Cell-free Fetal DNA Circulating in the Maternal Plasma as a Marker for Morbidly Adherent Placenta (DNA-Accreta)

Cell-free Fetal DNA Circulating in the Maternal Plasma as a Marker for Morbidly Adherent Placenta in a High Risk Population

The purpose of this study is to determine whether, in a high risk population (placenta praevia and previous caesarean or prenatal suspicion of morbidly adherent placenta (MAP)), the concentration of cell-free fetal DNA circulating in the maternal plasma is significantly increased in the subgroup of morbidly adherent placenta (MAP) cases , in order to determine if the dosage of cell-free fetal DNA circulating in the maternal plasma may be a useful biological tool to detect MAP, alone or in addition to the imagery findings (ultrasonography and RMI).

Study Overview

• Status: Unknown
• Conditions: Placenta Accreta; Morbidly Adherent Placenta; Placenta Percreta; Placenta Increta
• Intervention / Treatment: Biological: Women at high risk of MAP

Detailed Description

Background: Morbidly adherent placenta (MAP) is a life-threatening condition characterized by placental villi being abnormally adherent to the myometrium. Prenatal identification of MAP is essential to anticipate the risk and plan optimal delivery conditions for these women while this is associated to a maternal outcome improvement. Prenatal identification based on Doppler ultrasound and/or MRI is associated with high rates of false-positive or false-negative findings responsible for adverse effects. Some cases reports have suggested that the concentration of cell-free fetal DNA circulating in the maternal plasma is significantly increased in a context of morbidly adherent placenta (MAP).

Objective: The primary objective is to determine whether the concentration of cell-free fetal DNA circulating in the maternal plasma is significantly increased in women with morbidly adherent placenta (MAP) compared to women with placenta praevia and previous caesarean. Secondary objectives are to determine whether cell-free fetal DNA circulating in the maternal plasma is a useful biological tool to detect MAP, alone or in addition to the imagery findings (ultrasonography and RMI), in a high risk population (placenta praevia and previous caesarean or only prenatal suspicion of MAP).

Design: Prospective observational study of pregnant women with placenta praevia and previous cesaeran or with prenatal suspicion of placenta accreta, conducted in 5 centers.

Methods: We expect to include 83 women at risk of MAP in two years, of whom approximately 17 (20%) will have a MAP.

Main outcome measures: The primary outcome measure is concentration of cell-free fetal DNA circulating in maternal plasma.

Conclusion: This study will be the first prospective study to include women at risk of placenta accreta and to investigate whether the concentration of cell-free fetal DNA circulating in maternal plasma is increased in MAP women and whether it is a useful biological marker to detect prenatally MAP in a high risk population.

• Study Type: Observational
• Enrollment (Actual): 63

Contacts and Locations

Study Locations

• France
  • Angers, France, 44933
    • Angers University Hospita

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Women delivering in 5 maternity units that participate in a Population-based prospective observational study of pregnant women with a placenta praevia and previous cesarean or with prenatal suspicion of accreta (PACCRETA)

Description

Inclusion Criteria:

Every woman:

• delivering in one of the 5 maternity units that participate to a Population-based prospective observational study of pregnant women with a placenta praevia and previous cesarean or with prenatal suspicion of accreta (PACCRETA) .
• With a placenta praevia and at least one previous cesarean delivery or having a prenatal suspicion of placenta accreta
• aged 18 or more

Exclusion Criteria:

Every woman:

• not understanding French.
• refusing to participate in the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Concentration of cell-free fetal DNA circulating in the maternal plasma	from 24 weeks gestation to delivery

Secondary Outcome Measures

Outcome Measure	Time Frame
Sensitivity of the concentration of cell-free fetal DNA	from 24 weeks gestation to delivery
Specificity of the concentration of cell-free fetal DNA	from 24 weeks gestation to delivery
Positive predictive value of concentration of cell-free fetal DNA	from 24 weeks gestation to delivery
Negative predictive value of the concentration of cell-free fetal DNA	from 24 weeks gestation to delivery
Sensitivity, specificity, positive predictive value (PPV) and negative (NPV) of the concentration of cell-free fetal DNA in association with clinical criteria ( risk factors for MAP)	from 24 weeks gestation to delivery
Sensitivity, specificity, positive predictive value (PPV) and negative (NPV) of concentration of cell-free fetal DNA in association with imaging criteria magnetic resonance	from 24 weeks gestation to delivery
Sensitivity, specificity, positive predictive value (PPV) and negative (NPV) of the concentration of cell-free fetal DNA and clinical criteria in association with clinical criteria, sonographic criteria and with magnetic resonance imaging criteria	from 24 weeks gestation to delivery

Collaborators and Investigators

• Sponsor: University Hospital, Angers
• Collaborators: Assistance Publique - Hôpitaux de Paris; Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Study Director: Catherine Deneux-Tharaux, MD, PhD, Inserm U1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Paris, France

Publications and helpful links

General Publications

• Sekizawa A, Jimbo M, Saito H, Iwasaki M, Sugito Y, Yukimoto Y, Otsuka J, Okai T. Increased cell-free fetal DNA in plasma of two women with invasive placenta. Clin Chem. 2002 Feb;48(2):353-4. No abstract available.
• Jimbo M, Sekizawa A, Sugito Y, Matsuoka R, Ichizuka K, Saito H, Okai T. Placenta increta: Postpartum monitoring of plasma cell-free fetal DNA. Clin Chem. 2003 Sep;49(9):1540-1. doi: 10.1373/49.9.1540. No abstract available.
• Kayem G, Deneux-Tharaux C, Sentilhes L; PACCRETA group. PACCRETA: clinical situations at high risk of placenta ACCRETA/percreta: impact of diagnostic methods and management on maternal morbidity. Acta Obstet Gynecol Scand. 2013 Apr;92(4):476-82. doi: 10.1111/aogs.12078. Epub 2013 Feb 15.
• Sentilhes L, Goffinet F, Kayem G. Management of placenta accreta. Acta Obstet Gynecol Scand. 2013 Oct;92(10):1125-34. doi: 10.1111/aogs.12222.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): November 1, 2015
• Study Completion (Anticipated): November 1, 2016

Study Registration Dates

• First Submitted: May 19, 2016
• First Submitted That Met QC Criteria: May 24, 2016
• First Posted (Estimate): May 27, 2016

Study Record Updates

• Last Update Posted (Estimate): May 27, 2016
• Last Update Submitted That Met QC Criteria: May 24, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Biological markers; Placenta accreta; previous caesarean; placenta praevia; Cell-free fetal DNA
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Placenta Diseases; Placenta Accreta
• Other Study ID Numbers: DC-2011-1467

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No