The diagnosis of a haemodynamically significant patent ductus arteriosus (sPDA) in preterm infants is often difficult, with echocardiography remaining the gold standard.1 However, availability and cost pose some difficulties. B‐type natriuretic peptide (BNP) may assist diagnosis, but cut‐off levels vary widely in the literature. No data exist on the applicability of the byproduct N‐terminal pro‐B‐type natriuretic peptide (NTpBNP), which is more stable and has a longer half life.2 We hypothesised that NTpBNP may be useful in the management of preterm infants with sPDA and aimed to investigate its usefulness as a marker of sPDA and treatment success.
Method
The local ethics committee approved the study, and informed written parental consent was obtained from all parents prior to enrolment in the study.
We carried out echocardiographic and NTpBNP determinations at 12 h and 48 h of life, including measurements of PDA absolute and Doppler jet diameters, shortening fraction, descending aorta end‐diastolic velocity, and left atrial to aortic ratio, in 48 preterm infants.3 The cohort was divided in to two groups based on the presence or absence of an sPDA. Infants with sPDA were treated with two courses of ibuprofen, which was followed by surgical ligation if the medical treatment was unsuccessful. Both groups of infants underwent another assessment following successful treatment. The results were analysed using Mann–Whitney U test for non‐parametric data, and correlations were tested using Spearman's correlation coefficient.
Results
We carried out 131 echocardiographic examinations coupled with NTpBNP determinations (table 1). Table 2 summarises the NTpBNP levels in the two groups on days 1, 3 and after treatment. On day 3, NTpBNP significantly correlated with PDA absolute and jet diameters (r = 0.48 and r = 0.51, respectively, p<0.001), left atrial to aortic ratio (r = 0.46, p = 0.001), and descending aorta end‐diastolic velocity (r = 0.73, p<0.001). There was no correlation between NTpBNP and shortening fraction. NTpBNP levels were significantly higher in the PDA group compared with controls on day 3 (p<0.001) and fell significantly from 6792 pmol/l to 1199 pmol/l after successful PDA closure (p = 0.001). A receiver operating characteristic curve was constructed for NTpBNP and the presence of a PDA with an area under the curve of 0.866 (95% CI 0.763 to 0.969, p<0.0001). A cut‐off value of 5000 pmol/l had a sensitivity of 70% and a specificity of 87%.
Table 1 Characteristics of the study cohort*.
| Control group n = 23 | PDA group n = 25 | |
|---|---|---|
| Gestation (weeks) | 28 (26.1–29.5) | 27 (25.9–28.3) |
| Birth weight (g) | 1121 (948–1253) | 980 (823–1220) |
| Antenatal steroids | 10 (43) | 7 (28) |
| Apgar at 1 min | 5 (3–7) | 4 (3–7) |
| Apgar at 5 min | 7 (5–8) | 7 (6–8) |
| Caesarean section | 11 (48) | 9 (36) |
| Maternal pre‐eclampsia | 2 (9) | 4 (16) |
| Chorioamnionitis | 3 (13) | 6 (24) |
| Ventilation at birth | 17 (74) | 23 (92) |
| Surfactant at birth | 17 (74) | 23 (92) |
| Ibuprofen | ||
| One course | NA | 17 (68) |
| Two courses | NA | 8 (32) |
| Surgical ligation | NA | 5 (20) |
NA, not applicable; PDA, patent ductus arteriosus.
*Data are median (interquartile range or percentage).
There were no significant differences between the two groups.
Table 2 Median N‐terminal pro‐B‐type natriuretic peptide (NTpBNP) levels (pmol/l) in the two study groups on days 1, 3 and after treatment for the patent ductus arteriosus (PDA).
| Day 1 | Day 3 | Post‐treatment | ||||
|---|---|---|---|---|---|---|
| Control | PDA | Control | PDA | Control | PDA | |
| NTpBNP | 1435 | 1267 | 1127 | 6792 | 279 | 1199 |
| 25–75th centiles | 894–2550 | 531–2398 | 509–2884 | 3250–17309 | 93–484 | 401–2998 |
| Range | 185–5407 | 98–10700 | 94–8030 | 402–35353 | 36–18989 | 188–9478 |
| p Value | 0.735 | <0.001 | 0.001 | |||
Levels were significantly higher in the PDA group on day 3 and post treatment.
Mann–Whitney U test was used to compare the medians.
Discussion
Our study shows the potential use of NTpBNP in the management of a PDA in preterm infants. Several studies have established NTpBNP reference values for healthy term newborns at day 1 of life, ranging from 65 pmol/l to 641 pmol/l.2 The higher levels in our cohort are probably multifactorial and reflect the demands placed on the preterm heart during the transitional phase. The lack of correlation between NTpBNP and the presence of a PDA at 12 h of age probably reflects the low degree of shunting during this transitional period. Validation in larger samples is needed to establish NTpBNP as a diagnostic and follow‐up tool for PDA. The clinical applicability of NTpBNP may stem from its role in screening infants for the possible presence of an sPDA, with a high level indicating the need for echocardiographic evaluation, and may be of benefit at centres without onsite echocardiography.
Acknowledgements
The authors thank the Neonatal Department, National Maternity Hospital, and Dr John Murphy, Director of the Department, for accommodating the project.
Footnotes
This project was funded by the hospital's research fund which is accumulated from private donations from parents. Corporate donations are not used for research in this institution. We do not accept donations or sponsorships from drug companies.
Competing interests: None.
References
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