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.

Emotion-modulated startle in anxiety disorders is blunted by co-morbid depressive episodes.

BACKGROUND: While anxiety has been associated with exaggerated emotional reactivity, depression has been associated with blunted, or context insensitive, emotional responding. Although anxiety and depressive disorders are frequently co-morbid, surprisingly little is known about emotional reactivity when the two disorders co-occur. METHOD: We utilized the emotion-modulated startle (EMS) paradigm to examine the effects of a concurrent depressive episode on emotional reactivity in young adults with anxiety disorders. Using an archival dataset from a multi-disciplinary project on risk factors in childhood-onset depression, we examined eye-blink startle reactions to late-onset auditory startle probes while participants viewed pictures with affectively pleasant, unpleasant and neutral content. EMS response patterns were analyzed in 33 individuals with a current anxiety (but no depressive) disorder, 24 individuals with a current anxiety disorder and co-morbid depressive episode and 96 healthy controls. RESULTS: Control participants and those with a current anxiety disorder (but no depression) displayed normative linearity in startle responses, including potentiation by unpleasant pictures. By contrast, individuals with concurrent anxiety and depression displayed blunted EMS. CONCLUSIONS: An anxiety disorder concurrent with a depressive episode is associated with reactivity that more closely resembles the pattern of emotional responding that is typical of depression (i.e. context insensitive) rather than the pattern that is typical for anxiety (i.e. exaggerated).

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.

OBJECTIVES: To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18-22 months corrected age in extremely low birth weight infants. METHOD: Total plasma bilirubin and unbound bilirubin were measured in 1101 extremely low birth weight infants at 5 +/- 1 days of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18-22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow-up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors. RESULTS: Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow-up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow-up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants. CONCLUSIONS: In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma bilirubin and death or adverse neurodevelopmental outcomes at 18-22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants.

Randomized trial of sterile water by gavage drip in the fluid management of extremely low birth weight infants.

OBJECTIVE: To determine whether extremely low birth weight infants who receive enteral sterile water have a reduction in treated patent ductus arteriosus or death by 28 days compared to infants with routine management. STUDY DESIGN: A total of 214 infants were enrolled and randomized by 36 h of age to receive up to 50 ml kg(-1) per day of enteral sterile water (n=109) for 7 days or routine fluid management (n=104). Patent ductus arteriosus treatment was defined as either indomethacin treatment or surgical ligation. RESULT: The proportion of infants with a treated patent ductus arteriosus or death at <28 days of age was 63% in the sterile water group vs 64% in the control group (relative risk 0.99, 95% confidence interval 0.81 to 1.22). There were no differences in the proportion of infants in the sterile water group vs control group with a treated patent ductus arteriosus (55 vs 48%), death (21 vs 28%), necrotizing enterocolitis or death (24 vs 32%), or bronchopulmonary dysplasia or death at <28 days (80 vs 77%). Daily mean glucose levels were significantly higher (P=0.04) in control infants than sterile water infants. CONCLUSION: The use of sterile water did not decrease the incidence of patent ductus arteriosus or other adverse clinical outcomes. The role of enteral sterile water in the fluid management of extremely low birth weight infants remains uncertain.

Hyperglycemia and morbidity and mortality in extremely low birth weight infants.

OBJECTIVE: The purpose of this study was to determine the association between hyperglycemia and mortality and late-onset infections (>72 h) in extremely low birth weight (ELBW) infants. STUDY DESIGN: Retrospective analysis of a prospective cohort study of 201 ELBW infants who survived greater than 3 days after birth. Mean morning glucose levels were categorized as normoglycemia (<120 mg/dl), mild-moderate hyperglycemia (120 to 179 mg/dl) and severe hyperglycemia (> or =180 mg/dl). Hyperglycemia was further divided into early (first 3 days of age) and persistent (first week of age). Logistic regression was performed to assess whether hyperglycemia was associated with either mortality or late-onset culture-proven infection, measured after 3 and 7 days of age. RESULTS: Adjusting for age, the odds ratio (OR) for either dying or developing a late infection was 5.07 (95% confidence interval (CI): 1.06 to 24.3) for infants with early severe hyperglycemia and 6.26 (95% CI: 0.73 to 54.0) for infants with persistent severe hyperglycemia. Adjusting for age, both severe early and persistent hyperglycemia were associated with increased mortality. Among survivors, there was no significant association between hyperglycemia and length of mechanical ventilation or length of hospital stay. Persistent severe hyperglycemia was associated with the development of Stage II/III necrotizing enterocolitis, after adjusting for age and male gender (OR: 9.49, 95% CI: 1.52 to 59.3). CONCLUSION: Severe hyperglycemia in the first few days after birth is associated with increased odds of death and sepsis in ELBW infants.

Prophylaxis for respiratory syncytial virus with respiratory syncytial virus-immunoglobulin intravenous among preterm infants of thirty-two weeks gestation and less: reduction in incidence, severity of illness and cost.

OBJECTIVE: To determine the impact of respiratory syncytial virus (RSV) prophylaxis among preterm infants of < or =32 weeks gestation by comparing the severity of illness and cost of RSV-related care during the two winter seasons before (1994 to 1995, 1995 to 1996) with the two seasons after initiation of prophylaxis (1996 to 1997, 1997 to 1998). METHODS: Preterm infants of < or =32 weeks gestation at risk for hospitalization with RSV infection were identified retrospectively from the infants hospitalized in our neonatal units. Infants were included if they (1) were born 6 months before or during four winter seasons (1994 to 1998), (2) were discharged from the neonatal unit and (3) had remained in the university outpatient clinic system during at least the first winter of life. Preterm infants of < or =32 weeks gestation hospitalized with RSV were identified from our RSV database (which includes cost of hospitalization, duration of hospital stay, pediatric intensive care unit stay and intubation). Infants receiving prophylaxis were identified prospectively. RESULTS: The incidence of hospitalization with RSV was significantly lower among the cohort of infants born after initiation of prophylaxis: 8.7% (17 of 195) vs. 22% (35 of 159), P = 0.00049 by two tailed Fisher's exact test. Among the cohort of infants born after initiation of prophylaxis (n = 195), 100 infants received prophylaxis. The gestational and chronologic ages of the prophylaxis-treated infants were significantly lower than those of the non-prophylaxis-treated infants (n = 95). The prophylaxis-treated infants also were more likely to have bronchopulmonary dysplasia. Only 1 (1%) of the prophylaxis-treated infants required hospitalization for RSV. Comparison of the cohort of infants born before initiation of prophylaxis to the cohort born after initiation of prophylaxis (includes prophylaxis-treated and non-prophylaxis-treated infants) revealed a significant reduction in severity of illness and cost. The length of stay in the cohort born before initiation of prophylaxis was reduced 83.8%: 373.6 days per 100 infants at risk vs. 60.5 (P = 0.00055). The length of stay in the pediatric intensive care unit was reduced 92.7%: 218.2 days per 100 infants at risk vs. 15.9 (P = 0.00029). The duration of intubation was reduced 95.6%: 187.4 days per 100 infants at risk vs. 8.2 (P = 0.00024). The dollars spent for RSV-related care (hospitalizations and prophylaxis) per 100 infants at risk for RSV was reduced 65% in the cohort of infants born after prophylaxis: $670,590 per 100 infants at risk vs. $234,596 (P = 0.00056). This reduction remained significant (64.9%) if the cost of ribavirin (drug and administration fees) was excluded from the cost of hospitalization. CONCLUSIONS: These data reveal that RSV prophylaxis significantly reduced the incidence of RSV hospitalizations and severity of illness as well as the cost of RSV-related care among these infants.

Physiological effects of sound on the newborn.

Excessive sound is an acknowledged problem in neonatal intensive care units (NICUs); however, there is relatively little objective information about the effects of sound on the newborn. The cardiovascular and respiratory systems have been the most extensively studied systems. The patterns of response in these systems may be influenced by a variety of factors, including: the intensity of the sound, the infant's behavioral state, the infant's maturity and postnatal age, and the perinatal history. This article reviews the known cardiovascular, respiratory, and other physiological effects of sound on neonates.

Feeding, medical factors, and developmental outcome in premature infants.

This is a prospective, longitudinal study of premature infants investigating whether the length of time needed to reach full enteral feedings (FEF) or full nipple feedings (FNF) is related to medical complications and/or developmental outcome at 24 months corrected age. Premature infants (n = 161) from three institutions with birth weights less than 1,600 grams were followed up from birth to 24 months corrected age. The infants were stratified into groups by the severity of medical complications. Bayley Scales of Infant Development were performed at 24 months corrected age. Multiple linear regression was used to analyze the association between feeding milestones, medical complications, and developmental outcomes. Our results show that when controlling for birth weight and gestational age (GA), the severity of respiratory complications was significantly related to reaching FEF (p = 0.024) and FNF (p = 0.0014). Furthermore, when controlling for the severity of respiratory complications, GA, and socioeconomic status, an increased length of time to FEF was significantly associated with a poorer mental outcome (p = 0.0013). We conclude that there is an association between the length of time to reach FEF and mental developmental outcome at 24 months corrected age. Infants who reach full enteral feedings at an earlier age appear to have a better developmental outcome despite their GA and severity of respiratory complications.