Labor and delivery", "pregnancy", "Miscarriage and stillbirth", "Obstetrics and gynecology", "stillbirth"], "article_id"=>1090653, "categories"=>["Biological Sciences"], "users"=>["Sinéad M. O'Neill", "Esben Agerbo", "Louise C. Kenny", "Tine B. Henriksen", "Patricia M. Kearney", "Richard A. Greene", "Preben Bo Mortensen", "Ali S. Khashan"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001670.t002", "stats"=>{"downloads"=>2, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Causes_of_stillbirth_by_mode_of_delivery_1982_8211_1996_/1090653", "title"=>"Causes of stillbirth by mode of delivery (1982–1996).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-01 03:41:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1576861"], "description"=>"<p>Data available from 1982–2010 (cohort size = 832,996 women).</p>a<p>Number of events of the outcome of interest for each mode of delivery in parentheses.</p>b<p>Model 1: adjusted for maternal age; maternal origin; previous stillbirth, miscarriage, or ectopic pregnancy; mother's marital status; birth year; and measures of socio-economic status including mother's educational attainment and mother's and father's gross income.</p>c<p>Model 2: adjusted for Model 1 plus medical complications in the first live birth including delivery type (singleton versus twins or more), diabetes, gestational diabetes, placental abruption, placenta praevia, and hypertensive disorders (including eclampsia and preeclampsia).</p>d<p>Model 3: adjusted for Model 2 plus gestational age and birth weight.</p>e<p>All emergency, elective, and maternally requested cesarean sections (where applicable, i.e., from 2002–2010) combined.</p><p>*Where the number of events was less than ten for maternally requested cesarean, these were combined with the elective cesarean group for analyses.</p>", "links"=>[], "tags"=>["epidemiology", "urology", "infertility", "subfertility", "Female subfertility", "women's health", "Maternal health", "birth", "Labor and delivery", "pregnancy", "Miscarriage and stillbirth", "Obstetrics and gynecology", "ectopic"], "article_id"=>1090652, "categories"=>["Biological Sciences"], "users"=>["Sinéad M. O'Neill", "Esben Agerbo", "Louise C. Kenny", "Tine B. Henriksen", "Patricia M. Kearney", "Richard A. Greene", "Preben Bo Mortensen", "Ali S. Khashan"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001670.t003", "stats"=>{"downloads"=>4, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cesarean_section_and_rate_of_subsequent_stillbirth_miscarriage_or_ectopic_pregnancy_/1090652", "title"=>"Cesarean section and rate of subsequent stillbirth, miscarriage, or ectopic pregnancy.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-01 03:41:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1576858"], "description"=>"<p>Cohort 1982–2010 (<i>n</i> = 832,996 women).</p>a<p>Number of events of the outcome of interest for each mode of delivery in parentheses. Outcome refers to a composite outcome whereby the odds of pregnancy failure (stillbirth, miscarriage, or ectopic pregnancy) were compared simultaneously using multinomial logistic regression models. The reference group was live birth (<i>n</i> = 514,191). Women with no recorded second pregnancy event (<i>n</i> = 236,425) were not included in this analysis.</p>b<p>Model 1: adjusted for maternal age; maternal origin; previous stillbirth, miscarriage, or ectopic pregnancy; mother's marital status; birth year; and measures of socio-economic status including mother's educational attainment and mother's and father's gross income.</p>c<p>Model 2: adjusted for Model 1 plus medical complications in the first live birth including delivery type (singleton versus twins or more), diabetes, gestational diabetes, placental abruption, placenta praevia, and hypertensive disorders (including eclampsia and preeclampsia).</p>d<p>Model 3: adjusted for Model 2 plus gestational age and birth weight.</p><p>*Where the number of events was less than ten for maternally requested cesarean, these were combined with the elective cesarean group for analyses.</p>", "links"=>[], "tags"=>["epidemiology", "urology", "infertility", "subfertility", "Female subfertility", "women's health", "Maternal health", "birth", "Labor and delivery", "pregnancy", "Miscarriage and stillbirth", "Obstetrics and gynecology", "ectopic", "multinomial", "logistic", "regression"], "article_id"=>1090649, "categories"=>["Biological Sciences"], "users"=>["Sinéad M. O'Neill", "Esben Agerbo", "Louise C. Kenny", "Tine B. Henriksen", "Patricia M. Kearney", "Richard A. Greene", "Preben Bo Mortensen", "Ali S. Khashan"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001670.t006", "stats"=>{"downloads"=>6, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cesarean_section_and_the_odds_of_stillbirth_miscarriage_or_ectopic_pregnancy_8212_a_multinomial_logistic_regression_analysis_/1090649", "title"=>"Cesarean section and the odds of stillbirth, miscarriage, or ectopic pregnancy—a multinomial logistic regression analysis.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-01 03:41:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1576856"], "description"=>"<p>Women were followed up for a maximum of 3 y from the date of the first live birth until the subsequent event to test for informative censoring due to live birth. Cohort 1982–2010 (<i>n</i> = 832,996 women).</p>a<p>Number of events of the outcome of interest for each mode of delivery in parentheses.</p>b<p>Model 1: adjusted for maternal age; maternal origin; previous stillbirth, miscarriage, or ectopic pregnancy; mother's marital status; birth year; and measures of socio-economic status including mother's educational attainment and mother's and father's gross income.</p>c<p>Model 2: adjusted for Model 1 plus medical complications in the first live birth including delivery type (singleton versus twins or more), diabetes, gestational diabetes, placental abruption, placenta praevia, and hypertensive disorders (including eclampsia and preeclampsia).</p>d<p>Model 3: adjusted for Model 2 plus gestational age and birth weight.</p><p>*Where the number of events was less than ten for maternally requested cesarean, these were combined with the elective cesarean group for analyses.</p>", "links"=>[], "tags"=>["epidemiology", "urology", "infertility", "subfertility", "Female subfertility", "women's health", "Maternal health", "birth", "Labor and delivery", "pregnancy", "Miscarriage and stillbirth", "Obstetrics and gynecology", "ectopic"], "article_id"=>1090647, "categories"=>["Biological Sciences"], "users"=>["Sinéad M. O'Neill", "Esben Agerbo", "Louise C. Kenny", "Tine B. Henriksen", "Patricia M. Kearney", "Richard A. Greene", "Preben Bo Mortensen", "Ali S. Khashan"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001670.t005", "stats"=>{"downloads"=>3, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cesarean_section_and_rate_of_subsequent_stillbirth_miscarriage_or_ectopic_pregnancy_8212_3_y_follow_up_/1090647", "title"=>"Cesarean section and rate of subsequent stillbirth, miscarriage, or ectopic pregnancy—3-y follow-up.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-01 03:41:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1576857"], "description"=>"<p>Cohort 1982–1996 (<i>n</i> = 427,498 women); cohort 1997–2010 (<i>n</i> = 405,498 women).</p>a<p>Number of events of the outcome of interest for each mode of delivery in parentheses.</p>b<p>Model 1: adjusted for maternal age; maternal origin; previous stillbirth, miscarriage, or ectopic pregnancy; mother's marital status; birth year; and measures of socio-economic status including mother's educational attainment and mother's and father's gross income.</p>c<p>Model 2: adjusted for Model 1 plus medical complications in the first live birth including delivery type (singleton versus twins or more), diabetes, gestational diabetes, placental abruption, placenta praevia, and hypertensive disorders (including eclampsia and preeclampsia).</p>d<p>Model 3: adjusted for Model 2 plus gestational age and birth weight.</p>e<p>Explained and unexplained stillbirth refer to a cause-specific competing risks for each type of stillbirth. Data for the causes of stillbirth were available from 1982–1996 only (cohort size = 427,498).</p><p>*Where the number of events was less than ten for maternally requested cesarean, these were combined with the elective cesarean group for analyses.</p>", "links"=>[], "tags"=>["epidemiology", "urology", "infertility", "subfertility", "Female subfertility", "women's health", "Maternal health", "birth", "Labor and delivery", "pregnancy", "Miscarriage and stillbirth", "Obstetrics and gynecology", "explained", "unexplained"], "article_id"=>1090648, "categories"=>["Biological Sciences"], "users"=>["Sinéad M. O'Neill", "Esben Agerbo", "Louise C. Kenny", "Tine B. Henriksen", "Patricia M. Kearney", "Richard A. Greene", "Preben Bo Mortensen", "Ali S. Khashan"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001670.t004", "stats"=>{"downloads"=>6, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cesarean_section_and_rate_of_subsequent_explained_or_unexplained_stillbirth_/1090648", "title"=>"Cesarean section and rate of subsequent explained or unexplained stillbirth.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-01 03:41:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1576864", "https://ndownloader.figshare.com/files/1576865", "https://ndownloader.figshare.com/files/1576866", "https://ndownloader.figshare.com/files/1576867", "https://ndownloader.figshare.com/files/1576868"], "description"=>"<div><p>Background</p><p>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.</p><p>Methods and Findings</p><p>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 (<i>n</i> = 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.</p><p>Conclusions</p><p>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.</p><p><i>Please see later in the article for the Editors' Summary</i></p></div>", "links"=>[], "tags"=>["epidemiology", "urology", "infertility", "subfertility", "Female subfertility", "women's health", "Maternal health", "birth", "Labor and delivery", "pregnancy", "Miscarriage and stillbirth", "Obstetrics and gynecology", "ectopic", "danish", "register-based", "cohort"], "article_id"=>1090655, "categories"=>["Biological Sciences"], "users"=>["Sinéad M. O'Neill", "Esben Agerbo", "Louise C. Kenny", "Tine B. Henriksen", "Patricia M. Kearney", "Richard A. Greene", "Preben Bo Mortensen", "Ali S. Khashan"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1001670.s001", "https://dx.doi.org/10.1371/journal.pmed.1001670.s002", "https://dx.doi.org/10.1371/journal.pmed.1001670.s003", "https://dx.doi.org/10.1371/journal.pmed.1001670.s004", "https://dx.doi.org/10.1371/journal.pmed.1001670.s005"], "stats"=>{"downloads"=>16, "page_views"=>31, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cesarean_Section_and_Rate_of_Subsequent_Stillbirth_Miscarriage_and_Ectopic_Pregnancy_A_Danish_Register_Based_Cohort_Study_/1090655", "title"=>"Cesarean Section and Rate of Subsequent Stillbirth, Miscarriage, and Ectopic Pregnancy: A Danish Register-Based Cohort Study", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-07-01 03:41:03"}

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Relative Metric

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