Impact of Prior Cesarean Delivery on Pregnancy Outcomes and Hemorrhage Risks in Complete Placenta Previa: A Decade-Long Retrospective Analysis

Introduction

Placenta previa (PP) is the complete or partial covering of the internal os of the cervix with the placenta after 28 weeks of gestation [1]. In accordance with current recommendation, PP is classified into 2 subtypes: complete placenta previa (CPP), in which the placenta completely covers the cervical os, and low-lying placenta, in which the placenta edge is located ≤20 mm from the cervical os [2]. The worldwide incidence rate of PP is estimated as 5.2 per 1000 births, and is increasing with the increase in cesarean deliveries worldwide [3]. PP is a major risk factor for postpartum hemorrhage and can lead to morbidity and mortality of the mother and neonate [4,5].

Since 2016, the implementation of China’s second child policy has led to a significant increase in the incidence of PP in China, from 1.25% to 4.12%, with varying trends across regions [6]. This increase can be attributed to the substantial increase in the rate of cesarean deliveries [7]. Major risk factors for PP include advanced maternal age, prior cesarean delivery, maternal smoking, and use of assisted reproductive technology (ART) [8–11].

Research has shown that CPP is a significant risk factor for adverse maternal and neonatal outcomes, including placenta accreta spectrum disorders (PAS), postpartum hemorrhage, hysterectomy, preterm labor, and neonatal intensive care unit (NICU) admission [12]. Therefore, it is important to identify the risk factors of CPP and closely monitor patients with this condition. However, little research exists on the relationship between prior cesarean delivery and pregnancy outcomes in CPP cases, and the effect of prior cesarean delivery on hemorrhagic risk in such patients is uncertain. To address this research gap, this study aimed to investigate clinical characteristics and adverse pregnancy outcomes in CPP, focusing on prior cesarean delivery, and to identify risk factors for massive hemorrhage.

Therefore, in this 10-year retrospective study, we analyzed 476 patients with CPP who underwent cesarean delivery at a single tertiary hospital, by collecting data from medical records. We compared 156 patients with prior cesarean delivery with 320 patients without, focusing on risk factors and outcomes. Clinical characteristics, pregnancy outcomes, and hemorrhage determinants were examined. Logistic regression identified independent predictors of hemorrhage. The findings aim to improve patient management and enrich knowledge on CPP, ultimately enhancing maternal-fetal health.

Material and Methods

STUDY DESIGN:

This retrospective analysis was performed at a single tertiary referral medical center, spanning from January 2013 to December 2022. All data on maternal and neonatal characteristics were obtained via a manual search of the electronic medical record system. Due to the retrospective nature of the study, patients were informed and signed informed consent forms at their first antenatal visit at the International Peace Maternity and Child Health Hospital, a teaching hospital for Shanghai JiaoTong University School of Medicine. This study was approved by the Ethics Committee of our hospital.

The baseline data encompassed maternal age, primipara/multipara, miscarriages, use of ART, previous cesarean delivery, prior hysteroscopic surgery, uterine fibroids surgery, history of endometriosis, gestational diabetes, gestational hypertension, and antenatal bleeding. Maternal and neonatal outcomes encompassed placental issues (PP, placental position, and PAS), blood loss, need for blood transfusion, management of postpartum hemorrhage, maternal postpartum complications (DIC and hysterectomy), gestational age at delivery, neonatal weight, preterm birth, Apgar score, and NICU admission.

INCLUSION CRITERIA:

The inclusion criteria were as follows: (1) singleton pregnancy with cesarean delivery at ≥28 weeks gestation; (2) the last ultrasound and/or magnetic resonance imaging examination before cesarean delivery, which was performed by chief ultrasound physician/chief radiologist, confirmed the diagnosis of CPP, with placenta completely covering the os; (3) a definite clinical description during cesarean delivery confirmed the diagnosis of CPP: if the placenta completely covered the cervical opening during surgery, the diagnosis was CPP.

EXCLUSION CRITERIA:

The exclusion criteria were as follows: information loss or missing data, delivery at another hospital, pregnancy termination before 28 weeks of gestation, low-lying placenta, in which the placenta edge is located ≤20 mm from the cervical os, severe underlying diseases or other serious pregnancy complications leading to pregnancy termination, and twin pregnancies.

RELATED INDICTOR AND MAIN OUTCOMES:

After we applied the study criteria, 476 participants with CPP were finally included in this study. Patients were grouped naturally by cesarean delivery history: prior cesarean delivery group (156 patients) and no-prior cesarean delivery group (320 patients). These 2 groups were compared in terms of maternal age, gestational age at delivery, reproductive history, placental attachment site, intraoperative bleeding, and rates of hysterectomy, preterm birth, neonatal asphyxia, and NICU admission. The estimated intraoperative blood loss was measured by weighing or by the shock index. In addition, based on the occurrence of massive hemorrhage, patients were divided into a massive hemorrhage group (n=80) and control group (n=396). Univariate and multivariate logistic regression were used to identify risk factors for massive hemorrhage in patients with CPP. The presence or absence of hemorrhage was the dependent variable, and significant univariate indicators were included in a multifactorial logistic regression model, with stepwise selection.

Patients with massive hemorrhage caused by non-placental factors during surgery were excluded. Massive hemorrhage was defined as ongoing blood loss of more than 1000 mL within 24 h, and massive life-threatening postpartum hemorrhage was ongoing blood loss of more than 2500 mL [13]. Magnesium sulfate was recommended for all women at risk of imminent preterm birth before 32 weeks of gestation for prevention of cerebral palsy, and antenatal corticosteroids were recommended for women at 24+0 to 33+6 weeks with established preterm labor [14].

In all cases, further confirmation was made on direct visualization during the cesarean delivery to determine the presence and depth of abnormal placentation, according to the 2018 FIGO classification. After delivery, cord traction was done to detach the placenta, in the absence of suspicion of placenta percreta or heavy bleeding. If removal failed, surgical procedures such as manual removal, clamping/resecting tissue, suturing, and uterine wall reconstruction were performed. Intraoperative hemostasis methods such as compression sutures, gauze packing, balloon tamponade, and artery ligation were used. If conservative therapies failed, hysterectomy was decided by 2 experienced surgeons.

CLINICAL DATA COLLECTION:

Data in the perinatal database was documented by attending physicians after delivery. Medical secretaries reviewed the information before entry. Coding was done after prenatal care records and hospital documents were evaluated. This ensured completeness and accuracy. The database included demographic information, perinatal assessments, maternal morbidities, and newborn outcomes. Records were anonymized before analysis. The hospitalization database included demographic information and International Classification of Diseases, ninth revision codes (ICD-9) for all diagnoses.

STATISTICAL METHODS:

Comparative data are expressed as the mean ± standard deviation and were evaluated using the t test. Categorical variables are expressed as rates and were evaluated using the χ² test, corrected χ² test, or Fisher’s exact test, as appropriate. Univariate and multivariate logistic regression analyses were used to explore the risk factors of massive hemorrhage in patients with CPP. Multivariate analysis was performed using binary logistic regression analysis. Statistical analysis was performed using SPSS 26.0 software (IBM Corp, Armonk, NY, USA). All tests were 2-sided, and P<0.05 was considered as statistically significant.

Results

GENERAL CHARACTERISTICS ACCORDING TO PRIOR CESAREAN SECTION:

Maternal age (36 [3.7] vs 34.2 [4.2], P=0.012), proportions of advanced maternal age (46.2% vs 39.1%, P=0.004), multipara (100% vs 24.4%, P<0.001), and number of miscarriages (1.4 [1.2] vs 0.8 [1.0], P<0.001) were significantly higher in the prior cesarean delivery group than in the no-prior cesarean delivery group (Table 1). In contrast, the proportions of ART (30.0% vs 3.8%, P<0.001) and endometriosis history (14.1% vs 8.3%, P<0.001) were significantly higher in the no-prior cesarean delivery group than in the prior cesarean delivery group (Table 1). There were no significant differences between the 2 groups in terms of previous hysteroscopic surgeries, uterine fibroid surgeries, gestational diabetes, gestational hypertension, antenatal bleeding, or emergency surgeries (P>0.05; Table 1).

INTRAPARTUM CONDITIONS AND PREGNANCY OUTCOMES ACCORDING TO PRIOR CESAREAN SECTION:

Volume of intraoperative blood loss (982.9 [202.9] vs 588.8 [134.2], P=0.001), proportion of massive blood transfusion (≥10 units; 7.1% vs 2.2%, P=0.009), DIC (9.6% vs 1.6%, P<0.001), hysterectomy (6.4% vs 0.9%, P=0.002), prophylactic abdominal aorta balloon occlusion (42.3% vs 9.7%, P<0.001], and placenta percreta (34.6% vs 20.6%, P=0.002] were significantly higher in the prior cesarean delivery group than in the no-prior cesarean delivery group (Table 2). The neonates in the prior cesarean delivery group exhibited lower birth weight than those in the no-prior cesarean delivery group (2855.4 [491.6] vs 2989.4 [460.2], P=0.004), while the proportions of preterm births (60.9% vs 36.6%, P<0.001) and neonates with Apgar score ≤7 at 1 min (10.9% vs 3.4%, P=0.001) and NICU admission rate (13.5% vs 6.3%, P=0.008) were significantly higher in the prior cesarean delivery group than in the no-prior cesarean delivery group (Table 2).

GENERAL CHARACTERISTICS ACCORDING TO MASSIVE HEMORRHAGE:

The massive hemorrhage group consisted of 80 patients, while the control group consisted of 396 patients without massive hemorrhage. The massive hemorrhage group had significantly higher proportions of antepartum bleeding (32.5% vs 14.6%, P<0.001), prior cesarean delivery (36.3% vs 28.3%, P<0.001), anterior placenta (52.5% vs 18.4%, P<0.001), and placenta percreta (67.5% vs 16.4%, P<0.001) than the control group (Table 3). There were no significant differences between the 2 groups in terms of maternal age and proportions of multiparous women, multiple history of miscarriages, ART, previous hysteroscopic surgeries, uterine fibroid surgeries, history of endometriosis, uterine diverticula, history of scar pregnancies, gestational diabetes, gestational hypertension, and emergency surgeries (P>0.05; Table 3).

FACTORS RELATED TO MASSIVE HEMORRHAGE:

The univariate analysis for the risk factors of massive hemorrhage showed that gestational age, prior cesarean delivery, anterior placenta, placenta percreta, and antepartum bleeding were significantly associated with massive hemorrhage (P<0.05; Table 4). Furthermore, multivariate logistic regression analysis of these factors indicated that a history of cesarean delivery (adjusted odds ratio (aOR) 1.67, 95% CI 1.01–2.86), 2 or more previous cesarean deliveries (aOR 5.22, 95% CI 3.07–12.75), anterior placenta (aOR 2.53, 95% CI 1.17–5.49), placenta percreta (aOR 5.24, 95% CI 2.73–10.96), and antepartum bleeding (aOR 1.90, 95% CI 1.66–4.44) were independent risk factors for massive hemorrhage (Table 4).

Discussion

The current investigation contrasted the clinical features and risk factors associated with massive hemorrhage in women diagnosed with CPP, stratified by the presence or absence of prior cesarean delivery. The group with prior cesarean delivery showed higher maternal age and more miscarriages, massive hemorrhage, hysterectomy, premature births, and neonatal hospitalization than did those without prior cesarean delivery. In contrast, the no-prior cesarean delivery group had higher rates of ART and endometriosis. Multivariate logistic regression analysis identified prior cesarean delivery (especially 2 or more), anterior placenta, abnormal placentation, and antepartum bleeding as independent risk factors of massive hemorrhage in patients with CPP.

Prior cesarean delivery is a high-risk factor for PP in subsequent pregnancies and can lead to emergency cesarean delivery, preterm birth, postpartum hemorrhage, and hysterectomy, thus endangering maternal life [15]. Miscarriage, multiple deliveries, and prior cesarean delivery can cause endometrium damage, which is the main cause of PP [16]. Cesarean section damages not only the endometrium but also the uterine muscle layer. This can result in the thinning, or even absence, of the uterine muscle layer in subsequent pregnancies, increasing the likelihood of scar pregnancies and abnormal placentation, and leading to increased bleeding during placental separation [17]. Pregnant women with prior cesarean delivery have a 7-fold higher risk of persistent PP than do those without [16], causing maternal morbidity, such as severe hemorrhage, hypovolemic shock, fetal hypoxia, and preterm labor or delivery [18]. Furthermore, women with a history of prelabor cesarean delivery have an increased risk of PP in subsequent pregnancies, compared with women with a history of vaginal delivery of their first child. However, no significant association has been found between cesarean delivery during labor and the development of PP [19]. Additionally, a previous study reported no cases of PAS among women without prior cesarean delivery, while the incidences of PAS in women with a history of 1, 2, 3, 4, and 5 prior cesarean deliverys were 26.7%, 43.5%, 65.5%, 55.6%, and 66.7%, respectively [20].

Zhou et al [21] reported endometriosis and ART as independent risk factors of PP in primipara pregnant women. Women with endometriosis are at a higher risk of developing PP and preterm birth during pregnancy, whether conceived via ART or natural means [22]. In addition, women with endometriosis are at an increased risk of adverse pregnancy and neonatal outcomes, which is consistent with the findings of the present study [23–25]. In women after ART, as well as in women with endometriosis, the frequency and amplitude of uterine contractions in the implantation period are enhanced. This can cause abnormal uterine peristalsis, leading to abnormal embryo implantation near the cervical os, resulting in a lower implantation of the placenta. The act of transporting the blastocyst directly into the uterine cavity via transcervical catheterization can disrupt the normal placentation process, increasing the risk for development and persistence of PP [26].

Women with prior cesarean delivery have higher incidences of PAS, postpartum hemorrhage, hysterectomy, and maternal mortality [27]. Compared with PP patients without prior cesarean delivery, those with prior cesarean delivery had significantly higher rates of cesarean hysterectomy (OR 20.462), urinary tract injuries (OR 12.361), associated PAS (OR 4.375), moderate/heavy intra-operative bleeding (OR 2.153), and need for transfusion (OR 1.849) [28]. Furthermore, women with prior cesarean delivery were found to have significantly higher rates of preterm births and NICU admission [29], which is consistent with the findings of the present study. In women with PP, the risk of obstetric hysterectomy is significantly associated with prior cesarean delivery, particularly in those with 3 or more prior cesarean deliveries [30]. Consequently, the early identification and prediction of adverse pregnancy outcomes are necessary for women with CPP and prior cesarean delivery.

Delivery timing should be tailored based on antenatal symptoms, and for uncomplicated placenta praevia, 36+0 to 37+0 weeks of gestation is recommended. After 36 weeks, risk of hemorrhage increases; therefore, caesarean section is advised. For PP, cesarean delivery termination is recommended between 36 and 36+6 weeks with risk factors, and between 37 and 37+6 weeks without. Women with a placental edge <20 mm from the internal os in the third trimester may need to undergo cesarean delivery, based on edge thickness or echo/marginal sinus. A trial of labor is recommended for a low-lying placenta with an edge 11 to 20 mm from the cervical os, and can be considered for ≤10 mm in selected cases. For a low-lying placenta, cesarean delivery is advised at 37+0 to 37+6 weeks with risk factors, or at 38+0 to 38+6 weeks without. Early identification of risk factors can reduce adverse pregnancy outcomes, including antepartum bleeding, thick placental margin (>1 cm), marginal sinus, shortened cervical length (<3 cm), prior cesarean delivery, and abnormal placentation [2]. In the present study, we found that prior cesarean delivery increases abnormal placentation, leading to earlier termination, higher preterm infant proportion, and higher neonatal hospitalization rate.

A retrospective analysis by Baba et al [31] found that abnormal placentation, prior cesarean delivery, CPP, and anterior placenta were independent risk factors for massive bleeding (>2400 mL) during surgery. In addition, another study [32] demonstrated that the rate of abnormal placentation in pregnant women with coexisting PP was significantly higher than in those without PP (72.3% vs 6.9%, P<0.001), which resulted in increased intraoperative blood loss, transfusion volume, and hysterectomy rate. PP complicated by antepartum bleeding increases the risk of adverse maternal and fetal outcomes, with preterm labor contractions and a shortened cervical length (<2.5 cm) as significant risk factors for antepartum bleeding in such cases [33]. Findik and Icen [34] found that those with an anterior placenta had a significantly higher average number of prior cesarean deliveries, abnormal placentation rate, and estimated blood loss during surgery than those with non-anterior placenta. Therefore, prior cesarean delivery, anterior placenta, abnormal placentation, and antepartum bleeding are independent risk factors for massive hemorrhage in patients with CPP. To minimize unfavorable outcomes, it is essential to increase awareness, promptly recognize these factors, and provide appropriate management during the perinatal period.

The present study has advantages and limitations. First, this was a retrospective review of cases treated at our hospital over the past decade. The study period was extensive and the sample size was substantial. However, this was a single-center retrospective study, which can limit the generalizability of the findings. Therefore, it is crucial to confirm our results in large-scale multicenter prospective cohort studies. Additionally, because this was a cohort study, it was challenging to avoid selection bias, and unknown confounding factors may have influenced the results. Therefore, randomized controlled trials are needed in the future to further validate these results.

Conclusions

Prior cesarean delivery increases the risks of hemorrhage, hysterectomy, premature birth, and neonatal hospitalization in patients with CPP. Independent risk factors for massive hemorrhage in patients with CPP include prior cesarean delivery, anterior placenta, abnormal placentation, and prenatal bleeding, particularly in those with 2 or more prior cesarean deliveries. Early identification of risk factors for postpartum hemorrhage and accurate prediction of adverse pregnancy outcomes are crucial for women with CPP and a history of cesarean delivery, as they are essential in preventing maternal morbidity and mortality.