Biochemical Screening for Pulmonary Hypertension in Preterm Infants with Bronchopulmonary Dysplasia

Abstract

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.

Identification of gaps in the current knowledge on pulmonary hypertension in extremely preterm infants: A systematic review and meta‐analysis

“…We included two articles by scanning the reference lists. Finally, 25 articles, 16 retrospective and 9 prospective studies, were eligible for inclusion in the study . The flow chart of this excluding process is given in Figure .…”

“…The results of the assessment of the risk of bias are shown in Table . Eight studies that were included provided clearly defined objectives, study populations, and outcome measures . However, 17 of the 25 included studies had a retrospective design and included a selected study population .…”

“…In total 25 prevalences were reported in 21 eligible studies, 10 of these 25 prevelances were reported in prospective studies, whereas 15 of 25 prevalences were reported in retrospective studies . Eleven prevalences were derived from studies that reported a well‐defined time of PH‐assessment . Fourteen prevalences were derived from studies that did not report a well‐defined time point of assessment of PH …”

“…Gestational age was reported in 12 nonoverlapping studies, that is five studies on infants with and without BPD and seven studies with BPD infants only …”

“…Necrotising enterocolitis (NEC) was reported eight times in seven similar and not‐overlapping studies, that is three studies on infants with and without BPD, three studies on infants with BPD only and one study on both infants with and without BPD as infants with BPD only . Meta‐analysis with BPD infants only identified a strong association between the presence of NEC and PH (RR 3.4, 95% CI 1.1, 10.2).…”