Risk factors for obstetric anal sphincter injury recurrence: A systematic review and meta‐analysis

Abstract Background Women with previous obstetric anal sphincter injuries (OASIs) are at a higher risk of recurrence in the subsequent pregnancy, which may lead to the development or worsening of anal incontinence. Due to a lack of evidence, few recommendations can be made about the factors that may affect the risk of OASI recurrence. Objective We sought to conduct a systematic review and meta‐analysis to investigate potential risk factors for recurrent OASIs. Search strategy Studies up to May 2019 were identified from PubMed, Scopus, Cochrane Library, and ISI Web of Science. Selection criteria Studies assessing the impact of risk factors on OASI recurrence in subsequent pregnancies were included. Reviews, letters to the editor, conference abstracts, book chapters, guidelines, Cochrane reviews, and expert opinions were excluded. Data collection and analysis Data were extracted by two independent reviewers. Odds ratio and standardized mean difference were chosen as effect measures. Pooled estimates were calculated using the random‐effects model. Main results The meta‐analysis showed that maternal age, gestational age, occiput posterior presentation, oxytocin augmentation, operative delivery, and shoulder dystocia were associated with the risk of recurrent OASIs in the subsequent delivery. Conclusion Prenatal and intrapartum risk factors are associated with recurrence of OASI. PROSPERO registration no. CRD42020178125.

are associated with short-and long-term morbidity, which can have psychological effects and seriously affect quality of life. Overall outcomes after primary repair are encouraging, with 62% of women asymptomatic after a primary repair. 7 However, data show a worsening of anal incontinence after a subsequent vaginal delivery in 17%-24% of women with previous OASIs. 8 Moreover, the rate of recurrent anal sphincter injuries is increased compared with primary events by up to 13.4% 9 . Finally, it is unclear whether cesarean section is effective in preventing the development of anal incontinence in women with previous OASIs. As a consequence, it is difficult to properly counsel women with previous OASIs about the risk of anal continence worsening after a subsequent delivery. In particular, few recommendations can be made about the mode of delivery and factors that may affect the risk of OASI recurrence. The lack of systematic reviews or meta-analysis affects the counseling that can be given by caregivers, failing to address patients' concerns about the risks of recurrence, and even acting as a deterrent to further childbirth.
A better understanding of the factors that contribute to recurrent OASIs would enable women and clinicians to make better informed decisions about the preferred method of subsequent deliveries.
The aim of the present systematic review was to investigate the risk factors for recurrent OASIs, describing their impact in terms of significance and strength of association.

| Study protocol
The present systematic review was conducted and reported according to both the PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses 10 and the Meta-Analysis of Observational Studies in Epidemiology guidelines (Files S1 and S2). 11 Study objectives, eligibility criteria, outcome definitions, search strategy, data extraction process, statistical analyses, and method of study quality assessment were all defined in a protocol. All investigators were experienced in systematic reviews. 12

| Eligibility criteria and outcomes definition
Studies assessing the impact of risk factors on OASI recurrence in the subsequent pregnancies were included. Reviews, letters to the editor, conference abstracts, book chapters, guidelines, Cochrane reviews, and expert opinions were excluded. We considered outcomes variables investigated as potential risk factors for OASI recurrence in the subsequent pregnancies.

| Data source and literature search
To identify potentially eligible studies, we searched PubMed, Scopus, Cochrane Library, and ISI Web of Science (up to May 10, 2019), using EndNote x8 (Clarivate Analytics). No language restrictions were applied. We used a combination of keywords and text words represented by "OASIS", "anal sphincter injuries", "severe obstetrical tears", "third degree tears", "fourth degree tears", "subsequent pregnancies", "future pregnancies", "recurrence", and "risk factors". An example of the complete search strategy used for the PubMed search is presented in Appendix S1. Two reviewers independently screened the titles and abstracts of the records that were retrieved through the database searches. We also performed a manual search to include additional relevant articles, using the reference lists of key articles published in English. Both reviewers independently recommended studies for the full-text review. Full texts of records recommended by at least one reviewer were screened independently by the same two reviewers and assessed for inclusion in the systematic review. Disagreements between reviewers were solved by consensus.

| Data extraction and study quality evaluation
Data were extracted using a piloted form specifically designed for capturing information on study characteristics (sample size, outcomes, and considered variables). Data on all variables investigated by the study as possible risk factors were collected. These included maternal characteristics, index delivery characteristics, subsequent pregnancy characteristics, neonatal characteristics, and others. For clinically relevant variables, such as episiotomy and instrumental delivery types, data were collected when available for subanalysis. Data for continuous variables were extracted as means and standard deviations; for categorical variables, data were extracted as absolute values. Data were extracted independently by two authors to ensure accuracy and consistency. Authors of excluded studies were emailed if we felt that potentially they may have unpublished data about OASI recurrence. We received some answers, but no new dataset was obtained. Two reviewers independently screened full texts of records included in the systematic review. The scale contained four items under the selection domain, one item under the comparability domain, and three items under the outcome domain. A star scoring system, from zero to nine stars, was used for the assessment of study quality, such that the highest quality studies were awarded one star per item, except for the comparability domain, for which two stars for a single item could be assigned. Disagreements between reviewers were solved by consensus.

| Statistical analysis
For each risk factor of interest, pooling of results was carried out according to the random-effects method of DerSimonian and Laird. 13 For binary risk factors, the odds ratio was considered as the measure of effect, adding a correction factor of 0.5 to the event frequency of studies where no patient had the outcome in either one of the exposure groups. 14 For numerical risk factors, studies applying categorical analysis were excluded due to heterogeneous cut-offs used.
For numerical risk factors, the standardized mean difference was chosen as the measure of effect. For studies reporting only median and range or interquartile range, the method of Wan et al. 15 was used to approximate mean and standard deviation. I 2 and τ 2 indexes were used to quantify heterogeneity between studies and the null hypothesis that all studies share a common effect size was tested.
For the meta-analysis of risk factors where at least nine studies were available, a funnel plot was produced and the Egger test was performed. 16 All analyses were performed using the R package (R Foundation for Statistical Computing, Vienna, Austria) "meta". 17 For risk factors considered in only one study and statistically significant, a narrative description was adopted.

| Study assessment
The electronic database search provided a total of 3237 results  Table 1. Different study designs resulted from the selection process, including register-based and retrospective studies. The studies included were very heterogeneous clinically. All the risk factors proposed by the considered studies were analyzed for a total of 34 variables, grouped in five categories (see Table 1). A funnel plot and the Egger test were only possible for two index delivery characteristics (episiotomy and operative delivery; Fig. S1). Forest plots demonstrating significant associations are shown in Figure 2. The meta-analysis not demonstrating significant associations is available in Figure S2.
Maternal body mass index was analyzed by five studies. 19,21,25,26,30 Data pooling was available for three studies. 19,21,30 No differences were found in recurrent sphincter tears according to body mass index. The role of ethnicity was evaluated by two studies. 24,25 However, data pooling was not possible due to a lack of data in one of them. According to Edozien et al., 24 Asian ethnicity represented a risk factor for recurrent OASI, with an adjusted odds ratio of 1.59 (confidence interval 1.48-1.71). Cigarette smoke was only considered by one study 30 and no association was found with recurrent sphincter tears. Parity was not related to variations in OASI recurrence risk according to the only study available. 31 Two studies considered social status as a possible risk factor 24,30 ; one of them reported an association between recurrent OASIs and living in the least deprived communities. 24 However, data pooling was not possible due to heterogeneity.

| Index delivery characteristics
The index delivery characteristics were: epidural analgesia, operative delivery, type of obstetric tear (third degree vs fourth degree), concomitant episiotomy, suture material, wound-related complications, neonatal weight, diabetes. The grade of obstetric tear (third degree vs fourth degree) during the index delivery was considered by three papers. 18,19,21 Data pooling failed to show any association with the risk of OASI recurrence. Episiotomy at the index delivery was evaluated by three studies. 18,19,21 The meta-analysis of the studies did not show any relationship with sphincter tears in the subsequent deliveries. The roles of epidural analgesia and operative delivery during the index pregnancy were evaluated by two of the above three studies 18,19 ; no association was found with the risk of OASI recurrence. Diabetes and neonatal weight in the index pregnancy were considered only by Ampt et al., 18

F I G U R E 2
Forest plot for variables with significant correlation with obstetric anal sphincter injury recurrence papers evaluated the interval between the index delivery and the subsequent delivery. 18,20,24,26 However, data pooling was not possible as only one study reported the measure as a continuous variable. 26 This last study identified a significantly longer inter-delivery interval (2.9 vs 2.7 years; P < 0.001) in patients with recurrent OASIs.
Hypertension 18 and diabetes 30 were analyzed by only one study, without evidence of any association with the considered outcome.

| Neonatal characteristics
Neonatal characteristics included weight, difference in weight compared with index pregnancy, gender, cranial circumference. Neonatal weight was considered by 14 studies. 9,18-22,24-31 Data pooling was possible for four of them. 9,19,21,26 The meta-analysis did not show any relationship with OASI recurrence. One study 21 evaluated the difference in weight between the newborn in the index pregnancy and in the subsequent delivery, finding that the birth weight of subsequent neonates of women who did not sustain a recurrent severe tear was significantly lower than that of their previous child. Head circumference was not associated with the risk of recurrent OASI according to data pooling carried on two studies. 19,26 The role of neonatal gender was considered by two papers, 18,19 but no relationship was found with the risk of OASI recurrence.  The third point is that the papers investigated the impact of individual risk factors, but little information was available about the association between them. Jangö et al. 26 reported that almost half of patients with OASI recurrence have two or more risk factors. Similar considerations can be made for risk factors identified by this review.

| DISCUSS ION
For instance, shoulder dystocia can be associated with both vacuum extraction and oxytocin augmentation, and also with advanced gestational age and advanced maternal age. 35 As a consequence, it is to be determined if the combination of individual risk factors is cumulative. Moreover, due to the low number of studies pooled, it was not possible to properly assess the presence of publication bias in the meta-analyses performed, except for those for episiotomy and operative delivery. In these two cases, no evidence of publication bias was detectable according to the funnel plot and Egger test.
Finally, identified risk factors were either unmodifiable or poorly modifiable, and no protective measures were identified.
Only maternal age is known prenatally and available when counseling women about the mode of delivery. Advanced gestational age can also be potentially considered in counseling, but the absolute difference in gestational age between recurrent and non-recurrent OASIs is probably clinically non-significant. The other risk factors, which include oxytocin augmentation, instrumental delivery, occiput posterior position, and shoulder dystocia, develop intrapartum, and very little or nothing can be done to prevent them. These limitations are similar to those applicable to models developed in the last few years to predict and prevent primary OASI. 35

| CON CLUS ION
The meta-analysis showed that maternal age, gestational age, oc-