You are here
Placenta previa with early opening of the uterine isthmus is associated with high risk of bleeding during pregnancy, and massive haemorrhage during caesarean delivery
European Journal of Obstetrics & Gynecology and Reproductive Biology, June 2016, Pages 7 - 11
To demonstrate the relationship between the timing of opening of the uterine isthmus and bleeding during pregnancy and caesarean section in patients with placenta previa.
A prospective observational study was conducted at a single perinatal centre. All patients with placenta previa, diagnosed between 20 and 22 weeks of gestation, who were followed up at the study hospital and underwent caesarean section were enrolled.
The condition of the uterine isthmus was examined every 2 weeks. The timing (in gestational weeks) of complete opening of the uterine isthmus was determined. Patients were divided into two groups: patients in whom the uterine isthmus opened before 25 weeks of gestation (EO-previa), and patients in whom the uterine isthmus opened after 25 weeks of gestation (LO-previa). The frequency of bleeding during pregnancy and the amount of intra-operative bleeding were compared between the two groups.
Forty-four cases of EO-previa and 55 cases of LO-previa were analysed. Complete placenta previa at delivery was observed more frequently in the EO-previa group than in the LO-previa group (88.6% vs 47.3%, p < 0.001). An emergency caesarean section due to active bleeding was performed more frequently in the EO-previa group (48%) than in the LO-previa group (25%) (p = 0.021). The frequency of massive haemorrage (>2500 ml) during caesarean section was higher in the EO-previa group than in the LO-previa group (25% vs 9%, p = 0.033).
Placenta previa was associated with a high risk of bleeding leading to emergency caesarean section during pregnancy, and massive haemorrhage during caesarean section in patients in whom the uterine isthmus opened before 25 weeks of gestation.
Keywords: Placenta previa, Uterine isthmus, Caesarean section, Haemorrhage, Atonic bleeding, Ultrasound.
Placenta previa is a major cause of massive haemorrhage during pregnancy and delivery. However, massive haemorrhage does not occur in all cases of placenta previa, and the prediction of cases that are at high risk for massive haemorrhage is important for management of the condition. As such, there has been a great deal of discussion regarding the prediction of cases at high risk of placenta previa through sonographic evaluation. Short cervical length , placenta lacunae, sponge-like echo in the cervix, and the lack of a clear zone  and  are currently considered to be sonographic risk factors for massive bleeding.
The uterine isthmus is usually closed during early pregnancy, but opens with advancing gestation. This phenomenon also occurs in patients with placenta previa. Consequently, it was hypothesized that patients with placenta previa in whom the uterine isthmus opens earlier are more likely to experience complications, such as sudden bleeding during pregnancy and massive haemorrhage during caesarean section, because changes in the lower part of the uterus that occur during slight contractions may lead to separation of the placenta and the decidua during pregnancy, and because atonic bleeding may occur frequently when the uterine isthmus is dilated and expanded for a long period of time (from earlier gestation to delivery by caesarean section).
This study distinguished the uterine isthmus from the uterine cervix by precise ultrasound examinations. The aim of this study was to demonstrate the relationship between the timing of opening of the uterine isthmus and bleeding during pregnancy and caesarean section in patients with placenta previa.
Materials and methods
A prospective cohort study was performed at Showa University Hospital, Tokyo, Japan between 2009 and 2014. The study population included all patients with placenta previa, diagnosed between 20 and 22 weeks of gestation, who were followed up at the study hospital and underwent caesarean section.
Placenta previa was diagnosed by experienced obstetricians based on a transvaginal ultrasonic finding of placental tissue covering the lowest ostium of the uterine cavity (amniotic cavity) between 20 and 22 weeks of gestation. During the ultrasound examination, the pregnant patients were placed in a supine position after urination. Ultrasound examination was taken when uterine contraction was not investigated. The uterine cervix was defined as same as the endocervical mucosa (cervical gland), which was usually visualized as a leaf-like echo area with low echogenicity compared with the surrounding tissues. The uterine isthmus was defined as the region from the highest point of the cervical gland to the lowest point of the internal ostium of uterine cavity.
Following a diagnosis of placenta previa, the uterine isthmus, the uterine cervix and the location of the placenta were observed by transvaginal ultrasound every 2 weeks. As the uterine isthmus opens with advancing gestation, the timing (in gestational weeks) of opening was detected and recorded. An open isthmus was defined as a completely opened isthmus (i.e. an isthmus region was undetectable); if this condition was not met, the isthmus was considered to be closed (Fig 1 and Fig 2).
The subjects were divided into two groups: those in whom the uterine isthmus opened before 25 weeks of gestation (early opening isthmus; EO-previa) and those in whom the uterine isthmus opened after 25 weeks of gestation (late opening isthmus; LO-previa). The frequency of bleeding during pregnancy, and the amount of bleeding during caesarean section were compared between the two groups. Three authors (M.G., T.A. and H.T.) used ultrasound images to determine if the isthmus was open. When one author reported a different diagnosis from the other two authors, the diagnosis made by the two authors was taken.
When a hysterectomy was performed following a caesarean section, the amount of bleeding during the hysterectomy was included. In the present study, massive haemorrhage was defined as more than 2500 ml during surgery.
Elective caesarean sections were planned between 36 and 37 weeks of gestation. Emergency caesarean sections were performed before planned caesarean sections in the case of more than 100 ml of bleeding, uncontrollable uterine contractions or premature rupture of membranes.
All statistical analyses were performed using Statistical Package for Social Science Version 20.0J (IBM Corp., Armonk, NY, USA). Continuous variables were reported as median (range) and compared using the Mann–Whitney U-test. Categorical variables were reported as percentages and compared using Fisher's exact test. Significant variables associated with EO-previa on univariate analysis, including complete placenta previa, were used in the multivariable analysis. p < 0.05 was considered to indicate statistical significance.
This study was approved by the hospital ethics committee. Informed consent was obtained in writing from all patients before they underwent ultrasound scans.
Two hundred and ninety cases of suspected placenta previa were identified between 20 and 22 weeks of gestation. The suspected placenta previa resolved at delivery in 189 cases, so this study included 101 patients with placenta previa. Two cases were excluded: one case in which intra-uterine fetal death occurred due to another perinatal complication, and one case of a twin pregnancy. Thus, 99 cases were classified into two groups based on the timing of opening of the uterine isthmus. The three authors agreed on the diagnosis of an open or closed isthmus for 96% of ultrasound images (607/635). Forty-four cases were classified as EO-previa and 55 cases were classified as LO-previa. The opening of the uterine isthmus occurred after a median gestation period of 22 weeks (range 20–24 weeks) in the EO-previa group, and 30 weeks (range 25–37 weeks) in the LO-previa group. There were no cases in which the isthmus opened gradually during transvaginal investigation with or without fundal pressure test.
The background characteristics of patients in the EO-previa and LO-previa groups are shown in Table 1. There were no significant differences between the two groups, and cervical length at 28 weeks of gestation did not differ between the two groups.
|Opening of uterine isthmus||p-Value|
|Before 25 weeks of gestation (n = 44)||After 25 weeks of gestation (n = 55)|
|Opening of isthmus, gestational weeks||22 (20–24)||30 (25–37)|
|Maternal age (years)||35 (26–49)||36 (25–42)||0.772|
|Gravida||1 (0–4)||1 (0–4)||0.158|
|Parity||1 (0–2)||0 (0–2)||0.327|
|Primipara||45.5% (20)||54.5% (30)||0.369|
|Previous caesarean section||22.7% (10)||9.1% (5)||0.110|
|Cervical length at 28 weeks (mm)||34 (18–46)||34 (18–46)||0.984|
|Placenta on anterior wall||20.5% (9)||10.9% (6)||0.188|
Data presented as median (range) or % (n).
The fetal and maternal outcomes in terms of bleeding are shown in Table 2. There was no significant difference in the frequency of bleeding during pregnancy in the two groups (EO-previa, 64%; LO-previa, 49%). An emergency caesarean section was performed due to active bleeding before the planned caesarean section in 48% and 25% of the EO-previa and LO-previa cases, respectively (p = 0.021). Complete placenta previa was observed more often in the EO-previa group than the LO-previa group (88.6% vs 47.3%, p < 0.001). The median amount of bleeding during caesarean section was 1823 ml in the EO-previa group and 1510 ml in the LO-previa group (p = 0.013). The frequency of massive haemorrhage during caesarean section was higher in the EO-previa group than the LO-previa group (25% vs 9%, p = 0.033).
|Opening of uterine isthmus||p-Value|
|Before 25 weeks of gestation (n = 44)||After 25 weeks of gestation (n = 55)|
|Bleeding during pregnancy||64% (28)||49% (27)||0.148|
|Emergency caesarean section due to bleeding||48% (21)||25% (14)||0.021|
|Caesarean section due to PROM or uterine contractions||4.6% (2)||3.6% (2)||0.663|
|During caesarean section|
|Complete placenta previa at delivery||88.6% (39)||47.3% (26)||<0.001|
|Amount of bleeding during operation (ml)||1823 (325–6050)||1510 (395–7580)||0.013|
|Massive bleeding during operation (>2500 ml)||25% (11)||9% (5)||0.033|
|Placenta accreta||11.4% (5)||1.8% (1)||0.085|
|Gestational weeks at delivery||36 w 0 d (25 w 5 d–37 w 5 d)||36 w 5 d (25 w 3 d–38 w 0 d)||0.305|
|Neonatal birth weight (g)||2499 (921–3211)||2574 (833–3893)||0.281|
|1 min||7 (1–9)||8 (1–9)||0.073|
|5 min||9 (4–10)||9 (2–10)||0.260|
|Umbilical artery pH||7.31 (7.1–7.39)||7.31 (7.16–7.54)||0.727|
PROM, premature rupture of membrances; w, weeks; d, days.
Data presented as median (range) or % (n).
In the EO-previa group, the adjusted odds ratio for emergency caesarean section due to bleeding was 2.7 [95% confidence interval (CI) 1.1–6.2], while that for massive haemorrhage was 3.3 (95% CI 1.1–10.5) (Table 3).
|Odds ratio (95% confidence interval)||p-Value|
|Emergency caesarean section due to bleeding|
|Early-opening uterine isthmus||2.7 (1.1–6.2)||0.023|
|Massive bleeding during caesarean section|
|Early-opening uterine isthmus||3.3 (1.1–10.5)||0.039|
Covariate: complete previa.
Emergency caesarean section due to bleeding was defined as a caesarean section performed before a planned caesarean section due to uncontrollable bleeding of more than 100 ml. Massive bleeding was defined as more than 2500 ml of bleeding during surgery.
This study found that the frequency of emergency caesarean section due to active bleeding during pregnancy, and the amount of bleeding during caesarean section were significantly higher in the EO-previa group than the LO-previa group, whereas the frequency of bleeding during pregnancy did not differ between the two groups.
The uterine isthmus opens gradually with advancing gestation. It has been reported that only one-quarter of the uterine isthmus is open at 13 weeks of gestation . In a previous investigation, the authors found that the uterine isthmus was completely open at 20 weeks of gestation in half of cases with normal placenta. However, the present study found that the uterine isthmus was completely open in 19% (19/99) of patients in the study population.
In cases of LO-previa, as the uterine isthmus is not open at 20 weeks of gestation, the placenta may develop predominantly in the lower uterine body instead of in the uterine isthmus. Consequently, it is hypothesized that the decidual tissue of the uterine isthmus does not receive rich blood flow in patients with LO-previa. However, in patients with EO-previa, as the placenta in the uterine isthmus is likely to be developed from early gestation, blood-rich decidua may form in the uterine isthmus. With uterine contractions that occur with advancing gestation, decidua with a rich blood flow is likely to undergo destructive changes, resulting in bleeding during pregnancy. Consequently, emergency caesarean section is required more frequently in patients with EO-previa than in patients with LO-previa.
EO-previa was also associated with a high frequency of massive haemorrhage during caesarean section. It was assumed that the placenta widely covered the uterine isthmus which is difficult for the spiral artery to contract. Thus, atonic bleeding following placental separation is more likely to occur in patients with EO-previa. In previous studies, the length of the uterine cervix was associated with massive haemorrhage and the frequency of emergency caesarean section in patients with placenta previa , , and . Fukushima et al.  investigated cases of placenta previa that were categorized based on a cervical length of 30 mm, and demonstrated that a shorter cervical length was a risk factor for both massive intra-operative blood loss and placental adherence. Mimura et al.  also concluded that a short cervical length, which indicated the presence of an extended lower uterine segment, was associated with massive bleeding during caesarean section because the condition is likely to involve atonic bleeding after placental removal. Similar to previous studies that investigated the association with the uterine cervix, this study found that massive haemorrhage occurred frequently during caesarean section in patients with EO-previa due to weak contraction at the isthmus following placental separation. However, it was assumed that there was less extension of the lower uterine segment and the attached area of the isthmus in patients with LO-previa than in patients with EO-previa.
A limitation of the present study is the determination of when the isthmus opened. Although there were no cases in which the isthmus opened gradually during transvaginal investigation, the effects of uterine contraction are considerable for such timing. As ultrasound evaluations were performed every 2 weeks, a margin of error of up to 2 weeks should be tolerated. In this study, outcomes were compared between patients in whom the isthmus opened before and after 25 weeks of gestation. Accurate ultrasound diagnosis of placenta previa should be made after opening of the isthmus, because the opening isthmus has a large effect on placental migration. The authors believe that uterine isthmus findings following a diagnosis of placenta previa could provide useful information for further management of placenta previa.
Patients with placenta previa in whom the uterine isthmus opened early showed a high risk for bleeding during pregnancy, and massive haemorrhage during caesarean section, irrespective of placental adherence and placental location (i.e. complete or incomplete placenta previa). The results of this study, which began accumulating data in the mid-gestational period, could lead to improvements in fetal and maternal outcomes.
Conflict of interest
The study protocol was approved by the Institutional Review Board of Showa University School of Medicine. Written informed consent form was obtained from all patients.
-  T. Mimura, J. Hasegawa, M. Nakamura, et al. Correlation between the cervical length and the amount of bleeding during cesarean section in placenta previa. J Obstet Gynaecol Res. 2011;37:830-835 Crossref
-  J. Hasegawa, R. Matsuoka, K. Ichizuka, et al. Predisposing factors for massive hemorrhage during cesarean section in patients with placenta previa. Ultrasound Obstet Gynecol. 2009;34:80-84 Crossref
-  M. Saitoh, K. Ishihara, T. Sekiya, T. Araki. Anticipation of uterine bleeding in placenta previa based on vaginal sonographic evaluation. Gynecol Obstet Invest. 2002;54:37-42 Crossref
-  J. Hasegawa, M. Nakamura, S. Hamada, K. Ichizuka, A. Sekizawa, T. Okai. Opening of the uterine isthmus at 11–13 weeks’ gestation is not related to developmental abnormalities of the placenta. Early Hum Dev. 2013;89:973-976 Crossref
-  M.M. Zaitoun, M.M. El Behery, A.A. Abd El Hameed, B.S. Soliman. Does cervical length and the lower placental edge thickness measurement correlates with clinical outcome in cases of complete placenta previa?. Arch Gynecol Obstet. 2011;284:867-873 Crossref
-  K. Fukushima, A. Fujiwara, A. Anami, et al. Cervical length predicts placental adherence and massive hemorrhage in placenta previa. J Obstet Gynaecol Res. 2012;38:192-197 Crossref
a Department of Obstetrics and Gynaecology, Showa University School of Medicine, Tokyo, Japan
b Department of Obstetrics and Gynaecology, St. Marianna University School of Medicine, Kanagawa, Japan
⁎ Corresponding author at: Department of Obstetrics and Gynaecology, St. Marianna University School of Medicine, 2-16-1 Sugao Miyamaeku, Kawasaki 216-8511, Kanagawa, Japan. Tel.: +81 449778111.
© 2016 Elsevier Ireland Ltd, All rights reserved.