Respiratory Medications in Infants <29 Weeks during the First Year Postdischarge: The Prematurity and Respiratory Outcomes Program (PROP) Consortium.

OBJECTIVE: To determine patterns of respiratory medications used in neonatal intensive care unit graduates. STUDY DESIGN: The Prematurity Respiratory Outcomes Program enrolled 835 babies <29 weeks of gestation in the first week. Of 751 survivors, 738 (98%) completed at least 1, and 85% completed all 4, postdischarge medication usage in-person/telephone parental questionnaires requested at 3, 6, 9, and 12 months of corrected age. Respiratory drug usage over the first year of life after in neonatal intensive care unit discharge was analyzed. RESULTS: During any given quarter, 66%-75% of the babies received no respiratory medication and 45% of the infants received no respiratory drug over the first year. The most common postdischarge medication was the inhaled bronchodilator albuterol; its use increased significantly from 13% to 31%. Diuretic usage decreased significantly from 11% to 2% over the first year. Systemic steroids (prednisone, most commonly) were used in approximately 5% of subjects in any one quarter. Inhaled steroids significantly increased over the first year from 9% to 14% at 12 months. Drug exposure changed significantly based on gestational age with 72% of babies born at 23-24 weeks receiving at least 1 respiratory medication but only 40% of babies born at 28 weeks. Overall, at some time in the first year, 55% of infants received at least 1 drug including an inhaled bronchodilator (45%), an inhaled steroid (22%), a systemic steroid (15%), or diuretic (12%). CONCLUSION: Many babies born at <29 weeks have no respiratory medication exposure postdischarge during the first year of life. Inhaled medications, including bronchodilators and steroids, increase over the first year.

Weaning of Moderately Preterm Infants from the Incubator to the Crib: A Randomized Clinical Trial.

OBJECTIVE: To assess whether length of hospital stay is decreased among moderately preterm infants weaned from incubator to crib at a lower vs higher weight. STUDY DESIGN: This trial was conducted in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants with gestational ages 29-33 weeks, birthweight <1600 g, and in an incubator were randomly assigned to a weaning weight of 1600 or 1800 g. Within 60 to 100 g of weaning weight, the incubator temperature was decreased by 1.0°C to 1.5°C every 24 hours until 28.0°C. The infants were weaned to the crib following stable temperature at 36.5°C to 37.4°C for 8 to 12 hours. Clothing and bedcoverings were standardized. The primary outcome was length of hospital stay from birth to discharge; secondary outcomes included length of stay and growth velocity from weaning to discharge. Adverse events were monitored. RESULTS: Of 1565 infants screened, 885 were eligible, and 366 enrolled-187 to the 1600-g and 179 to the 1800-g group. Maternal and neonatal characteristics did not differ among weight groups. Length of hospital stay was a median of 43 days in the lower and 41 days in the higher weight group (P = .12). Growth velocity from completion of weaning to discharge was higher in the lower weight group, 13.7 g/kg/day vs 12.8 g/kg/day (P = .005). Groups did not differ in adverse events. CONCLUSIONS: Among moderately preterm neonates, weaning from incubator to crib at a lower weight did not decrease length of stay, but was safe and was accompanied by higher weight gain after weaning. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02160002.

Delivery Room Resuscitation and Short-Term Outcomes in Moderately Preterm Infants.

OBJECTIVES: To describe the frequency and extent of delivery room resuscitation and evaluate the association of delivery room resuscitation with neonatal outcomes in moderately preterm (MPT) infants. STUDY DESIGN: This was an observational cohort study of MPT infants delivered at 290/7 to 336/7 weeks' gestational age (GA) enrolled in the Neonatal Research Network MPT registry. Infants were categorized into 5 groups based on the highest level of delivery room intervention: routine care, oxygen and/or continuous positive airway pressure, bag and mask ventilation, endotracheal intubation, and cardiopulmonary resuscitation including chest compressions and/or epinephrine use. The association of antepartum and intrapartum risk factors and discharge outcomes with the intensity of resuscitation was evaluated. RESULTS: Of 7014 included infants, 1684 (24.0%) received routine care and no additional resuscitation, 2279 (32.5%) received oxygen or continuous positive airway pressure, 1831 (26.1%) received bag and mask ventilation, 1034 (14.7%) underwent endotracheal intubation, and 186 (2.7%) received cardiopulmonary resuscitation. Among the antepartum and intrapartum factors, increasing GA, any exposure to antenatal steroids and prolonged rupture of membranes decreased the likelihood of receipt of all levels of resuscitation. Infants who were small for GA (SGA) had increased risk of delivery room resuscitation. Among the neonatal outcomes, respiratory support at 28 days, days to full oral feeds and length of stay were significantly associated with the intensity of delivery room resuscitation. Higher intensity of resuscitation was associated with increased risk of mortality. CONCLUSIONS: The majority of MPT infants receive some level of delivery room resuscitation. Increased intensity of delivery room interventions was associated with prolonged respiratory and nutritional support, increased mortality, and a longer length of stay.

Blood Cytokine Profiles Associated with Distinct Patterns of Bronchopulmonary Dysplasia among Extremely Low Birth Weight Infants.

OBJECTIVE: To explore differences in blood cytokine profiles among distinct bronchopulmonary dysplasia (BPD) patterns. STUDY DESIGN: We evaluated blood spots collected from 943 infants born at ≤1000 g and surviving to 28 days on postnatal days 1, 3, 7, 14, and 21 for 25 cytokines. Infants were assigned to the following lung disease patterns: (1) no lung disease (NLD); (2) respiratory distress syndrome without BPD; (3) classic BPD (persistent exposure to supplemental oxygen until 28 days of age); or (4) atypical BPD (period without supplemental oxygen before 28 days). Median cytokine levels for infants with BPD were compared with the IQR of results among infants with NLD. RESULTS: The distribution of enrolled infants by group was as follows: 69 (NLD), 73 (respiratory distress syndrome), 381 (classic BPD), and 160 (atypical BPD). The remaining 260 infants could not be classified because of missing data (104) or not fitting a predefined pattern (156). Median levels of 3 cytokines (elevated interleukin [IL]-8, matrix metalloproteinase-9; decreased granulocyte macrophage colony-stimulating factor) fell outside the IQR for at least 2 time points in both infants with atypical and classic BPD. Profiles of 7 cytokines (IL-6, IL-10, IL-18, macrophage inflammatory protein-1α, C-reactive protein, brain-derived neurotrophic factor, regulated on activation, normal T cell expressed and secreted) differed between infants with classic and atypical BPD. CONCLUSIONS: Blood cytokine profiles may differ between infants developing classic and atypical BPD. These dissimilarities suggest the possibility that differing mechanisms could explain the varied patterns of pathophysiology of lung disease in extremely premature infants.

Developmental outcomes of very preterm infants with tracheostomies.

OBJECTIVES: To evaluate the neurodevelopmental outcomes of very preterm (<30 weeks) infants who underwent tracheostomy. STUDY DESIGN: Retrospective cohort study from 16 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network over 10 years (2001-2011). Infants who survived to at least 36 weeks (N = 8683), including 304 infants with tracheostomies, were studied. Primary outcome was death or neurodevelopmental impairment (NDI; a composite of ≥1 of developmental delay, neurologic impairment, profound hearing loss, severe visual impairment) at a corrected age of 18-22 months. Outcomes were compared using multiple logistic regression. We assessed the impact of timing by comparing outcomes of infants who underwent tracheostomy before and after 120 days of life. RESULTS: Tracheostomies were associated with all neonatal morbidities examined and with most adverse neurodevelopmental outcomes. Death or NDI occurred in 83% of infants with tracheostomies and 40% of those without (OR adjusted for center 7.0, 95% CI 5.2-9.5). After adjustment for potential confounders, odds of death or NDI remained higher (OR 3.3, 95% CI 2.4-4.6), but odds of death alone were lower (OR 0.4, 95% CI 0.3-0.7) among infants with tracheostomies. Death or NDI was lower in infants who received their tracheostomies before, rather than after, 120 days of life (aOR 0.5, 95% CI 0.3-0.9). CONCLUSIONS: Tracheostomy in preterm infants is associated with adverse developmental outcomes and cannot mitigate the significant risk associated with many complications of prematurity. These data may inform counseling about tracheostomy in this vulnerable population.

An evidence-based catheter bundle alters central venous catheter strategy in newborn infants.

OBJECTIVE: To assess whether introduction of an evidence-based percutaneously inserted central catheter (PICC) care bundle reduced the risk of central line-associated bloodstream infection (CLABSI), thus altering the comparative risk of CLABSI in infants. STUDY DESIGN: This retrospective cohort study included all infants for whom an umbilical venous catheter (UVC) was placed as part of routine care between Jan 1, 2006, and Dec 31, 2009, a period during which standardized PICC insertion and care bundles were introduced. Duration of UVC use was divided in ≤ 7 days and >7 days. RESULTS: Infants in the ≤ 7 days UVC group had 1.0 CLABSI/1000 catheter days, and infants in the >7 days UVC group had 4.0 CLABSI/1000 catheter days (P < .001). Controlling for birth weight, gestational age, and antibiotic use, the >7 days UVC group had a greater risk of CLABSI (OR, 5.48) than the ≤ 7 days UVC group. CLABSI rate increased more rapidly in UVC than PICC with increasing duration of catheter rose. CONCLUSIONS: Replacement of a UVC with a PICC when central venous access is needed after 7 days of age may reduce CLABSI.

Cytokine elaboration in critically ill infants with bacterial sepsis, necrotizing entercolitis, or sepsis syndrome: correlation with clinical parameters of inflammation and mortality.

OBJECTIVE: To test the hypothesis that cytokines might distinguish critically ill infants with bacterial sepsis or necrotizing enterocolitis (NEC) from those with sepsis syndrome and that these elevations would be correlated with clinical variables of inflammation and mortality. STUDY DESIGN: We measured plasma and tracheal aspirate (TA) levels of interleukin-8 (IL-8), epithelial neutrophil activating peptide (ENA-78), IL-10, and IL-18 in 84 neonates with suspected sepsis or NEC. Thirty-one infants had bacterial sepsis, 19 had NEC, and 34 infants with negative results on cultures had sepsis syndrome. RESULTS: Plasma IL-8 and IL-10 levels were significantly increased in infants with bacterial sepsis compared with those in infants with sepsis syndrome. Plasma IL-8, ENA-78, and IL-10 levels were elevated in infants with NEC compared with those in infants with sepsis syndrome. TA IL-8 and IL-10 levels were also increased in infants with bacterial sepsis; TA ENA-78, and IL-18 were not elevated in infants with sepsis or NEC when compared with infants with sepsis syndrome. Plasma and TA cytokine levels correlated with hematologic parameters. Plasma cytokine levels were higher in infants who did not survive than in infants who did survive. CONCLUSIONS: Plasma and TA cytokine levels are elevated in critically ill infants with bacterial sepsis or NEC compared with those in infants with sepsis syndrome. Our results suggest distinct patterns of cytokine elaboration in different disease states.