Jon E. Tyson

Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infants

BACKGROUND Septicemia is a major antecedent of morbidity and mortality in very low birth weight (501- to 1500-g) infants. Our purpose was to determine prospectively the incidence, clinical presentation, laboratory features, risk factors, morbidity and mortality associated with late onset septicemia in infants 501 to 1500 g. METHODS Clinical data were prospectively collected for 2416 infants enrolled in a multicenter trial to determine the efficacy of intravenous immunoglobulin in preventing nosocomial infections. Septicemia was confirmed by positive blood culture in 395 symptomatic infants. Multivariate analyses of factors associated with septicemia were performed. RESULTS Sixteen percent of VLBW infants developed septicemia at a median age of 17 days. Factors associated with septicemia by logistic regression included male gender, lower gestational age and birth weight and decreased baseline serum IgG concentrations. Increasing apnea (55%), feeding intolerance, abdominal distension or guaiac-positive stools (43%), increased respiratory support (29%), lethargy and hypotonia (23%) were the dominant presenting features of septicemia. An abnormal white blood cell count (46%), unexplained metabolic acidosis (11%) and hyperglycemia (10%) were the most common laboratory indicators. Septicemic infants, compared with nonsepticemic infants, had significantly increased mortality (21% vs. 9%), longer hospital stay (98 vs. 58 days) and more serious morbidity, including severe intraventricular hemorrhage, bronchopulmonary dysplasia and increased ventilator days (P < 0.001). CONCLUSIONS Late onset septicemia is common in very low birth weight infants, and the rate is inversely proportional to gestational age and birth weight. Septicemia is more common in males and those with low initial serum IgG values. A set of clinical signs (apnea, bradycardia, etc.) and laboratory values (leukocytosis, immature white blood cells and neutropenia) increase the probability of late onset sepsis, but they have poor positive predictive value.

Dexamethasone therapy increases infection in very low birth weight infants.

Background. Infection is a major complication of preterm infants, resulting in increased morbidity and mortality. We recently reported the results of a multicenter trial of dexamethasone initiated at 14 or 28 days in very low birth weight (VLBW) infants who were at risk for chronic lung disease; the results showed an increase in nosocomial bacteremia in the group receiving dexamethasone. This study is an in-depth analysis of bacteremia/sepsis and meningitis among infants enrolled in the trial. Methods. Data on cultures performed and antibiotic therapy were collected prospectively. Infections were classified as definite or possible/clinical. Results. A total of 371 infants were enrolled in the trial. There were no baseline differences in risk factors for infection. For the first 14 days of study, infants received either dexamethasone (group I, 182) or placebo (group II, 189). During this period, infants in group I were significantly more likely than those in group II to have a positive blood culture result (48% vs 30%) and definite bacteremia/sepsis/meningitis (22% vs 14%). Over the 6-week study period, 47% of those cultured had at least one positive blood culture result (53% in group I vs 41% in group II) and 25% of the infants had at least one episode of definite bacteremia/sepsis/meningitis (29% in group I vs 21% in group II). Among infants with definite infections, 46.8% were attributable to Gram-positive organisms, 26.6% to Gram-negative organisms and 26.6% to fungi. The factors present at randomization were evaluated for their association with infection. Group I assignment and H2blocker therapy (before study entry) were associated with increased risk of definite infection, whereas cesarean section delivery and increasing birth weight were associated with decreased risk. Conclusions. Infants who received a 14-day course of dexamethasone initiated at 2 weeks of age were more likely to develop a bloodstream or cerebrospinal fluid infection while on dexamethasone therapy than were those who received placebo. Physicians must consider this increased risk of infection when deciding whether to treat VLBW infants with dexamethasone.

Inaccuracy of Ballard scores before 28 weeks’ gestation

OBJECTIVE Ballard scores are commonly used to estimate gestational age (GA). The purpose of this study was to determine the accuracy of the New Ballard Score (NBS) for infants <28 weeks GA by accurate menstrual history and to evaluate NBS as an outcome predictor. METHODS Infants weighing 401 to 1500 g in 12 National Institute of Child Health and Human Development Neonatal Research Network centers had NBS performed before age 48 hours. Accuracy of NBS estimates of GA was assessed for infants with GA determined by accurate menstrual history. In a larger cohort of infants, NBS was included in regression models of the association of NBS and death, poor outcome, and duration of hospital stay. RESULTS At each week from 22 to 28 weeks GA by accurate menstrual history, NBS estimates exceeded GA by dates by 1.3 to 3.3 weeks, and estimates varied widely (range of widths of 95% CIs for the observations, 6.8 to 11.9 weeks). NBS did not contribute significantly to regression models of death, poor outcome, or duration of hospital stay. CONCLUSIONS Inaccuracies in GA determined by the NBS should be considered when treating extremely premature infants, particularly in decisions to forego or administer intensive care. Refinement of GA scoring systems is needed to optimize clinical benefit.

Does aggressive phototherapy increase mortality while decreasing profound impairment among the smallest and sickest newborns

Objective:Aggressive phototherapy (AgPT) is widely used and assumed to be safe and effective for even the most immature infants. We assessed whether the benefits and hazards for the smallest and sickest infants differed from those for other extremely low-birth-weight (ELBW; ⩽1000 g) infants in our Neonatal Research Network trial, the only large trial of AgPT.Study Design:ELBW infants (n=1974) were randomized to AgPT or conservative phototherapy at age 12 to 36 h. The effect of AgPT on outcomes (death, impairment, profound impairment, death or impairment (primary outcome), and death or profound impairment) at 18 to 22 months of corrected age was related to BW stratum (501 to 750 g; 751 to 1000 g) and baseline severity of illness using multilevel regression equations. The probability of benefit and of harm was directly assessed with Bayesian analyses.Result:Baseline illness severity was well characterized using mechanical ventilation and FiO2 at 24 h age. Among mechanically ventilated infants ⩽750 g BW (n=684), a reduction in impairment and in profound impairment was offset by higher mortality (P for interaction <0.05) with no significant effect on composite outcomes. Conservative Bayesian analyses of this subgroup identified a 99% (posterior) probability that AgPT increased mortality, a 97% probability that AgPT reduced impairment, and a 99% probability that AgPT reduced profound impairment.Conclusion:Findings from the only large trial of AgPT suggest that AgPT may increase mortality while reducing impairment and profound impairment among the smallest and sickest infants. New approaches to reduce their serum bilirubin need development and rigorous testing.

Efficacy of phototherapy devices and outcomes among extremely low birth weight infants: multi-center observational study

Objective:Evaluate the efficacy of phototherapy (PT) devices and the outcomes of extremely premature infants treated with those devices.Study Design:This substudy of the National Institute of Child Health and Human Development Neonatal Research Network PT trial included 1404 infants treated with a single type of PT device during the first 24±12 h of treatment. The absolute (primary outcome) and relative decrease in total serum bilirubin (TSB) and other measures were evaluated. For infants treated with one PT type during the 2-week intervention period (n=1223), adjusted outcomes at discharge and 18 to 22 months corrected age were determined.Result:In the first 24 h, the adjusted absolute (mean (±s.d.)) and relative (%) decrease in TSB (mg dl−1) were: light-emitting diodes (LEDs) −2.2 (±3), −22%; Spotlights −1.7 (±2), −19%; Banks −1.3 (±3), −8%; Blankets −0.8 (±3), −1%; (P<0.0002). Some findings at 18 to 22 months differed between groups.Conclusion:LEDs achieved the greatest initial absolute reduction in TSB but were similar to Spots in the other performance measures. Long-term effects of PT devices in extremely premature infants deserve rigorous evaluation.

Erratum: Influence of clinical status on the association between plasma total and unbound bilirubin and death or adverse neurodevelopmental outcomes in extremely low birth weight infants (Acta Paediatrica, International Journal of Paediatrics (2010) 99 (673-678)

To the editor: We recently discovered that the unbound bilirubin values shown in figure 1 of our paper entitled ‘Influence of clinical status on the association between plasma total and unbound bilirubin and death or adverse neurodevelopmental outcomes in extremely low birth weight infants’, Acta Paediatrica, 2010 99: 673–678 may be confusing to the readers (1). In the process of performing the logistic regression probability plots to correlate the unbound bilirubin with various outcome variables, we have standardized the unbound bilirubin by dividing the actual values by the standard deviations which is 0.3. The standardized values (in units) were used in the presentation of data in this figures which appear to be 0–3.0 units. The actual unbound bilirubin values are 0–0.9 mcg/dL A footnote should have been appended. We apologize for this omission. W Oh, MD, DK Stevenson, JE Tyson, BH Morris, CE Ahlfors, G Jesse Bender, RJ Wong, R Perritt, BR Vohr, KP Van Meurs, HJ Vreman, A Das, DL Phelps, T Michael O’Shea, and RD Higgins.