Objective: To evaluate B-type natriuretic peptide (BNP) as a longitudinal biomarker of clinical outcome in infants with congenital diaphragmatic hernia (CDH).
Study design: We conducted a retrospective study of 49 infants with CDH, classifying the cohort by respiratory status at 56 days, based on a proposed definition of bronchopulmonary dysplasia for infants ≥32 weeks' gestation: Good Outcome (alive with no respiratory support) and Poor Outcome (ongoing respiratory support or death). BNP levels were available at weeks 1-5 of age. Longitudinal BNP trends were assessed using mixed effects modeling. ROC curves were generated to identify BNP cut-offs maximizing correct outcome classification at each time point. Time to reach BNP cut-off by outcome was assessed using Kaplan-Meier curves for weeks 3-5.
Results: Twenty-nine infants (59%) had Poor Outcome. Infants with Poor versus Good Outcome were more likely to have liver herniated into the thorax (90% versus 50%, p=0.002) and undergo non-primary repair (93% versus 35%, P < .001). Mixed effects modeling demonstrated a differing decline in BNP over time by outcome group (p=0.003 for interaction). BNP accurately predicted outcome at 3-5 weeks (AUC 0.81-0.82). BNP cut-offs that maximized correct outcome classification decreased over time: 285 pg/mL, 100 pg/mL and 48 pg/mL at 3, 4 and 5 weeks. Time to reach cut-offs of 100 pg/mL and 48 pg/mL were longer in Poor Outcome (log-rank p-value 0.006 and <0.0001, respectively).
Conclusion: Elevated BNP accurately predicts Poor Outcome in infants with CDH at 3-5 weeks of age, with declining cut-offs over 3-5 weeks of age.
DOI: 10.1016/j.jpeds.2020.09.064
