Risk Factors of Neonatal Respiratory Distress for Newborns With Prenatally Diagnosed Congenital Lung Malformations (MALFPULM)
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|ClinicalTrials.gov Identifier: NCT02352207|
Recruitment Status : Active, not recruiting
First Posted : February 2, 2015
Last Update Posted : March 25, 2019
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.
|Condition or disease||Intervention/treatment|
|Foetus With Congenital Pulmonary Malformation||Other: identification of a pulmonary malformation in the fetus|
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.
|Study Type :||Observational|
|Actual Enrollment :||436 participants|
|Official Title:||Prospective Identification of Predictors of Neonatal Respiratory Distress for Newborns With Prenatally Diagnosed Congenital Lung Malformations : A Population-based, Nationally Representative Study|
|Actual Study Start Date :||March 17, 2015|
|Actual Primary Completion Date :||November 30, 2018|
|Estimated Study Completion Date :||May 30, 2021|
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
Other: identification of a pulmonary malformation in the fetus
- Respiratory distress [ Time Frame: 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
- Necessity of antenatal treatment [ Time Frame: At Birth of the child ]Thoracic drainage, amniotic drainage, corticosteroids
- Therapeutic abortion - fetal death [ Time Frame: At Birth of the child ]
- Severe respiratory distress [ Time Frame: 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
- Identification of KRAS mutation [ Time Frame: 2 years ]PCR analysis of known K-RAS mutations in codons 12 and 13
- Level in delta Forskoline/IBMX Short Circuit Current (µA/cm2) [ Time Frame: 2 years ]CFTR activity evaluation
- CFTR gene expression [ Time Frame: 2 years ]quantitative PCR
- CFTR protein expression [ Time Frame: 2 years ]immunohistochemistry
- Basal short circuit current : Isc Basal [ Time Frame: 2 years ]
- Effects of other potentiators on CFTR activity : ΔGenistein, ΔVX-770 [ Time Frame: 2 years ]
- Inhibition of CFTR (inh-172) : ΔInh-172 [ Time Frame: 2 years ]
- Response to ENaC inhibitors : ΔAmiloride, Δbenzamil [ Time Frame: 2 years ]
- Activation of Calcium Dependant Channels : ΔUTP [ Time Frame: 2 years ]
- Inhibition of SLC26A9 : ΔGlyH-101 [ Time Frame: 2 years ]
- Response to inhibitors of basolateral K+ secretion : ΔBarium ; ΔChromanol [ Time Frame: 2 years ]
- Secretion of HCO3- in response to forskoline : Δ HCO3- primary culture [ Time Frame: 2 years ]
- Gene expression of other channels : ENaC, SLC26A9, CaCC, KVLQT1 and KCa3.1 [ Time Frame: 2 years ]quantitative PCR
- Protein expression of other channels : ENaC, SLC26A9, CaCC, KVLQT1 and KCa3.1 [ Time Frame: 2 years ]immunohistochemistry
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02352207
|Hôpital Necker - Enfants Malades|
|Paris, France, 75015|
|Study Director:||Laurent SALOMON, MD, PhD||Hospital Necker - Enfants Malades|