Mode of Delivery in Women With Low-lying Placenta

Study Overview
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Brief Summary
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Multicentre study; observational, longitudinal prospective, case-control

Detailed Description
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This is a new protocol to evaluate the mode of birth in women with a low-lying placenta. In particular, we intend to propose a vaginal birth in women having a low-lying placenta with a distance between the inferior placental edge and the internal cervical os, called internal-os-distance (IOD) of > 5 mm, as assessed in the late III trimester using transvaginal sonography. Duration of the study: Duration of the study: 54 months Duration of enrollment: 42 months Duration of follow-up completion of enrolled cases: 6 months Duration of data analysis: 6 months Study Design: During the II trimester scan, all women presenting a placenta located in the lower uterine segment will undergo evaluation by Transvaginal Sonography (TVS). If a placenta previa or a low-lying placenta will be confirmed, the woman will be recruited and asked to participate in our study, by signing a written informed consent. In addition women attending the Maternity Triage with vaginal bleeding at < 316/7 weeks of gestation, with a diagnosis of placenta previa or low-lying placenta and not requiring an emergency delivery will be asked to participate and will be recruited after signing the informed consent. An expert Obstetrician will perform the TVS as scheduled, after inviting the woman to void. The assessment will include: the measurement of the IOD (first caliper on the internal cervical os and second caliper on the inferior placental edge). In case of a marginal sinus, the distance between the internal cervical os and the marginal sinus will also be assessed; the cervical length (defined as shortened if ≤25 mm); the placental edge thickness, measured within 1 cm from the meeting point between the basal and the chorionic plate. The placental edge will be considered thick if > 1cm or if the angle is >45°. All women with a resolution of a previa or low-lying placenta will be assessed in accordance with the protocol of each participating Maternity Unit, including a scan assessment at 38-39 weeks of gestation or within 28 days from the due date. Calculation of sample size / power: Considering that the incidence of previa and low-lying placenta is approximately 2% at the II trimester scan and 0.4% at birth, and assuming a C.I. of 19% in the probability of vaginal birth in women with low-lying placenta/resolved low-lying (> 20 mm), 27 women will be needed for each participating Maternity Unit at the late III trimester scan. Anticipating a 10% drop out, 30 women will be needed to achieve a 95% statistical power to identify a clinically relevant difference in the rate of vaginal birth. This leads to the need of recruiting 150 women at the II trimester scan. CRF and data management: All data will be recorded through CRF provided by the promoter center and the database will be based on Microsoft Excel. A sample of about 20-30 patients for each enrollment center is necessary to have a statistical power of 95% in detecting a clinically relevant difference in outcomes in the various study groups. Analysis plan: Descriptive statistics will be performed for all variables evaluated in the study population. Variables will be described by mean and standard deviation if normally distributed, otherwise by median and interquantile range; proportions will be used for categorical variables. The quantitative variables, among the study groups defined by the IOD at the last TVS, will be compared by parametric and non-parametric tests, whereas the categorical variables will be compared using Pearson's chi2 test (Fisher exact test where appropriate). The analyses for the primary outcome measure will be performed among women admitted to labor. A multivariate analysis will be conducted to assess the association between obstetric variables and vaginal birth. A p-value<0.05 will be considered significant.

Official Title
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Mode of Delivery in Women With Low-lying Placenta: an Italian Multicentre Study

Conditions
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Low-Lying; Placenta, Hemorrhage, Complicating Delivery

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Minimum age of 18 Women with placenta previa or low-lying placenta confirmed by TVS at 19-23 6/7 weeks of gestation. Women attending Maternity Triage with vaginal bleeding at < 32 weeks of gestation, with a diagnosis of placenta previa or low-lying placenta and not requiring an emergency delivery. Women with a normally located placenta at the II trimester ultrasound scan, at 19-23 6/7 week of gestation (control group) Single pregnancy Signature of the informed consent to participate in the study Note: Women of the control group will be recruited in a 1:3 ratio. After the inclusion of 1 case, 3 women with a normally located placenta will be recruited, according to the parity of the woman representing the case (e.g.: 1 CASE= nulliparous woman, 3 CONTROLS= 3 nulliparous women). Exclusion Criteria: Suspected or confirmed invasive placentation (i.e., placenta accreta) Vaginal bleeding requiring emergency delivery Inability to meet the conditions set out in the study protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Women having a persistent low-lying placenta with an IOD between 6 and 20 mm<br>Women having a persistent low-lying placenta with an IOD between 6 and 20 mm who will be offered a vaginal birth, considering 3 subgroups: 1) 6-10 mm; 2) 11-20mm; 3) > 20 mm (resolution of previa or low-lying placenta) | |
| Women with normal located placenta<br>Women with a normally located placenta at the II trimester scan will represent the control group. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of vaginal delivery and urgent cesarean section | Rate of vaginal birth and emergency cesarean section in labor due to vaginal bleeding | Until the end of the study (approximately 54 months). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of resolution of placenta previa or low-lying | Frequency of resolution of placenta previa or low-lying in relation to the placental location at the time of diagnosis and in relation to maternal history of hysterotomy | Until the end of the study (approximately 54 months). | 
| Placental migration speed and its correlation with different variables | Description of time needed for resolution of previa or low-lying placenta in relation to placental location at diagnosis (anterior/posterior; praevia/low-lying), and maternal history of hysterotomy, and its correlation to the mode of birth and risk of bleeding during pregnancy and in labor. | Until the end of the study (approximately 54 months). | 
| Frequency of ultrasound visualization of the marginal breast in low-lying placentas and other variables | Frequency of marginal sinus in women with low-lying placenta and its relation with mode of birth and risk of ante-, intra-, and post-partum bleeding. | Until the end of the study (approximately 54 months). | 
| Refusal of elective caesarean section | Rate of women declining the mode of birth suggested by clinicians during counselling. | Until the end of the study (approximately 54 months). | 
| Morbidity associated with the various groups of placental distance analyzed by the antepartum hemorrhage incidence. | Incidence of antepartum hemorrhage requiring hospital admission or immediate delivery. | Until the end of the study (approximately 54 months). | 
| Morbidity associated with the various groups of placental distance studied with the intrapartum hemorrhage incidence. | Incidence of intrapartum hemorrhage requiring emergency CS. | Until the end of the study (approximately 54 months). | 
| Morbidity associated with the various groups of placental distance through the severe postpartum hemorrhage incidence. | Incidence of severe postpartum hemorrhage, defined as bleeding ≥ 1000 ml following birth and administration of uterotonic drugs, use of balloon tamponade, uterine artery embolization, ligature of uterine arteries, hysterectomy, blood transfusion; | Until the end of the study (approximately 54 months). | 
| Morbidity associated with the various groups of placental distance associated with the admission to Intensive Care Unit (ICU) | The maternal admission to ICU. | Until the end of the study (approximately 54 months). | 
| Morbidity associated with the various groups of placental distance described by the preterm bith incidence | Incidence of preterm birth can described the morbidity associated wiith the various groups of placenta distance. | Until the end of the study (approximately 54 months). | 
| Morbidity associated with the various groups of placental distance described through the preterm incidence less than 32 weeks. | Incidence of preterm birth < 32 weeks. | Until the end of the study (approximately 54 months). | 
| Morbidity associated with the various groups of placental distance according to the neonatal admission to ICU | Neonatal admission to Neonatal ICU and length of stay. | Until the end of the study (approximately 54 months). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mode of birth, low-lying placenta, labor and birth