ABCA3 Gene and RDS in Late Preterm and Term Infants

Study Overview
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Brief Summary
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Respiratory distress syndrome (RDS) is the most common respiratory cause of mortality and morbidity in very preterm infants, but it also could be seen in late preterm and term infants. Some genetic mechanisms were involved in the pathogenesis of RDS in late preterm and term infants. ATP-binding cassette transporter A3 (ABCA3) is essential for the production of pulmonary surfactant, whose mutation is the most common monogenetic cause of RDS in newborns. It also takes a vital role on unexplained RDS (URDS) in late preterm and term infants. Some previous studies showed that URDS with homozygous or compound heterozygous ABCA3 mutations had high mortality, while different mutation types could lead to different outcomes. However, most of the study focused on URDS with ABCA3 gene mutations, and there is no evidence that URDS without confirmed gene mutations have relatively better or worse outcomes. Furthermore, all the population in previous study are non-Asian races, which indicated that all the study conclusion is not applicable in Asia. Based on the next-generation sequencing technology, exome sequencing has been widely used in the clinic. In our neonatal intensive care unit (NICU), a clinic exome sequencing was usually performed in infants with fatal URDS. The present study was designed to compare the URDS with ABCA3 gene mutations with those without confirmed gene mutations and to establish the relationship between various ABCA3 gene mutations and variant RDS severity and outcomes.

Official Title
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ABCA3 Gene Mutations in Late Preterm and Term Infants With Fatal Unexplained Respiratory Distress Syndrome

Conditions
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Respiratory Distress Syndrome, Newborn

Intervention / Treatment
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* Other: no intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: infants ≥34 weeks' gestation meet the fatal respiratory distress syndrome as following: (1) manifestations and chest radiograph are compatible with RDS; (2) at least 7days on invasive ventilation with FiO2 ≥60%, or persistent hypoxemic respiratory failure on FiO2 100% regardless of duration of invasive ventilation undergone exome sequencing Exclusion Criteria: culture-positive sepsis cardiopulmonary malformations pulmonary hypoplasia known surfactant mutations such as SFTPB, SFTPC, CHPT1, LPCAT1 and PCYT1B were excluded.

Ages Eligible for Study
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Maximum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| homozygous or compound heterozygous ABCA3 mutations<br>patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated homozgyous or compound heterozygous ABCA3 mutations. | Other: no intervention<br>* there is no intervention in this study, only observation.<br>|
| single ABCA3 mutation<br>patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated single mutations. | Other: no intervention<br>* there is no intervention in this study, only observation.<br>|
| no ABCA3 mutations<br>patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which exclude all gene mutations involving in the respiratory disease. | Other: no intervention<br>* there is no intervention in this study, only observation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | the ratio of dead patients against the corresponding group population | through study completion, an average of 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Onset of Respiratory Distress Syndrome | the age when the patients presented with respiratory distress sydnrome | up to 1 week | 
| the Age of Developing Severe RDS Marked With Oxygenation Index of 16 | the age when the patients develop severe RDS,which is marked with an oxygenation index of 16 | through study of completion, an average of 1 month | 
| Radiological Score | The chest x-ray was rated in three sections on both sides of the lung: apex to the carina, carina to the lower pulmonary vein, and lower pulmonary vein to diaphragm. The incidence of radiological features, including ground-glass opacity, reticular pattern, air bronchogram, atelectasis, and air leak, was evaluated for each lung section, respectively. Each finding was scored as 0=none, 1=discrete，2=diffuse, and 3= strong at each section. An overall cumulative score was calculated by adding the individual section scores together, making a minimum of 0, and a maximum of 18 for each patient. Higher scores mean the higher severity of the radiological apperance, and commonly predict worse respiratory outcomes. | through study of completion, an average of 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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respiratory distress syndrome, ABCA3 gene, exome sequencing