Clinical trial NCT02352207: Risk Factors of Neonatal Respiratory Distress for Newborns With Prenatally Diagnosed Congenital Lung Malformations
Official title: Prospective Identification of Predictors of Neonatal Respiratory Distress for Newborns With Prenatally Diagnosed Congenital Lung Malformations : A Population-based, Nationally Representative Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Foetus With Congenital Pulmonary Malformation
Keywords: Neonatal respiratory distress
prenatal lung malformation
KRAS mutation
pregnant woman
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2015-02-02
Enrollment: 436
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pregnant women referred to a Center of Prenatal Diagnosis, because of the identification of a pulmonary malformation in the fetus

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.

Eligibility criteria: 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

Primary outcomes:
measure: Respiratory distress
timeFrame: At Birth of the child
Secondary outcomes:
measure: Necessity of antenatal treatment
timeFrame: At Birth of the child
measure: Therapeutic abortion - fetal death
timeFrame: At Birth of the child
measure: Severe respiratory distress
timeFrame: At Birth of the child
measure: Identification of KRAS mutation
timeFrame: 2 years
measure: Level in delta Forskoline/IBMX Short Circuit Current (µA/cm2)
timeFrame: 2 years
measure: CFTR gene expression
timeFrame: 2 years
measure: CFTR protein expression
timeFrame: 2 years
measure: Basal short circuit current : Isc Basal
timeFrame: 2 years
measure: Effects of other potentiators on CFTR activity : ΔGenistein, ΔVX-770
timeFrame: 2 years
measure: Inhibition of CFTR (inh-172) : ΔInh-172
timeFrame: 2 years
measure: Response to ENaC inhibitors : ΔAmiloride, Δbenzamil
timeFrame: 2 years
measure: Activation of Calcium Dependant Channels : ΔUTP
timeFrame: 2 years
measure: Inhibition of SLC26A9 : ΔGlyH-101
timeFrame: 2 years
measure: Response to inhibitors of basolateral K+ secretion : ΔBarium ; ΔChromanol
timeFrame: 2 years
measure: Secretion of HCO3- in response to forskoline : Δ HCO3- primary culture
timeFrame: 2 years
measure: Gene expression of other channels : ENaC, SLC26A9, CaCC, KVLQT1 and KCa3.1
timeFrame: 2 years
measure: Protein expression of other channels : ENaC, SLC26A9, CaCC, KVLQT1 and KCa3.1
timeFrame: 2 years
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Necker - Enfants Malades
Study officials:
affiliation: Hospital Necker - Enfants Malades
name: Laurent SALOMON, MD, PhD
role: STUDY_DIRECTOR
References:
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; , for the MALFPULM study group; members of the MALFPULM study group:. Predicting the risk of respiratory distress in newborns with congenital pulmonary malformations. Eur Respir J. 2022 Feb 3;59(2):2100949. doi: 10.1183/13993003.00949-2021. Print 2022 Feb.
citation: 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 malformations: MALFPULM population-based cohort study. Ultrasound Obstet Gynecol. 2019 Sep;54(3):381-388. doi: 10.1002/uog.20130.