Longitudinal changes of brain-type natriuretic peptide in preterm neonates.

OBJECTIVE: To determine age-related concentrations of brain-type natriuretic peptide in preterm infants using bedside Triage brain-type natriuretic peptide test and correlate it to the presence or absence of the patent ductus arteriosus and ventilatory support. METHODS: Serum brain-type natriuretic peptide levels were measured in infants who were born at <32 weeks' gestation from birth to 2 months of age. Serial echocardiograms were performed, until closure of the patent ductus arteriosus, or until discharge. Brain-type natriuretic peptide levels were correlated to the day of life, gestational age, presence or absence of the patent ductus arteriosus, and the degree of ventilatory support. Nineteen preterm infants (gestational age: 24-31 weeks; birth weight: 645-1670 g) were enrolled prospectively during the first 2 weeks of life. Serum brain-type natriuretic peptide levels (pg/mL) were determined in 177 blood samples, and 87 paired echocardiograms were performed. RESULTS: Significant negative correlation was found between brain-type natriuretic peptide levels and the day of life and remained significant when the patients were stratified by gestational age (< or =28 weeks and >28 weeks). Higher brain-type natriuretic peptide levels correlated with increasing grade of the patent ductus arteriosus. Significant differences in brain-type natriuretic peptide levels were seen with increasing ventilatory support. Comparisons between the size of patent ductus arteriosus and the degree of ventilatory support to brain-type natriuretic peptide levels revealed that the size of the patent ductus arteriosus was the major determinant of both brain-type natriuretic peptide levels and the degree of ventilatory support. CONCLUSIONS: Similar to term infants, brain-type natriuretic peptide levels of preterm infants are related to the chronological age and decline during the first month of life. Rapid bedside Triage brain-type natriuretic peptide is a potentially valuable and practical assay in determining the hemodynamic changes in preterm infants.

The use of a bedside assay for plasma B-type natriuretic peptide as a biomarker in the management of patent ductus arteriosus in premature neonates.

OBJECTIVE: To test the utility of the bedside plasma concentration of B-type natriuretic peptide (BNP) assay as a screen for patent ductus arteriosus (PDA) in premature neonates. STUDY DESIGN: Newborn infants admitted to the neonatal intensive care unit (NICU) had paired echocardiography and BNP measurements at enrollment and every 4 to 5 days. RESULTS: Twenty neonates (gestational age approximately 28.6 weeks and birth weight approximately 1161 g) had 81 paired echocardiography and BNP determinations. BNP ranged from 5 to 3900 pg/mL. Fifty-six of 81 echocardiograms showed PDA. Significant correlations were found between BNP and ductal size and degree of shunting. Correlation was greater in infants >2 days of age. BNP >300 pg/mL predicted significant PDA, whereas BNP <105 pg/mL predicted absence of significant PDA. CONCLUSION: Bedside measurement of BNP correlates with magnitude of PDA in premature newborns, particularly beyond day 2, and may be useful in guiding diagnostic and management strategies.

Functional residual capacity (FRC) does not predict response to surfactant in preterm infants.

We tested the hypothesis that the initial functional residual capacity (FRC) of preterm infants with hyaline membrane disease (HMD) could predict the response to surfactant replacement (Survanta, 4 mL/kg/dose), with a better initial FRC being correlated with a greater improvement in PaO2, a/A PO2 ratio, and FRC. Thirty-four preterm infants were studied on 41 occasions. FRC and arterial blood gases were measured immediately prior to treatment. FRC was measured by the helium dilution method. Arterial blood gases were measured again after 30, 60, and 120 minutes. FRC was measured after 120 minutes. Twenty-seven treatments resulted in an increase in PaO2 >10 mmHg (responders); 14 did not (nonresponders). There was no correlation between initial FRC, change in FRC, and change in PaO2 (r2 = 0.07). These results suggest that there is no relationship between initial FRC and response to surfactant treatment.

Lymphocyte subpopulations in bronchopulmonary dysplasia.

A key role for inflammation in the etiology of bronchopulmonary dysplasia (BPD) has been proposed. In the present study we have evaluated lymphocyte subpopulations in 39 premature infants with respiratory distress syndrome (RDS) who did or did not develop BPD. The absolute number of lymphocytes was lower among infants with RDS who developed BPD compared with those who did not over the first two weeks of life ( p < 0.020) as were percentage and absolute number of CD4(+) T cells. By contrast, the proportions of CD3(+)CD8(+) lymphocyte cells were not statistically different between non-BPD and BPD infants. B cell percentage was significantly decreased in BPD infants only on day 7. NK "bright" cells (CD56(+)) were highly enriched in all RDS groups. Interestingly, the percentage of CD4(+) T cells expressing CD62L was selectively reduced in BPD infants. As a whole these data suggest that reduction of CD4(+) T cells and especially those important in tissue migration and immune surveillance may be a factor in the pathogenesis of BPD.

Soluble E-selectin, soluble L-selectin and soluble ICAM-1 in bronchopulmonary dysplasia, and changes with dexamethasone.

OBJECTIVE: To evaluate longitudinal change in arterial blood plasma levels of soluble adhesion molecules in infants of <30 weeks' gestation with respiratory distress syndrome (RDS) and to look for differences in these levels in neonates who subsequently developed bronchopulmonary dysplasia (BPD) compared with those neonates who did not, and also to investigate the effect of dexamethasone treatment on levels of soluble adhesion molecules in plasma. METHODS: We measured plasma concentrations of soluble L-selectin (sL-selectin), soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 on days 1, 3, 7, 14, 21, and 28 of life and before and 2 to 3 days after initiating a 6-day course of dexamethasone treatment. Infants with RDS were followed until discharge and were classified as non-BPD and either 1) BPD day 28 reflecting oxygen requirement on day 28 but not at 36 corrected weeks or 2) BPD 36 weeks reflecting oxygen requirement at 36 (corrected) weeks' gestation. The classification of presence or absence of BPD by oxygen requirement was supported by and was consistent with radiologic findings of BPD for all infants. The difference between BPD day 28 and BPD 36 weeks was supported by more extensive radiologic effects in the latter. RESULTS: The arterial plasma level of sL-selectin in infants who had RDS and did not develop BPD was significantly decreased compared with term healthy infants, as was the level of sE-selectin. Compared with infants who had RDS and did not develop BPD, sL-selectin levels were even further decreased in infants who had RDS and did develop BPD both at birth and throughout the first 4 weeks of life (day 1 through day 28). Infants with BPD also showed increasing levels of sE-selectin during this period of time, whereas infants without BPD did not. Levels of soluble intercellular adhesion molecule-1 in infants without BPD were not different from infants with BPD initially but increased in infants with BPD compared with infants without BPD, significant on day 28 in both groups. Dexamethasone treatment increased concentration of sL-selectin and decreased concentration of sE-selectin. CONCLUSIONS: Low sL-selectin may be an early indicator of enhanced risk for BPD. Low levels of sL-selectin and increasing levels of sE-selectin may be risk factors for BPD. The effects of dexamethasone treatment include significant modulation of adhesion molecules.

Basement membrane biomarkers in very low birth weight premature infants. Association with length of NICU stay and bronchopulmonary dysplasia.

Basement membranes, critical for vital organs like the lungs, consist of two interwoven homopolymers, one assembled by type IV collagens and one by laminins. We hypothesized their serum antigens C-IV and P1, respectively, to be global measures for the maturity of these organs. In 39 very low birth weight premature neonates (means: gestational age, 25.8 weeks; birth weight, 779 g) requiring intensive care, we analyzed these biomarkers during the first two months post partum. Median C-IV and P1 exceeded adult levels by one order of magnitude. The individuals with the lowest first week C-IV values (mean: 667 ng/ml) required significantly longer neonatal intensive care unit stays than those with the highest values (mean: 2,467 ng/ml), on average 109 vs. 80 days (p = 0.008) irrespective of gestational age. Patients diagnosed with bronchopulmonary dysplasia (BPD) at 36 weeks postconceptional age, already in their first week of life displayed C-IV levels lower than in controls, suggesting a defect in pulmonary basement membrane remodeling. This is the first identification by a matrix biomarker of a BPD-antecedent state.

Diagnostic value of cytokines and C-reactive protein in the first 24 hours of neonatal sepsis.

The first objective of this article was to determine the diagnostic accuracy of tumor necrosis factor-alpha, interleukin-6 (IL-6), and interleukin-8 (IL-8) in differentiating infected from noninfected neonates during the first 24 hours of suspected sepsis and to compare them to the currently used laboratory parameters: C-reactive protein (CRP), immature-to-total neutrophil ratio, and leukocyte and platelet count. The secondary objective was to compare the cytokine levels in subpopulations of neonates. Seventy-five premature and 30 term infants were enrolled. Blood samples for the "currently used laboratory tests" and the cytokine levels were obtained at the first suspicion of sepsis ("0-hour") and 18 to 30 hours later ("24-hours"). Patients were classified as septic (48) or nonseptic (57). Thirty-two septic patients had positive blood cultures and 16 showed clinical signs of sepsis. Twenty septic patients had early-onset and 28 had late-onset sepsis. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated for each test. Receiver-operating characteristic curves were analyzed to determine the optimal thresholds. A combination of CRP > 10 pg/mL plus IL-6 > 18 pg/mL (sensitivity = 89%, specificity = 73%, PPV = 70%, NPV = 90%) was the best "0-hour" test, and CRP (sensitivity = 78%, specificity = 94%) was the best "24-hours" test. Lower IL-6 at 0-hour (p = 0.018) and IL-8 at 24 hours (p = 0.023) were detected among the patients infected with coagulase-negative staphylococci then with other bacteria. In conclusion, a combination of CRP + IL-6 provided additional diagnostic accuracy for differentiation between septic and nonseptic patients during the first 24 hours of suspected sepsis.