Respiratory Distress Syndrome, Newborn
Conditions
Keywords
respiratory distress syndrome, ABCA3 gene, exome sequencing
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.
Interventions
OTHERno intervention
there is no intervention in this study, only observation.
Sponsors
Children's Hospital of Chongqing Medical University
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 6 Months
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | through study completion, an average of 1 month | the ratio of dead patients against the corresponding group population |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the Onset of Respiratory Distress Syndrome | up to 1 week | the age when the patients presented with respiratory distress sydnrome |
| 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 |
| 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. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
no intervention: there is no intervention in this study, only observation. | 7 |
| Single ABCA3 Mutation 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. | 10 |
| 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.
no intervention: there is no intervention in this study, only observation. | 22 |
| Total | 39 |
Baseline characteristics
| Characteristic | Total | Homozygous or Compound Heterozygous ABCA3 Mutations | no ABCA3 Mutations | Single ABCA3 Mutation |
|---|---|---|---|---|
| Age, Customized Gestational age | 37.08 weeks STANDARD_DEVIATION 2.09 | 36.85 weeks STANDARD_DEVIATION 2.12 | 37.27 weeks STANDARD_DEVIATION 2.27 | 36.80 weeks STANDARD_DEVIATION 1.81 |
| Birthweight(grams) | 3007.08 grams STANDARD_DEVIATION 395.04 | 2996.57 grams STANDARD_DEVIATION 351.92 | 3043.59 grams STANDARD_DEVIATION 358.03 | 2934.10 grams STANDARD_DEVIATION 517.68 |
| Cesarean section (n, %) | 24 Participants | 5 Participants | 14 Participants | 5 Participants |
| Fetal distress (n, %) | 9 Participants | 2 Participants | 4 Participants | 3 Participants |
| Maternal history gestational diabetes mellitus | 11 Participants | 2 Participants | 7 Participants | 2 Participants |
| Maternal history Preeclampsia | 5 Participants | 1 Participants | 3 Participants | 1 Participants |
| Maternal history premature rupture of membrane | 10 Participants | 2 Participants | 5 Participants | 3 Participants |
| Meconium stained amniotic fluid (n, %) | 7 Participants | 2 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 39 Participants | 7 Participants | 22 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Resuscitation (n, %) | 14 Participants | 4 Participants | 6 Participants | 4 Participants |
| Sex: Female, Male Female | 18 Participants | 3 Participants | 10 Participants | 5 Participants |
| Sex: Female, Male Male | 21 Participants | 4 Participants | 12 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 7 | 3 / 10 | 11 / 22 |
| other Total, other adverse events | 0 / 7 | 0 / 10 | 0 / 22 |
| serious Total, serious adverse events | 0 / 7 | 0 / 10 | 0 / 22 |
Outcome results
Primary
Mortality
the ratio of dead patients against the corresponding group population
Time frame: through study completion, an average of 1 month
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Homozygous or Compound Heterozygous ABCA3 Mutations | Mortality | 5 Participants |
| Single ABCA3 Mutation | Mortality | 3 Participants |
| no ABCA3 Mutations | Mortality | 5 Participants |
Secondary
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.
Time frame: through study of completion, an average of 1 month
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Homozygous or Compound Heterozygous ABCA3 Mutations | Radiological Score | ground glass opacity | 15.29 score on a scale | Standard Deviation 1.38 |
| Homozygous or Compound Heterozygous ABCA3 Mutations | Radiological Score | reticular pattern | 15.14 score on a scale | Standard Deviation 1.22 |
| Homozygous or Compound Heterozygous ABCA3 Mutations | Radiological Score | air bronchogram | 11.86 score on a scale | Standard Deviation 2.34 |
| Homozygous or Compound Heterozygous ABCA3 Mutations | Radiological Score | atelectasis | 5.57 score on a scale | Standard Deviation 2.82 |
| Homozygous or Compound Heterozygous ABCA3 Mutations | Radiological Score | air leakage | 1.43 score on a scale | Standard Deviation 1.99 |
| Homozygous or Compound Heterozygous ABCA3 Mutations | Radiological Score | cysts | 1.86 score on a scale | Standard Deviation 2.04 |
| Single ABCA3 Mutation | Radiological Score | cysts | 1.00 score on a scale | Standard Deviation 1.25 |
| Single ABCA3 Mutation | Radiological Score | ground glass opacity | 12.90 score on a scale | Standard Deviation 2.03 |
| Single ABCA3 Mutation | Radiological Score | atelectasis | 3.20 score on a scale | Standard Deviation 2.35 |
| Single ABCA3 Mutation | Radiological Score | air leakage | 1.20 score on a scale | Standard Deviation 1.4 |
| Single ABCA3 Mutation | Radiological Score | reticular pattern | 14.90 score on a scale | Standard Deviation 0.88 |
| Single ABCA3 Mutation | Radiological Score | air bronchogram | 11.00 score on a scale | Standard Deviation 1.25 |
| no ABCA3 Mutations | Radiological Score | reticular pattern | 13.23 score on a scale | Standard Deviation 2.11 |
| no ABCA3 Mutations | Radiological Score | air bronchogram | 7.86 score on a scale | Standard Deviation 3.09 |
| no ABCA3 Mutations | Radiological Score | cysts | 0.50 score on a scale | Standard Deviation 0.86 |
| no ABCA3 Mutations | Radiological Score | atelectasis | 2.64 score on a scale | Standard Deviation 0.91 |
| no ABCA3 Mutations | Radiological Score | ground glass opacity | 10.77 score on a scale | Standard Deviation 1.95 |
| no ABCA3 Mutations | Radiological Score | air leakage | 0.91 score on a scale | Standard Deviation 1.07 |
Secondary
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
Time frame: through study of completion, an average of 1 month
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Homozygous or Compound Heterozygous ABCA3 Mutations | the Age of Developing Severe RDS Marked With Oxygenation Index of 16 | 1.06 days |
| Single ABCA3 Mutation | the Age of Developing Severe RDS Marked With Oxygenation Index of 16 | 5.3 days |
| no ABCA3 Mutations | the Age of Developing Severe RDS Marked With Oxygenation Index of 16 | 4.5 days |
Secondary
the Onset of Respiratory Distress Syndrome
the age when the patients presented with respiratory distress sydnrome
Time frame: up to 1 week
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Homozygous or Compound Heterozygous ABCA3 Mutations | the Onset of Respiratory Distress Syndrome | 1.83 hours |
| Single ABCA3 Mutation | the Onset of Respiratory Distress Syndrome | 4.6 hours |
| no ABCA3 Mutations | the Onset of Respiratory Distress Syndrome | 5.24 hours |