ABCA3 Gene and RDS in Late Preterm and Term Infants

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

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Distress Syndrome, Newborn
• Intervention / Treatment: Other: no intervention

• Study Type: Observational
• Enrollment (Actual): 39

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400014
      • Children's Hospital of Chongqing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 10 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
homozygous or compound heterozygous ABCA3 mutations; patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated homozgyous or compound heterozygous ABCA3 mutations.	Other: no intervention; there is no intervention in this study, only observation.
single ABCA3 mutation; patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated single mutations.	Other: no intervention; there is no intervention in this study, only observation.
no ABCA3 mutations; 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; there is no intervention in this study, only observation.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Children's Hospital of Chongqing Medical University
• Investigators: Principal Investigator: Wang Jianhui, Doctor, Children's Hospital of Chongqing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: October 20, 2019
• First Submitted That Met QC Criteria: October 22, 2019
• First Posted (Actual): October 24, 2019

Study Record Updates

• Last Update Posted (Actual): August 6, 2021
• Last Update Submitted That Met QC Criteria: July 15, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: respiratory distress syndrome; ABCA3 gene; exome sequencing
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn
• Other Study ID Numbers: 00020191017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No