Robert A. Sinkin

Prevention of central venous catheter-related coagulase-negative staphylococcal sepsis in neonates

A randomized, double-blind, controlled trial was conducted to determine whether vancomycin added to parenteral alimentation solution given via a central venous catheter would decrease the incidence of catheter-related coagulase-negative staphylococcal sepsis. Seventy infants with a central venous catheter (CVC) in place were randomly selected to receive total parenteral nutrition--either the standard solution or a solution containing 25 micrograms of vancomycin per milliliter. Catheter-related sepsis was defined as the isolation of the same bacterial species from specimens of both peripheral and CVC blood with the concentration of bacteria at least tenfold greater in the specimen obtained from the CVC. Specimens from the CVCs were cultured on removal of the catheters to determine colonization. The colonization of catheters by coagulase-negative staphylococci was reduced from 40% to 22% (p = 0.03) in the vancomycin group; catheter-related sepsis was reduced from 15% to no cases (p = 0.004). Fewer infants required CVC reinsertion in the vancomycin-treated group (p = 0.02), who also regained birth weight earlier (13.4 vs 17.1 days (p = 0.014)). Adverse effects of vancomycin infusion were not observed. We conclude that vancomycin added to the solution used for total parenteral nutrition effectively reduces catheter-related sepsis in the neonatal intensive care unit and offers other potential benefits such as the need for fewer catheters and earlier weight gain. However, we do not recommend widespread implementation of this technique until there are data regarding the emergence of vancomycin-resistant organisms.

Two doses of early intravenous dexamethasone for the prevention of bronchopulmonary dysplasia in babies with respiratory distress syndrome

ABSTRACT: Bronchopulmonary dysplasia is an important complication of ventilation in babies for which treatment with steroids has been advocated. We report the results of a phase I study of early i.v. dexamethasone to prevent the development of bronchopulmonary dysplasia in a high-risk population of ventilated premature babies, < 30 wk gestation, with surfactant-treated respiratory distress syndrome. This study used a limited dexamethasone dosing regimen to minimize toxicity but used administration early in the course of acute lung disease to interrupt the injury cycle. Forty babies were enrolled; 19 were randomized to receive dexamethasone (0.5 mg/kg birth weight at 12–18 h of age and a second dose 12 h later) and 21 were randomized to receive placebo (i.v. saline). The dexamethasone group required less ventilatory support (mean airway, peak in-spiratory and end expiratory pressures, and intermittent mandatory ventilation) and supplemental oxygen after study d 4 (all p < 0.05, repeated measures analysis of variance). Improved tidal volume in the dexamethasone group, as measured by pulmonary function testing of infants who remained intubated, was seen on study d 7 (p = 0.02, t test). The dexamethasone group required shorter hospitalizations (median of 95 d versus 106 d, p = 0.01) (proportional hazards regression). Survival in the dexa methasone group was 89% versus 67% in the placebo group (p = 0.08, x2 analysis). Survival without bronchopulmonary dysplasia, diagnosed at 36 wk corrected gestational age, was 68% in the dexamethasone group versus 43% in the placebo group (p = 0.14). Mean blood pressure was elevated on study d 4 through 7 in the dexamethasone group, but this difference resolved by study d 10 without pharmacologic intervention. No differences in hyperglycemia, incidence of intraventricular hemorrhage (or its severity), or days to regain birth weight were seen. Early administration of dexamethasone resulted in short-term and suggested long-term benefits without significant complications. The results of this trial justify a large scale, broader-based (phase II) trial in premature babies with respiratory distress syndrome to determine the limits of effectiveness and the incidence of less-frequent potential side effects.

Amnioinfusion during labor complicated by particulate meconium-stained amniotic fluid decreases neonatal morbidity

OBJECTIVE Our purpose was to evaluate the efficacy of prophylactic amnioinfusion in decreasing neonatal morbidity associated with labor complicated by particulate meconium-stained amniotic fluid and to assess potential complications of this procedure. STUDY DESIGN One hundred five laboring pregnant women with particulate (moderate or thick) meconium by subjective clinical analysis were randomly assigned to receive amnioinfusion or to receive standard obstetric care without amnioinfusion. Patients with any antepartum complications, other than the presence of meconium, were excluded from the study. Statistical analyses consisted of the two-tailed and paired Student t tests, Pearson chi 2 test, and Wilcoxon nonparametric test. Significance was set at p < 0.05. RESULTS The study included 47 patients in the study group and 58 patients in the control group. A significantly greater proportion of study patients demonstrated decreased meconium concentration between rupture of membranes and delivery (46 of 46 vs 15 of 58, p < 0.001). The relative dilution of meconium consistency by objective analysis was significantly different between the study group and the control group (77.1% decrease vs 9.3% increase, p < 0.001). The proportion of neonates with meconium below the vocal cords was reduced in the study group (two of 47 vs 36 of 58, p < 0.001). Umbilical artery pH was increased in the study group neonates (7.29 +/- 0.01 vs 7.25 +/- 0.009, p < 0.05). The rate of neonatal acidemia was reduced in the study group (4 of 45 vs 12 of 50, p < 0.05). The rate of meconium aspiration syndrome was reduced in the study group (1 of 47 vs 8 of 58, p < 0.05). Maternal and neonatal morbidity rates were similar. CONCLUSION Prophylactic amnioinfusion should be considered a possible addition to the intrapartum management of patients with particulate meconium-stained amniotic fluid.

Comparison of tracheal aspirate and bronchoalveolar lavage specimens from premature infants

Lung fluid obtained by tracheal aspiration (TA) or bronchoalveolar lavage (BAL) has been used to study bronchopulmonary dysplasia (BPD). These two sample collection methods have seldom been compared. Paired BAL and TA specimens were collected 1, 3, 7 and 28 days after birth in 40 infants <34 weeks’ gestation during a randomized, controlled trial of dexamethasone for BPD prophylaxis. Interleukin 8 (IL-8) and cell counts were measured. Compared to subjects without BPD, those who developed BPD or died by 28 days had elevated IL-8 in epithelial lining fluid on day 1 in both BAL specimens (20 ng/ml vs. 2 ng/ml) and TA specimens (101 ng/ml vs. 18 ng/ml). IL-8 levels (r = 0.55) and neutrophil proportions (r = 0.51) were moderately correlated between BAL and TA samples. TA specimens may be suitable substitutes for BAL samples in some studies of newborn lung fluid.

Vascular Endothelial Growth Factor in Pulmonary Lavage Fluid from Premature Infants: Effects of Age and Postnatal Dexamethasone

Corticosteroids are used to ameliorate bronchopulmonary dysplasia (BPD). They also affect normal development, including the expression of growth factors such as vascular endothelial growth factor (VEGF). Deep pulmonary lavage specimens were collected on days 1, 3, 7 and 28 of life in 40 infants of <34 weeks of gestation at birth during a randomized controlled trial of two doses of dexamethasone (DEX) at 12 and 24 h of age for BPD prophylaxis. VEGF was measured by enzyme-linked immunosorbent assay. The 18 DEX and 21 control subjects had similar gestations, birth weights and oxygen requirements at study entry. Lavage VEGF tripled between day 1 and 3 in both groups. The day 7 levels were higher in DEX subjects than in controls. DEX and control values were similar on day 28. Higher lavage VEGF levels on days 1 and 3 were also correlated with lower gestational age at birth. Lavage VEGF levels were not associated with the development of BPD. We speculate that these DEX- and age-associated changes in VEGF may affect pulmonary angiogenesis.

Frequency of Elevations in Markers of Cardiomyocyte Damage in Otherwise Healthy Newborns

Myocardial damage in infancy is a risk factor for eventual cardiac disease. Given that myocardial stress is greatest during the perinatal period and that the neonatal period is when most pediatric heart failure occurs, the aim of this study was to determine whether even otherwise healthy neonates might have subclinical myocardial damage and, if so, what characteristics might identify them. Umbilical cord and neonatal serum samples from 32 normal neonates were assayed for biomarkers of myocardial injury. No neonate had clinical evidence of cardiac or other abnormalities. Serum cardiac troponin T was elevated in 19 of 25 cords (76%) and in 16 of 17 neonates (94%); levels indicating myocardial infarction (> or =0.2 ng/ml) were found in 2 patients (1 umbilical cord and 1 neonatal sample). Creatine kinase-MB was elevated in 6 of 16 cords (38%) and in 8 of 15 neonates (53%). Cardiac troponin I was elevated in 11% and 17% of samples, myoglobin in 4% and 17%, and high-sensitivity C-reactive protein in 9% and 40%. Measures of myocardial injury were associated with longer hospitalization (r = 0.50, p = 0.04), non-Caucasian race (p = 0.012), lower birth weights (p = 0.014), positive maternal cervical cultures (r = 0.41, p = 0.046), and elevated high-sensitivity C-reactive protein (r = 0.66, p = 0.005). In conclusion, clinically occult myocardial injury appears to occur in some healthy newborns, although whether it is pathologic or not remains to be determined.

Prenatal ultrasonographic diagnosis of intracranial teratoma and massive craniomegaly with associated high-output cardiac failure

Congenital intracranial teratomas are rare and usually fatal. We present prenatal diagnosis of such a case associated with scalp, facial, and body skin edema, hepatomegaly, extramedullary hematopoiesis, polyhydramnios, and a hydropic placenta. These manifestations of high-output cardiac failure were thought to be the result of the large cardiac output required by massive intracranial tumor arteriovenous shunting.

Differential Cytokine mRNA Expression by Neonatal Pulmonary Cells

The purpose of this study was to describe cytokine profiles of human neonatal pulmonary cells isolated by tracheal aspiration (TA) and by deep pulmonary lavage (DPL). We hypothesized that mRNA phenotyping, using the technique of reverse transcriptase polymerase chain reaction (RT-PCR), would reveal differences in cytokine expression patterns between cells from proximal and distal airway compartments. We reasoned that cells derived by DPL may reflect pathogenic pathways indicative for the development of bronchopulmonary dysplasia in the premature infant. Here we have described the detection of mRNA for IL-1α, IL-1β, IL-6, IL-8, and tumor necrosis factor-α. Fourteen paired TA and DPL samples from six premature infants were collected at 1, 7, or 28 d of age. Two of 14 samples were negative forβ-actin (a ubiquitous mRNA) by RT-PCR and were excluded from further analysis. Each of the remaining 12 samples expressed IL-8. Furthermore, each cytokine could be expressed by TA or DPL cells. Cytokine mRNA phenotype profiles were found to differ between TA and DPL cells in four of five paired samples. Our results show that cells retrieved from these two pulmonary compartments are sources for these cytokines and suggest that RT-PCR of TA/DPL cells can be used to test hypothetical predictive markers for the development of bronchopulmonary dysplasia.

New Strategies for the Prevention of Bronchopulmonary Dysplasia

This article reviews the progress being made into the prevention or arrest of this complex respiratory disease. The key elements in the pathophysiology are reviewed; the current problems in defining, classifying, and predicting the development of this disorder are discussed and potentially useful interventions also are introduced.

Fibronectin expression in bronchopulmonary dysplasia.

ABSTRACT Bronchopulmonary dysplasia (BPD) is a chronic fibrotic lung disease of neonates. Fibronectin (FN), a component of the extracellular matrix, is increased in the tracheobronchial effluent of neonates destined to develop BPD. Pulmonary FN is derived from plasma and local cellular synthesis. In order to identify which pulmonary cells synthesize FN and to test the hypothesis that FN is more abundant in lungs with BPD, we examined the distribution of pulmonary FN by in situ hybridization (for mRNA) and immunohistochemistry (for protein) in neonatal autopsy lung specimens, comparing lungs with BPD to those without. We used a staging system in which BPD is characterized by disruption of alveolar architecture, severe vascular changes, airway epithelial necrosis, smooth muscle hypertrophy, and peribronchial fibrosis. FN mRNA and protein were found in vascular endothelium, macrophages, fibroblasts, vascular and airway smooth muscle, and chondrocytes as well as in the pulmonary parenchyma in neonates with and without BPD. Hyaline membranes, when present, immunostained intensely for FN protein. FN mRNA was not seen in airway epithelial cells of either group. FN mRNA and protein were first increased in early acute BPD with their levels appearing greatest during the chronic reparative stage of BPD. In long-standing “healed” BPD, lower levels of FN mRNA and protein were seen. These findings are consistent with the association of increased FN with adult fibrotic lung disease and the previously reported increase in FN tracheal effluent levels in infants with BPD. Our results suggest an important role for pulmonary cell-derived FN in the early inflammatory and later proliferative stages of BPD.