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Completed

NCT Number: NCT02352207

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

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.

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Key information

Age range

18 year and older

Sex eligibility

Female

Study type

Observational

Primary location

Hôpital Necker - Enfants Malades

Paris, 75015, France

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

identification of a pulmonary malformation in the fetus

Other

Primary outcomes

  1. 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

Secondary outcomes

  1. Necessity of antenatal treatment

    Time frame: At Birth of the child

    Thoracic drainage, amniotic drainage, corticosteroids

  2. Therapeutic abortion - fetal death

    Time frame: At Birth of the child

  3. 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

  4. Identification of KRAS mutation

    Time frame: 2 years

    PCR analysis of known K-RAS mutations in codons 12 and 13

  5. Level in delta Forskoline/IBMX Short Circuit Current (µA/cm2)

    Time frame: 2 years

    CFTR activity evaluation

  6. CFTR gene expression

    Time frame: 2 years

    quantitative PCR

  7. CFTR protein expression

    Time frame: 2 years

    immunohistochemistry

  8. Basal short circuit current : Isc Basal

    Time frame: 2 years

  9. Effects of other potentiators on CFTR activity : ΔGenistein, ΔVX-770

    Time frame: 2 years

  10. Inhibition of CFTR (inh-172) : ΔInh-172

    Time frame: 2 years

  11. Response to ENaC inhibitors : ΔAmiloride, Δbenzamil

    Time frame: 2 years

  12. Activation of Calcium Dependant Channels : ΔUTP

    Time frame: 2 years

  13. Inhibition of SLC26A9 : ΔGlyH-101

    Time frame: 2 years

  14. Response to inhibitors of basolateral K+ secretion : ΔBarium ; ΔChromanol

    Time frame: 2 years

  15. Secretion of HCO3- in response to forskoline : Δ HCO3- primary culture

    Time frame: 2 years

  16. Gene expression of other channels : ENaC, SLC26A9, CaCC, KVLQT1 and KCa3.1

    Time frame: 2 years

    quantitative PCR

  17. Protein expression of other channels : ENaC, SLC26A9, CaCC, KVLQT1 and KCa3.1

    Time frame: 2 years

    immunohistochemistry

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Collaborators

  • URC-CIC Paris Descartes Necker Cochin

Registry information

Official study title

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

Acronym: MALFPULM

Important dates

Study start
2015
Primary completion
2018
Study completion
2021
First posted
Feb 2, 2015
Registry last updated
Nov 20, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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