Risk of Perinatal Death Associated With Labor After Previous Cesarean Delivery in Uncomplicated Term Pregnancies FREE

Increasing rates of cesarean delivery are a major cause for concern in almost all developed countries.¹ A number of strategies have been proposed that aim to reduce the overall proportion of cesarean deliveries, including trial of labor after previous cesarean deliveries.² Observational studies^3- 4 suggest that trial of labor is associated with a significantly increased risk of uterine rupture. A meta-analysis reported an increased risk of perinatal death associated with trial of labor⁵ but included premature births between 28 and 36 weeks' gestation and breech deliveries.⁶ There is no large-scale study of the relative and absolute risks of perinatal death among women previously delivered by cesarean method but with an uncomplicated pregnancy at term. In the present study, we sought to address this by linking national registers of pregnancy discharge data and perinatal deaths.

The analysis was designed to determine the risk of intrapartum stillbirth or neonatal death unrelated to congenital abnormality among women with an uncomplicated term pregnancy who had a trial of labor following at least 1 previous cesarean delivery. Trial of labor was defined as any vaginal or emergency (unplanned) cesarean delivery occurring at or beyond 37 weeks' gestation in a woman who had previously been delivered by cesarean method. These women were compared with 3 groups: (1) women having planned repeat cesarean delivery, (2) other multiparous women at term not delivered by planned cesarean method, and (3) nulliparous women at term not delivered by planned cesarean method. Nulliparous women were women with no previous pregnancies or whose previous pregnancies all ended in abortion.

The Scottish Morbidity Record (SMR2) collects information on clinical and demographic characteristics and outcomes for all patients discharged from Scottish maternity hospitals. The register is subjected to regular quality assurance checks and has been more than 99% complete since the late 1970s.⁷ An analysis of 1414 records from 1996 through 1997 demonstrated that the register was free of significant errors in more than 98% of records in all the fields used in the present analysis, with the exception of postcode (94.0%), height (96.2%), estimated gestation (94.4%), and method of induction of labor (93.6%) (Jim Chalmers, MBChB, Information and Statistics Division, National Health Service, Edinburgh, Scotland, written communication, April 2001). The SMR2 records were linked to records from the Scottish Stillbirth and Neonatal Death Enquiry. This national register has routinely classified all perinatal deaths in Scotland since 1983. It is almost 100% complete and has been described in detail elsewhere.⁸

The study group consisted of all births in Scotland between January 1, 1992, and December 31, 1997. The exclusion criteria for the study group were multiple pregnancy, noncephalic presentation, delivery outside the range of 37 to 43 weeks' gestation, perinatal deaths due to congenital anomaly, antepartum stillbirth not due to congenital anomaly, and deliveries by planned cesarean method, except among women who had been delivered by cesarean method in a previous pregnancy.

The main outcome of this study was delivery-related perinatal death, defined as intrapartum stillbirth or neonatal death not caused by congenital anomaly. Stillbirths were defined as newborns that showed no signs of life following delivery. Stillbirths were subdivided into antepartum (deaths before the onset of labor) and intrapartum (deaths during labor). Neonatal death was defined as death during the first 4 weeks of life in a live newborn. Deaths caused by congenital anomaly were defined as any structural or genetic defect incompatible with life or potentially treatable but causing death.

In the comparison of risk of perinatal death among groups of women, the following factors were considered as possible confounders: socioeconomic deprivation, smoking, maternal age, maternal height, gestational age, and birth weight. Postcode of residence was used to derive Carstairs socioeconomic deprivation scores.⁹ These are based on 1991 census data on car ownership, unemployment, overcrowding, and social class within postcode sectors of residence that contain, on average, approximately 1600 residents. The deprivation scores were then used to categorize women into quintiles of socioeconomic deprivation within the study cohort. Higher quintiles indicate a greater degree of deprivation. Smoking was defined as the smoking status of the woman at the time of first attendance for antenatal care. Maternal age was defined as the age of the mother at the time of birth. Maternal height was measured in centimeters, and the value used was that documented in each woman's clinical record. Height is generally measured using a free-standing or wall-mounted height measure. Gestational age at birth was defined as completed weeks of gestation on the basis of the estimated date of delivery in each woman's clinical record. Gestational age has been confirmed by ultrasound in the first half of pregnancy in more than 95% of women in the United Kingdom since the early 1990s.¹⁰ Birth weight was categorized into sex- and gestational age-specific deciles, using a method previously described in detail.¹¹ Low birth weight was defined as birth weight of less than 2500 g.

The cause of perinatal death was classified according to a hierarchical system that is described in detail elsewhere.¹² Deaths were initially classified according to the following direct obstetric causes (in order): toxemia, hemorrhage, mechanical, maternal, and none of these obstetric causes. Mechanical was defined as death from uterine rupture, cord compression (including prolapse), birth trauma, or asphyxia associated with disproportion. In the absence of any of the listed direct obstetric causes, the deaths were classified by the pediatric diagnoses and these were grouped into intrapartum anoxia, other (pulmonary causes, intracranial hemorrhage, infection, other hemorrhage, and miscellaneous), and unexplained. The hierarchy dictates that a perinatal death where there was severe preeclampsia complicated by abruption would be classified as being due to toxemia because toxemia is above both hemorrhage and intrapartum anoxia in the hierarchy.

Continuous variables were summarized by the median and interquartile range, and comparisons between groups were performed using the Mann-Whitney U test. Univariate comparisons of dichotomous data were performed using the χ² test (>5 observations in all cells) or Fisher exact test (≤5 observations in ≥1 cells). Ordinal data were compared using the χ² test for trend. The P values for all hypothesis tests were 2-sided and .05 was the significance level. Adjusted rates were obtained using direct standardization. Crude and adjusted odds ratios (ORs) were obtained using logistic regression analysis. Cases with missing values were excluded from the multivariate analysis. The statistical significance of interaction terms was assessed using the likelihood ratio test. Model goodness-of-fit was assessed using the Hosmer-Lemeshow test based on deciles of probability.¹³ All statistical analyses were performed using version 7.0 of the Stata software package (Stata Corp, College Station, Tex).

Of the SMR2 records with a perinatal death documented, 97.8% could be linked to a corresponding record in the Stillbirth and Neonatal Death Enquiry. From 1992 through 1997, there were 356 958 records of singleton births in Scotland in the SMR2 database. Among these records, there were 697 (0.2%) with missing values for gestational age, 4873 (1.4%) with missing values for presentation at delivery, and 8 (<0.1%) with missing values for number of previous cesarean deliveries. A total of 5564 records had 1 or more missing values, leaving 351 394 records. Among this group, there were 16 427 fetuses (4.7%) with a noncephalic presentation, 621 perinatal deaths (0.2%) related to congenital anomaly, 1479 antepartum stillbirths (0.4%) unrelated to congenital anomaly, 20 628 births (5.9%) outside the range of 37 to 43 weeks' gestational age, and 9827 births (2.8%) by planned cesarean method where the women had not had a previous cesarean delivery. A total of 38 156 records had 1 or more exclusion criteria, resulting in a study group of 313 238 (87.8% of all singleton births during the study period).

The study group was subdivided into 15 515 women previously delivered by cesarean method who had a trial of labor, 9014 women who had previously been delivered by cesarean method who delivered by planned cesarean method in the current pregnancy, 137 160 nulliparous women who were not delivered by planned cesarean method, and 151 549 multiparous women who had not had a previous cesarean delivery and did not deliver by planned cesarean method in the current pregnancy. Within the study group, there were missing values for maternal height in 26 825 women (8.6%), for smoking status in 29 730 (9.5%), for deprivation quintile in 4 975 (1.6%), for birth weight in 61 (<0.1%), and for 5-minute Apgar score in 36 (<0.1%).

The study group characteristics and basic outcome data are given in Table 1. The highest rate of perinatal death (12.9 per 10 000 women) was seen among women having a trial of labor (Table 2). The risk of a delivery-related perinatal death among women having a trial of labor was more than 11 times (OR, 11.6; 95% confidence interval [CI], 1.6-86.7) that of women having a planned repeat cesarean delivery (Table 3). The risk of death associated with a trial of labor was similar when compared with nulliparous women in labor (OR, 1.3; 95% CI, 0.8-2.1) but was more than twice that of other multiparous women in labor (OR, 2.2; 95% CI, 1.3-3.5). When delivery-related perinatal deaths among all women who had previously been delivered by cesarean method were analyzed, it was estimated that 91% (95% CI, 36%-99%) could be attributed to the increased risk of death associated with a trial of labor.

Statistical comparison with the planned repeat cesarean delivery group was problematic because there was only a single death among the 9014 women. All the records with missing values were among the 9013 survivors and, therefore, excluding missing records resulted in a weaker association between trial of labor and perinatal death compared with planned repeat cesarean delivery simply by reducing the denominator in the latter group (Table 3). However, among the cases with nonmissing values, adjusting for maternal age, smoking status, height, deprivation quintile, gestational age at birth, and birth weight decile strengthened the association between trial of labor and perinatal death when compared with elective repeat cesarean delivery (OR, 11.7; 95% CI, 1.4-101.6). When women having a trial of labor were compared with nulliparous and other multiparous women, adjusting for maternal age, smoking status, height, deprivation quintile, gestational age at birth, and birth weight decile had no effect on the ORs (Table 3).

When the analyses were confined to births at or after 40 weeks' gestation, the results were similar (Table 2). Although there were no deaths among the 1064 planned repeat cesarean deliveries at or after 40 weeks' gestation, the numbers were too small to be statistically significantly lower than the trial of labor group. Among births at or after 40 weeks' gestation, the risk of death associated with a trial of labor was similar when compared with nulliparous women in labor (OR, 1.2; 95% CI, 0.6-2.2) but higher when compared with other multiparous women in labor (OR, 2.7; 95% CI, 1.4-5.2).

Among women previously delivered by cesarean method, 369 (2.4%) of those having a trial of labor had more than 1 previous cesarean delivery, whereas 2962 (32.9%) of those delivered by planned cesarean method had more than 1 previous cesarean delivery. Of the 20 perinatal deaths among women having a trial of labor, 19 women (95%) had only 1 previous cesarean delivery. Among women previously delivered by cesarean method, 5206 (33.6%) of those having a trial of labor had previously had a vaginal birth, whereas 988 (11.0%) of those delivered by planned cesarean method had previously had a vaginal birth. Of the 20 perinatal deaths among women having a trial of labor, 5 women (25%) had previously had a vaginal birth. Among the trial of labor group, there were 12 perinatal deaths among 3945 neonates born by emergency cesarean delivery and 8 deaths among 11 570 neonates delivered vaginally (P = .001).

The rates of perinatal death due to different causes differed among the 4 groups (Table 4). Compared with other multiparous women, women having a trial of labor had more than 8 times the risk of a perinatal death due to a mechanical cause (OR, 8.5; 95% CI, 3.2-22.3) and almost 3 times the risk of a perinatal death due to intrapartum anoxia (OR, 2.8; 95% CI, 1.3-6.5). When compared with nulliparous women, women having a trial of labor had an increased risk of perinatal death due to mechanical causes alone (OR, 8.8; 95% CI, 3.2-24.2).

Women undergoing a trial of labor were less likely to have a prostaglandin E₂ (PGE₂) induction, had shorter labors, had lower rates of operative vaginal delivery, and had higher rates of emergency cesarean delivery than nulliparous women (Table 5). Women undergoing a trial of labor were more likely to have a PGE₂ induction, had longer labors, and had higher rates of both operative vaginal and cesarean delivery than other multiparous women. Among women having a trial of labor, there were 3 perinatal deaths among 2395 women induced with PGE₂ and 17 deaths among 13 120 women not treated with PGE₂ (P>.99).

In addition to the 15 515 women who fulfilled the criteria for trial of labor at term, there were 35 women who fulfilled the same criteria except that the newborn was an antepartum stillbirth not caused by congenital abnormality at term. Fifteen of these women delivered before 39 weeks, 10 delivered in the 39th week of gestation, and 10 delivered at or after 40 weeks' gestation.

The ideal means to determine the risks and benefits of trial of labor vs planned repeat cesarean delivery would be a randomized controlled trial. In practice, this would be difficult to perform because many women would be unhappy to have such a decision made in a random manner and large numbers of women would be required for a study powered to detect differences in such rare outcomes as uterine rupture and perinatal death. In the absence of randomized controlled trial evidence, analysis of observational data must be used to estimate the risks of these rare outcomes. A recent observational study⁴ has reported on the relative and absolute risks of uterine rupture associated with trial of labor. Herein, we report the risk of perinatal death associated with trial of labor among women at term with a singleton pregnancy in a cephalic presentation.

In the present study, the risk of delivery-related perinatal death among women having a trial of labor was more than 11 times that of women having a planned repeat cesarean delivery. Women having a planned repeat cesarean delivery experienced the lowest death rate among any of the groups. The low rate of death was explained by the absence of any risk of intrapartum stillbirth and a significantly lower risk of neonatal death. The risk associated with planned repeat cesarean delivery at term was so low that only a single death occurred in Scotland during the 6 years of the study period. Multivariate statistical comparison among groups is problematic when the number of events is so small, and larger studies will be required to analyze adequate numbers of deaths following planned cesarean delivery. However, selection bias is unlikely to explain the lower risk of death among women having a planned repeat cesarean delivery, because they are more likely to have medical and obstetric complications than women offered a trial of labor.⁴ Consistent with this, adjusting for maternal age, smoking status, height, deprivation quintile, gestational age at birth, and birth weight decile for gestational age strengthened the association between trial of labor and perinatal death when compared with women having a planned repeat cesarean delivery, though the CIs were wide because of the small number of cases.

Our observed rate of perinatal death associated with planned repeat cesarean delivery, 1.1 per 10 000 women, is much lower than previously cited.⁵ However, previously published perinatal mortality figures for both trial of labor and planned cesarean delivery did not exclude breech presentations and preterm newborns delivered between 28 and 36 weeks' gestation.⁶ Since prematurity and breech presentation are associated with an excess of perinatal mortality,^14- 15 these data are unhelpful in informing women who reach term with a fetus presenting cephalically. This group accounted for 84% of women with a previous cesarean delivery in our study.

When compared with other multiparous women in labor, women having a trial of labor had approximately twice the rate of delivery-related perinatal death. This finding was due to an increased risk of death due to mechanical causes, including uterine rupture, and death due to intrapartum anoxia not related to uterine rupture. The overall rate of delivery-related perinatal death among women having a trial of labor was not significantly greater than nulliparous women in labor. The increased number of deaths due to mechanical causes among women having a trial of labor compared with nulliparous women was offset by a lower rate of death due to other causes. The observation that the level of risk of nonmechanical perinatal death among women having a trial of labor was intermediate between other multiparous and nulliparous women probably reflects the fact that approximately one third of women having a trial of labor had previously had a vaginal birth. There are other possible factors that could contribute to differences in outcome among the groups that were not recorded in the database, such as epidural anesthesia, use of electronic fetal monitoring, and details of maternal medical and obstetric complications. Further studies will be required to determine whether systematic variation in any of these variables may contribute to differences in the risk of delivery-related perinatal death among these groups.

The data presented in this article are collected nationally and form an extract of a larger data set, which is reported in detail elsewhere.¹² Overall, the statistics were comparable with previous analyses of perinatal deaths. The overall rate of intrapartum stillbirth unrelated to congenital abnormality of 2.5 per 10 000 births was comparable with previous studies from Scandinavia,¹⁶ and the total proportion of all stillbirths that were classified as intrapartum was 11%, which is similar to national data from England.¹⁷ The number of neonatal deaths observed in our study was lower than a report from Wales,¹⁸ which described 7.4 neonatal deaths attributable to an intrapartum event per 10 000 births. However, that study included neonates of all gestational ages, using a birth-weight cutoff of more than 1499 g, which would have included a significant proportion of preterm births.

Current recommendations are that planned cesarean delivery should be performed in the 39th week of gestation to reduce the risk of neonatal respiratory morbidity.¹⁹ It could be argued that uterine rupture may occur in earlier weeks of gestation and that the apparent protective effect of planned cesarean delivery is exaggerated. However, 85% of delivery-related perinatal deaths at term among women having a trial of labor occurred at or after 39 weeks' gestation. This is consistent with the observation that approximately 15% of multiparous women will undergo labor between the start of the 37th week and the start of the 39th week of gestation.²⁰ Therefore, it seems likely that most deaths could have been avoided by planned cesarean delivery at the start of the 39th week of gestation. Moreover, planned cesarean delivery at this time would also avoid exposure to the risk of antepartum stillbirth while awaiting the onset of labor. There were 20 antepartum stillbirths among women having a trial of labor at or after 39 weeks' gestation and a proportion of these may also have been prevented by planned cesarean delivery at the start of the 39th week of gestation. Therefore, the potential protective effect on perinatal death of planned cesarean delivery over trial of labor may be greater than estimated in the present study of intrapartum stillbirths and neonatal deaths.

The definition of a trial of labor used in this study was that a woman who had previously been delivered by cesarean method was delivered at term by a method other than planned cesarean. However, it is likely that a small proportion of these women were due to have a planned cesarean delivery but presented in labor before their scheduled date and an emergency cesarean delivery was performed in early labor. Moreover, the database did not include information on the nature of the incision used in the previous cesarean delivery. For this reason, we repeated the analysis confined to births at or after 40 weeks' gestation. By this time, all women scheduled for planned cesarean delivery should have had the procedure, including any women who had previously had a classic cesarean delivery. The risks of perinatal death were virtually unchanged, suggesting that our results are robust. The outcome of trial of labor was comparable with previous studies: 75% had a vaginal delivery, which was almost identical to an analysis of more than 17 000 trials of labor from Switzerland.⁶

Our data provide essential information for women to make an informed choice about a trial of labor. Overall, the point estimate of the risk of a perinatal death associated with a trial of labor is 1 in 775, and the 95% CIs indicate that the risk is unlikely to be higher than 1 in 500. The point estimate of the risk of a perinatal death due to uterine rupture associated with a trial of labor is 1 in 2200, and the 95% CIs indicate that the risk is unlikely to be higher than approximately 1 in 1000.

Considerable caution should be applied when extrapolating these data to considering possible benefits of planned cesarean delivery among women who have not previously had a cesarean birth. More than one third of delivery-related perinatal deaths among multiparous women who had not previously been delivered by cesarean method were observed before 39 weeks of gestation. Scheduling planned cesarean delivery for the start of the 39th week of gestation may have failed to prevent many of these deaths. Moreover, we present no data on the risk of perinatal death following planned cesarean delivery among nulliparous women.

Obstetricians have faced pressure from government and health care insurers to advocate vaginal birth after cesarean delivery as one strategy to reduce the overall rate of cesarean delivery. However, this pressure has been exerted in the absence of any reliable information on the risks to the newborn for most women. This study is the first to our knowledge that is adequately powered and analyzed to provide information on the risks of perinatal death associated with the management of women with a history of cesarean delivery but an otherwise uncomplicated pregnancy at term.