Risk Factors of Neonatal Respiratory Distress for Newborns With Prenatally Diagnosed Congenital Lung Malformations
- Conditions
- Foetus With Congenital Pulmonary Malformation
- Interventions
- Other: identification of a pulmonary malformation in the fetus
- Registration Number
- NCT02352207
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
This research focuses on lung malformations detected in fetuses during prenatal ultrasound exams. Pathogenic mechanisms of these rare malformations are poorly understood. Improved knowledge is needed, to give families better information, and to better standardize treatment decisions The main goal is to better predict neonatal complications associated with these malformations, by identifying key predictive markers during the fetal period.
To achieve this objective, it is planned to include 400 pregnant women with prenatal diagnosis of pulmonary malformation in 45 health centers in France. This is the largest study on this topic at the international level.
- Detailed Description
The main objective of the study is to develop a prognostic model for estimating the risk of neonatal respiratory distress in children with prenatally diagnosed congenital pulmonary malformation.
The study will be offered to all pregnant women referred to a Center for Prenatal Diagnosis (CPD), due to the identification of a congenital lung malformations in the fetus. This study does not induce any changes in clinical and therapeutic monitoring proposed by the team in charge of the mother. At inclusion, and at each prenatal evaluation, prenatal parameters are entered in an e-CRF. In an effort to minimize any potential intra- and interoperator variability in malformation measurements over time, this study includes a standardized and centralized evaluation of ultrasound and MRI (if available) acquisitions of volume measurements. When the place of delivery is determined, a contact is made before birth with the teams (maternity, neonatology, intensive care unit), so that neonatal data are also collected prospectively. A phone call to the family is planned for the end of the first postnatal month, to identify any respiratory event that would have occurred between returning home after childbirth and the first month.
The routine follow-up of these children is then ensured in accordance with current national recommendations, in conjunction with the reference centers for rare respiratory diseases in children (28 university hospitals, spread across all regions of France). A telephone survey every 6 months with the referring physician in this specialized center or, alternatively, with the family, will collect clinical outcome until the age of 2 years. If a surgical intervention is planned within this interval, consent to collect part of the surgical specimen for research purposes will be solicited. This tissue will be immediately frozen at -80 ° C, to allow laser microdissection and DNA extraction from epithelial cells lining the malformation (Inserm U955). Frozen tissue will be conserved at the biobank of Necker-Enfants Malades.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 436
- Prenatal identification of a congenital pulmonary malformation (hyperechoic and/or cystic pulmonary lesion)
- consent of the mother for participation to the study
- Absence of consent for participation
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description identification of a pulmonary malformation in the fetus identification of a pulmonary malformation in the fetus pregnant women referred to a prenatal Center, because of the identification of a pulmonary malformation in the fetus
- Primary Outcome Measures
Name Time Method Respiratory distress At Birth of the child Respiratory distress at birth is defined by a breathing frequency \> 60/min, or by the presence of chest retraction signs (Silverman score greater than or equal to 2). At least one of these signs must be persistent at 15' of life
- Secondary Outcome Measures
Name Time Method CFTR gene expression 2 years quantitative PCR
Response to ENaC inhibitors : ΔAmiloride, Δbenzamil 2 years Protein expression of other channels : ENaC, SLC26A9, CaCC, KVLQT1 and KCa3.1 2 years immunohistochemistry
Effects of other potentiators on CFTR activity : ΔGenistein, ΔVX-770 2 years Activation of Calcium Dependant Channels : ΔUTP 2 years Inhibition of CFTR (inh-172) : ΔInh-172 2 years Therapeutic abortion - fetal death At Birth of the child Severe respiratory distress At Birth of the child Severe respiratory distress at birth will be defined by the presence of at least one of the following parameters: persistent need at 15' of supplemental oxygen; Persistent need at 15' for a ventilatory support (non-invasive or invasive); neonatal death
CFTR protein expression 2 years immunohistochemistry
Response to inhibitors of basolateral K+ secretion : ΔBarium ; ΔChromanol 2 years Inhibition of SLC26A9 : ΔGlyH-101 2 years Secretion of HCO3- in response to forskoline : Δ HCO3- primary culture 2 years Gene expression of other channels : ENaC, SLC26A9, CaCC, KVLQT1 and KCa3.1 2 years quantitative PCR
Necessity of antenatal treatment At Birth of the child Thoracic drainage, amniotic drainage, corticosteroids
Identification of KRAS mutation 2 years PCR analysis of known K-RAS mutations in codons 12 and 13
Level in delta Forskoline/IBMX Short Circuit Current (µA/cm2) 2 years CFTR activity evaluation
Basal short circuit current : Isc Basal 2 years
Trial Locations
- Locations (1)
Hôpital Necker - Enfants Malades
🇫🇷Paris, France