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Objective Two recent studies indicate an increased risk of stillbirth in the pregnancy that follows a pregnancy delivered by caesarean section. In this study, we report an analysis designed to test the hypothesis that delivery by caesarean section is a risk factor for explained or unexplained stillbirth in any subsequent pregnancy. We also report on the proportion of stillbirths in our study population, which may have been attributable to previous delivery by caesarean section.
Design Retrospective cohort study.
Population Linked statistical data set of 81 784 singleton deliveries registered in Oxfordshire and West Berkshire between 1968 and 1989.
Methods The crude and adjusted hazard ratios for stillbirth in deliveries following a previous delivery by caesarean section, compared with no previous caesarean, were estimated using Cox regression.
Main outcome measure Stillbirth.
Results The unadjusted hazard ratios for all, explained, and unexplained stillbirths were 1.54 (95% CI 1.04–2.29); 2.13 (1.22–3.72); and 1.19 (0.68–2.09), respectively. After adjustment for maternal age, parity, social class, previous adverse outcome of pregnancy, body mass indexand smoking the hazard ratios were 1.58 (0.95–2.63), 2.08 (1.00–4.31) and 1.24 (0.60–2.56).
Conclusions Pregnancies in women following a pregnancy delivered by caesarean section are at an increased risk of stillbirth. In our study, the risk appears to be mainly concentrated in the subgroup of explained stillbirths. However, there are sufficient inconsistencies in the developing literature about stillbirth risk that further research is needed.
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For reasons which remain largely unclear, rates of delivery by caesarean section in the UK, and elsewhere, have risen over the past 20–30 years.1,2 In addition to an increased risk of immediate complications for both the mother and baby, this major operative procedure has also been associated with an increased risk of specific adverse events in subsequent pregnancies, which include placenta praevia, abruption and uterine rupture during labour.3,4 A recent analysis of routinely collected Scottish maternity data found a doubling in the risk of unexplained antepartum stillbirth5 in the pregnancy following the one delivered by caesarean section. A study using the Missouri linked maternity data set found a borderline significant increase in the risk of stillbirth following caesarean section overall, with no significant association in white mothers but a significant elevation of risk of about 40% in black mothers.6 These studies are, as yet, the only reports on this association and it therefore merits investigation in other large data sets.7 We report here an analysis designed to test the hypothesis that delivery by caesarean section in any previous pregnancy is a risk factor for (a) any stillbirth, (b) explained stillbirth and (c) unexplained stillbirth in a subsequent pregnancy. We also report on the proportion of stillbirths in our study population, which may have been attributable to previous delivery by caesarean section.
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There were 111 586 second or subsequent singleton births recorded in the ORLS between 1968 and 1989. After exclusions due to missing data, implausible interpregnancy interval or rhesus incompatibility, there were 81 784 births eligible for inclusion in the analysis of which 367 were stillbirths. We excluded stillbirths in which the causes of death were congenital anomalies (n= 56, 15%) and stillbirths which were miscoded (n= 21, 6%). The remaining 81 707 deliveries included 290 stillbirths classified as explained (n= 113, 39%) or unexplained (n= 177, 61%) stillbirths.
A comparison of the characteristics of those deliveries exposed to previous delivery by caesarean section and those deliveries not exposed to a previous caesarean section is shown in Table 1. Mothers who had undergone previous delivery by caesarean section were generally older, of lower parity, of higher social class and more likely to have had previous adverse pregnancy outcomes than mothers who had not had a previous caesarean section.
Table 1. Comparison of maternal and perinatal characteristics in those pregnancies following any previous delivery by caesarean section and those not, showing numbers of records with data on each characteristic
| ||All (n= 81 707)||No previous caesarean (n= 75 868)||Any previous caesarean (n= 5839)||P-value*|
|Maternal age||81 649|| ||<0.001|
|<20||1746 (2.3)||89 (1.5)|
|20–25||23 485 (31.0)||1500 (25.7)|
|26–30||30 343 (40.0)||2223 (38.1)|
|31–35||15 791 (20.8)||1481 (25.4)|
|36–40||3982 (5.3)||464 (8.0)|
|>40||465 (0.6)||80 (1.4)|
|Parity||80 389|| ||<0.001|
|1||47 718 (63.9)||3790 (68.0)|
|2||17 882 (24.0)||1381 (24.0)|
|3||5916 (8.0)||401 (7.0)|
|≥4||3125 (4.2)||176 (3.1)|
|Previous adverse pregnancy outcome**||81 707|| ||<0.001|
|No||69 643 (91.8)||4899 (83.9)|
|Yes||6225 (8.2)||940 (16.1)|
|BMI||48 042|| ||<0.001|
|<18.5||861 (2.0)||67 (1.5)|
|18.5–24.9||27 245 (62.4)||2518 (57.7)|
|25–29.9||11 931 (27.3)||1274 (29.2)|
|30+||3638 (8.3)||508 (11.6)|
|Smoking||51 776|| ||0.182|
|No||36 245 (76.7)||3493 (77.6)|
|Yes||11 027 (23.3)||1011 (22.5)|
|Social class||69 821|| ||0.002|
|I||6503 (10.0)||597 (11.8)|
|II||14 075 (21.7)||1130 (22.3)|
|III||30 485 (47.1)||2304 (45.5)|
|IV||9114 (14.1)||696 (13.7)|
|V||3778 (5.8)||280 (5.5)|
|Other||797 (1.2)||62 (1.2)|
The risk of stillbirth in the group of deliveries not exposed to a previous caesarean section was 263/75 868 = 3.5 per 1000 (95% CI 3.1–3.9) and in the group exposed to previous caesarean section it was 27/5839 = 4.6 per 1000 (95% CI 3.0–6.7). This yielded an RR of 1.30 (95% CI 0.91–1.87) and an unadjusted risk difference of 1.16 per 1000 births (95% CI 0.79–2.73) without adjustment for potential confounders or for women having more than two deliveries included in the study.
A classification of the cause of stillbirth by exposure or nonexposure to delivery by previous caesarean section is shown in Table 2. Stillbirths that occurred in the group of deliveries exposed to previous caesarean section were more likely to be explained than those in the unexposed group. Furthermore, in the group of deliveries exposed to previous caesarean section, stillbirths were more likely to be classified as being associated with an abruption/haemorrhage or mechanical causes than those occurring in the unexposed group.
Table 2. Causes of stillbirth* in the index pregnancy classified by exposure to delivery by caesarean section in any previous pregnancy or no exposure
|Disease group||No previous caesarean||Any previous caesarean|
|Explained||99 (37.6)||14 (51.9)|
|Maternal diseases and complications of pregnancy||43 (16.3)||2 (7.7)|
|Abruption/haemorrhage||35 (13.3)||8 (30.8)|
|Mechanical||15 (5.7)||3 (11.5)|
|Fetal haematological disorders (nonrhesus)||6 (2.3)||1 (3.9)|
|Unexplained||164 (62.4)||13 (48.2)|
|Total||263 (100)||27 (100)|
The hazard ratio for stillbirth associated with exposure to previous caesarean section was 1.54 (95% CI 1.04–2.29). After adjustment for maternal age, parity, social class and previous adverse outcome of pregnancy in the deliveries with complete recording of these items, the hazard ratio was 1.53 (95% CI 1.00–2.34); and in the smaller subset with further adjustment for BMI and smoking it was 1.58 (95% CI 0.95–2.63; Table 3).
Table 3. HR for stillbirth following any previous delivery by caesarean section
|Group of stillbirths||Unadjusted HR (95% CI)||Adjusteda HR (95% CI)||Adjustedb HR (95% CI)|
|nd= 81 707||nd= 68 669||nd= 40 004|
|All stillbirthsc||1.54 (1.04–2.29)||1.53 (1.00–2.34)e||1.58 (0.95–2.63)j|
|Explained stillbirths||2.13 (1.22–3.72)||2.11 (1.16–3.84)f||2.08 (1.00–4.31)k|
|Maternal diseases and complications of pregnancy||0.71 (0.17–2.91)||0.75 (0.18–3.24)g||1.34 (0.29–6.34)l|
|Abruption/haemorrhage||3.20 (1.48–6.94)||3.57 (1.57–8.13)h||3.02 (1.06–8.63)m|
|Unexplained stillbirths||1.19 (0.62–2.13)||1.15 (0.62–2.13)i||1.24 (0.60–2.56)n|
Adjusted hazard ratios for the association between delivery by caesarean section and explained stillbirths and unexplained stillbirths were 2.08 (95% CI 1.00–4.31) and 1.24 (95% CI 0.60–2.56), respectively (Table 3), although estimates were much less precise because of the small number of stillbirths in these subgroups.
The increased risk of stillbirth is small in absolute terms but nevertheless it may account for a significant proportion of the stillbirths in those exposed to caesarean section. If this increased risk represents a causal process and is not simply a noncausal association, we can calculate the proportion of all stillbirths (explained and unexplained) in the whole population attributable to delivery by caesarean section as given below. Using a hazard ratio of 1.58 to approximate the adjusted RR in a population with a caesarean section rate of 7.1% and an average stillbirth rate of 0.35%, around 4% of all stillbirths in the population may be attributable to previous delivery by caesarean section.
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The results of the present study show that pregnancies occurring in women previously delivered by caesarean section are associated with an increased risk of stillbirth.
The estimated hazard ratios appear robust to adjustment for a number of potential confounders which have been shown to be associated with stillbirth including socio-economic status,17 pre-pregnancy weight,18 maternal age and parity,19 smoking20 and previous adverse outcome of pregnancy, although in the adjusted models the confidence intervals were also consistent with no effect. As shown in Table 3, the hazard ratios remain remarkably similar in the adjusted and unadjusted samples we considered. Therefore, there seems to have been little confounding in our study by measured confounders although we cannot rule out residual, unmeasured confounding. If the association between caesarean section and subsequent stillbirth is causal then around 4% of all stillbirths in the population may be attributable to previous delivery by caesarean section.
The ORLS21–25 includes information on a wide range of potential confounders including BMI and individual-level social class. There are, however, some limitations of the present study. First, we were unable to distinguish between antepartum stillbirths from intrapartum stillbirths in this data set. Second, we had no information on the indication for caesarean section for the majority of records. Third, the pregnancies occurred between 27 and 47 years ago. Since that time, there have been a number of changes in prenatal and neonatal care in addition to a change in the caesarean section rate. These changes, in practice, mean that the balance of risk factors influencing an association between delivery by caesarean section and subsequent stillbirth may have changed.
We are aware of two other published studies on the association between delivery by caesarean section and subsequent stillbirth.5,6 In contrast to our study in which we considered all pregnancies, both studies limited their analyses to a woman’s first two pregnancies. We also analysed our data using this definition and the findings (data not shown) were similar to those reported here.
Smith et al.5 used a large Scottish database of births between 1992 and 1998. They were able to control for some important potential confounders and they had enough details on stillbirths to select the subset of unexplained antepartum stillbirths. Smith et al. found an increased risk of unexplained antepartum stillbirth from 34 weeks of gestation onward, an effect that was not attenuated after adjustment for confounding.
Our study differed from that of Smith et al. in a number of ways. First, we did not concentrate on antepartum stillbirths because we could not distinguish them from intrapartum stillbirths in our data set. Second, Smith et al. used a modified Wigglesworth26 classification of stillbirth, whereas the cause of the stillbirth in the ORLS is classified by ICD8 and ICD9 coding. We, therefore, created categories roughly analogous to those of Wigglesworth classification, treating unexplained stillbirth as a residual category. Third, we were able to examine a greater range of confounders than Smith et al. including BMI and individual-level social class. Fourth, the average rate of caesarean section in the Smith et al. study was 14.7%, whereas our study had an average rate of 7.1% showing the difference in obstetric practice in different study periods.
Salihu et al.6 used the Missouri maternally linked cohort data set between 1978 and 1997 and determined the average caesarean section rate as 18.1%. The rates of stillbirth were 0.44% in those women with a history of delivery by caesarean section in their previous (first) pregnancy compared with 0.41% in those not delivered by caesarean section in their previous pregnancy, a difference that was not statistically significant. Their adjusted estimate of risk of stillbirth in the two groups was borderline significant at 1.1 (95% CI 1.0–1.3). They did, however, find differences between black mothers and white mothers. There was no effect of previous caesarean section among the white women but in the black women there was an increased risk associated with caesarean section (OR 1.4, 95% CI 1.1–1.7). Thus, albeit in different subgroups, all three studies – the Scottish study, that from Missouri and ours – show an association between caesarean section and subsequent stillbirth.
The average rate of caesarean section in the ORLS between 1968 and 1989 was only 7.1%. Given that rates of caesarean section are now around 25% on average in the UK population,27 it seems possible that if this study was conducted today the fraction of stillbirths attributable to caesarean section in the whole population could be much higher than 4%, making caesarean section account for a higher percentage of all stillbirths. This might also explain why stillbirth rates have ceased to fall and have increased according to Confidential Enquiry into Maternal and Child Health report.28
However, a noncausal association is also possible. It is plausible that an association between previous caesarean section and subsequent stillbirth could be mediated through abnormal placentation and subsequent placental dysfunction. It is possible, for example, that some women may have a genetic predisposition to, or may be exposed to, an environmental factor which could lead to a recurrent tendency to placental dysfunction/growth restriction in all their pregnancies.29 In a first pregnancy this might produce problems leading to a caesarean section and in a second pregnancy to stillbirth. Therefore, caesarean section may not have caused placental dysfunction, rather the placental dysfunction may have influenced the clinical factors that increase the indications for caesarean section in the first pregnancy and the risk of stillbirth in the second. However, when the analysis of Smith et al.5 was confined to women delivered by caesarean section after being in labour for more than 10 hours, an association with subsequent stillbirth was still apparent. A proportion of these caesarean deliveries will have been performed for ‘failure to progress’, which would weaken the hypothesis that the association could be explained by abnormal placentation. The other possibility is that the operation of caesarean section itself may lead to abnormal placentation.5
Caesarean section guidelines from National Institute for Health and Clinical Excellence30 published in 2004 include the increased risk of antepartum stillbirth in future pregnancies as an adverse effect of caesarean section. These guidelines have been based only on the study of Smith et al. The evidence of an adverse effect is now mounting with data from two further studies but these studies remain inconsistent in the details of affected subgroups. Therefore, further information is required to determine whether this association is found consistently, whether the association is causal and what causal mechanisms may be involved.