Major risk factors of maternal adverse outcome in women with two or more previous cesarean sections

Bacground/Aim. Maternal morbidity is defined as any condition that is attributed to or aggravated by pregnancy and childbirth that has a negative impact on the woman's wellbeing. In recent years, a growing trend of cesarean section rates can be seen throughout the world. The aim of this study was to assess factors that might have major impact on maternal adverse outcome in women with two or more previous cesarean sections. Methods. This retrospective study included women with single term pregnancy after two or more cesarean deliveries in a 10-year period (2004−2013) in the University Clinic “Narodni front” in Belgrade, Serbia. Medical records were reviewed for clinical data for maternal intraoperative and early postoperative complications regarding gestational age at delivery, the number of previous cesarean sections and mode of surgery (elective or emergency). Results. A total of 551 patients were included in the study. At 37 completed weeks delivered 14.1%, at 38 delivered 45.2% and at 39 completed weeks 40.7% patients. Women younger than 35 years more often delivered after 39 completed weeks compared with those over 35 years (69.2% vs 30.8%, p < 0.05). The overall rate of maternal complications in the study group was 16.5% with no statistical difference by gestational age at delivery. The overall rate of maternal adverse outcome was significantly less in the patients with three as compared with those with four or more cesareans (10.4% vs 66.7%, p < 0.05). There was a statistically significant difference between these groups of women regarding complications: scar dehiscence, the presence of adhesions, blood transfusion and admission in intensive care unit. Elective cesarean delivery was with less maternal complications compared with emergency cesarean deliveries (12.9% vs 27.3%, p < 0.05). Conclusion. Termination of pregnancy before completed 39 weeks does not decrease maternal morbidity. The major impact on maternal complications has the number of previous cesarean deliveries (≥ 3), as well as emergency cesarean section. Patients should be informed about potential risks for maternal health with increasing number of cesarean deliveries, especially after the first cesarean section when counseling in elective repeat cesarean vs trial of labor.

complications in the study group was 16.5% with no statistical difference by gestational age at delivery.The overall rate of maternal adverse outcome was significantly less in the patients with three as compared with those with four or more cesareans (10.4% vs 66.7%, p < 0.05).There was a statistically significant difference between these groups of women regarding complications: scar dehiscence, the presence of adhesions, blood transfusion and admission in intensive care unit.Elective cesarean delivery was with less maternal complications compared with emergency cesarean deliveries (12.9% vs 27.3%, p < 0.05).Conclusion.Termination of pregnancy before completed 39 weeks does not decrease maternal morbidity.The major impact on maternal complications has the number of previous cesarean deliveries (≥ 3), as well as emergency cesarean section.Patients should be informed about potential risks for maternal health with increasing number of cesarean deliveries, especially after the first cesarean section when counseling in elective repeat cesarean vs trial of labor.Key words: cesarean section; morbidity; risk factors; obstetric labor complications; fetal development.

Introduction
The increasing number of cesarean sections (CS) in the last decade (up to 30%) and the decreasing one of vaginal births after CS (less than 10%) emphasize the problem of multiple cesarean deliveries impact on maternal morbidity 1,2 .
There are several significant maternal complications such as: uterine rupture, scar dehiscence, hysterectomy, thromboembolic disease, transfusions, wound infection, maternal death, etc, most of which increased as a trend with increasing number of repeated operations.Even half of cesarean hysterectomies are in women with one or more prior CS 3 .Besides that, as early or immediate complications, more difficult to quantify are late risks for bowel obstructions and pelvic pain from peritoneal adhesive disease, both of which increase with each successive CS 4 .
The aim of this study was to determine the impact of scheduled gestational age for planned CS, the number of previous CS and unplanned, emergency CS on short-term maternal adverse outcome in women with two or more previous CSs.

Methods
This retrospective study included all patients who had repeated three or more CS in a 10-year period, from January 1st 2004 to December 31st 2013 in the tertiary medical center, University Obstetric and Gynecology Clinic "Narodni Front" in Belgrade, Serbia.We analysed the data from the patients medical records that included maternal age, parity, gestational age at delivery, neonatal birth weight and 5minute Apgar score.Adverse maternal outcome included maternal death, the presence of adhesiones, scar dehiscence, uterine rupture, hysterectomy, placenta previa, transfusions, urinary bladder lesions, wound complications and intensive care unit (ICU) admission.Gestational age on delivery was determined in completed weeks of gestation confirmed by early ultrasound, elective CS was planned the day before and unplanned, emergency CS was performed short time after admission in patients who were admitted in labor.Hospital department policy dictated that all patients with two or more CS are ended with CS.Maternal death included only those resulting from complications related to childbirth.Uterine rupture was defined as a complete disruption or tear of the uterine muscles and serosa, while scar dehiscence was defined as uterine muscle disruption but with intact serosa.Wound infection was based on the diagnosis of superficial or deep infection involving the cesarean incision site.Placenta previa, bladder injury and adhesiones were intraoperative findings.Excluded criteria were labor before completed 37 weeks and twin pregnancies.The study group included patients with single, term pregnancies with previous two or more CS.All these patients were divided into 3 groups according to gestational age at birth: 37 to 37 + 6/7 weeks, 38 to 38 + 6/7 weeks, > 39 weeks, to assess the best timing of elective repeat CS at term on the basis of maternal adverse outcome.Maternal complications were assessed on the basis of the number of previous CS and mode of surgery (elective or emergency), as well.
All the patients had transverse, lower segment uterine incision, exept one case of classical incision in the patient with accrete placenta previa followed by hysterectomy.
The data were coded, tabulated and entered into an IBM compatibile computer.The incidence of adverse maternal outcome was calculated for each completed week of gestation at the time of cesarean delivery.Continuous variables were expressed as mean with standard deviation and compared by using the indepedenant Student t-test.Discrete variables were expressed as percentages and compared by χ 2 test.The test of significance was set at the 0.05 level.The statistical programs SPSS 17.0 (SPSS Inc., Chicago, IL) and Medcalc (Medcalc Software, Mariakerke, Belgium) were used for the data analysis.
The study has been approved by the Institutional Ethical Commitee.

Results
In a 10-year period, from January 1st, 2004 till December 31st, 2013, there were 67,639 deliveries in the University Obstetrics and Gynecology Clinic "Narodni front" Belgrade.In this period of time the incidence of cesarean deliveries increased from 18% in 2004 to 32% in 2013.At the same time the incidence of vaginal births after CS decreased from 13% to 8%.Out of 67,639 deliveries in this period, 16

Discussion
The timing of repeated CS after two or more previous CS has to be not too soon for the baby and not too late for the mother.Some studies show that neonatal morbidity associated with elective CS at term increases as gestational age at delivery decreases from 39 to 37 weeks 5,6 .Despite these recommendations, over the third of pre-labor elective repeat CS, in a US multicenter cohort study, were delivered prior to 39 weeks 7 and this figure is as high as 50−80% in some European cohort studies 6,8 .Concern that delivery at 39 weeks, among women with repeated CS, compared to earlier delive-ries may be associated with adverse maternal outcome has been suggested as one reason for elective delivery prior to 39 weeks 9,10 .For the last ten years, at our Clinic, 59.3% delivered prior to 39 and 40.7% after 39 completed weeks.Maternal age influenced the time of elective repeated CS, because in the third group (> 39 weeks) 70% of the patients were aged under 35 and only 30% was 35 or more years old.The highest incidence of emergency CS was in the 39 weeks group, but the difference was not statistically significant.Different results were obtained in some other studies where elective CS deliveries > 39 weeks were associated with a significant increase in the number of emergency CS 10,11  neonatal characteristics there were no significant differences even for the 5-minute Apgar score less than 7 which was the highest rate in the 37 weeks group.
The lowest incidence of maternal adverse outcome was in the 38 weeks group, but the difference was not statistically significant.The study, that comparing maternal adverse outcome at 38 and 39 weeks in women after 2 or more CS, revealed that the lowest rate of any adverse outcome was observed when CS scheduled to 38 + 1 weeks 12 .Much bigger study revealed that elective repeat CS at 37 or 38 weeks as compared with delivery at 39 (for neonatal benefit) is not associated with decreased maternal morbidity with no apparent maternal benefit compared to elective delivery in the 39th week 13,14 .The severe complications of repeat CS include maternal death, uterine rupture and hysterectomy 13 .In our study these complications were rare: no maternal death, two complete uterine rupture (0.4%) and one hysterectomy (0.2%) that is similar with other bigger studies 13,15 .
The overall incidence of adverse maternal outcome by the number of previous CS showed a significant difference (p < 0.05).Almost all individual maternal complications were more frequent in the group ≥ 3 CS, but a significant difference was obtained in scar dehiscence, the presence of adhesions, blood transfusion and ICU admission.In our study the fourth CS was associated with more potential risks for adverse maternal outcome.Cook et al. 16 , from the United Kingdom Obstetric Surveillance System (UKOSS), comparing fifth or bigger number of CS with those from the second to the fourth procedure, concluded that those having five or more CS had significantly increased rates of morbidity, such as major hemorrhage rate increased 18-fold, mostly due to 18% with placenta previa or accrete syndrome, visceral damage 17-fold, critical care admission 15-fold and delivery < 37 weeks 6-fold 16 .The risk for uterine rupture after two CS was 0.2% and it was similar in patients with one previous CS (0.3%) 17 .In our study the patients with 3 or more CS incidence of uterine rupture was 1.6% and scar dehiscence 11.7%.In one previous review even 27% of patients with 3 or more previous CS had fenestration of uterine scar 18 , but recent studies describe the rates ranging from 1% to 10% in women undergoing anywhere from a fifth to a ninth CS 15,19,20 .A systematic review and meta-analysis of 21 observational studies revealed that maternal morbidity increases in a doseresponse fashion with each additional CS, especially for women with ≥ 3 CS who are at statistically significant increased risk of previa, accrete placentan and hysterectomy 2,21 .
The incidence of placenta previa in our study was 3.3% in the group ≥ 3 CS compared with 0.2 in the group 2 SC without significant difference, but the number of cases was small, although similar results were obtained in some other studies 8 .
The highest rate of emergency CS was after 39 weeks, although there were no statistically significant difference.In some other studies, despite improvement in neonatal outcome, scheduling elective CS deliveries at ≥ 39 weeks is associated with a significant increase in the number of emergency CS 11,12,22 .In our study the rate of composite maternal complications in emergency (27.3%) compared with elective CS (12.9%) showed significant difference (p > 0.05), as it was obtained in the study of intraoperative surgical complications during CS 23,24 .Possible explanation of this could be the reason for emergency CS such as uterine contractions, rupture of membranes or low station of the presenting part.
Despite the limitations of our study, the obtained data suggest that optimal timing for elective CS regarding maternal complications may be the 39th week.Since USA National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network (MFMU) published that elective repeat cesarean delivery at 37 or 38 weeks compared to 39 completed weeks of gestation is associated with adverse neonatal outcomes 5,7 , therefore elective delivery prior to 39 weeks is discouraged, unless fetal lung maturity has been confirmed 25 , the question is that it maybe too late for the mother regarding her complications.Our study, also, did not revealany decrease in maternal morbidity if patients delivered prior 39 weeks.Among all women undergoing pre-labor elective repeat Cesarean at term, our findings apply directly to the majority who maintain this elective status at the actual time of delivery 13 .

Conclusion
The obtained data show that the factors that directly influence the adverse maternal outcome are the number of previous CS and emergency CS.The fourth CS and more are associated with more risks for maternal complications and they might be delivered prior to 39 weeks.
Because of serious complications, patients should be informed about any potential risks for their health with increasing number of CS, especially after the first CS, when counseling regarding elective repeat CS vs trial of labor.

are presented as percentage (number); ґ − mean value; SD -standard deviation; ns -no significant difference. Table 2 Incidence of adverse maternal outcome by gestational age at cesarean delivery
emergency CS, birth weight, macrosomia, 5 min Apgar score, fetal death, except for maternal age.The patients under 35 years of age were significantly more often delivered after 39 completed weeks compared with those over 35 years (69.2% vs 30.8%, p < 0.05).The incidence of individual and composite adverse maternal outcomes by gestational age at delivery is shown in Table2.There were no maternal death and only one hysterectomy in 37 plus weeks due to the accrete placenta previa with excessive bleeding.Overall incidence of maternal adverse outcome was 16.5% and there was no significant difference in composite or individual complications by gestational age at delivery.The incidence of adverse maternal outcome by the number of CS is presented in Table3.Three or more CS had 60 (10.9%) of the patients: 54 with 3, 5 with 4 and 1 with 5 previous CS.The incidence of all adverse outcomes was much higher in the group with 3 or more CS and the difference was statistically significant (66.7% vs 10.4%, p < 0.05).Almost all individual complications were more frequent in ≥ 3 group, but a statistically significant difference was obtained in: scar dehiscence, the presence of adhesiones, blood transfusion and ICU admission.The incidence of emergency and elective CS regarding maternal adverse outcome is presented in Table4.Emergency CS was performed in 139 (25.2%) of the patients and elective in 412 (74.8%) of the patients.The incidence of the composite adverse maternal outcome was higher in the emergency CS group and the difference was statistically significant, but no other individual outcome showed any significant difference.Data are presented as percentage (number).*Composite of all adverse outcomes: maternal death, hysterectomy, rupture of the uterus, scar dehiscence, placenta previa, bladder injury, blood transfusion, wound complication, adhesions, ICU admission, deep vein thrombosis; ns -no significant difference; ICU − intensive care unit.Egić A, et al.Vojnosanit Pregl 2016; 73(8): 751-756.Vol.73, No. 8 Egić A, et al.Vojnosanit Pregl 2016; 73(8): 751-756.