ABCA3 Gene and RDS in Late Preterm and Term Infants

Chongqing Medical University

Status: Completed

Conditions: Respiratory Distress Syndrome, Newborn

Treatments: Other: no intervention

Study type: Observational

Funder types: Other

Identifiers

NCT04137783

00020191017

Details and patient eligibility

About

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.

Enrollment: 39 patients

Sex: All

Ages: Under 6 months old

Volunteers: No Healthy Volunteers

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.

Trial design

39 participants in 3 patient groups

homozygous or compound heterozygous ABCA3 mutations

Description:

patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated homozgyous or compound heterozygous ABCA3 mutations.

Treatment:

Other: no intervention

single ABCA3 mutation

Description:

patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated single mutations.

Treatment:

Other: no intervention

no ABCA3 mutations

Description:

patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which exclude all gene mutations involving in the respiratory disease.

Treatment:

Other: no intervention