Risk Factors of Neonatal Respiratory Distress for Newborns With Prenatally Diagnosed Congenital Lung Malformations

Foetus With Congenital Pulmonary Malformation Clinical Trial

— MALFPULM  

Official title:

Prospective Identification of Predictors of Neonatal Respiratory Distress for Newborns With Prenatally Diagnosed Congenital Lung Malformations : A Population-based, Nationally Representative Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02352207
• Other study ID #: NI13005
• Status: Completed
• Start date: March 17, 2015
• Est. completion date: March 10, 2021

Study information

• Verified date: October 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 436
• Est. completion date: March 10, 2021
• Est. primary completion date: November 30, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Prenatal identification of a congenital pulmonary malformation (hyperechoic and/or cystic pulmonary lesion)

• consent of the mother for participation to the study

Exclusion Criteria:

• Absence of consent for participation

Related Conditions & MeSH terms

• Congenital Abnormalities
• Foetus With Congenital Pulmonary Malformation
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn

Intervention

Other:
• identification of a pulmonary malformation in the fetus

Locations

Country	Name	City	State
France	Hôpital Necker - Enfants Malades	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (2)

Delacourt C, Bertille N, Salomon LJ, Benachi A, Henry E, Massardier J, Mottet N, Rosenblatt J, Sartor A, Thong-Vanh C, Valat-Rigot AS, Winer N, Lelong N, Khoshnood B; Prenatal MALFPULM Study Group. Prenatal natural history of congenital pulmonary malforma — View Citation

Delacourt C, Bertille N, Salomon LJ, Rahshenas M, Benachi A, Bonnard A, Choupeaux L, Fouquet V, Goua V, Hameury F, Hervieux E, Jouannic JM, Khen-Dunlop N, Le Bouar G, Massardier J, Roditis L, Rosenblatt J, Sartor A, Thong-Vanh C, Lelong N, Khoshnood B; , — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Respiratory distress	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	At Birth of the child
Secondary	Necessity of antenatal treatment	Thoracic drainage, amniotic drainage, corticosteroids	At Birth of the child
Secondary	Therapeutic abortion - fetal death		At Birth of the child
Secondary	Severe respiratory distress	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	At Birth of the child
Secondary	Identification of KRAS mutation	PCR analysis of known K-RAS mutations in codons 12 and 13	2 years
Secondary	Level in delta Forskoline/IBMX Short Circuit Current (µA/cm2)	CFTR activity evaluation	2 years
Secondary	CFTR gene expression	quantitative PCR	2 years
Secondary	CFTR protein expression	immunohistochemistry	2 years
Secondary	Basal short circuit current : Isc Basal		2 years
Secondary	Effects of other potentiators on CFTR activity : ?Genistein, ?VX-770		2 years
Secondary	Inhibition of CFTR (inh-172) : ?Inh-172		2 years
Secondary	Response to ENaC inhibitors : ?Amiloride, ?benzamil		2 years
Secondary	Activation of Calcium Dependant Channels : ?UTP		2 years
Secondary	Inhibition of SLC26A9 : ?GlyH-101		2 years
Secondary	Response to inhibitors of basolateral K+ secretion : ?Barium ; ?Chromanol		2 years
Secondary	Secretion of HCO3- in response to forskoline : ? HCO3- primary culture		2 years
Secondary	Gene expression of other channels : ENaC, SLC26A9, CaCC, KVLQT1 and KCa3.1	quantitative PCR	2 years
Secondary	Protein expression of other channels : ENaC, SLC26A9, CaCC, KVLQT1 and KCa3.1	immunohistochemistry	2 years