The risk factor of postpartum hemorrhage after cesarean section for placenta previa: A retrospective study

Background Placenta previa could induce postpartum hemorrhage (PPH). Even cases with less intraoperative hemorrhage during cesarean section had the potential risk to develop PPH. But, there were less report about the predictive factor of PPH associated with placenta previa. The aim of this study was to identify the predictive factor for PPH for women with placenta previa after cesarean section. Methods Women with placenta previa who underwent cesarean section at our institution between January 2003 and February 2015 were identied. Women that received any hemostatic procedure such as intrauterine balloon tamponade and gauze inltration during cesarean section were excluded. All women were classied into two groups: Group A or with PPH, dened as over 500 ml of hemorrhage after cesarean section, and Group B or without PPH. A retrospective analysis to identify the predictive factor of PPH was conducted. Results Out of 128 women, 10 (7.8%) women were included in Group A and 118 (92.2%) women in Group B. There was no statistical signicance in maternal history between both groups. The number of women suspected to have placental adhesion was higher in Group A than Group B (p=0.006). Furthermore, the amount of intraoperative hemorrhage in Group A was higher than that in Group B (p=0.025). As treatment for PPH, more women in Group A received allogenic blood transfusion (p=0.003), and uterine artery embolization (p = 0.010). In univariate analysis, placental adhesion suspected by surgeon during cesarean section was the predictive factor for PPH with placenta previa (p=0.046). When placental adhesion suspected by surgeons during cesarean section, additional hemostatic procedure should be performed for possible PPH.

balloon tamponade and gauze in ltration during cesarean section were excluded. All women were classi ed into two groups: Group A or with PPH, de ned as over 500 ml of hemorrhage after cesarean section, and Group B or without PPH. A retrospective analysis to identify the predictive factor of PPH was conducted. Results Out of 128 women, 10 (7.8%) women were included in Group A and 118 (92.2%) women in Group B. There was no statistical signi cance in maternal history between both groups. The number of women suspected to have placental adhesion was higher in Group A than Group B (p=0.006). Furthermore, the amount of intraoperative hemorrhage in Group A was higher than that in Group B (p=0.025). As treatment for PPH, more women in Group A received allogenic blood transfusion (p=0.003), and uterine artery embolization (p = 0.010). In univariate analysis, placental adhesion suspected by surgeon during cesarean section was the predictive factor for PPH with placenta previa (p=0.046).
Conclusion When placental adhesion is suspected by surgeons during cesarean section, additional hemostatic procedure should be performed for possible PPH.
Background Until now, placenta previa has caused maternal and neonatal mortality and morbidity by massive hemorrhage [1,2]. As a result, a more precise and appropriate strategies of prediction and preparation should be developed with the purpose of avoiding these adverse obstetrical outcomes [3,4]. The timing of massive hemorrhage for placenta previa was either in the operative or in the postoperative period [5]. Consequently, prediction and strategies for intraoperative hemorrhage or postpartum hemorrhage (PPH) are needed.
Placenta previa is well known to be one of the diseases which induced massive PPH [21]. Even cases with less intraoperative hemorrhage during cesarean section had the potential risk to develop massive PPH [22]. Without rapid and appropriate treatment, massive PPH might induce adverse obstetrical outcomes including maternal death [22]. As a strategy for massive PPH associated with placenta previa, previous studies demonstrated that intrauterine balloon tamponade was useful to decrease massive PPH [23][24][25]. In these reports, the timing of insertion of balloon was after massive PPH [23,24]. Once massive PPH developed, the mother frequently received several treatments including blood transfusion [21]. Therefore, if predictive factors of massive PPH related with placenta previa are identi ed, hazardous situations can be avoided before massive PPH develop. Therefore, the purpose of this study was to identify predictive factors of massive PPH after cesarean section in cases with placenta previa.

Methods
All singleton pregnancy cases who underwent cesarean section due to placenta previa at our institution, between January 2003 and February 2015, were identi ed. The inclusion and exclusion criteria were decided according to surgical procedures. The details were indicated as follows. The basic surgical procedure for placenta previa was performed as previously described by Soyama et al [25]. Brie y, after abdominal wall incision, a transverse incision into the lower segment of the uterus was done. In cases with a placenta in the anterior uterine wall, surgeons avoided the placenta and, incision was guided by ultrasound [25]. After delivery and until 24 h after cesarean section, oxytocin 5 IU was started intravenously in a 500-mL saline drip. Methods to remove the placenta and to treat postoperative hemorrhage were as follows: surgeon did not remove the placenta by hand and waited until the placenta separated from uterine wall spontaneously; after, placenta was gently removed by hand when part of placenta was exfoliated and another part was retained in the uterine wall. If intraoperative hemorrhage developed, gauze packing or brace sutures, such as placental bed sutures or compression sutures, alone or combined, were performed at the surgeon's discretion. Cases that did not receive any hemostatic procedures, as mentioned above, were included in our study. Hence, when no sign of placenta separation was completely developed, placenta was not removed and surgeons closed uterine wall and skin incision, performing instead prophylactic uterine artery embolization (UAE) before the development of massive PPH. All these cases were excluded from this study.
Maternal history and intraoperative information were obtained from medical charts and operative records. In all cases, US and MRI examinations for the diagnosis of placenta previa were performed by experienced obstetricians and radiologists after 30 weeks of gestation. At our institution, elective cesarean section was performed before 38 weeks of gestation according to the Guidelines for Obstetrical Practice in Japan [26]. However, if persistent antenatal bleeding over 100 ml or uncontrollable uterine contractions occurred before prearranged date of cesarean section, an emergency cesarean section was performed. Antenatal bleeding was de ned as painless genital bleeding from the placenta. The amount of intraoperative hemorrhage was measured from the time of the skin incision to the time of scar closure, based on suction count and towel weight. PPH was de ned as the amount of bleeding from the end of the cesarean section procedure until 24 h after surgery and, PPH as a blood loss over 500 ml within 24 hours after birth [27]. All included cases were categorized into two groups: Group with PPH (Group A) and Group without PPH (Group B). Cases that underwent allogenic blood transfusion included patients who received blood transfusion at pre-parturition, intraoperation, and postpartum time. Placental adhesion was de ned by the surgeon's clinical judgement when attempting to remove the placenta, after appearance of the placenta peeling sign, but the placenta did not separate smoothly.
We classi ed placenta previa into two categories according to Calì et al [28]. If the placenta edge covered internal os, it was diagnosed as major type. If, instead, the placenta edge did not cover cervical internal os and was located in the lower uterine segment, it was classi ed as minor type.

Results
During the period of this study, 243 cases with placenta previa were identi ed. Among them, 115 cases were excluded. One case had twin pregnancy and 114 cases received hemostatic procedures during cesarean section. Finally, the total number of 128 cases were included in our study. The rate of cesarean section was 100% and incidence of postpartum hemorrhage was 7.8%.
The clinical characteristics of both groups are presented in Table 1. All cases underwent cesarean section. There was no statistically signi cant difference in maternal history. According to operative information, there were more patients with suspected placental adhesion in Group A than in Group B (p=0.006). Furthermore, the amount of intraoperative hemorrhage was higher in Group A (p=0.025). The number of cases with antenatal diagnosis of placenta accrete spectrum was 3 in Group A and 7 in Group B. Also, nal pathological ndings revealed 3 cases in Group A and 2 cases in Group B was complicated with placenta accrete spectrum. Table 2 showed the procedure after hemorrhage. More cases in Group A received uterine artery embolization (p=0.010) and allogenic blood transfusion (p=0.003) as additional treatment for PPH.
Univariate analysis for massive PPH with placenta previa revealed that placental adherence was the predictive factor (Table 3).

Discussion
In our study, multivariate analysis revealed that only placental adhesion suspected by surgeon during cesarean section was a predictive factor for PPH in placenta previa.
In this study, patients who received any hemostatic procedure, such as intrauterine balloon tamponade, during cesarean section were excluded. The reasoning was that intrauterine balloon tamponade was the effective management of PPH associated with placenta previa. In fact, some reports demonstrated that intrauterine balloon tamponade was effective to decrease both intraoperative and postoperative hemorrhage [19,23,24]. In our institution since March 2015, rapid insertion of intrauterine balloon tamponade to reduce hemorrhage have been performed after spontaneous separation of the placenta and it succeeded in reducing PPH [25]. To make the predictive model for PPH, we considered that the exclusion criteria was valid.
Also, placental adhesion was de ned by surgeon's intraoperative judgement in this study. The de nition of placental adhesion by surgeon might be different from that of true placental adhesion using pathological examination [29]. The reason for diagnosing placental adhesion clinically rather than pathologically in our study was because PPH of placenta previa occurred suddenly, particularly within one day after termination [27], and we could not afford to wait for a pathological diagnosis. Therefore, from this point of view, we considered the design of our study to be an appropriate clinical model to predict PPH.
Our results might suggest, that if surgeons suspect placental adhesion, any hemostatic procedures should be performed even though intraoperative massive hemorrhage do not develop. Although our study did not examine the appropriate strategy for PPH, the development of PPH was the urgent problem. According to Soyama et al., intrauterine balloon tamponade could decrease PPH [25]. Also, some studies reported the e cacy of routine prophylactic use of uterotonic drug, such as oxytocin and tranexamic acid [30,31]. Further studies need to examine the effective methods, including these, for patients with a risk factor of PPH.
This study has some limitations which have to be point out. The retrospective design, single institutional study and the small sample size did not allow us to develop an appropriate strategy for this problem. Our study has a strong selection bias because of our exclusion criteria. Further prospective studies are necessary to reveal the correlation between PPH with placenta previa and risk factors and, to develop appropriate strategies.

Conclusions
Placental adhesion was the predictive factor for PPH associated with placenta previa. The prevention for PPH might be necessary for women with placental adhesion.

Consent to publication
All data was anonymised so individual consent for publication was not applicable.

Availability of data and materials
All data analysed in this study are available from the corresponding author upon reasonable request.

Competing interests
All authors declare that they have no competing interests.