BACKGROUND:Prior studies have identified individual risk factors that are associated with necrotizing enterocolitis (NEC); however, the small sample sizes of these previous studies have not allowed the analysis of potential interaction between multiple variables and NEC. Our purpose was to describe the incidence and risk factors for NEC in premature neonates admitted for intensive care. METHODS:We identified neonates as having NEC if they met accepted diagnostic criterion for necrotizing enterocolitis. Using a national database, we assessed the association between NEC and a battery of risk factors previously reported in peer-reviewed literature. RESULTS:There were 15,072 neonates that met inclusion criteria; 14,682 did not have NEC, while 390 (2.6%) met criterion for NEC. Multivariate analysis showed that low birth weight was the most important risk factor for NEC. Other factors that were associated with an increased risk of NEC were exposure to antenatal glucocorticoids, vaginal delivery, need for mechanical ventilator support, exposure to both glucocorticoids and indomethacin during the first week of life, absence of an umbilical arterial catheter, and low Apgar score at 5 minutes. Length of hospital stay and mortality were higher in neonates with NEC than in neonates without NEC. CONCLUSIONS:NEC remains an important cause of morbidity and mortality in prematurely born neonates. In contrast to previous studies, we found that exposure to antenatal glucocorticoids was associated with an increased risk for NEC independent of birth weight.

Objective To assess the utility of clinical predictors of persistent respiratory morbidity in extremely low gestational age newborns (ELGAN). Study Design We enrolled ELGAN (<29 weeks’ gestation) at ≤7 postnatal days and collected antenatal and neonatal clinical data through 36 weeks’ post-menstrual age. We surveyed caregivers at 3, 6, 9 and 12 months corrected age to identify post-discharge respiratory morbidity, defined as hospitalization, home support (oxygen, tracheotomy, ventilation), medications, or symptoms (cough/wheeze). Infants were classified as post-prematurity respiratory disease (PRD, the primary study outcome), if respiratory morbidity persisted over ≥2 questionnaires. Infants were classified with severe respiratory morbidity if there were multiple hospitalizations, exposure to systemic steroids or pulmonary vasodilators, home oxygen after 3 months or mechanical ventilation, or symptoms despite inhaled corticosteroids. Mixed effects models generated with data available at one day (perinatal) and 36 weeks’ postmenstrual age were assessed for predictive accuracy. Results Of 724 infants (918±234g, 26.7±1.4 weeks’ gestational age) classified for the primary outcome, 68.6% had PRD; 245/704 (34.8%) were classified as severe. Male sex, intrauterine growth restriction, maternal smoking, race/ethnicity, intubation at birth, and public insurance were retained in perinatal and 36-week models for both PRD and respiratory morbidity severity. The perinatal model accurately predicted PRD (c-statistic 0.858). Neither the 36-week model nor the addition of bronchopulmonary dysplasia (BPD) to the perinatal model improved accuracy (0.856, 0.860); c-statistic for BPD-alone was 0.907. Conclusion Both BPD and perinatal clinical data accurately identify ELGAN at risk for persistent and severe respiratory morbidity at one year. Trial registration ClinicalTrials.gov: NCT01435187

BACKGROUND: Exogenous surfactants to treat respiratory distress syndrome (RDS) are approved for tracheal instillation only; this requires intubation, often followed by positive pressure ventilation to promote distribution. Aerosol delivery offers a safer alternative, but clinical studies have had mixed results. We hypothesized that efficient aerosolization of a surfactant with low viscosity, early in the course of RDS, could reduce the need for intubation and instillation of liquid surfactant. METHODS: A prospective, multicenter, randomized, unblinded comparison trial of aerosolized calfactant (Infasurf) in newborns with signs of RDS that required noninvasive respiratory support. Calfactant was aerosolized by using a Solarys nebulizer modified with a pacifier adapter; 6 mL/kg (210 mg phospholipid/kg body weight) were delivered directly into the mouth. Infants in the aerosol group received up to 3 treatments, at least 4 hours apart. Infants in the control group received usual care, determined by providers. Infants were intubated and given instilled surfactant for persistent or worsening respiratory distress, at their providers’ discretion. RESULTS: Among 22 NICUs, 457 infants were enrolled; gestation 23 to 41 (median 33) weeks and birth weight 595 to 4802 (median 1960) grams. In total, 230 infants were randomly assigned to aerosol; 225 received 334 treatments, starting at a median of 5 hours. The rates of intubation for surfactant instillation were 26% in the aerosol group and 50% in the usual care group (P &lt; .0001). Respiratory outcomes up to 28 days of age were no different. CONCLUSIONS: In newborns with early, mild to moderate respiratory distress, aerosolized calfactant at a dose of 210 mg phospholipid/kg body weight reduced intubation and surfactant instillation by nearly one-half.

Neonates manifest a unique host response to sepsis even among other children. Preterm neonates may experience sepsis soon after birth or during often-protracted birth hospitalizations as they attain physiologic maturity. We examined the transcriptome using genome-wide expression profiling on prospectively collected peripheral blood samples from infants evaluated for sepsis within 24 h after clinical presentation. Simultaneous plasma samples were examined for alterations in inflammatory mediators. Group designation (sepsis or uninfected) was determined retrospectively on the basis of clinical exam and laboratory results over the next 72 h from the time of evaluation. Unsupervised analysis showed the major node of separation between groups was timing of sepsis episode relative to birth (early, <3 d, or late, ≥3 d). Principal component analyses revealed significant differences between patients with early or late sepsis despite the presence of similar key immunologic pathway aberrations in both groups. Unique to neonates, the uninfected state and host response to sepsis is significantly affected by timing relative to birth. Future therapeutic approaches may need to be tailored to the timing of the infectious event based on postnatal age.