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Keywords:

  • Caesarean section;
  • placenta accreta;
  • placenta praevia

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Objective

To evaluate the risk of placenta praevia accreta following primary (first) elective or primary emergency caesarean section in a pregnancy complicated by placenta praevia.

Design

Retrospective matched case–control study, employing variable matching.

Setting

Tertiary referral centre between 1993 and 2008.

Population

Sixty-five cases and 102 controls were used for the analysis from a total of 82 667 births during the study period.

Methods

Relevant data were abstracted from clinical records. Matching of cases with controls was based on co-existing placenta praevia, number of previous caesarean sections, and age, with one or two controls per case. Results are presented as odds ratios (ORs) with 95% confidence intervals (95% CIs).

Main outcome measures

Placenta accreta in a pregnancy complicated by placenta praevia following a primary elective or emergency caesarean section, and morbidity associated with pregnancies complicated by placenta accreta.

Results

Significantly more cases than controls had an elective caesarean section for their primary caesarean delivery (46.2 versus 18.6%; < 0.001). There were no differences between groups for previous pregnancy loss, uterine surgery, and vaginal delivery, before or after the primary caesarean section. Compared with primary emergency caesarean section, primary elective caesarean section significantly increased the risk of placenta accreta in a subsequent pregnancy in the presence of placenta praevia (OR 3.00; 95% CI 1.47–6.12; P = 0.025).

Conclusions

Our results suggest that women with a primary elective caesarean section without labour are more likely, compared with those undergoing primary emergency caesarean section with labour, to develop an accreta in a subsequent pregnancy with placenta praevia.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Although not common, recent epidemiological studies have shown a dramatic rise in the rate of abnormal human placentation, including placenta praevia and placenta accreta.[1-4] Abnormal location of the placenta over or proximal to the cervix, known as placenta praevia, is the most common aberrance.[5] Placenta accreta is typified by the abnormal adherence of the placenta to the myometrial surface.[4, 5] Abnormalities that are more serious include placenta increta, where there is villous infiltration of the myometrium, and placenta percreta, with complete infiltration of the placenta through the myometrium and the possibility of adjacent organ invasion.

These placental aberrations threaten maternal life because of the risk of massive haemorrhage at the time of delivery.[6] Additionally, there is significant morbidity because of the need for peripartum hysterectomy, transfusion of blood and blood products, damage to surrounding organs, and prolonged hospitalisation, including admission to an Intensive Care Unit (ICU).

The aetiology remains unknown; however, epidemiological studies have consistently shown an increasing risk of placenta accreta in older women, women with placenta praevia in the present pregnancy, and women with a history of previous caesarean delivery.[7-9] Increasing numbers of previous caesarean section magnify this risk, with an eight-fold increase in the incidence of placenta accreta after two or more caesarean sections.[9, 10] Caesarean section delivery rates have risen significantly in recent years in most Western countries. In the USA, rates have increased 50% between 1996 and 2006, with up to 1.3 million caesarean sections performed annually.[11, 12] Consequently, caesarean section is estimated to be the most common surgical procedure in women.[1] Importantly, the rate of primary elective caesarean section (caesarean section performed in women who are not in established labour) in women with no clear clinical justification has risen from 3% in 1996 to 7% in 2004.[11]

Although it is widely accepted that the aforementioned risk factors increase a woman's chance of developing an accreta, the effect of the reason for prior caesarean section on the subsequent occurrence of abnormal placentation has been poorly explored to date. In particular, it is not known whether placenta accreta is more likely to follow a primary elective caesarean section (a woman's first caesarean section, performed without prior labour), in which the surgical incision is made through a thick myometrium and the woman is not in labour, or primary caesarean section with labour, in which the incision traverses a much thinner uterine wall (emergency caesarean section). The aim of this study was to investigate, by means of a case–control study, the association between placenta accreta in a pregnancy complicated by placenta praevia and the type of primary caesarean section.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Study design

The institutional ethics committee granted ethics approval for this study. All data were de-identified for analysis and presentation. The study was a matched case–control study of women with placenta accreta and placenta praevia over the 15-year period from January 1993 to May 2008. The setting was a tertiary referral centre in Perth, WA. The hospital is the only referral centre for high-risk pregnancies in the state, delivering over 6000 births per year. The data analysis was conducted using a variably matched set, defined by specific criteria detailed below. The analysis examined the effects of the mode of the primary caesarean section on the subsequent development of placenta accreta, or its variants, in a pregnancy complicated by placenta praevia. A prospective design was considered; however, given the relative rarity of the disease being studied, and the time it would require to gather sufficient women for a meaningful analysis, a retrospective design was deemed more appropriate by the authors.

The primary outcome was the influence of the indication for a woman's primary caesarean section (elective without labour or emergency after some labour) on her subsequent risk of developing a placenta accreta. The secondary outcomes were the risk of a placenta accreta given the following variables: parity; gravidity; uterine surgery prior to the primary caesarean section; and vaginal delivery prior to and following the primary caesarean section. The morbidity associated with the disease at this institution over time was also examined.

Case ascertainment

Placenta accreta was defined primarily as a histopathology report of an adherent placenta. In a few cases preoperative ultrasound assessment and a clinical diagnosis, based on an operative report of a difficult manual and/or piecemeal removal of the placenta during surgery, with heavy bleeding from the placental site requiring hysterectomy or transfer to another institution for further surgical or radiological intervention, and requiring subsequent intensive care admission, was used. Placenta praevia was defined as a placenta situated over the internal cervical os or in close proximity. Primary caesarean section was defined as the first caesarean section delivery, regardless of whether the woman had a vaginal delivery before or after the first caesarean section.

All cases meeting the criteria of placenta accreta with or without praevia over the study period were analysed to determine the changing trend of the disease over time and its associated morbidity.

In the subsequent matched analysis designed to answer the primary question, a subset of cases were included if they had a placenta praevia, a co-existing placenta accreta, and a history of one or more caesarean sections. Nulliparous women and those with an accreta in the absence of a prior caesarean section delivery were excluded.

All cases were identified from three separate but overlapping sources: the hospital electronic database of all births (STORK), the state hospital morbidity data system (HMDS), and the handwritten birth register. The paper medical record files of all cases and controls were reviewed by an obstetric resident and a maternal fetal medicine specialist to confirm the diagnosis, and to abstract demographic, obstetric, peripartum, and neonatal data.

The collection of HMDS data commenced in 1970. It includes all in-patient episodes for patients admitted to public, private, and freestanding day hospitals in WA. At present, the database contains nearly 60 data items, including diagnosis and procedure codes, and currently receives information for almost 700 000 in-patient episodes per year. KEMH is a public hospital and is required to forward at least 80% of their morbidity information for inclusion in the HMDS within 2 weeks of the discharge of the patient from hospital. The remaining 20% is required within 8 weeks. Once received, they are subject to editing, validation, and corrections, entered within ten working days. Morbidity information for all admissions from 1 July 2006 used the International Statistical Classification of Diseases and Health Related Problems, Tenth Revision, Australian Modification, (ICD-10-AM). The ninth revision was used for the study period preceding this date.

Stork is a Microsoft sql application that captures perinatal data about women giving birth at King Edward Memorial Hospital for Women in WA. It is accessible on the hospital's local area network to over 40 ward and office locations. It stores data for the 50 000 births that have occurred at the hospital since December 1997. Registered midwives enter the data within hours of key events occurring in a woman's pregnancy, birth, and postnatal care. These data include the antenatal booking visit, admission for birth, the following birth, and the time of discharge from the hospital. The Western Australian Midwives Notification System receives this data as mandated by the Western Australian Health Act 1911. Stork data are used to report on unit activity and clinical outcomes, as well as quality audit and research.

In addition, the handwritten birth register for the period was reviewed for women with invasive placentation, peripartum hysterectomy, or massive peripartum haemorrhage to ensure the near complete ascertainment of cases.

Potential controls were identified using the same sources. The final selection of appropriate controls was performed by manual review of patient paper records to determine eligibility and compliance with matching criteria. Eligibility criteria for controls included: placenta praevia; delivery during the study period at the study hospital; and a prior history of at least one caesarean section. All controls were matched with cases by the number of previous caesarean sections, placenta praevia, and maternal age to within 2 years. This reduced to a minimum the confounding effects of age and previous caesarean sections on the risk exerted by the primary caesarean section.

Where possible, each case was matched to two controls. Given that the rate of placenta accreta rises significantly with each delivery by caesarean section, it was not possible to obtain a complete matched set of two controls per case.

A sample size of 100 cases and 200 matched controls was estimated to attain an 80% power to detect an increase in risk of placenta accreta associated with a primary elective caesarean section, with an odds ratio of 2.0.

Statistical methods

Medians and ranges were used to summarise continuous data, and frequency distributions were used to summarise categorical data. Unmatched univariate comparisons of outcomes between cases and controls were conducted using Mann–Whitney U-tests and Fisher's exact tests for continuous and categorical data, respectively. Conditional logistic regression accounting for the matching factors and variable matching design was used to examine the effects of the first caesarean section on the risk of accreta. The effects of a primary elective caesarean section on placental invasion and other risk factors were summarised using odds ratios (ORs) and 95% confidence intervals (95% CIs). Statistical analysis was performed using sps 18 for windows (SPSS Inc., Chicago, IL, USA) and logxact 8.1 (Cytel Software Corporation, Cambridge, MA, USA). All hypothesis tests were two-sided and P < 0.05 was considered statistically significant.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Over the study period there were 82 667 live births at the study hospital, with the birth rate increasing steadily. Eighty-eight cases of placenta accreta were identified. Overall, the rate of accreta was 0.1 per 1000 births, increasing from 0.09 per 1000 births in 1993 to 0.13 per 1000 births in 2007. Over the same period, the rate of caesarean section births increased from 24.7 to 34.5% (Figure 1).

image

Figure 1. Diagrammatic representation of the rate of placenta accreta and that of caesarean sections over the study period at King Edward Memorial Hospital, Perth, WA.

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Seventeen cases without a co-existing placenta praevia or a history of at least one previous caesarean section were excluded from the case–control analysis for the primary question, as they did not fit the matching criteria, and their associated morbidity was not compared with controls. Of the 71 remaining cases fitting the matching criteria, 36 were matched with two controls each, 29 were matched with one control each, and six were excluded from the analysis because of a lack of suitable matching controls. This resulted in a study set of 65 women with placenta accreta or its variants matched with 101 controls (Figure 2).

image

Figure 2. Schematic flow chart of study design, showing the identification of cases and matching controls. Details of matching, inclusion, and exclusion criteria can be found in the main text.

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We found that 67% of cases delivered before 37 weeks of gestation, in comparison with 38% of controls. A total of 37 (56.9%) of all cases were classified as placenta accreta, with 15 (23.1%) classified as placenta increta and 13 (20.0%) classified as placenta percreta. Hysterectomy was required at delivery in 76% of cases, compared with 3% of controls (< 0.001). All cases with hysterectomy had a histological diagnosis of placenta accreta confirmed. Three cases were transferred to a sister centre for intensive care admission because of significant haemorrhage at surgery. The position of the placenta was anterior in 88.9%, posterior in 8.6%, and anterior posterior in 2.5% of cases.

Consistent with the matching criteria, there were no differences between cases and controls in maternal age, gravidity, or parity (Table 1). Significantly more cases than controls had received private health care during pregnancy (= 0.002). There were no differences in any other demographic or socio-economic factors (all P > 0.05; Table 1).

Table 1. Comparison of demographic and pregnancy characteristics between placenta accreta cases and controls
 CaseControl 
Maternal characteristicsn = 65n = 102P
  1. Data are n (%), unless otherwise specified.

  2. a

    Median (range).

  3. b

    Three missing values.

  4. c

    Six missing values.

Maternal age (years)a32 (20–42)33 (21–41)0.451
Gestational age (weeks)a36 (27–40)37 (23–43)0.063
Gestational age <37 weeks39 (67.2)35 (38.5)0.001
Gravidity
27 (10.8)15 (14.7) 
315 (23.1)18 (17.6) 
4+43 (66.2)69 (67.6)0.585
Parity   0.581
118 (27.7)30 (29.4) 
219 (29.2)20 (19.6) 
3+28 (43.1)52 (51.0)0.344
Number of previous CS
130 (46.2)54 (52.9) 
219 (29.2)29 (28.4) 
3+16 (24.6)19 (18.6)0.591
Type of first CS
Elective30 (46.2)19 (18.6) 
Emergency35 (53.8)83 (81.4)<0.001
Previous miscarriage b23 (35.4)42 (42.4)0.416
Previous pregnancy termination b16 (24.6)22 (22.2)0.850
Vaginal delivery before primary CS 17 (26.2)30 (29.4)0.725
Vaginal delivery after primary CS 22 (33.8)38 (37.3)0.741
Other uterine surgery 26 (40.0)40 (39.2)0.999
Year of accreta 1993–20081993–20080.635
White European ethnicity 52 (82.5)77 (78.0)0.607
Private antenatal care 8 (12.3)1 (1.0)0.002
Inadequate antenatal care 14 (21.9)12 (11.8)0.123
Smoking c23 (36.5)35 (35.7)0.999
Alcohol use c12 (19.0)19 (19.4)0.999
Illicit drug use c6 (9.5)4 (4.1)0.191

Significantly more cases than controls had an elective caesarean section for their primary caesarean delivery (46.2% cases versus 18.6% controls; < 0.001). There were no differences between groups for previous pregnancy loss, uterine surgery, and vaginal delivery before or after the primary caesarean section (Table 1).

Among women with primary emergency caesarean section there were no significant differences between cases and controls in cervical dilatation or length of labour in the primary labour. Similarly, there were no significant differences in gestational age or presentation between cases and controls whose primary caesarean section occurred without labour.

Univariate analysis showed that the indication for a woman's primary caesarean section was significantly associated with the presence of placenta accreta (Table 1). There was no relationship between a subsequent placenta accreta and a woman's gravidity, parity, previous vaginal delivery, and previous uterine surgery. The relationship persisted after multivariate adjustment for factors such as gravidity, parity, number of previous caesarean section, previous vaginal delivery, previous uterine surgery, and the indication for a woman's primary caesarean section. Compared with women in whom the primary caesarean section occurred after some labour, women whose primary caesarean section occurred without labour were significantly more likely to develop a placenta accreta (adjusted OR 3.00; 95% CI 1.47–6.12; = 0.025). Gravidity (OR 0.79; 95% CI 0.61–1.03, = 0.063), parity (OR 1.12; 95% CI 0.75–1.66; = 0.588), previous vaginal delivery (OR 0.85; 95% CI 0.60–1.21; = 0.364), and previous uterine surgery (OR 1.06; 95% CI 0.53–2.15; = 0.866) were not associated with placenta accreta in the setting of a co-existing placenta praevia (Table 2).

Table 2. Logistic regression results showing adjusted odds ratios for covariates thought to play a role in abnormal placentation
Model termOdds ratio95% confidence intervalTwo-sided P
Vaginal delivery before first CS0.850.60–1.210.364
Gravidity0.790.61–1.030.063
Parity1.120.75–1.160.588
Past uterine surgery1.060.53–2.150.866
Elective versus emergency CS3.001.47–6.120.025

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

It is widely accepted that the recent growth in the prevalence of placenta accreta is caused by the increasing rate of caesarean section, particularly in the setting of a co-existing placenta praevia.[4-7] The present study demonstrates that the absence of labour in the woman's first caesarean section modifies the risk of placenta accreta. We have shown that women who undergo a caesarean section without labour as a primary event are three times more likely to develop a placenta accreta in a subsequent pregnancy complicated by placenta praevia, compared with women whose primary caesarean section occurred after the onset of labour. Furthermore, this increased risk is independent of gravidity, parity, or vaginal delivery before the first caesarean section. The risk remained unchanged, regardless of a history of uterine surgery before the primary caesarean section, and regardless of subsequent successful labour after the first caesarean section.

In Australia, the proportion of women who underwent an elective caesarean section increased from 6% in 1984–1988 to 13% in 1999–2003.[13] Significantly, the rate of elective caesarean section increased by 30% in comparison with a 19% increase in emergency caesarean section (i.e. caesarean section performed in women who are already in labour). Increases are higher among nulliparous and older women.[13] Similarly, caesarean section rates in the USA have increased by 50% between 1996 and 2006, with up to 1.3 million caesarean sections performed annually.[11, 12] There is no evidence that the risk profile of women undergoing caesarean section has changed significantly during this period, suggesting that this increase may be explained by a rise in maternal requests for caesarean section.[11, 12] Furthermore, there is evidence that caesarean section is not a benign procedure in western societies, with risks of neonatal mortality, prolonged admission to the neonatal nursery, maternal morbidity, and mortality in subsequent pregnancies, including abnormal placentation and uterine rupture.[8, 14]

The incidence of placenta accreta in our study increased over time, consistent with published reports.[3-9, 15-18] This abnormal placentation was associated with massive haemorrhage and very high hysterectomy rates. In contrast with other studies, we found a high number of deep infiltrative pathology (Table 3).[4, 8, 9]

Table 3. Distribution of abnormal placentation among cases
Abnormal placentationFrequency (%)
Accreta37 (56.9)
Increta15 (23.1)
Percreta13 (20)

In this study we included exclusively cases and controls with a coexisting placenta praevia and a history of at least one previous caesarean delivery. This was undertaken in order to account for these factors, which prior studies had already established increased the risk of placenta accreta.[2-4, 8-10, 19] Our finding that, independent of these factors, placenta accreta is substantially more likely to occur if the primary caesarean occurred without labour is a major strength of this study.

We hypothesise that the true risk of subsequent adherent placentation after a primary elective caesarean section is derived from the act of cutting into a thick quiescent uterus, in contrast to an incision through the thinned myometrium during labour. The gross morphological, biochemical, molecular, and immunological changes seen in the human uterus as it moves from being inactive during pregnancy to an actively contracting system in labour presents two phenotypically distinct entities.[20] In contrast to the prelabour quiescent uterus, uterine activation during labour leads to high-frequency, high-amplitude contractions. The myometrium becomes excitable and highly responsive to exogenous prostaglandins and other uterotonic agents, thereby facilitating the beginnings of parturition. In addition, there is a decrease in the hydroxyproline content of the cervix, a marked decrease in the compactness and cohesiveness of the collagen fibres immediately after vaginal delivery, and gradual changes in maternal immune tolerance.[20-22] We propose that the absence of this uterine activation results in the potential for aberrant placentation in a subsequent pregnancy.

There was no indication that parity modified the risk of an accreta in this setting, or that vaginal delivery before and after the first caesarean section impacted significantly on this risk. We suggest that the two uteri respond differently to the insult of a caesarean section scar in subsequent pregnancies, with possible differences in inflammatory mediators and hypoxic or oxidative stress leading to this variability in placental implantation. The growth and reconstitution of the decidua basalis, or the ability of the decidua to contain and modulate infiltrative trophoblast, may be significantly altered by the initial surgical insult.

Interestingly, a recent study of transabdominal ultrasound measurements of uterine thickness in women near term has shown that the lower uterine segment during the current pregnancy is thinner in women who had a previous caesarean section without labour, than in those who had their previous caesarean section after the onset of labour.[23] Although the thickness of the endometrial layer was not measured in the present study, a reasonable assumption is that the decidua over the previous scar would also be less developed. This is supported by findings of absent decidua at the site of the placental accreta on evaluation of placental histopathology in an earlier case series.[7] These data correlate well with our findings of the increased incidence of placenta accreta in women whose previous caesarean section had been performed before the onset of active labour, and suggest that a less developed decidua in a subsequent pregnancy after elective caesarean section may be responsible for the placental adherence. Similarly, others have shown an increased risk of uterine rupture during attempted vaginal birth after previous elective caesarean section.[14]

Study limitations

Being hospital based, this study is vulnerable to referral bias. It is conceivable that as the awareness of placenta accreta increased more cases were referred to the hospital, resulting in the potential for a spuriously increased rate of occurrence and possibly a false elevation in the risk of the condition. In contrast, a low index of suspicion in the earlier years of the study may have resulted in an under-representation of cases. This may result in the true risk of elective surgery in the population not being appreciated. Similarly, controls were selected from the hospital alone, where the majority of women had no private health insurance. In contrast, a number of cases were transferred to the hospital after having received private antenatal care. However, the difference in health insurance status did not influence the major findings. There was also a possible confounding effect from the small number of cases (12%) that did not have a histological confirmed diagnosis of placenta accreta. Furthermore, despite reviewing every possible control over the 10-year period, we were unable to match each case with two controls. This may be a source of bias. We employed variable matching, which was an option available to us in the statistical software package used. We were also unable to perform complex multivariate assessments because of limitations in the sample size.

Implications

These data suggest that the indication for a primary caesarean section influences the risk of placenta accreta in subsequent pregnancies complicated by placenta praevia. Clinicians need to be aware of this risk and use the information when counselling women for whom caesarean section is an option. Furthermore, clinicians need to re-examine their reason for performing a primary elective caesarean section on a case-by-case basis. Consideration should be given to limiting the availability of elective caesarean section as a birthing choice to women in whom the alternatives of labour with vaginal delivery or the possibility of an emergency caesarean section pose an unacceptable risk to the wellbeing of both the mother and the fetus.

Disclosure of interests

There are no applicable conflicts of interests or disclosure of interests that apply.

Contribution to authorship

MK colleceted data, performed statistical analysis, and authored the article. JJH reviewed and co-authored the article. DAD reviewed the article and performed statistical analysis. JED reviewed the article. CEP supervised the project, reviewed the article, and conceived the study.

Details of ethics approval

Ethics approval was granted by the Women's and Children's Health Service Human Research Ethics Committee, Perth, WA: ref. no. 93408221.

Funding

This work received no external funding.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

This body of research and subsequent publication received no funding from external sources. It is fully work completed by the School of Women's and Infants Health at the University of Western Australia based at The King Edward Memorial Hospital, Perth, WA.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References