Brenda H. Morris

Target ranges of oxygen saturation in extremely preterm infants.

BACKGROUND Previous studies have suggested that the incidence of retinopathy is lower in preterm infants with exposure to reduced levels of oxygenation than in those exposed to higher levels of oxygenation. However, it is unclear what range of oxygen saturation is appropriate to minimize retinopathy without increasing adverse outcomes. METHODS We performed a randomized trial with a 2-by-2 factorial design to compare target ranges of oxygen saturation of 85 to 89% or 91 to 95% among 1316 infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. The primary outcome was a composite of severe retinopathy of prematurity (defined as the presence of threshold retinopathy, the need for surgical ophthalmologic intervention, or the use of bevacizumab), death before discharge from the hospital, or both. All infants were also randomly assigned to continuous positive airway pressure or intubation and surfactant. RESULTS The rates of severe retinopathy or death did not differ significantly between the lower-oxygen-saturation group and the higher-oxygen-saturation group (28.3% and 32.1%, respectively; relative risk with lower oxygen saturation, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P=0.21). Death before discharge occurred more frequently in the lower-oxygen-saturation group (in 19.9% of infants vs. 16.2%; relative risk, 1.27; 95% CI, 1.01 to 1.60; P=0.04), whereas severe retinopathy among survivors occurred less often in this group (8.6% vs. 17.9%; relative risk, 0.52; 95% CI, 0.37 to 0.73; P<0.001). There were no significant differences in the rates of other adverse events. CONCLUSIONS A lower target range of oxygenation (85 to 89%), as compared with a higher range (91 to 95%), did not significantly decrease the composite outcome of severe retinopathy or death, but it resulted in an increase in mortality and a substantial decrease in severe retinopathy among survivors. The increase in mortality is a major concern, since a lower target range of oxygen saturation is increasingly being advocated to prevent retinopathy of prematurity. (ClinicalTrials.gov number, NCT00233324.)

Aggressive vs. conservative phototherapy for infants with extremely low birth weight

BACKGROUND It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less). METHODS We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments. RESULTS Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P<0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g. CONCLUSIONS Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.)

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 (⩾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.

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 infants behavioral state, the infants maturity and postnatal age, and the perinatal history. This article reviews the known cardiovascular, respiratory, and other physiological effects of sound on neonates.

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.

Rehospitalization of Extremely Low Birth Weight (ELBW) Infants: Are There Racial/Ethnic Disparities?

BACKGROUND:Premature infants are at increased risk for rehospitalization after discharge from the hospital. Racial disparities are known to exist in pediatric health care.OBJECTIVE:To evaluate whether racial disparities exist in the proportion of extremely low birth weight (ELBW) infants rehospitalized prior to 18 months corrected age and the causes of rehospitalization.METHODS:The National Institute of Child Health and Human Development Neonatal Research Network database was used to identify all ELBW infants (n=2446) who were born between November 1, 1998 and May 31, 2000 at the 14 participating centers and discharged alive (n=1591). Infants were seen at 18–22 months corrected age for followup. Data related to maternal variables, race, socioeconomic status, medical morbidities, insurance, and rehospitalizations were recorded from the medical record and parent interview. Logistic regression analyses were used to examine the relationship of race/ethnicity and rehospitalization while controlling for gestational age, gender, center, maternal education, family income, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, ventriculoperitoneal (VP) shunt, respiratory syncytial virus (RSV) prophylaxis, and insurance type.RESULTS:In all, 1405 (88%) infants were evaluated at followup. The racial distribution of infants admitted, discharged, seen at followup, and rehospitalized were similar. Rehospitalization occurred at least once in 49% of the infants. In the logistic regression analyses, race was not a significant predictor for rehospitalization. The odds of rehospitalization were related to low family income, type of insurance, BPD, VP shunt, RSV prophylaxis, and center.CONCLUSION:Race was not a predominant variable in the risk of rehospitalization in this cohort of ELBW infants. Medical morbidities and low family income appear to be the major risk factors for rehospitalization.

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 FNF 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 FNF 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.

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 ≤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 ≤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 ≤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 Fishers 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:

Patterns of Physical and Neurologic Development in Preterm Children

670 590 per 100 infants at risk vs.

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

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.