Clinical trial NCT02442518: Antenatal Diagnosis of Placental Attachment Disorders
Official title: Antenatal Diagnosis of Placental Attachment Disorders
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Placenta Accreta
Placenta Previa
Keywords: placenta accreta
placenta previa
ultrasound
Lead sponsor: Università degli Studi di Brescia
Sponsor class: OTHER
Collaborators: name: Azienda Ospedaliera San Gerardo di Monza
name: IRCCS Burlo Garofolo
name: Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
name: Azienda Ospedaliero-Universitaria di Parma
name: ARNAS Civico di Cristina Benefratelli, Palermo
name: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
name: University of Milan
name: A.O.U. Città della Salute e della Scienza
name: Ospedale Valduce, Como
name: Azienda Ospedaliera Bolognini di Seriate Bergamo
First posted: 2015-05-13
Enrollment: 2254
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: women with placenta previa diagnosed at antenatal ultrasound in the third trimester of pregnancy (lower placental edge within 20 mm from the internal os above 26 week's gestation)

Brief summary: The accuracy of sonographic prenatal detection of invasive placentation is unclear. The objective of this prospective, multicenter, observational study is to assess the performance of ultrasound for prenatal identification of invasive placentation in women with placenta previa.

This study involves more than 25 hospitals in Italy.

Detailed description: Background: Morbidly adherent placenta is a spectrum of conditions characterized by an abnormal adherence of the placenta to the implantation site. Three major variants of adherent placentation can be recognized according to the degree of trophoblastic invasion through the myometrium and the uterine serosa: placenta accreta, placenta increta and placenta percreta. All varieties of invasive placentation are associated with a significant increase in maternal morbidity.Placenta previa and previous uterine surgery represent the major risk factors for invasive placentation. Prenatal diagnosis of invasive placentation is associated with a reduced risk of maternal complications such as peripartum blood loss, need for transfusions and rate of hysterectomy, as it allows a preplanned treatment of the condition, however the performance of antenatal ultrasound and of different sonographic signs is not consistent across published studies because of limited sample size, retrospective design, variability of inclusion criteria and definition of invasive placentation.

Objectives: The aim of this study is to systematically assess the performance of ultrasound in the prenatal diagnosis of placenta accreta and its variants and to evaluate the role of the different specific ultrasound signs in predicting disorders of invasive placentation. The sonographic signs assessed in this study were: (1) vascular lacunae within the placenta, (2) loss of normal hypoechoic retroplacental zone, (3) interruption of the bladder line and/or focal exophytic masses extending into the bladder space, considered together and labeled as 'abnormalities of the uterus - bladder interface.

Design:prospective, multicenter, observational study of pregnant women with placenta previa.

Methods: The investigators hypothesized that ultrasound has a sensitivity of at least 80% and a specificity of at least 97%, with 10% confidence intervals, for antenatal diagnosis of invasive placentation.The investigators would require 2048 women with placenta previa, of whom approximately 61 (3%) will have morbidly adherent placenta, to test the null hypothesis with a 0.05 risk of type I error (alpha). Supposing a 10% of women with incomplete follow up the investigators aim to enroll 2254 women in this study.

Diagnostic criteria that suggested placenta accreta, increta, or percreta included one or more of the following situations: (1) obliteration of the clear space, defined as the obliteration of any part of the echolucent area located between the uterus and placenta; (2) visualization of placental lacunae, defined as multiple linear, irregular vascular spaces within the placenta; and (3) interruption of the posterior bladder wall-uterine interface such that the usual continuous echolucent line appears instead as a series of dashes.

The degree of placental invasion was defined as follows: (i) placenta accreta was assumed when placental 'cones' disrupted the decidual zone with mildly increased vascularization around these cones ; (ii) placenta increta was diagnosed when placental invasion into the myometrium was sonographically suspected as a result of the presence of irregular and diffuse demarcation of the placental - uterine wall interface and thinning of the myometrium that was overlying the placental - myometrial tissue. Placenta increta was also characterized by increased vascularization and irregularly shaped intraplacental vascular lacunae, resembling the characteristic 'moth damage' appearance ; and (iii) the sonographic finding of placenta percreta was defined by a complete absence of the myometrium, with the placenta extending to the serosa, or beyond, including vascular breakthrough.In addition, placenta percreta was also characterized by massive subplacental hypervascularization, with vessels extending irregularly into the placental - myometrial tissue and with numerous large intraplacental lacunae.

Clinical and histopathological assessment of placental invasion:

Sonographic findings were compared with the clinical outcome during and after delivery and the histomorphological examination of the placenta, performed by pathologists experienced in obstetric histopathology, who were blinded to the sonographic findings.

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Main Outcomes measure:

Primary Outcome: sensitivity (SN), specificity(SP), positive likelihood ratio (LR+), negative likelihood ratio (LR - ) and diagnostic odds ratio (DOR) of antenatal ultrasound and different sonographic signs for in prediction of morbidly adherent placenta.

Secondary Outcome: to evaluate whether the maximum degree of placental invasion (placenta accreta, increta or percreta) can be predicted with antenatal ultrasound.

Eligibility criteria: Inclusion Criteria:

* Placenta previa diagnosed with ultrasound above 26 weeks' gestation (lower edge reached and/or overlapped the internal cervical os, or the lower edge was between 0.1 and 20.0 mm from the internal cervical os)

Exclusion Criteria:

* Age \< 18 years
* prepartum bleeding or fetal distress requiring immediate emergency Cesarean section before the enrollment of the woman

Primary outcomes:
measure: diagnostic accuracy of sonographic prenatal detection of invasive placentation
timeFrame: clinical and histopathological assessment of placental invasion at delivery
Secondary outcomes:
measure: maximum degree of placental invasion
timeFrame: clinical and histopathological assessment of placental invasion at delivery
Other outcomes:
Locations:
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo di Monza
state: MB
city: Brescia
country: Italy
facility: Brescia University, Spedali Civili Di Brescia
city: Palermo
country: Italy
facility: ARNAS CIVICO di Cristina Benefratelli
Study officials:
affiliation: BRESCIA UNIVERSITY, SPEDALI CIVILI DI BRESCIA
name: NICOLA FRATELLI, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: ARNAS Civico di Cristina Benefratelli
name: GIUSEPPE CALI, MD
role: PRINCIPAL_INVESTIGATOR
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