ABCA3 Gene and RDS in Late Preterm and Term Infants

• Sponsor: Children's Hospital of Chongqing Medical University (Other)
• Overall Status: Completed
• CT.gov ID: NCT04137783
• Collaborator: (none)
• Enrollment: 39
• Location: 1
• Actual Duration (Months): 19.1
• Patients Per Site Per Month: 2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Respiratory Distress Syndrome, Newborn	Other: no intervention

Study Design

• Study Type: Observational
• Actual Enrollment: 39 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: ABCA3 Gene Mutations in Late Preterm and Term Infants With Fatal Unexplained Respiratory Distress Syndrome
• Actual Study Start Date: May 1, 2019
• Actual Primary Completion Date: Dec 1, 2020
• Actual Study Completion Date: Dec 1, 2020

Arms and Interventions

Arm	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.

Outcome Measures

Primary Outcome Measures

1. Mortality [through study completion, an average of 1 month]

   the ratio of dead patients against the corresponding group population

Secondary Outcome Measures

1. the Onset of Respiratory Distress Syndrome [up to 1 week]

   the age when the patients presented with respiratory distress sydnrome

2. the Age of Developing Severe RDS Marked With Oxygenation Index of 16 [through study of completion, an average of 1 month]

   the age when the patients develop severe RDS,which is marked with an oxygenation index of 16

3. Radiological Score [through study of completion, an average of 1 month]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 6 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's hospital of Chongqing Medical University	Chongqing	Chongqing	China	400014

Sponsors and Collaborators

• Children's Hospital of Chongqing Medical University

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 16, 2021

More Information

Publications

None provided.

• Responsible Party: Wang Jianhui, Attending Doctor, Children's Hospital of Chongqing Medical University
• ClinicalTrials.gov Identifier: NCT04137783
• Other Study ID Numbers: 00020191017
• First Posted: Oct 24, 2019
• Last Update Posted: Aug 6, 2021
• Last Verified: Jul 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Wang Jianhui, Attending Doctor, Children's Hospital of Chongqing Medical University: respiratory distress syndrome; ABCA3 gene; exome sequencing
• Additional relevant MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Syndrome

Study Results

Participant Flow

Arm/Group Title	Homozygous or Compound Heterozygous ABCA3 Mutations	Single ABCA3 Mutation	no ABCA3 Mutations
Arm/Group Description	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated homozgyous or compound heterozygous ABCA3 mutations. no intervention: there is no intervention in this study, only observation.	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated single mutations. no intervention: there is no intervention in this study, only observation.	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which exclude all gene mutations involving in the respiratory disease. no intervention: there is no intervention in this study, only observation.
Period Title: Overall Study
STARTED	7	10	22
COMPLETED	7	10	22
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Homozygous or Compound Heterozygous ABCA3 Mutations	Single ABCA3 Mutation	no ABCA3 Mutations	Total
Arm/Group Description	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated homozgyous or compound heterozygous ABCA3 mutations. no intervention: there is no intervention in this study, only observation.	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated single mutations. no intervention: there is no intervention in this study, only observation.	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which exclude all gene mutations involving in the respiratory disease. no intervention: there is no intervention in this study, only observation.	Total of all reporting groups
Overall Participants	7	10	22	39
Age, Customized (weeks) [Mean (Standard Deviation) ]
Gestational age	36.85 (2.12)	36.80 (1.81)	37.27 (2.27)	37.08 (2.09)
Sex: Female, Male (Count of Participants)
Female	3 42.9%	5 50%	10 45.5%	18 46.2%
Male	4 57.1%	5 50%	12 54.5%	21 53.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	7 100%	10 100%	22 100%	39 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Birthweight(grams) (grams) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [grams]	2996.57 (351.92)	2934.10 (517.68)	3043.59 (358.03)	3007.08 (395.04)
Cesarean section (n, %) (Count of Participants)
Count of Participants [Participants]	5 71.4%	5 50%	14 63.6%	24 61.5%
Resuscitation (n, %) (Count of Participants)
Count of Participants [Participants]	4 57.1%	4 40%	6 27.3%	14 35.9%
Fetal distress (n, %) (Count of Participants)
Count of Participants [Participants]	2 28.6%	3 30%	4 18.2%	9 23.1%
Meconium stained amniotic fluid (n, %) (Count of Participants)
Count of Participants [Participants]	2 28.6%	2 20%	3 13.6%	7 17.9%
Maternal history (Count of Participants)
premature rupture of membrane	2 28.6%	3 30%	5 22.7%	10 25.6%
gestational diabetes mellitus	2 28.6%	2 20%	7 31.8%	11 28.2%
Preeclampsia	1 14.3%	1 10%	3 13.6%	5 12.8%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Homozygous or Compound Heterozygous ABCA3 Mutations	Single ABCA3 Mutation	no ABCA3 Mutations
Arm/Group Description	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated homozgyous or compound heterozygous ABCA3 mutations. no intervention: there is no intervention in this study, only observation.	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated single mutations. no intervention: there is no intervention in this study, only observation.	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which exclude all gene mutations involving in the respiratory disease. no intervention: there is no intervention in this study, only observation.
Measure Participants	7	10	12
Count of Participants [Participants]	5 71.4%	3 30%	5 22.7%

2. Secondary Outcome

Title	the Onset of Respiratory Distress Syndrome
Description	the age when the patients presented with respiratory distress sydnrome
Time Frame	up to 1 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Homozygous or Compound Heterozygous ABCA3 Mutations	Single ABCA3 Mutation	no ABCA3 Mutations
Arm/Group Description	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated homozgyous or compound heterozygous ABCA3 mutations. no intervention: there is no intervention in this study, only observation.	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated single mutations. no intervention: there is no intervention in this study, only observation.	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which exclude all gene mutations involving in the respiratory disease. no intervention: there is no intervention in this study, only observation.
Measure Participants	7	10	12
Mean (Full Range) [hours]	1.83	4.6	5.24

3. Secondary Outcome

Title	the Age of Developing Severe RDS Marked With Oxygenation Index of 16
Description	the age when the patients develop severe RDS,which is marked with an oxygenation index of 16
Time Frame	through study of completion, an average of 1 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Homozygous or Compound Heterozygous ABCA3 Mutations	Single ABCA3 Mutation	no ABCA3 Mutations
Arm/Group Description	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated homozgyous or compound heterozygous ABCA3 mutations. no intervention: there is no intervention in this study, only observation.	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated single mutations. no intervention: there is no intervention in this study, only observation.	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which exclude all gene mutations involving in the respiratory disease. no intervention: there is no intervention in this study, only observation.
Measure Participants	7	10	12
Mean (Full Range) [days]	1.06	5.3	4.5

4. Secondary Outcome

Title	Radiological Score
Description	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.
Time Frame	through study of completion, an average of 1 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Homozygous or Compound Heterozygous ABCA3 Mutations	Single ABCA3 Mutation	no ABCA3 Mutations
Arm/Group Description	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated homozgyous or compound heterozygous ABCA3 mutations. no intervention: there is no intervention in this study, only observation.	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated single mutations. no intervention: there is no intervention in this study, only observation.	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which exclude all gene mutations involving in the respiratory disease. no intervention: there is no intervention in this study, only observation.
Measure Participants	7	10	12
ground glass opacity	15.29 (1.38)	12.90 (2.03)	10.77 (1.95)
reticular pattern	15.14 (1.22)	14.90 (0.88)	13.23 (2.11)
air bronchogram	11.86 (2.34)	11.00 (1.25)	7.86 (3.09)
atelectasis	5.57 (2.82)	3.20 (2.35)	2.64 (0.91)
air leakage	1.43 (1.99)	1.20 (1.40)	0.91 (1.07)
cysts	1.86 (2.04)	1.00 (1.25)	0.50 (0.86)

Adverse Events

Time Frame	through study completion, an average of 1 month
Arm/Group Title	Homozygous or Compound Heterozygous ABCA3 Mutations		Single ABCA3 Mutation		no ABCA3 Mutations
Arm/Group Description	patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated homozgyous or compound heterozygous ABCA3 mutations. no intervention: there is no intervention in this study, only observation.		patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which indicated single mutations. no intervention: there is no intervention in this study, only observation.		patients meet the criteria for fatal respiratory distress sydrome and undergone exome sequencing, which exclude all gene mutations involving in the respiratory disease. no intervention: there is no intervention in this study, only observation.
All Cause Mortality
	Homozygous or Compound Heterozygous ABCA3 Mutations		Single ABCA3 Mutation		no ABCA3 Mutations
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/7 (71.4%)		3/10 (30%)		11/22 (50%)
Serious Adverse Events
	Homozygous or Compound Heterozygous ABCA3 Mutations		Single ABCA3 Mutation		no ABCA3 Mutations
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/10 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Homozygous or Compound Heterozygous ABCA3 Mutations		Single ABCA3 Mutation		no ABCA3 Mutations
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/10 (0%)		0/22 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.