Risk factor for postoperative hemorrhage after cesarean section for placenta previa : A retrospective study

Postoperative Abstract Background Placenta previa can cause postoperative hemorrhage. Even cases with less intraoperative hemorrhages during cesarean section have the potential risk of developing postoperative hemorrhage. However, there are few reports on the predictive factors of postoperative hemorrhage associated with placenta previa. The aim of this study was to identify the predictive factor for postoperative hemorrhage after cesarean section in women with placenta previa. Methods We identified women with placenta previa who underwent cesarean section at our institution between January 2003 and February 2015. All women who received any hemostatic procedure, such as intrauterine balloon tamponade and gauze infiltration during cesarean section were excluded. All women were classified into two groups: Group A, women with massive postoperative hemorrhage, defined as over 500 ml of hemorrhage after cesarean section, and Group B, women without postoperative hemorrhage. A retrospective analysis to identify the predictive factors for postoperative hemorrhage was conducted. Results Out of 128 women, 10 (7.8%) were included in Group A and 118 (92.2%) in Group B. There was no statistically significant difference in maternal history between the groups. The number of women suspected to have placental adhesion was higher in Group A than in 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 postoperative hemorrhage, 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 the surgeon during cesarean section was the predictive factor for postoperative hemorrhage with placenta previa (p=0.002). Conclusions When placental adhesion is suspected by surgeons during a cesarean section, additional hemostatic procedures should be performed to prevent possible postoperative hemorrhage.

the balloon was inserted after the massive postoperative hemorrhage had occurred [23,24]. Once a massive postoperative hemorrhage develops, the mother requires several treatments including blood transfusion [21]. Therefore, if predictive factors of massive postoperative hemorrhage related with placenta previa are identified, hazardous situations can be avoided before massive postoperative hemorrhage develops. The purpose of this study was to identify predictive factors of massive postoperative hemorrhage after cesarean section in cases with placenta previa.

Methods
All singleton pregnancy cases that underwent cesarean section due to placenta previa at our institution, between January 2003 and February 2015, were identified. The inclusion and exclusion criteria were decided according to surgical procedures. The basic surgical procedure for placenta previa was performed as previously described by Soyama et al. [25]. Briefly, after abdominal wall incision, a transverse incision into the lower segment of the uterus was performed. In cases with a placenta in the anterior uterine wall, surgeons avoided the placenta and the incision was guided by ultrasound [25]. After delivery and until 24 h after the 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: the surgeon did not remove the placenta by hand and waited until the placenta separated from the uterine wall spontaneously; afterwards, the placenta was gently removed by hand when part of the 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 the placenta did not separate, surgeons did not remove the placenta, closed the uterine wall and skin incision, and performed prophylactic uterine artery embolization (UAE). 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 the prearranged date of cesarean section, an emergency cesarean section was performed. Antenatal bleeding was defined as painless genital bleeding stemming 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.
Massive postoperative hemorrhage was defined as the amount of bleeding from the end of the cesarean section procedure until 24 h after surgery and a blood loss over 500 ml within 24 hours after birth [27].Lochia, which attached to maternity pads to measure postoperative hemorrhage was assessed. All included cases were categorized into two groups: Group A, massive postoperative hemorrhage and Group B, all cases without massive postoperative hemorrhage. Cases that underwent allogenic blood transfusion included patients who received blood transfusion at pre-parturition, intraoperation, and postpartum time. Placental adhesion was defined as no natural removal of the placenta after 2 minutes from the time of delivery.
We classified placenta previa into two categories according to Calì et al. [28]. If the placental edge covered the internal os, it was diagnosed as major type. If the placental edge did not cover the cervical internal os and was located in the lower uterine segment, it was classified as minor type.
Antenatal diagnosis of adherent placenta was assessed by MRI for uterine bulging, heterogeneous placenta, adjacent organ invasion, and cervical varicosities [16][17][18]. The pathological diagnosis of placenta accreta spectrum was performed using the placenta.
We routinely used uterotonic drugs for all cases after performing cesarean section. When massive postoperative hemorrhage developed, the amount of uterotonic drugs was increased. If postoperative hemorrhage was uncontrollable, intrauterine balloon tamponade was performed. If all interventions failed, uterine artery embolization was performed.
Statistical analysis was performed using JMP Pro 14 software (SAS Institute Inc., Cary, NS, USA

Results
During the period of this study, 242 cases with placenta previa were identified. A total of 114 cases which received hemostatic procedures during cesarean section were excluded.
A total number of 128 cases were included in our study. The rate of cesarean section was 100% and incidence of massive postoperative hemorrhage was 7.8%.
The clinical characteristics of both groups are presented in Table 1. All cases underwent cesarean section. There was no statistically significant 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 accreta spectrum was 3 in Group A and 7 in Group B. Also, final pathological findings revealed 3 cases in Group A and 2 cases in Group B with placenta accreta 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 massive postoperative hemorrhage. In group B, 4 patients received UAE and 1 patient underwent hysterectomy due to uncontrollable massive hemorrhage.
Univariate analysis for massive postoperative hemorrhage with placenta previa revealed that placental adherence was the predictive factor (Table 3).

Discussion
In our study, univariate analysis revealed that only placental adhesion suspected by surgeon during cesarean section was a predictive factor for massive postoperative hemorrhage in placenta previa.
Placenta previa caused massive postoperative hemorrhage because the lower uterine segment is only weakly contractible [29]. Thus, the appropriate strategy was required.
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 an effective management of postoperative hemorrhage associated with placenta previa. In fact, some reports demonstrated that intrauterine balloon tamponade was effective in decreasing both intraoperative and postoperative hemorrhage [19,23,24]. In our institution, since March 2015, rapid insertion of intrauterine balloon tamponade has been performed to reduce hemorrhage after spontaneous separation of the placenta and has succeeded in reducing postoperative hemorrhage [25]. To design the predictive model for massive postoperative hemorrhage, we considered that the exclusion criteria were valid.
Moreover, placental adhesion was defined by the surgical findeings in this study. The definition of placental adhesion by a surgeon might be different from that of true placental adhesion using pathological examination [30]. The reason for diagnosing placental adhesion clinically rather than pathologically in our study was that massive postoperative hemorrhage of placenta previa occurred spontaneously, particularly within one day after termination [27], and timing for pathological diagnosis was impractical.
Therefore, we considered the design of our study to be an appropriate clinical model to predict massive postoperative hemorrhage.
Our results suggest that any hemostatic procedures should be performed if surgeons suspect placental adhesion. Although our study did not examine the appropriate strategy for postoperative hemorrhage, the development of postoperative hemorrhage was a critical problem. According to Soyama et al., intrauterine balloon tamponade could decrease postoperative hemorrhage [25]. In addition, some studies reported the efficacy of routine prophylactic use of uterotonic drugs, such as oxytocin and tranexamic acid [31,32]. Further studies are required to examine the effective methods, including these, for patients with a risk factor for postoperative hemorrhage.
This study has some limitations. First, the retrospective study focused on data from a single institution, leading to a small sample size, which did not permit the development of an appropriate strategy for this problem. Second, this study has a strong selection bias due to the exclusion criteria. Third, our study performed only univariate analysis. Further prospective studies are necessary to reveal the correlation between postoperative hemorrhage with placenta previa and risk factors and, to develop appropriate strategies.

Conclusions
Placental adhesion was the predictive factor for postoperative hemorrhage associated with placenta previa. The prevention of postoperative hemorrhage was needed for women with placental adhesion to prepare for massive postoperative hemorrhage even though a

Consent to publication
All data were anonymized and individual consent for publication was not required.

Availability of data and materials
The datasets used and analyzed in this study are available from the corresponding author upon reasonable request.

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

Funding
The authors received no specific funding for this work.

Author Contributions
Protocol

Conflict of Interest Statement and Funding/Support Statement
None.  Uterotonic drugs; several drugs including oxytocin, methylergometrine, and dinoprost.