Factors Associated with Early-childhood Ipsilateral Perfusion Abnormalities in CDH Patients

Background: Prior work demonstrated abnormalities in ipsilateral lung perfusion among congenital diaphragmatic hernia (CDH) patients. Multicenter pulmonary outcome data were not available for these patients until 2021, when the CDH Study Group (CDHSG) began collecting pilot data for a long-term follow up (LTFU) extension of the primary neonatal dataset. The purpose of this study was to evaluate long-term pulmonary outcomes using a multicenter cohort of CDH patients to describe patterns of perfusion and identify factors associated with perfusion abnormalities in these patients.

Methods: An international multicenter database of CDH infants seen in long-term follow-up was established. Data were retrospectively collected from the medical record during the perinatal period, the time of discharge, and during early childhood. Only patients with left-sided CDH were included in this analysis, and the primary outcome was ipsilateral lung perfusion at 2-years of age. Variables of interest included degree of pulmonary hypertension at the time of discharge, and defect severity (CDHSG stage).

Results: A total of 258 patients with left-sided CDH from four centers were entered in the CDH LTFU database. Mean birthweight was 3.0±0.6kg, and mean gestational age was 37.8±2.4 weeks. 213 patients (83%) had follow-up data at 2-years (median age at visit: 2.01y, IQR: 1.8-2.2y), and 100 had follow-up at 5-years (median age at visit: 5.01y, IQR: 4.8-5.2y). 173 patients (68%) had low-risk (CDHSG A/B) defects. At the time of discharge 58 (22%) patients required supplemental oxygen and 56 (25%) had pulmonary hypertension on echocardiogram. 121 patients (47%) had a perfusion scan performed at 2-years-of-age, and 38 (15%) had a perfusion scan performed at 5-years-of-age. There was no association identified between presence of pulmonary hypertension on discharge echocardiogram and ipsilateral perfusion at 2 years of age (p=0.11). Compared to normal left-lung perfusion of 45%, ipsilateral perfusion at 2-years of age was abnormal in all patients (mean perfusion 36.2%, p < 0.001). Mean ipsilateral perfusion at 2 years of age was 38.2±7.5% in patients with CDHSG A/B defects and 30.2±7.7% in patients with CDHSG C/D defects. Patients with lower-risk defects had significantly higher ipsilateral perfusion at 2 years of age than patients with higher-risk defects (difference in means 8.1, 95% CI: 4.7-11.4, p < 0.001).

Conclusion: In this pilot multicenter study from the CDHSG-LTFU database we found that compared to baseline all patients had abnormal ipsilateral perfusion at 2-years of age. Only CDH defect size was significantly associated with ipsilateral pulmonary perfusion at 2-years of age. Interestingly, the degree of pulmonary hypertension in the neonatal period was not statistically significantly associated with a decrease in ipsilateral pulmonary perfusion as measured on perfusion scan in early childhood. While additional investigation is necessary, these results can be used to provide anticipatory guidance to families of CDH patients.