N-terminal probrain natriuretic peptide and patent ductus ... - Nature

Journal of Perinatology (2009) 29, 137–142 r 2009 Nature Publishing Group All rights reserved. 0743-8346/09 $32 www.nature.com/jp

ORIGINAL ARTICLE

N-terminal probrain natriuretic peptide and patent ductus arteriosus in preterm infants P Nuntnarumit, A Khositseth and P Thanomsingh Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

Objective: To determine whether plasma N-terminal probrain natriuretic peptide (NT-proBNP) in premature infants could identify hemodynamically significant patent ductus arteriosus (HsPDA) and to determine the correlation between serial plasma NT-proBNP and echocardiographic assessment of ductal shunting.

Study Design: An observational study involving 35 preterm infants who underwent echocardiographic assessment for PDA on day 2, 4 and 7 of life with simultaneous blood sampling for determination of NT-proBNP concentrations. HsPDA was diagnosed by left-to-right ductal shunt on color Doppler, measuring diameter >1.5 mm on two-dimensional echocardiography plus X2 clinical features of PDA. Result: Plasma NT-proNBP levels on day 2 in the HsPDA group (n ¼ 12) were significantly higher than in non-HsPDA group (n ¼ 23) with a median of 16 353 pg ml1 (interquartile range (IQR), 12 360– 33 459; range, 10 316–104 998) vs 3914 pg ml1 (IQR, 2601–5782; range, 1535–19 516) (P160 min1), hyperactive precordium, bounding pulse, pulse pressure >25 mm Hg, hepatomegaly, pulmonary hemorrhage (defined as blood or blood-stained fluid aspirated from the endotracheal tube in association with a respiratory deterioration and radiographic evidence of pulmonary hemorrhage), increasing respiratory support by 20% increase in oxygen supplementation or in pressure support and chest radiographic evidence of cardiomegaly or pulmonary congestion. Indomethacin or ibuprofen was administered after HsPDA had been diagnosed. The selection of medication was based on the discretion of the physician. The initial dose of indomethacin was 0.2 mg kg1, followed by two additional doses of 0.1 mg kg1 given intravenously at 12-h intervals. For ibuprofen, the initial dose of 10 mg kg1 was followed by two additional doses of 5 mg kg1 given orally at 24-h intervals. Statistical analysis Data collections included body weight changes, fluid intake and output, respiratory and cardiovascular status and echocardiographic parameters of ductal shunting. The attending physicians were unaware of the plasma NT-proBNP values. To compare HsPDA group and non-PDA group, w2-test or Fisher’s exact test was used for categorical variables. Student’s t-test was used for continuous variables or Mann–Whitney U-test if the data were not normally distributed. Pearson’s correlation coefficient was used to test for correlation between plasma NT-proBNP level and LA/Ao ratio, LAV index and PDA diameter. The receiver operator characteristic (ROC) curve was used to select the best cut-off point for detection of HsPDA. P-value less than 0.05 was considered statistical significance.

Results There were 52 infants, born at less than 33 weeks of gestation during the study period: 5 died within 2 days after birth, 2 were expected to die within a few days due to extreme prematurity (grade 2 CLD Total fluid in the first 24 h (ml kg1 per day)

1250 29 4 12 8

(925–1540) (27–31) (50) (100) (67)

4.5 (1–9) 8 (4–10) 6 (50) 0 2 (16) 66 (60–85)

non-HsPDA (n ¼ 23) 1360 31 8 22 14

(730–1830) (28–33) (53) (96) (61)

6 (1–9) 9 (2–10) 0 1 1 (4) 76 (52–93)

P-value 0.29 0.01* 0.9 0.5 0.7 0.15 0.33 0.001* 0.5 0.2 0.04*

Abbreviations: CLD, chronic lung disease; HsPDA, hemodynamically significant patent ductus arteriosus; IVH, intraventricular hemorrhage; RDS, respiratory distress syndrome. Values are expressed as numbers (%) of infants or median (interquartile range). *P-value 25 mm Hg Increased apnea or respiratory support Bounding pulse Hyperactive precordium Persistent tachycardia >160 min1 Cardiomegaly or pulmonary congestion

Frequency of occurrence n (%) 6 6 5 3 3 2 2

(50) (50) (42) (25) (25) (17) (17)

Abbreviations: PDA, patent ductus arteriosus.

of age, and 2 had severe birth asphyxia. Therefore, 39 infants were eligible for the study and 4 of these infants were excluded (2 due to early septic shock and 2 due to indomethacin treatment before blood sampling for NT-proBNP). Of 35 enrolled infants, 12 had HsPDA and received indomethacin or ibuprofen with a closure rate of 66.7% (8/12). Thus, four infants in this group received the second course of indomethacin resulting in ductus closure in all infants. Total of 23 infants were in non-HsPDA group; 20 infants had no ductus detected by echocardiogram on day 2 and still remained closed thereafter, whereas the other 3 infants in this group had asymptomatic PDA detected by flow across the ductus. On day 4 of life, two out of three infants had spontaneous PDA closure, whereas the remaining infant still had a small PDA and received one course of indomethacin per the discretion of the primary physician. The characteristics of these two groups are summarized in Table 1. There were no significant differences observed in gestational age, gender, delivery type, Apgar scores at 1 and 5 min and the use of antenatal steroid. No maternal indomethacin

tocolysis was used during the study period and no infants developed sepsis during the first 7 days of life. The infants in the HsPDA group had a significantly lower birth weight and more respiratory distress syndrome, and received lower total fluid in the first 24 h of life. Echocardiographic results and clinical findings of HsPDA Compared with the non-HsPDA group, infants in HsPDA group had larger PDA diameter (2.7±1.1 vs 1.2±0.3 mm, P