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Cesarean delivery in the first birth increased the risk of unexplained stillbirth in the second pregnancy
ARTICLE IN PRESS OBSTETRICS
Cesarean delivery in the first birth increased the risk of unexplained stillbirth in the second pregnancy Smith GCS, Pell JP, Dobbie R.Cesarean section and risk of unexplained stillbirth in subsequent pregnancy. Lancet 2003; 362:1779^1784.
OBJECTIVE To determine if previous cesarean delivery increases the risk of stillbirth in the next pregnancy.
DESIGN Retrospective cohort study.
SETTING Population-based study in Scotland, UK.
SUBJECTS A total of 120,633 second singleton births at 24^43 weeks gestation that occurred in Scotland in 1992^1998. Excluded were those with birthweight o500 g or perinatal death due to congenital anomaly or rhesus isoimmunization, and records with missing data.
METHODS Second births meeting the inclusion criteria were identi¢ed from the Scottish Morbidity Record and linked to the ¢rst birth (meeting the same criteria) in the same woman. Information on mode of delivery in the ¢rst birth was obtained from this register. Stillbirths were identi¢ed from the Scottish Stillbirth and Infant Death Enquiry, which records the cause of death.
MAIN OUTCOME MEASURES Incidence of unexplained stillbirth in the second birth in women with and without a cesarean delivery in the ¢rst birth. MAIN RESULTS There were 17,754 second births in women with a previous cesarean birth and 102,879 second births in women with no previous cesarean
1361-259x/$ - see front matter & 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.ebobgyn.2004.09.003
birth. The number (incidence per 1000 births per week) of all antepartum stillbirths was 68 (0.24) in the previous cesarean group and 244 (0.14) in the no cesarean group (p=0.0001) and the numbers of unexplained stillbirths were 43 (0.15) and 163 (0.10), respectively (p=0.004). Overall, the hazard ratio (HR) for unexplained stillbirth was 1.6 (95% CI 1.2^2.3) in women with a previous cesarean birth, compared to women with no cesarean birth. No di¡erence was found in the risk of unexplained stillbirth prior to 34 weeks gestation (HR 1.0, CI 0.5^1.8), but the risk was increased in births occurring at 34 weeks or later (HR 2.2, CI 1.5^3.4). Adjusting for maternal characteristics and features of the ¢rst birth, women with a previous cesarean birth had signi¢cantly increased risks for unexplained stillbirth at X34 weeks (HR 2.7, CI 1.7^ 4.3), birthweight o5th percentile (odds ratio (OR) 1.2, CI 1.04^1.3), and moderately preterm birth (33^36 weeks, OR 1.2, CI 1.05^1.3). The increases in the risks for birthweight 495th percentile (OR 1.1, CI 0.99^1.1) and very preterm delivery (24^32 weeks, OR 1.1, CI 0.9^1.3) were not signi¢cant. The absolute risk of stillbirth from 34 weeks gestation was estimated to be 1.8/1000 for women with a previous cesarean birth, compared to 0.9/1000 for other women (risk di¡erence 0.9, CI 0.2^1.5). The absolute risks of stillbirth between 34 and 39 weeks (for women planning elective cesarean delivery) were estimated at 1.1 and 0.5/1000, respectively (risk di¡erence 0.6, CI 0.1^1.1).
CONCLUSION Women who had cesarean delivery in their ¢rst birth had at least a 2-fold increased risk of unexplained stillbirth at 34 weeks or later in the second pregnancy. Risks of preterm birth and intrauterine growth restriction were also increased.
Evidence-based Obstetrics and Gynecology (2004) 6,171^172
171
ARTICLE IN PRESS Commentary To date, the primary research focus for birth following a previous cesarean section has been the risks associated with trial-of-labour.1 The risk of antepartum fetal death has not previously been studied. The present authors compared antepartum stillbirth rates in women who did or did not have a previous cesarean delivery, using a large population-based perinatal dataset. This study underscores the value of large, validated databases in assessing risks of rare outcomes. The Scottish Morbidity Record 1992^1998 included data on over144,000 women having a second birth.The f|rst of two main analyses included more than 120,000 women having a second birth. Sixteen percent of records were excluded, mainly because data were missing on maternal height and/or smoking status. A time-to-event analysis was used, with the time being gestation and the event being stillbirth. The analysis then focused only on unexplained stillbirths, with separate analyses for gestational ages o34 and X34 weeks. These gestational age groups were based on the f|t of the mathematical model, not clinical grounds. Detailed results were presented for X34 weeks (39% of all and 59% of unexplained stillbirths). The second part of the analyses included approximately 103,000 of these women, whose records could be linked to their f|rst pregnancy in order to adjust for inter-pregnancy interval and features of the f|rst pregnancy. Among the 120,000 women, there were 312 (2.6/1000) antepartum stillbirths after 24 weeks, of which 206 (66%) were unexplained. For women with previous cesarean delivery, the rate of antepartum stillbirth was 3.8/1000 overall and 2.4/1000 for unexplained antepartum stillbirth. The comparable rates for women with previous vaginal birth were 2.4 and 1.6/1000, respectively. There were 122 unexplained stillbirths after 34 weeks gestation. From 34 weeks the risk of unexplained stillbirth increased more steeply as gestation increased following previous cesarean birth, compared to prior vaginal birth. Adjustment for inter-pregnancy interval and features of the f|rst pregnancy (preterm birth, birthweight percentile, unexplained stillbirth, and other perinatal death) resulted in risk estimates that were similar to the crude risk. Many different estimates of risk were provided. However, given the low frequency of antepartum stillbirth, the absolute risks are likely to be the most useful to clinicians and women. Several things should be borne in mind when considering the results of this study. First, one should question whether the study population is representative of populations to whom the results may apply; in this study, the cesarean section rate was 15% in the f|rst pregnancy, the antepartum stillbirth rate was 2.6/1000 in the second pregnancy, the autopsy rate was 77%, and 66% of antepartum stillbirths were unexplained. Second, the association between stillbirth and previous cesarean birth in the excluded data (16%) was not reported. Women with a still-
172
Evidence-based Obstetrics and Gynecology (2004) 6,171^172
birth are more likely to have incomplete data than women with a live birth.2 Even though the event rate was low, a different distribution of stillbirths in the excluded data may have produced a biased result. Finally, the time-to-event analysis resulted in a somewhat higher estimate of risk (the hazard ratio) than the relative risk, because later gestation at time of stillbirth appears to confer a benef|t (increased time without an adverse event). The mechanism for an increased risk of stillbirth after cesarean section is unclear. It may be related to the procedure and its consequences, or it may be uncontrolled confounding of the risk prof|le that led to cesarean section in the f|rst birth.The authors hypothesized that the increased stillbirth rate after a primary cesarean delivery is related to altered uterine blood flow in the second pregnancy. If this is true, then one would expect a stronger association after more than one prior cesarean section, and an increased risk in women who have had other uterine surgery, such as myomectomy. If impaired placentation, secondary to altered blood flow, is thought to be responsible for an increased risk of antepartum stillbirth, knowledge of the placental site in the second pregnancy may be relevant. Equally, it may be an association between prior uterine surgery and infection that is responsible for the increased stillbirth rate. The latter raises questions about whether women who had a stillbirth were more likely to have had endometritis complicating their previous delivery or whether a manual removal of placenta or postpartum curettage in a f|rst pregnancy increases the risk of stillbirth in their next pregnancy. Whether these data are useful (rather than frightening) to women who have already had a cesarean section is debatable. Clinicians need further studies to conf|rm the risk by gestational age and elucidate possible causal pathways before this information will be clinically useful. Christine Roberts MBBS, DrPH and Emily Olive MBBS University of Sydney, Australia LeeTaylor MBBS New South Wales Department of Health, Sydney, Australia
Literature cited 1. Mozurkewich EL, Hutton EK, Elective repeat cesarean delivery versus trial of labor: a meta-analysis of the literature from 1989 to 1999. Am J Obstet Gynecol 1187; 183: 1187^1197. 2. Adams MM, Wilson HG, Casto DL, et al. Constructing reproductive histories by linking vital records. Am J Epidemiol 1997; 145: 339^348.
Cesarean delivery in the first birth increased the risk of unexplained stillbirth in the second pregnancy Smith GCS, Pell JP, Dobbie R.Cesarean section and risk of unexplained stillbirth in subsequent pregnancy. Lancet 2003; 362:1779^1784.
OBJECTIVE To determine if previous cesarean delivery increases the risk of stillbirth in the next pregnancy.
DESIGN Retrospective cohort study.
SETTING Population-based study in Scotland, UK.
SUBJECTS A total of 120,633 second singleton births at 24^43 weeks gestation that occurred in Scotland in 1992^1998. Excluded were those with birthweight o500 g or perinatal death due to congenital anomaly or rhesus isoimmunization, and records with missing data.
METHODS Second births meeting the inclusion criteria were identi¢ed from the Scottish Morbidity Record and linked to the ¢rst birth (meeting the same criteria) in the same woman. Information on mode of delivery in the ¢rst birth was obtained from this register. Stillbirths were identi¢ed from the Scottish Stillbirth and Infant Death Enquiry, which records the cause of death.
MAIN OUTCOME MEASURES Incidence of unexplained stillbirth in the second birth in women with and without a cesarean delivery in the ¢rst birth. MAIN RESULTS There were 17,754 second births in women with a previous cesarean birth and 102,879 second births in women with no previous cesarean
1361-259x/$ - see front matter & 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.ebobgyn.2004.09.003
birth. The number (incidence per 1000 births per week) of all antepartum stillbirths was 68 (0.24) in the previous cesarean group and 244 (0.14) in the no cesarean group (p=0.0001) and the numbers of unexplained stillbirths were 43 (0.15) and 163 (0.10), respectively (p=0.004). Overall, the hazard ratio (HR) for unexplained stillbirth was 1.6 (95% CI 1.2^2.3) in women with a previous cesarean birth, compared to women with no cesarean birth. No di¡erence was found in the risk of unexplained stillbirth prior to 34 weeks gestation (HR 1.0, CI 0.5^1.8), but the risk was increased in births occurring at 34 weeks or later (HR 2.2, CI 1.5^3.4). Adjusting for maternal characteristics and features of the ¢rst birth, women with a previous cesarean birth had signi¢cantly increased risks for unexplained stillbirth at X34 weeks (HR 2.7, CI 1.7^ 4.3), birthweight o5th percentile (odds ratio (OR) 1.2, CI 1.04^1.3), and moderately preterm birth (33^36 weeks, OR 1.2, CI 1.05^1.3). The increases in the risks for birthweight 495th percentile (OR 1.1, CI 0.99^1.1) and very preterm delivery (24^32 weeks, OR 1.1, CI 0.9^1.3) were not signi¢cant. The absolute risk of stillbirth from 34 weeks gestation was estimated to be 1.8/1000 for women with a previous cesarean birth, compared to 0.9/1000 for other women (risk di¡erence 0.9, CI 0.2^1.5). The absolute risks of stillbirth between 34 and 39 weeks (for women planning elective cesarean delivery) were estimated at 1.1 and 0.5/1000, respectively (risk di¡erence 0.6, CI 0.1^1.1).
CONCLUSION Women who had cesarean delivery in their ¢rst birth had at least a 2-fold increased risk of unexplained stillbirth at 34 weeks or later in the second pregnancy. Risks of preterm birth and intrauterine growth restriction were also increased.
Evidence-based Obstetrics and Gynecology (2004) 6,171^172
171
ARTICLE IN PRESS Commentary To date, the primary research focus for birth following a previous cesarean section has been the risks associated with trial-of-labour.1 The risk of antepartum fetal death has not previously been studied. The present authors compared antepartum stillbirth rates in women who did or did not have a previous cesarean delivery, using a large population-based perinatal dataset. This study underscores the value of large, validated databases in assessing risks of rare outcomes. The Scottish Morbidity Record 1992^1998 included data on over144,000 women having a second birth.The f|rst of two main analyses included more than 120,000 women having a second birth. Sixteen percent of records were excluded, mainly because data were missing on maternal height and/or smoking status. A time-to-event analysis was used, with the time being gestation and the event being stillbirth. The analysis then focused only on unexplained stillbirths, with separate analyses for gestational ages o34 and X34 weeks. These gestational age groups were based on the f|t of the mathematical model, not clinical grounds. Detailed results were presented for X34 weeks (39% of all and 59% of unexplained stillbirths). The second part of the analyses included approximately 103,000 of these women, whose records could be linked to their f|rst pregnancy in order to adjust for inter-pregnancy interval and features of the f|rst pregnancy. Among the 120,000 women, there were 312 (2.6/1000) antepartum stillbirths after 24 weeks, of which 206 (66%) were unexplained. For women with previous cesarean delivery, the rate of antepartum stillbirth was 3.8/1000 overall and 2.4/1000 for unexplained antepartum stillbirth. The comparable rates for women with previous vaginal birth were 2.4 and 1.6/1000, respectively. There were 122 unexplained stillbirths after 34 weeks gestation. From 34 weeks the risk of unexplained stillbirth increased more steeply as gestation increased following previous cesarean birth, compared to prior vaginal birth. Adjustment for inter-pregnancy interval and features of the f|rst pregnancy (preterm birth, birthweight percentile, unexplained stillbirth, and other perinatal death) resulted in risk estimates that were similar to the crude risk. Many different estimates of risk were provided. However, given the low frequency of antepartum stillbirth, the absolute risks are likely to be the most useful to clinicians and women. Several things should be borne in mind when considering the results of this study. First, one should question whether the study population is representative of populations to whom the results may apply; in this study, the cesarean section rate was 15% in the f|rst pregnancy, the antepartum stillbirth rate was 2.6/1000 in the second pregnancy, the autopsy rate was 77%, and 66% of antepartum stillbirths were unexplained. Second, the association between stillbirth and previous cesarean birth in the excluded data (16%) was not reported. Women with a still-
172
Evidence-based Obstetrics and Gynecology (2004) 6,171^172
birth are more likely to have incomplete data than women with a live birth.2 Even though the event rate was low, a different distribution of stillbirths in the excluded data may have produced a biased result. Finally, the time-to-event analysis resulted in a somewhat higher estimate of risk (the hazard ratio) than the relative risk, because later gestation at time of stillbirth appears to confer a benef|t (increased time without an adverse event). The mechanism for an increased risk of stillbirth after cesarean section is unclear. It may be related to the procedure and its consequences, or it may be uncontrolled confounding of the risk prof|le that led to cesarean section in the f|rst birth.The authors hypothesized that the increased stillbirth rate after a primary cesarean delivery is related to altered uterine blood flow in the second pregnancy. If this is true, then one would expect a stronger association after more than one prior cesarean section, and an increased risk in women who have had other uterine surgery, such as myomectomy. If impaired placentation, secondary to altered blood flow, is thought to be responsible for an increased risk of antepartum stillbirth, knowledge of the placental site in the second pregnancy may be relevant. Equally, it may be an association between prior uterine surgery and infection that is responsible for the increased stillbirth rate. The latter raises questions about whether women who had a stillbirth were more likely to have had endometritis complicating their previous delivery or whether a manual removal of placenta or postpartum curettage in a f|rst pregnancy increases the risk of stillbirth in their next pregnancy. Whether these data are useful (rather than frightening) to women who have already had a cesarean section is debatable. Clinicians need further studies to conf|rm the risk by gestational age and elucidate possible causal pathways before this information will be clinically useful. Christine Roberts MBBS, DrPH and Emily Olive MBBS University of Sydney, Australia LeeTaylor MBBS New South Wales Department of Health, Sydney, Australia
Literature cited 1. Mozurkewich EL, Hutton EK, Elective repeat cesarean delivery versus trial of labor: a meta-analysis of the literature from 1989 to 1999. Am J Obstet Gynecol 1187; 183: 1187^1197. 2. Adams MM, Wilson HG, Casto DL, et al. Constructing reproductive histories by linking vital records. Am J Epidemiol 1997; 145: 339^348.