Patent ductus arteriosus, systemic NT-proBNP concentrations and development of bronchopulmonary dysplasia in very preterm infants: retrospective data analysis from a randomized controlled trial

Abstract

Background Patent ductus arteriosus (PDA) is a common complication in very preterm infants. It is known that there is an association between PDA and development of bronchopulmonary dysplasia (BPD) or death before the postmenstrual age (PMA) of 36 weeks, but this association remains one of the most controversial aspects of the problem. The study aimed to evaluate the relationship between PDA, serum NT-proBNP levels at 2–3 and 8–9 days of life, and BPD/death in very preterm infants. Methods Data of 52 preterm infants with a gestational age < 32 weeks, chronological age < 72 h, and PDA diameter > 1.5 mm, enrolled in a randomized controlled trial, were used for the retrospective analysis. All patients underwent daily echocardiographic and two serum NT-proBNP measurements within the first 10 days after birth. Two groups of infants were formed retrospectively at PMA of 36 weeks depending on the outcome, BPD (n = 18)/death (n = 7) or survival without BPD (n = 27). Receiver operator characteristic (ROC) curve was used to evaluate the predictive performance of serum NT-proBNP levels for BPD/death occurrence. Results The percentage of infants who received pharmacological treatment for PDA did not differ between the groups. Based on the area under the ROC curve, serum NT-proBNP levels on the 2–3 day of life (AUC = 0.71; 95% confidence interval (CI): 0.56–0.9; p = 0.014)) and on the 8–9 day of life (AUC = 0.76; 95% CI: 0.6–0.9; p = 0.002) could reliably predict BPD/death in very preterm infants who had PDA diameter > 1.5 mm in the first 72 h of life. Hemodynamically significant PDA (hsPDA) was significantly more often detected in newborns with BPD/death, however, treatment of infants with hsPDA did not reduce the incidence of BPD/death. Conclusions In very preterm infants with PDA > 1.5 mm at the age of 24–48 h, serum NT-proBNP concentration could reliably predict the development of BPD or death, regardless of the persistence of PDA, with the highest diagnostic value at 8–9 days. Trial registration This study is registered in ClinicalTrials.gov - NCT03860428 on March 4, 2019.

Prediction Model for Bronchopulmonary Dysplasia in Preterm Newborns

“…In a retrospective analysis from a randomized controlled trial by Potsiurko et al the markers of hsPDA, that is the serum NT-proBNP concentration and diameter of PDA, were found to be significant indicators in the first days of life for the development of BPD or death at 36 weeks PMA. In this study, it was noted, that higher serum NT-proBNP at 8-9 days of life significantly corresponded with higher FiO2 at this age [36]. These conditions have a similar pathogenesis, and their development in immature newborns is usually provoked by high oxidative stress and the absence of corrective mechanisms.…”

Serum N-Terminal Pro-B-Type Natriuretic Peptide as a Biomarker of Critical Pulmonary Stenosis in Neonates

“…In a prospective observational study, urinary NT-proBNP levels were positively correlated with ductal diameter and decreased significantly when the PDA closed completely following medical treatment in preterm infants ( 14 ). In extremely preterm infants aged 24–48 h with PDA > 1.5 mm, serum NT-proBNP concentrations could reliably predict the development of BPD or death, with the highest diagnostic value at 8-9 days ( 18 ). Serum BNP levels have also been reported to be positively correlated with BPD-associated pulmonary hypertension at 36-week corrected gestational age in extremely preterm infants ( 7 ).…”

“…N-terminal pro-B natriuretic peptide (NT-proBNP) is an inactive by-product, which has a longer half-life in circulation and is more stable in serum. At present, NT-proBNP is relevant to various neonatal diseases, such as pulmonary hypertension (6, 7), PDA (8)(9)(10)(11)(12)(13)(14), valular diseases (15), respiratory distress syndrome (16), bronchopulmonary dysplasia (BPD) (7,17,18), and retinopathy of prematurity (19,20). However, limited information is available on the clinical value of NT-proBNP in neonatal PS.…”

Comparison of Different Definitions of Bronchopulmonary Dysplasia Based on Prediction of Adverse Outcomes: Followed Up to 18-24 Months Corrected Age

“…(1) Respiratory adverse outcomes; [14,15] (2) severe neurological outcomes de ned as brain retardation assessed by the Child Neurological Development Scale, developmental quotient (DQ) score < 85 assessed by the Gesell developmental schedules of infants, or brain damage requiring rehabilitation treatment assessed by a quali ed physical therapist; [16,17] and (3) low development level (height, weight or head circumference < 3rd percentile for corrected gestational age and sex, growth percentiles de ned using the World Health Organization Child Growth Standards) at 18-24 months corrected age; (4) retinopathy of prematurity (ROP) requiring laser therapy for treatment; [18,19] (5) haemodynamically signi cant patent ductus arteriosus (PDA) requiring surgical treatment; [20,21] and (6) death between 36 weeks PMA and 18-24 months follow-up for respiratory disease.…”