Prospective Identification of Predictors of Neonatal Respiratory Distress for Newborns With Prenatally Diagnosed Congenital Lung Malformations : A Population-based, Nationally Representative Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 436
- 试验地点
- 1
- 主要终点
- Respiratory distress
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Prenatal identification of a congenital pulmonary malformation (hyperechoic and/or cystic pulmonary lesion)
- •consent of the mother for participation to the study
排除标准
- •- Absence of consent for participation
结局指标
主要结局
Respiratory distress
时间窗: 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
次要结局
- Therapeutic abortion - fetal death(At Birth of the child)
- Severe respiratory distress(At Birth of the child)
- CFTR protein expression(2 years)
- Response to inhibitors of basolateral K+ secretion : ΔBarium ; ΔChromanol(2 years)
- CFTR gene expression(2 years)
- Response to ENaC inhibitors : ΔAmiloride, Δbenzamil(2 years)
- Protein expression of other channels : ENaC, SLC26A9, CaCC, KVLQT1 and KCa3.1(2 years)
- Effects of other potentiators on CFTR activity : ΔGenistein, ΔVX-770(2 years)
- Inhibition of CFTR (inh-172) : ΔInh-172(2 years)
- Activation of Calcium Dependant Channels : ΔUTP(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)
- Necessity of antenatal treatment(At Birth of the child)
- Identification of KRAS mutation(2 years)
- Level in delta Forskoline/IBMX Short Circuit Current (µA/cm2)(2 years)
- Basal short circuit current : Isc Basal(2 years)