Clinical trial NCT04137783: ABCA3 Gene and RDS in Late Preterm and Term Infants
Official title: ABCA3 Gene Mutations in Late Preterm and Term Infants With Fatal Unexplained Respiratory Distress Syndrome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Respiratory Distress Syndrome, Newborn
Keywords: respiratory distress syndrome
ABCA3 gene
exome sequencing
Lead sponsor: Children's Hospital of Chongqing Medical University
Sponsor class: OTHER
First posted: 2019-10-24
Enrollment: 39
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All the infants ≥34 weeks'gestation was admitted in neonatal intensive care unit of Children's Hospital of Chongqing Medical University from January 2013 to December 2018

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Mortality
timeFrame: through study completion, an average of 1 month
Secondary outcomes:
measure: the Onset of Respiratory Distress Syndrome
timeFrame: up to 1 week
measure: the Age of Developing Severe RDS Marked With Oxygenation Index of 16
timeFrame: through study of completion, an average of 1 month
measure: Radiological Score
timeFrame: through study of completion, an average of 1 month
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Children's hospital of Chongqing Medical University
state: Chongqing
Study officials:
affiliation: Children's Hospital of Chongqing Medical University
name: Wang Jianhui, Doctor
role: PRINCIPAL_INVESTIGATOR
References: