John L. Stefano

Decreased erythrocyte Na+, K+-ATPase activity associated with cellular potassium loss in extremely low birth weight infants with nonoliguric hyperkalemia

To determine whether a shift of potassium ions from the intracellular space to the extracellular space accounts, in part, for the hyperkalemia seen in extremely low birth weight infants, we examined potassium concentration in serum and erythrocytes from extremely low birth weight infants with hyperkalemia (n = 12) or with normokalemia (n = 27). In addition, to determine whether the shift of potassium was associated with low sodium-potassium-adenosinetriphosphatase (Na+,K(+)-ATPase) activity, we studied the activity of ATPase in the last 16 infants enrolled in the study. Fluid intake and output were measured during the first 3 days of life. Infants were considered to have hyperkalemia if the serum potassium concentration was 6.8 mmol/L or greater. Blood was obtained daily for intracellular sodium and potassium levels by means of lysis of erythrocytes. The remaining erythrocyte membranes were frozen and analyzed for Na+,K(+)-ATPase activity. There were significantly lower intracellular potassium/serum potassium ratios in the infants with hyperkalemia for each day of the 3-day study (p < 0.001). In the hyperkalemic group, there was lower Na+,K(+)-ATPase activity than in the infants with normokalemia (p = 0.006). Low Na+,K(+)-ATPase activity was associated with lower intracellular potassium/serum potassium ratios (p = 0.006), higher serum potassium values (p = 0.02), and lower intracellular potassium concentration (p = 0.009). The urinary data demonstrated that there was no difference in glomerulotubular balance between the two groups. We conclude that nonoliguric hyperkalemia in extremely low birth weight infants may be due, in part, to a shift of potassium from the intracellular space to the extracellular space associated with a decrease in Na+,K(+)-ATPase activity.

Soluble interleukin-2 receptor as a predictor of neonatal sepsis

We prospectively measured soluble interleukin-2 receptor levels in 56 premature infants with suspected sepsis and demonstrated significant differences between those with positive results on blood, urine, or cerebrospinal fluid cultures, and those with negative results. Soluble interleukin-2 receptor levels can be used to facilitate the diagnosis of sepsis in premature infants with negative blood culture results.

Increasing illness severity in very low birth weight infants over a 9-year period

BackgroundRecent reports have documented a leveling-off of survival rates in preterm infants through the 1990s. The objective of this study was to determine temporal changes in illness severity in very low birth weight (VLBW) infants in relationship to the outcomes of death and/or severe IVH.MethodsCohort study of 1414 VLBW infants cared for in a single level III neonatal intensive care unit in Delaware from 1993–2002. Infants were divided into consecutive 3-year cohorts. Illness severity was measured by two objective methods: the Score for Neonatal Acute Physiology (SNAP), based on data from the 1st day of life, and total thyroxine (T4), measured on the 5th day of life. Death before hospital discharge and severe intraventricular hemorrhage (IVH) were investigated in the study sample in relation to illness severity. The fetal death rate was also investigated. Statistical analyses included both univariate and multivariate analysis.ResultsIllness severity, as measured by SNAP and T4, increased steadily over the 9-year study period with an associated increase in severe IVH and the combined outcome of death and/or severe IVH. During the final 3 years of the study, the observed increase in illness severity accounted for 86% (95% CI 57–116%) of the variability in the increase in death and/or severe IVH. The fetal death rate dropped from 7.8/1000 (1993–1996) to 5.3/1000 (1999–2002, p = .01) over the course of the study.ConclusionThese data demonstrate a progressive increase in illness in VLBW infants over time, associated with an increase in death and/or severe IVH. We speculate that the observed decrease in fetal death, and the increase in neonatal illness, mortality and/or severe IVH over time represent a shift of severely compromised patients that now survive the fetal time period and are presented for care in the neonatal unit.

Transfusion volume in infants with very low birth weight: a randomized trial of 10 versus 20 ml/kg.

Background Although preterm infants often require transfusions of red blood cells for anemia of prematurity, the optimal volume of blood to be transfused has not been established. Observations Infants with birth weights between 500 and 1,500 g were randomly assigned to receive 10 or 20 mL/kg red blood cells. Infants with transfusions of 20 mL/kg had a greater hemoglobin (14.2 ± 1.9 vs. 12.0 ± 1.9 g/dL, P = 0. 003) and hematocrit (41.2 ± 5.9 vs. 32.3 ± 7.1%, P = 0.001) levels after transfusion compared with those who received transfusions of 10 mL/kg. There were no measured differences in pulmonary function in either group after transfusion. Conclusions Transfusion with 20 mL/kg red blood cells produces a significantly greater increase in hemoglobin and hematocrit levels than does a transfusion with 10 mL/kg, without any detrimental effects on pulmonary function.

Caesarean delivery and outcome in very low birthweight infants.

To determine the relationship between mode of delivery, intraventricular haemorrhage (IVH), and mortality in very low birthweight (VLBW) infants.

Nitrogen balance in extremely low birth weight infants with nonoliguric hyperkalemia

We measured nitrogen balance and urinary 3-methylhistidine molar ratios in 33 extremely low birth weight infants (12 with hyperkalemia and 21 without) for the first 3 days of life. Although all infants were in negative nitrogen balance during the study, there was no difference in the degree of negative nitrogen balance between the two groups. There was also no difference in the 3-methylhistidine/creatinine molar ratios, indicating that muscle protein catabolism did not differ. We conclude that it is unlikely that catabolism contributes to the development of nonoliguric hyperkalemia in extremely low birth weight infants.

ROLE OF FUROSEMIDE THERAPY AFTER BOOSTER-PACKED ERYTHROCYTE TRANSFUSIONS IN INFANTS WITH BRONCHOPULMONARY DYSPLASIA

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Thyroxine and Illness Severity in Very Low-Birth-Weight Infants

The objective of this study was to determine the relationship between thyroxine (T4) and illness severity in a population of preterm infants. We investigated a cohort of infants with birth weights 1,500 g or less from a single level III neonatal intensive care unit who received a minimum of one cranial sonogram to screen for intraventricular hemorrhage (IVH) and one newborn screen for T4 during a 2-year period, (n = 284). The Score for Neonatal Acute Physiology (SNAP) was used to measure illness severity. T4 and SNAP were investigated in relationship to mortality, IVH, and severe IVH. T4 correlated inversely with SNAP (R = -0.46, p < 0.01). Infants with severe IVH and mortality had lower T4 and higher SNAP scores when compared to infants without these conditions. These differences persisted after controlling for the confounding effect of gestational age. Analysis of receiver operator curves indicated that high SNAP and low T4 were equivalently associated with IVH, severe IVH, and mortality. Our data indicate that T4 is associated with illness severity in very low-birth-weight infants. Low T4 levels and high SNAP scores are both associated with the outcomes of IVH and mortality in very low-birth-weight infants.

Increased leukocytes in infants with intraventricular hemorrhage

The objective of this study was to investigate the relationship between intraventricular hemorrhage (IVH) and cystic periventricular leukomalacia (PVL) with changes in the peripheral blood count. Total peripheral leukocytes, absolute neutrophils, platelets, and nucleated erythrocytes from the first 3 days after birth were compared in very-low-birth-weight infants with (n = 100) and without (n = 388) IVH and cystic PVL (n = 16). After controlling for potential confounding variables, infants with IVH had an increase in total leukocytes and absolute neutrophils and a reduction in nucleated erythrocytes compared with infants without IVH. No difference in any parameters studied was evident with regard to cystic PVL. After controlling for potential confounding variables by logistic regression, infants with a peripheral leukocyte count greater than 25,000/mm(3) beyond 24 hours of age had an odds ratio of 2.1 (95% confidence interval = 1.1-4.3) for developing IVH. We conclude that IVH is associated with an increase in total leukocytes and absolute neutrophils for 72 hours after birth in very-low-birth-weight infants. Further investigation is required to determine whether this leukocytosis is important in the pathophysiology of brain injury or is an associated factor.

Cranial Sonography in Very-Low-Birth-Weight Infants: Do All Infants Need to Be Screened?

The objective of the study was to develop clinical screening criteria to diagnose infants with intraventricular hemorrhage (IVH) and cystic periventricular leukomalacia (PVL). We performed a case-control investigation of two cohorts of very-low-birth-weight infants (n=505, combined cohorts). Univariate and multivariate analyses were performed from data obtained in cohort 1 to develop screening criteria for IVH and cystic PVL. The screening criteria were then applied to cohort 2. The screening criteria for IVH had a sensitivity of only 51 %, a specificity of 62%, a positive predictive value of 31 %, and a negative predictive value of 79%. Screening criteria for cystic PVL had a sensitivity of only 22%, a specificity of 58% a positive predictive value of 2%, and a negative predictive value of 95%. These data suggest that using clinical criteria to determine which infants should receive screening cranial sonography for IVH and cystic PVL would miss a substantial number of infants with these conditions. Clin Pediatr. 1999;38:503-509