Supplementary Material for: Biochemical Screening for Pulmonary Hypertension in Preterm Infants with Bronchopulmonary Dysplasia

Background: Pulmonary hypertension (PH) in infants with bronchopulmonary dysplasia (BPD) is associated with increased morbidity and mortality. Elevated levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and decreased levels of amino acid precursors of nitric oxide (NO) have been associated with PH, but have not been studied in infants with PH secondary to BPD. Objective: The aim of this study was to identify a biochemical marker for PH in infants with BPD. Methods: Twenty infants, born at <27 weeks' gestational age (GA) and/or with a birth weight (BW) ≤750 g, who met the criteria for BPD at 36 weeks' corrected GA (CGA) were enrolled in this cross-sectional pilot study. A screening echocardiogram was conducted at 36-38 weeks' CGA and plasma NT-proBNP and amino acid levels were obtained within 1 week of the screening echocardiogram. Results: Five infants (25%) had echocardiographic evidence of PH. GA and BW were not significantly different between the 2 groups (a PH group and a No PH group). NT-proBNP was significantly elevated in the PH group (median 1,650 vs. 520 pg/ml; p = 0.001) but citrulline levels were significantly lower (median 21 vs. 36 μmol/l; p = 0.005). Arginine levels were not significantly different between the groups (median 78 vs. 79 μmol/l; p = 1). Conclusion: NT-proBNP and the NO precursor citrulline may be cost-effective biochemical markers for screening for the presence of PH in preterm infants who have BPD. If validated in a larger study, such biochemical markers may, in part, replace PH screening echocardiograms in these patients.