Respiratory Outcomes in Children With Neonatal Respiratory Distress Syndrome and Monoallelic ABCA3 Variants

Lung disease due to ABCA3 variants and resultant surfactant dysfunction is an autosomal recessive disease. However, monoallelic ABCA3 variants are overrepresented in term or late-preterm infants with non-fatal neonatal respiratory distress syndrome (RDS). The childhood respiratory outcomes of infants with monoallelic ABCA3 variants who present with neonatal RDS are unknown. In this study, we report the respiratory outcomes beyond neonatal hospitalization (median follow-up 1 year [range 1-9.4 years]) for infants with monoallelic ABCA3 variants and neonatal RDS.

Participants with monoallelic ABCA3 variants classified as pathogenic, likely pathogenic, or of uncertain significance with neonatal RDS identified in 3 cohorts (ChILD Registry n = 9, disease-based cohort n = 19, and nested case-control n = 20) were included in this retrospective, descriptive study. The primary outcome was duration of supplemental oxygen use. Secondary outcomes included respiratory morbidities after NICU discharge.

Of 48 infants who met inclusion criteria, 8 (17%) were discharged home on supplemental oxygen, including two who required home invasive mechanical ventilation. The ABCA3 pathogenic variant p.Glu292Val was the most common variant identified in the infants who required oxygen beyond NICU discharge (6 of 8). Oxygen was discontinued by 10 months of age in 50% of infants discharged from birth hospitalization on oxygen. Respiratory morbidities, including hospitalizations (62% vs. 8%, p = 0.005) and emergency department (ED) visits (71% vs. 35%, p < 0.01), were more common among participants discharged home on oxygen compared to those discharged home without oxygen.

These findings suggest that infants with monoallelic ABCA3 variants and neonatal RDS may require prolonged home oxygen or mechanical ventilation and experience increased risk for respiratory morbidities, including subsequent hospitalization and ED visits.