The prevalence of uterine rupture and associated factors in Ethiopia: A systematic review and Meta – analysis

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Study design and setting
A systematic review and meta-analysis, which aimed to estimate the overall prevalence of uterine rupture and associated factors was conducted in Ethiopia. Ethiopia is located in the eastern part of Africa bordered by Kenya to the south, Eritrea to the north, Djibouti and Somalia to the east, and Sudan and South Sudan to the west. In Ethiopia, nearly 78% of the population live in rural areas, and 48% of reproductive age  women also have no education [50].
The result is reported in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) checklist , and the PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of healthcare interventions (see checklist in Additional le 2).

Inclusion and exclusion criteria
The studies were included if they met the following inclusion criteria: (1) studies conducted in Ethiopia; (2) observational studies, including cross-sectional, case-control and cohort studies; (3) studies that reported prevalence and/or risk factors; (4) the outcome uterine rupture (4) both published and unpublished studies at any time were included. Additionally, we excluded editorials, commentaries, reviews, studies conducted non-English language were excluded.
These keywords were used in combination and separately using "AND" and "OR" Boolean operators. An example of the search details for PubMed illustrated in (Additional le 1: Table 1).
We looked at Google Scholar by using Combination of search items: Incidence OR prevalence OR outcome OR determinants OR factors) AND uterine rupture) OR (vaginal birth after cesarean/caesarean OR trial of labor/labour OR trial of scar OR labor/labour OR delivery OR vaginal birth OR vaginal delivery OR cesarean/caesarean OR home childbirth OR natural childbirth OR obstetrical extraction) AND Ethiopia.
Additionally, we looked at Cochrane Library, African Journals Online using database speci c subject headings associated with the above keywords used in PubMed.
For unpublished studies, master's thesis and PhD dissertation, the o cial website of Ethiopian's University research repository online library (University of Gondar and Addis Ababa University) was searched. Moreover, we searched from the reference lists of all the included studies (snowball technique) to identify any other studies that may have been missed by our search strategy. Finally, all studies were imported into reference management (Mendeley Desktop) software.

Outcome of interest
The primary outcome of this review was uterine rupture, which is tearing of the uterine wall either completely or partially during pregnancy or delivery. Ruptured uterus leads to extrusion of product of conception in to the abdominal cavity and massive hemorrhage especially when the rupture is of unscarred uterus: uterine rupture contributes signi cantly to both fetal and maternal mortality, serous morbidities and loss of fertility from hysterectomy.
The secondary outcomes were: the determinants of uterine rupture such as obstructed labour, contracted pelvis, previous cesarean section, maternal education, short inter-pregnancy interval, unmet need for family planning, multi-gravidity , not utilizing antenatal care, distance from health care facility, congenital uterine anomalies, fetal macrosomia, breech extraction, feto-pelvic disproportion, neglected labor and uterine instrumentation, home delivery, high parity, mal-presentation and unsafe obstetric practices such as inappropriate use of oxytocine, prostaglandins drugs for induction/augmentation of labor, fundal pressure in prolonged second stage, lack of infrastructure like transportation, electricity, poor knowledge of danger sign of pregnancy, and lack of birth preparedness and complication readiness plan.

Data extraction and quality Assessment
All essential data from the included studies were independently extracted by three (AAA,AAN, and BFZ) authors using a predesigned data abstraction form. Any disagreement was handled by the third reviewer (AAN) and repeated reading of the articles independently. Finally, consensus was reached through discussion between authors.
A prespeci ed form which was designed to extract data of methodological and scienti c quality was used. As recommended by PRISMA (44), the following data were extracted from each study: rst authors name, study setting , study period, study design, method of data collection, sample size, response rate, odds ratio (OR), and the possible associated factors of uterine rupture. The quality of each article was evaluated using Joanna Briggs Institute (JBI) quality appraisal criteria adapted for studies reporting prevalence data, cross-sectional, cohort and case-control studies [38]. The following items were used to appraise cross-sectional studies: (1) inclusion criteria; (2) valid and reliable measurement of exposure; (3) description of study subject and setting; (4) objective and standard criteria used; (5) strategies to handle confounder;(6) identi cation of confounder; (7) appropriate statistical analysis; and (8) outcome measurement. The following items were used for appraising cohort studies: (1) similarity of groups; (2) similarity of exposure measurement; (3) identi cation of confounder; (4) validity and reliability of measurement; (5) strategies to deal with confounder; (6) su ciency of follow up time; (7); appropriateness of groups/participants at the start of the study; validity and reliability of outcome measured (8) completeness of follow-up or descriptions of reason to loss to follow-up; (9) strategies to address incomplete follow-up; and (10) appropriateness of statistical analysis. The following items were used for appraising case-control study: (1) comparable groups; (2) appropriateness of cases and controls; (3) standard measurement of exposure; (4) criteria to identify cases and controls; (5) handling of confounder; (6) similarity in measurement of exposure for cases and controls; (7) strategies to handle confounder; (8) appropriateness of duration for exposure; (9) appropriateness of statistical analysis; and (10) standard assessment of outcome. During quality assessment checklist criteria's, studies considered low risk whenever tted to 50% and or above.

Statistical analysis
A weighted inverse variance random-effects model [39]was used to estimate the overall pooled prevalence. The pooled AOR of prolonged labour(>24hours) , not having antenatal care, grand multiparity, rural residency ,having cesarean section scar , not using partograph during labour, and obstructed labour was computed. Subgroup analysis was done by study region and year of study to adjust the variations in the pooled estimate of the prevalence. The heterogeneity of studies was assessed by using I2 test statistics. The heterogeneity of studies declared as as low, moderate, and high at the values of 25%, 50%, and 75% respectively [40] . Publication bias across studies was checked using funnel plot and Egger regression [41] were used to declare publication bias. STATA version 11 statistical software was used for all statistical analyses.

Studies included in the meta-analysis
The search strategy identi ed 250 articles from PubMed, 200 articles from Google Scholar, 110 articles from Cochrane Library, 102 articles from African Journals Online, 30 articles from Ethiopian's University research repository online library, and 10 articles through manual search. Of which, 242 were excluded due to duplication, 424 through review of titles and abstracts. Additionally 40 full-text articles were excluded for not reporting the outcome variable and other reasons. Finally, 16 studies were included (Fig. 1).

Publication bias
Funnel plot was assessed for asymmetry distribution of prevalence of uterine rupture among pregnant women by visual inspection (Fig.3). Egger's regression test showed with a p-value of 0.87 indicated the evidence for no publication bias.

Sensitivity analysis
This systematic review and meta-analysis showed that the point estimate of its omitted analysis lies within the con dence interval of the combined analysis (Fig.4). Therefore, trim and ll Analysis is no further computed.

Risk factors for uterine rupture
In this systematic review and Meta-analysis; prolonged labour(>24hours), not having antenatal care during pregnancy, grand multi parity, rural residents, having cesarean section scar ,not using partograph during childbirth , and obstructed labour were the factors for uterine rupture.
Rural residency and uterine rupture A total of seven articles were included to identify the association between rural residency and uterine rupture. Women who lived in rural area were 4 times more likely to have uterine rupture urban residents (OR: 4.17; 95% CI: 1.72, 10.12) (Fig. 5).
Not having antenatal care during pregnancy and uterine rupture Eight articles were included in this analysis [2,23,27,28,31,30,50,52]. There was a higher prevalence of uterine rupture among participants who did not have antenatal care during pregnancy. Women who don't have antenatal care during pregnancy were four times more likely to develop uterine rupture (OR: 3.7: 95% CI: 2.26, 6.08) ( Fig.7) Previous cesarean section scar and uterine rupture Three studies [23,25,32] showed a signi cant association between Previous cesarean section scar and uterine rupture. Women who had previous cesarean section scar were 9 times more likely to develop uterine rupture (OR: 8.5: 95% CI: 4.98, 14.59). Egger's regression test was showed a p-value of 0.26 (Fig.8).

Prolonged labour and uterine rupture
Six articles with were included in this analysis [25,27,31,32,50,52]. There was a higher prevalence of uterine rupture among women who had prolonged labour. Women who had prolonged labour were four times more likely to develop uterine rupture (OR=4.3, 95% CI:2.57, 7.19) (Fig.9). Egger's regression test was showed a p-value of 0.02.

No parthograh utilization during labour and uterine rupture
Three studies [2,23,52] showed a signi cant association between Not utilizing parthograh during labour and uterine rupture. Not using parthograh during active phase of labour increase the probability of uterine rupture by 3 times (OR:3.4:95% CI:1.62,7.29) (Fig.11). Egger's regression test was showed a p-value of 0.05.

Discussion
Our meta-analysis aimed to estimate the pooled prevalence of uterine rupture and its associated factors in Ethiopia. In this meta-analysis, the overall pooled prevalence rate of uterine rupture was 14.74%. In addition, Prolonged labour(>24hours), not having antenatal care during pregnancy, grand multiparity, rural residents, having cesarean section scar , not using partograph during labour , and obstructed labour were signi cant predictors for uterine rupture.
The prevalence of uterine rupture in the current study was higher than a study done in United Nation [42] and Turky [43]. Low antenatal care utilization, extensive home delivery, malnutrition, stunting, obstructed labour, inconsistent availability of infrastructures like roads, transportation, uterine trauma, short inter pregnancy interval, high unmet need for family planning, fetal anomalies, trial of vaginal birth at home, and maternal demographic characteristics like rural residency might cause the higher rate of uterine rupture in Ethiopia. Women who lived in rural area might have lower level of knowledge and awareness of mothers about birth preparedness and complication readiness plan which in turn attribute to high prevalence of uterine rupture in Ethiopia [44].
The subgroup analysis revealed that there was a signi cant variation among regions. Women from Amhara region had lower rates of uterine rupture as compared to Tgiray and Oromia regions. This discrepancy might be due to the fact that there might be the difference in antenatal service utilization, level of awareness about birth preparedness and complication readiness plan, family planning service utilization, level of partograph utilization, and home delivery status.
According to this study, women from the rural residence were four times more likely to develop uterine rupture. This could be due to living in rural area of Ethiopia, low knowledge to antenatal care, birth preparedness and complication readiness plan, high home delivery, high unmet need for family planning, short inter pregnancy interval, high proportion of mothers unaware of danger sign of pregnancy, lack of infrastructure, lower level of education and women empowerment.
In this study, women who had prolonged labour(>24hours) were nearly four times more likely to get uterine rupture compared to women who gave birth within normal time. This nding was in agreement with a study conducted in Angola [45]. This could be due to prolongrd labour causes increase the use of oxytocine, increases the risk of obstructed labour, instrumental delivery, and increase cesarean section rate which in turn increase uterine rupture.
This study also showed that women who did not have antenatal care follow up during pregnancy were nearly four times more likely to develop uterine rupture. This nding was in line with a study conducted in Nepal [46]. This might be the fact that not having antenatal care during pregnancy decrease women health status likes multiple pregnancy, gestational diabitus, uterine and fetal anomaies, and other risk factors for uterine rupture. Moreover, women who don't have antenatal care are prone to home delivery, poor awareness about birth preparedness and complication readiness plan, danger sign of pregnancy which in turn increase the risk of rupture.
Having cesarean section scar also identi ed as a key predictor of high rate of uterine rupture; women who had cesarean section scare were nearly nine times more likely to develop uterine rupture compared to those who did not have cesarean section scare. This nding agreed with studies in Turkey [43] and Nigeria [47]. This might be due to the fact that during labor, pressure builds as the baby moves through the mother's birth canal. This pressure can cause the mother's uterus to tear. Most of these women live where there is lack of facilities with comprehensive obstetric care, poor referral system and the transport facilities are poorly developed that even when they are referred, there is a poor chance of their reaching the hospital. Moreover, scared uterus is highly susceptible to rupture if combined with oxytocine use, trial of vaginal birth, multiple pregnancy and other obstetric manipulations.
Additionally, this study identi ed grand multiparity as a key predictor of high rate of uterine rupture; women who were grand multipara were nearly two times more likely to develop uterine rupture. This nding was supported by study in Nigeria [48]. The reason for this could be because grand multi parity increase the risk of gestational diabetes, macrosomia , abnormal fetal presentation, fetal anomalies, and Precipitous labor and delivery which in turn increase the risk of uterine rupture.
This review showed that women who had obstructed labour were nearly nine times more likely to develop uterine rupture. This nding was similar to studies conducted in Uganda [49] and USA [1]. The reason for this could be because during obstructed labour there is an impossible barrier (obstruction) preventing its descent despite strong uterine contractions, which increase risk of uterine rupture.
This study identi ed not using partograph during labour was as an important predictor of uterine rupture. Women who did not followed by partograph during labour were nearly three times more likely to develop uterine rupture as compared to women who were followed by partograph.
Adequate emphasis has not been given on this life threatening complication which might lead to increased maternal mortality and morbidity, hemorrhage, obstetric stula, psychological trauma, bladder injury, wound infection, sepsis, serous morbidities, loss of fertility from hysterectomy and fetal consequences are admitting to the neonatal intensive care unit, fetal hypoxia or anoxia, and neonatal death.
It could be reduced if all women delivered at health institutions, proper utilization of partograph, improve family planning service utilization, improve antenatal care follow up and improve birth preparedness and complication readiness plan, and health literacy about sexual and reproductive health, women's health and pregnancy. To achieve the WHO's reducing maternal mortality strategy, Ethiopia is rich in publicly stated commitments and policies aimed at reduction of maternal mortality by 2030, and implementing the health policy that focused on maternal health. However, the burden of maternal mortality and uterine rupture remains high in the Ethiopian population. Thus, the nding of this study would be important to develop further interventions and may have a signi cant impact on health service resource utilization. It will have direct or indirect importance in providing information to the joint United Nations Program on maternal mortality, Sustainable Development Goal: to reduce the global maternal mortality ratio to less than 70 per 100, 000 live births by 2030 and WHO declaration of no country should have an maternal mortality ratio greater than 140/100,000 live births.

Conclusion
The prevalence of uterine rupture was high in Ethiopia. Prolonged labour(>24hours), not having antenatal care during pregnancy, grand multiparity, rural residency, having cesarean section scar , not using partograph during labour, and obstructed labour were signi cant predictors for uterine rupture. A high index of suspicion and quick referral to a well-equipped center may reduce the incidence of this condition.
All patients with a history of cesarean section should deliver in hospitals with facilities for surgery and blood transfusion. Regular antenatal care and meticulous screening of high-risk patients are very important for effective prevention. Family-planning advice to reduce grand multiparity, improved access to maternal care, decentralization of obstetric services into peripheral units to prevent home deliveries and good supervision during labor can reduce the incidence of uterine rupture.

Strength and limitation
This review used a prede ned search strategy for both published and unpublished articles to reduce reviewer's bias and conducting data extraction and quality evaluation by two independent reviewers to minimize the possible reviewer bias. We also performed sensitivity and subgroup analysis based on the years of the study and study area. Besides, the effects of ve key predictors of uterine rupture were estimated. On the other hand, included articles were restricted to English language only; this is a limitation of the study as it missed studies published in other Ethiopian languages.  Table   Table 1: Descriptive summary of included studies on uterine rupture based on year of study, study design, sample size, region of study, response rate, and prevalence (n=16).