Randomized controlled trial of the "WISER" intervention to reduce healthcare worker burnout.

OBJECTIVE: Test web-based implementation for the science of enhancing resilience (WISER) intervention efficacy in reducing healthcare worker (HCW) burnout. DESIGN: RCT using two cohorts of HCWs of four NICUs each, to improve HCW well-being (primary outcome: burnout). Cohort 1 received WISER while Cohort 2 acted as a waitlist control. RESULTS: Cohorts were similar, mostly female (83%) and nurses (62%). In Cohorts 1 and 2 respectively, 182 and 299 initiated WISER, 100 and 176 completed 1-month follow-up, and 78 and 146 completed 6-month follow-up. Relative to control, WISER decreased burnout (-5.27 (95% CI: -10.44, -0.10), p = 0.046). Combined adjusted cohort results at 1-month showed that the percentage of HCWs reporting concerning outcomes was significantly decreased for burnout (-6.3% (95%CI: -11.6%, -1.0%); p = 0.008), and secondary outcomes depression (-5.2% (95%CI: -10.8, -0.4); p = 0.022) and work-life integration (-11.8% (95%CI: -17.9, -6.1); p < 0.001). Improvements endured at 6 months. CONCLUSION: WISER appears to durably improve HCW well-being. CLINICAL TRIALS NUMBER: NCT02603133; https://clinicaltrials.gov/ct2/show/NCT02603133.

Hypothermia and neonatal encephalopathy.

Data from large randomized clinical trials indicate that therapeutic hypothermia, using either selective head cooling or systemic cooling, is an effective therapy for neonatal encephalopathy. Infants selected for cooling must meet the criteria outlined in published clinical trials. The implementation of cooling needs to be performed at centers that have the capability to manage medically complex infants. Because the majority of infants who have neonatal encephalopathy are born at community hospitals, centers that perform cooling should work with their referring hospitals to implement education programs focused on increasing the awareness and identification of infants at risk for encephalopathy, and the initial clinical management of affected infants.

Death or neurodevelopmental impairment at 18 to 22 months corrected age in a randomized trial of early dexamethasone to prevent death or chronic lung disease in extremely low birth weight infants.

OBJECTIVE: To evaluate the incidence of death or neurodevelopmental impairment (NDI) at 18-22 months corrected age in subjects enrolled in a trial of early dexamethasone treatment to prevent death or chronic lung disease in extremely low birth weight infants. STUDY DESIGN: Evaluation of infants at 18-22 months corrected age included anthropomorphic measurements, a standard neurological examination, and the Bayley Scales of Infant Development-II, including the Mental Developmental Index and the Psychomotor Developmental Index. NDI was defined as moderate or severe cerebral palsy, Mental Developmental Index or Psychomotor Developmental Index <70, blindness, or hearing impairment. RESULTS: Death or NDI at 18-22 months corrected age was similar in the dexamethasone and placebo groups (65% vs 66%, P = .99 among those with known outcome). The proportion of survivors with NDI was also similar, as were mean values for weight, length, and head circumference and the proportion of infants with poor growth (50% vs 41%, P = .42 for weight less than 10th percentile); 49% of infants in the placebo group received treatment with corticosteroid compared with 32% in the dexamethasone group (P = .02). CONCLUSION: The risk of death or NDI and rate of poor growth were high but similar in the dexamethasone and placebo groups. The lack of a discernible effect of early dexamethasone on neurodevelopmental outcome may be due to frequent clinical corticosteroid use in the placebo group.

An intervention to improve transitions from NICU to ambulatory care: quasi-experimental study.

BACKGROUND: Infants born prematurely or with complex medical problems are surviving to discharge in growing numbers and often require significant monitoring and coordination of care in the ambulatory setting. Using Healthcare Failure Modes and Effects Analysis (HFMEA), we identified a large number of potentially serious error points in this transition of care. PURPOSE To test whether a multifaceted intervention that included a health coach to assist families and an enhanced personal health record to improve the quality of information available to parents and community professionals would decrease adverse events and improve family assessment of the transition. METHODS: Using a concurrent cohort design, infants in one geographic area (pod) of the intensive care nursery received the intervention; infants in two other pods received routine discharge care. Primary outcomes included deaths, sick visits, unplanned readmissions and missed appointments within 1 month of discharge. The family assessed the transition using a modified version of the Care Transitions Measure. RESULTS: 125 intervention infants (54% boys) and 104 control infants (48% boys) were enrolled over 18 months. The groups were similar in maternal education, insurance status, language spoken and number of adults in the home, birth weight and length of stay. At least one adverse outcome occurred in 63 (50.4%) intervention infants and 56 (53.8%) control infants (p=0.55). At 24­48 h post discharge, caregivers in the intervention group had significantly higher scores on the adapted care transitions measure (3.51 vs 3.27, p<0.0001); however, at 30 days, the difference was no longer significant (3.45 vs 3.40, p=0.27). CONCLUSIONS: A multicomponent discharge intervention designed to address specific problems identified using HFMEA did not reduce certain adverse outcomes in the post-discharge period. TRIAL REGISTRATION: NCT01088945.

Childhood outcomes after hypothermia for neonatal encephalopathy.

BACKGROUND: We previously reported early results of a randomized trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy showing a significant reduction in the rate of death or moderate or severe disability at 18 to 22 months of age. Long-term outcomes are now available. METHODS: In the original trial, we assigned infants with moderate or severe encephalopathy to usual care (the control group) or whole-body cooling to an esophageal temperature of 33.5°C for 72 hours, followed by slow rewarming (the hypothermia group). We evaluated cognitive, attention and executive, and visuospatial function; neurologic outcomes; and physical and psychosocial health among participants at 6 to 7 years of age. The primary outcome of the present analyses was death or an IQ score below 70. RESULTS: Of the 208 trial participants, primary outcome data were available for 190. Of the 97 children in the hypothermia group and the 93 children in the control group, death or an IQ score below 70 occurred in 46 (47%) and 58 (62%), respectively (P=0.06); death occurred in 27 (28%) and 41 (44%) (P=0.04); and death or severe disability occurred in 38 (41%) and 53 (60%) (P=0.03). Other outcome data were available for the 122 surviving children, 70 in the hypothermia group and 52 in the control group. Moderate or severe disability occurred in 24 of 69 children (35%) and 19 of 50 children (38%), respectively (P=0.87). Attention-executive dysfunction occurred in 4% and 13%, respectively, of children receiving hypothermia and those receiving usual care (P=0.19), and visuospatial dysfunction occurred in 4% and 3% (P=0.80). CONCLUSIONS: The rate of the combined end point of death or an IQ score of less than 70 at 6 to 7 years of age was lower among children undergoing whole-body hypothermia than among those undergoing usual care, but the differences were not significant. However, hypothermia resulted in lower death rates and did not increase rates of severe disability among survivors. (Funded by the National Institutes of Health and the Eunice Kennedy Shriver NICHD Neonatal Research Network; ClinicalTrials.gov number, NCT00005772.).

Cytokines and neurodevelopmental outcomes in extremely low birth weight infants.

OBJECTIVE: To determine if selected pro-inflammatory and anti-inflammatory cytokines and/or mediators of inflammation reported to be related to the development of cerebral palsy (CP) predict neurodevelopmental outcome in extremely low birth weight infants. STUDY DESIGN: Infants with birth weights ≤1000 g (n = 1067) had blood samples collected at birth and on days 3 ± 1, 7 ± 1, 14 ± 3, and 21 ± 3 to examine the association between cytokines and neurodevelopmental outcomes. The analyses were focused on 5 cytokines (interleukin [IL] 1ß; IL-8; tumor necrosis factor-α; regulated upon activation, normal T-cell expressed, and secreted (RANTES); and IL-2) reported to be most predictive of CP in term and late preterm infants. RESULTS: IL-8 was higher on days 0-4 and subsequently in infants who developed CP compared with infants who did not develop CP in both unadjusted and adjusted analyses. Other cytokines (IL-12, IL-17, tumor necrosis factor-ß, soluble IL rα, macrophage inflammatory protein 1ß) were found to be altered on days 0-4 in infants who developed CP. CONCLUSIONS: CP in former preterm infants may, in part, have a late perinatal and/or early neonatal inflammatory origin.

Trends in neonatal morbidity and mortality for very low birthweight infants.

OBJECTIVE: To document the mortality and morbidity of infants weighing 501-1500 g at birth according to gestational age, birthweight, and sex. STUDY DESIGN: Prospective collection of perinatal events and neonatal course to 120 days of life, discharge, or death from January 1990 through December 2002 for infants born at 16 participating centers of the National Institute of Child Health & Human Development Neonatal Research Network. RESULTS: Compared with 1995-1996, for 1997-2002 the survival of infants with birthweight of 501-1500 g increased by 1 percentage point (from 84% to 85%). Survival without major neonatal morbidity remained static, at 70%; this includes bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC). Survival increased for multiple births (26%, up from 22%), antenatal corticosteroid use (79%, up from 71%), and maternal antibiotics (70%, up from 62%) (P < .05). From 1997 to 2002, birthweight-specific survival was 55% for infants weighing 501-750 g, 88% for 751-1000 g, 94% for 1001-1250 g, and 96% for 1251-1500 g. More females survived. The incidence of NEC (7%), severe IVH (12%), and late-onset septicemia (22%) remained essentially unchanged, but BPD decreased slightly, from 23% to 22%. The use of postnatal corticosteroids declined from 20% in 1997-2000 to 12% in 2001-2002. Growth failure (weight <10th percentile) at 36 weeks' postmenstrual age decreased from 97% in 1995-1996 to 91% in 1997-2002. CONCLUSION: There have been no significant increases in survival without neonatal and long-term morbidity among VLBW infants between 1997 and 2002. We speculate that to improve survival without morbidity requires determining, disseminating, and applying best practices using therapies currently available, and also identifying new strategies and interventions.

Emotional regulation and its impact on development in extremely low birth weight infants.

The purposes of this study were to compare the Bayley Scales of Infant Development (BSID-II) scores at 8 and 18-22 months adjusted age of a cohort of 47 extremely low birth weight infants and to determine whether there was an association between changes in test scores and infant behavior as measured by the Behavioral Rating Scale of the BSID-II at 18-22 months adjusted age. Psychomotor Developmental Index scores did not differ between the two testing points (p = .17), whereas the Mental Developmental Index (MDI) scores dropped significantly (p = .006). Emotional regulation and low household income were both significantly associated with changes in MDI scores (p = .001 and p = .002, respectively). After adjusting for household income, the association between emotional regulation and changes in MDI scores remained significant (p = .02). Results suggest that infant behavioral characteristics, as well as family socioeconomic status, can adversely affect developmental outcome at 18-22 months adjusted age.

Outcome of very low birth weight infants exposed to antenatal indomethacin for tocolysis.

OBJECTIVE: Beginning in October 1995, and for several years thereafter, our institution used indomethacin as a first-line tocolytic drug. Our purpose is to compare the outcomes of very low birth weight infants who were exposed to antenatal indomethacin with those who were not exposed to this therapy. STUDY DESIGN: We used our center's component of the NICHD Neonatal Research Network's Generic Data Base which recorded the outcomes of all live born infants weighing less than 1500 g over a 5-year period. We abstracted data concerning neonatal morbidity (death, Grades III to IV intraventricular hemorrhage (IVH), necrotizing enterocolitis and patent ductus arteriosus), as well as other factors including gestational age, birth weight, antenatal corticosteroid treatment and maternal hypertension or pre-eclampsia. Univariate analysis was performed using Fisher's exact test. Multivariate analysis using logistic regression was performed to control for confounding factors. RESULTS: A total of 85 infants who were exposed to antenatal indomethacin were compared to 464 infants who were not exposed to the drug. In the univariate analysis, antenatal indomethacin exposure was not associated with a significant increase in the incidence of necrotizing enterocolitis or patent ductus arteriosus. The incidence of Grades III to IV IVH was 17.9% in those infants exposed to antenatal indomethacin compared to 7.1% in the nonexposed infants (p=0.008). The incidence of neonatal death in the exposed infants was 27.7 versus 16.4 in the nonexposed infants (p=0.02). After controlling for antenatal corticosteroids, maternal pre-eclampsia, gestational age and birth weight, antenatal indomethacin was significantly associated with an increased incidence of IVH, but not neonatal death. CONCLUSION: Antenatal indomethacin was associated with significantly higher rates of IVH. Additional studies assessing the potential risks of indomethacin tocolysis are needed before it is used as a first-line tocolytic therapy.

Neurodevelopmental outcome and growth at 18 to 22 months' corrected age in extremely low birth weight infants treated with early erythropoietin and iron.

BACKGROUND: Clinical trials evaluating the use of erythropoietin (Epo) have demonstrated a limited reduction in transfusions; however, long-term developmental follow-up data are scarce. OBJECTIVE: We compared anthropometric measurements, postdischarge events, need for transfusions, and developmental outcomes at 18 to 22 months' corrected age in extremely low birth weight (ELBW) infants treated with early Epo and supplemental iron therapy with that of placebo/control infants treated with supplemental iron alone. METHODS: The National Institute of Child Health and Human Development Neonatal Research Network completed a randomized, controlled trial of early Epo and iron therapy in preterm infants < or =1250 g. A total of 172 ELBW (< or =1000-g birth weight) infants were enrolled (87 Epo and 85 placebo/control). Of the 72 Epo-treated and 70 placebo/control ELBW infants surviving to discharge, follow-up data (growth, development, rehospitalization, transfusions) at 18 to 22 months' corrected age were collected on 51 of 72 Epo-treated infants (71%) and 51 of 70 placebo/controls (73%) by certified examiners masked to the treatment group. Statistical significance was determined using chi2 analysis. RESULTS: There were no significant differences between treatment groups in weight or length or in the percentage of infants weighing <10th percentile either at the time of discharge or at follow-up, and no difference was found in the mean head circumference between groups. A similar percentage of infants in each group was rehospitalized (38% Epo and 35% placebo/control) for similar reasons. There were no differences between groups with respect to the percentage of infants with Bayley-II Mental Developmental Index <70 (34% Epo and 36% placebo/control), blindness (0% Epo and 2% placebo/control), deafness or hearing loss requiring amplification (2% Epo and 2% placebo/control), moderate to severe cerebral palsy (16% Epo and 18% placebo/control) or the percentage of infants with any of the above-described neurodevelopmental impairments (42% Epo and 44% placebo/control). CONCLUSIONS: Treatment of ELBW infants with early Epo and iron does not significantly influence anthropometric measurements, need for rehospitalization, transfusions after discharge, or developmental outcome at 18 to 22 months' corrected age.

To tap or not to tap: high likelihood of meningitis without sepsis among very low birth weight infants.

CONTEXT: Neonatal meningitis is associated with significant morbidity and mortality. We speculated that meningitis may be underdiagnosed among very low birth weight (VLBW) infants because of the failure to perform lumbar punctures (LPs) in infants with suspected sepsis. OBJECTIVE: This study was undertaken to review the epidemiology of late-onset meningitis in VLBW (401-1500 g) infants and to evaluate the concordance of cerebrospinal fluid (CSF) and blood culture (BC) results. METHODS: VLBW infants (excluding those with intraventricular shunts) born at centers of the National Institute of Child Health and Human Development Neonatal Research Network from September 1, 1998, through December 31, 2001, were studied. Late-onset meningitis was defined by culture-based criteria and classified as meningitis with or without associated sepsis. Unadjusted comparisons were made using chi2 tests and adjusted comparisons using regression models. RESULTS: Of 9641 VLBW infants who survived >3 days, 2877 (30%) had > or = 1 LPs, and 6056 (63%) had > or = 1 BC performed after day 3. One hundred thirty-four infants had late-onset meningitis (1.4% of all patients; 5% of those with an LP). Pathogens associated with meningitis were similar to those associated with sepsis. One third (45 of 134) of the infants with meningitis had negative BCs. Lower gestational age and prior sepsis increased risk for meningitis. Compared with uninfected infants, those with meningitis had a longer time on mechanical ventilation (28 vs 18 days), had longer hospitalizations (91 vs 79 days), were more likely to have seizures (25% vs 2%), and were more likely to die (23% vs 2%). CONCLUSIONS: Meningitis is a serious complication among VLBW infants, associated with increased severity of illness and risk of death. Of note, one third of the infants with meningitis had meningitis in the absence of sepsis. Because CSF cultures were performed only half as often as BCs, this discordance in blood and CSF culture results suggests that meningitis may be underdiagnosed among VLBW infants.

Parenteral glutamine supplementation does not reduce the risk of mortality or late-onset sepsis in extremely low birth weight infants.

BACKGROUND: Glutamine is one of the most abundant amino acids in both plasma and human milk, yet it is not included in standard intravenous amino acid solutions. Previous studies have suggested that parenteral nutrition (PN) supplemented with glutamine may reduce sepsis and mortality in critically ill adults. Whether glutamine supplementation would provide a similar benefit to extremely low birth weight (ELBW) infants is not known. METHODS: We performed a multicenter, randomized, double-masked, clinical trial to assess the safety and efficacy of early PN supplemented with glutamine in decreasing the risk of death or late-onset sepsis in ELBW infants. Infants 401 to 1000 g were randomized within 72 hours of birth to receive either TrophAmine (control) or an isonitrogenous study amino acid solution with 20% glutamine whenever they received PN up to 120 days of age, death, or discharge from the hospital. The primary outcome was death or late-onset sepsis. RESULTS: Of the 721 infants who were assigned to glutamine supplementation, 370 (51%) died or developed late-onset sepsis, as compared with 343 of the 712 infants (48%) assigned to control (relative risk: 1.07; 95% confidence interval: 0.97-1.17). Glutamine had no effect on tolerance of enteral feeds, necrotizing enterocolitis, or growth. No significant adverse events were observed with glutamine supplementation. CONCLUSIONS: Parenteral glutamine supplementation as studied did not decrease mortality or the incidence of late-onset sepsis in ELBW infants. Consequently, although no harm was demonstrated, routine use of parenteral glutamine supplementation cannot be recommended in this population.

Effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants.

BACKGROUND: Glutamine is one of the most abundant amino acids in both plasma and human milk and may be conditionally essential in premature infants. However, glutamine is not provided by standard intravenous amino acid solutions. OBJECTIVE: We assessed the effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants receiving parenteral nutrition (PN). DESIGN: A total of 141 infants with birth weights of 401-1000 g were randomly assigned to receive a standard intravenous amino acid solution that did not contain glutamine or an isonitrogenous amino acid solution with 20% of the total amino acids as glutamine. Blood samples were obtained just before initiation of study PN and again after the infants had received study PN (mean intake: 2.3 +/- 1.0 g amino acids x kg(-1) x d(-1)) for approximately 10 d. RESULTS: Infants randomly assigned to receive glutamine had mean plasma glutamine concentrations that increased significantly and were approximately 30% higher than those in the control group in response to PN (425 +/- 182 and 332 +/- 148 micromol/L for the glutamine and control groups, respectively). There was no significant difference between the 2 groups in the relative change in plasma glutamate concentration between the baseline and PN samples. In both groups, there were significant decreases in plasma phenylalanine and tyrosine between the baseline and PN samples; the decrease in tyrosine was greater in the group that received glutamine. CONCLUSIONS: In extremely low-birth-weight infants, parenteral glutamine supplementation can increase plasma glutamine concentrations without apparent biochemical risk. Currently available amino acid solutions are likely to be suboptimal in their supply of phenylalanine, tyrosine, or both for these infants.

Minimal ventilation to prevent bronchopulmonary dysplasia in extremely-low-birth-weight infants.

OBJECTIVE: To determine whether minimal ventilation decreases death or bronchopulmonary dysplasia (BPD). STUDY DESIGN: Infants with birth weight 501 g to 1000 g and mechanically ventilated before 12 hours were randomly assigned to minimal ventilation (partial pressure of carbon dioxide [PCO(2)] target >52 mm Hg) or routine ventilation (PCO(2) target <48 mm Hg) and a tapered dexamethasone course or saline placebo for 10 days, using a 2 x 2 factorial design. The primary outcome was death or BPD at 36 weeks' postmenstrual age. RESULTS: After enrollment of 220 patients, the trial was halted because of unanticipated nonrespiratory adverse events related to dexamethasone therapy. The relative risk for death or BPD at 36 weeks in the minimal versus routine ventilation groups was 0.93 (95% CI, 0.77-1.12; P =.43). Ventilator support at 36 weeks was 1% in the minimal versus 16% in the routine group (P <.01). Major morbidities and long-term outcome were comparable in both treatment groups. CONCLUSIONS: With the sample size studied, minimal ventilation did not reduce the incidence of death or BPD. The reduced ventilator support at 36 weeks in the minimal ventilation group warrants further study of this intervention.

Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network.

OBJECTIVE: Late-onset sepsis (occurring after 3 days of age) is an important problem in very low birth weight (VLBW) infants. To determine the current incidence of late-onset sepsis, risk factors for disease, and the impact of late-onset sepsis on subsequent hospital course, we evaluated a cohort of 6956 VLBW (401-1500 g) neonates admitted to the clinical centers of the National Institute of Child Health and Human Development Neonatal Research Network over a 2-year period (1998-2000). METHODS: The National Institute of Child Health and Human Development Neonatal Research Network maintains a prospective registry of all VLBW neonates admitted to participating centers within 14 days of birth. Expanded infection surveillance was added in 1998. RESULTS: Of 6215 infants who survived beyond 3 days, 1313 (21%) had 1 or more episodes of blood culture-proven late-onset sepsis. The vast majority of infections (70%) were caused by Gram-positive organisms, with coagulase-negative staphylococci accounting for 48% of infections. Rate of infection was inversely related to birth weight and gestational age. Complications of prematurity associated with an increased rate of late-onset sepsis included patent ductus arteriosus, prolonged ventilation, prolonged intravascular access, bronchopulmonary dysplasia, and necrotizing enterocolitis. Infants who developed late-onset sepsis had a significantly prolonged hospital stay (mean length of stay: 79 vs 60 days). They were significantly more likely to die than those who were uninfected (18% vs 7%), especially if they were infected with Gram-negative organisms (36%) or fungi (32%). CONCLUSIONS: Late-onset sepsis remains an important risk factor for death among VLBW preterm infants and for prolonged hospital stay among VLBW survivors. Strategies to reduce late-onset sepsis and its medical, social, and economic toll need to be addressed urgently.

Whole-body hypothermia for neonatal encephalopathy: animal observations as a basis for a randomized, controlled pilot study in term infants.

OBJECTIVE: Modest reduction in brain temperature is a promising therapy to reduce brain damage after neonatal encephalopathy as a result of acute perinatal asphyxia. The efficacy of modest hypothermia may in part be dependent on the stability of the desired brain temperature. The objective of this study was 1) to evaluate in newborn animals a commercially available cooling system (Blanketrol II Hyperthermia-Hypothermia system) to control brain temperature during whole-body hypothermia and 2) to use the results of the animal experiments to perform a pilot study evaluating the feasibility of whole-body hypothermia as a neuroprotective therapy for newborns with encephalopathy at birth. METHODS: In the animal investigation, 3 miniature swine were instrumented and ventilated, and temperature probes were placed in the esophagus and the brain (1 cm and 2 cm beneath the parietal cortical surface and the dura). Body cooling was achieved using the automatic control mode (servo) of the cooling system. In the human investigation, 19 term infants with moderate or severe encephalopathy were randomized to either normothermia (n = 10) or hypothermia (n = 9) within 6 hours of birth. Whole-body hypothermia was achieved using the hyperthermia-hypothermia cooling system with servo control of esophageal temperature to 34.5 degrees C for 72 hours followed by slow rewarming. RESULTS: In the animal investigation, body cooling with the animal lying on a single blanket resulted in rapid cooling of the body within 90 minutes. Repetitive cyclical swings in esophageal temperature of 1.7 +/- 0.2 degrees C (mean +/- standard deviation) around the set point of 33.5 degrees C were reduced to 0.7 +/- 0.2 degrees C when a second, larger blanket was attached and suspended. Esophageal temperature was a good marker of deep brain temperature (esophageal to 2-cm brain difference: 0.1 +/- 0.3 degrees C). In the human investigation, the infants were randomized at 4.1 +/- 1.3 hours (mean +/- standard deviation) after birth. Age at randomization was similar in the 2 groups. Cooling was initiated at an average age of 5.3 hours. Target temperature of 34.5 degrees C was achieved within 30 minutes and remained constant throughout the intervention period. Heart rate decreased to 108 +/- 14 beats per minute (bpm) at 60 minutes and remained between 115 and 130 bpm for the duration of cooling compared with 130 to 145 bpm in the normothermia group. Blood pressure was similar in the 2 groups. No adverse events occurred during 72 hours of cooling. The mortality rate and frequency of persistent pulmonary hypertension, renal failure, hepatic dysfunction, and need for pressor support were similar in both groups. CONCLUSIONS: Animal studies showed that a simple modification of a commercially available cooling system (2 blankets attached, subject lying on 1 and the second hanging freely) results in stable core body and brain temperature when used in the automatic control mode. The pilot study in term infants with encephalopathy using this cooling system demonstrates feasibility of initiating whole-body hypothermia at <6 hours of age to a constant esophageal temperature using servo control and provides no evidence that hypothermia involved greater hazard than benefit.

Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants.

BACKGROUND: It is uncertain whether the rates and causes of early-onset sepsis (that occurring within 72 hours after birth) among very-low-birth-weight infants have changed in recent years, since antibiotics have begun to be used more widely during labor and delivery. METHODS: We studied 5447 very-low-birth-weight infants (those weighing between 401 and 1500 g) born at centers of the Neonatal Research Network of the National Institute of Child Health and Human Development between 1998 and 2000 who had at least one blood culture in the first three days of life and compared them with 7606 very-low-birth-weight infants born at centers in the network between 1991 and 1993. RESULTS: Early-onset sepsis (as confirmed by positive blood cultures) was present in 84 infants in the more recent birth cohort (1.5 percent). As compared with the earlier birth cohort, there was a marked reduction in group B streptococcal sepsis (from 5.9 to 1.7 per 1000 live births of infants weighing 401 to 1500 g, P<0.001) and an increase in Escherichia coli sepsis (from 3.2 to 6.8 per 1000 live births, P=0.004); the overall rate of early-onset sepsis was not significantly changed. Most E. coli isolates from the recent birth cohort (85 percent) were resistant to ampicillin, and mothers of infants with ampicillin-resistant E. coli infections were more likely to have received intrapartum ampicillin than were those with ampicillin-sensitive strains (26 of 28 with sensitivity data vs. 1 of 5, P=0.01). Infants with early-onset sepsis were more likely to die than uninfected infants (37 percent vs. 13 percent, P<0.001), especially if they were infected with gram-negative organisms. CONCLUSIONS: Early-onset sepsis remains an uncommon but potentially lethal problem among very-low-birth-weight infants. The change in pathogens over time from predominantly gram-positive to predominantly gram-negative requires confirmation by ongoing surveillance.

Neurodevelopmental outcome of premature infants after antenatal phenobarbital exposure.

OBJECTIVE: We previously demonstrated that antenatal phenobarbital does not decrease the risk of intracranial hemorrhage or early death in premature infants. The objective of the present study was to evaluate the impact of antenatal phenobarbital exposure on the neurodevelopmental outcome of premature infants born to women who were participating in the randomized clinical trial of antenatal phenobarbital exposure. STUDY DESIGN: Infants were evaluated at 18 to 22 months corrected age with a standard neurologic examination and the Bayley scales of infant development measuring the mental developmental index and the psychomotor developmental index. RESULTS: Of the 578 infants <34 weeks of gestational age who were born to women who were enrolled in the primary study, 7 infants died after discharge from the neonatal intensive care unit, and 135 infants were lost to follow-up. Infants who were lost to follow-up had a higher mean birth weight and gestational age and a lower maternal education, but the rates of intracranial hemorrhage were comparable to those infants who were evaluated. Among the infants who were evaluated (n = 436; 76%), the mean birth weight and gestational age, maternal education, and frequency and distribution of intracranial hemorrhage were similar in the antenatal phenobarbital exposed and placebo groups. Eighteen infants (8%) in the antenatal phenobarbital exposed group and 21 infants (11%) in the placebo group had cerebral palsy (P = not significant). There was no difference between the 2 groups in either the median Bayley II mental developmental index (85 in the antenatal phenobarbital and 86 in the placebo group) or the Psychomotor Developmental Index (91 in the antenatal phenobarbital and 91 in the placebo group). Infants with intracranial hemorrhage (23%) had significantly lower mental developmental index and psychomotor developmental index scores than infants with no intracranial hemorrhage, independent of antenatal phenobarbital exposure. In the total cohort of 436 infants, the presence of intracranial hemorrhage or periventricular leukomalacia was associated with lower mental developmental index and psychomotor developmental index scores; the presence of increasing birth weight, maternal education, and a complete course of antenatal steroids was associated with a higher mental developmental index score. CONCLUSION: Antenatal phenobarbital exposure did not favorably or adversely affect the neurodevelopmental outcome of premature infants at 18 to 22 months of age.