Discontinuing Nasal Continuous Positive Airway Pressure in Infants ≤32 Weeks of Gestational Age: A Randomized Control Trial.

OBJECTIVES: To compare immediate cessation of nasal continuous positive airway pressure (NCPAP) vs a stepwise decrease in pressure on the duration of NCPAP therapy in infants born prematurely. STUDY DESIGN: A single center study in infants 230-326 weeks of gestational age. NCPAP was stopped either at 5 cm H2O (control) or 3 cm H2O after a stepwise pressure wean (wean) using defined stability and failure criteria. Primary outcome is total NCPAP days. RESULTS: We enrolled 226 infants; 116 were randomly assigned to control and 110 to the wean group. There was no difference in the total NCPAP days between groups (median [25th, 75th percentiles] 16 [5, 36] vs 14 [7, 33] respectively). There were no differences between groups in secondary outcomes, including duration of hospital stay, critical care days, and oxygen supplementation. A higher proportion of control infants failed the initial attempt to discontinue NCPAP (43% vs 27%, respectively; P < .01) and required ≥2 attempts (20% vs 5%, respectively; P < .01). In addition, infants 23-27 weeks of gestational age in the wean group were 2.4-times more likely to successfully stop NCPAP at the first attempt (P = .02) vs controls. CONCLUSIONS: Discontinuation of NCPAP after a gradual pressure wean to 3 cm H2O did not decrease the duration of NCPAP therapy compared with stopping from 5 cm H2O in infants ≤32 weeks of gestational age. However, weaning decreased failed initial attempts to stop NCPAP, particularly among infants <28 weeks of gestational age. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02064712.

Screening and Serial Neutrophil Counts Do Not Contribute to the Recognition or Diagnosis of Late-Onset Neonatal Sepsis.

OBJECTIVE: To determine the validity of screening and serial neutrophil counts in predicting the absence/presence of late-onset sepsis (LOS) in infants with central venous catheters. STUDY DESIGN: Retrospective study of infants admitted to the neonatal intensive care unit (2009-2013) at Parkland Hospital with a central venous catheter and ≥1 LOS evaluations. Infants were categorized as proven or suspect LOS or uninfected based on results of blood cultures, clinical illness, and duration of antibiotics. Receiver operating curves (ROCs) were constructed to predict the absence or presence of LOS using Manroe reference ranges for total and immature neutrophils and the immature to total neutrophil ratio at 0, 12, and 24 hours after blood culture and the neutrophil value score, which assesses serial values. RESULTS: Of the 497 infants with a central venous catheter, 179 underwent ≥1 LOS evaluations, and 140 of 179 (78%) had ≥1 complete evaluations (2 blood cultures and neutrophil values at 0, 12, and 24 hours), resulting in 188 complete LOS evaluations. The gestational age was 28 ± 4 weeks and LOS evaluation occurred at 29 ± 34 days (SD; 4-197 days). Sixty-one (35%) infants had proven LOS, 48 (23%) were suspect, and 71 (38%) were noninfected. ROC comparing proven vs noninfected was ≤0.56 for total neutrophils, immature neutrophils, and immature to total neutrophil ratio at 0, 12, and 24 hours and similar for proven + suspect vs noninfected. ROC for neutrophil value scores and absence of LOS was 0.56. CONCLUSIONS: Screening neutrophil values are poor predictors of LOS in neonates with a central venous catheter, as are serial neutrophils and the neutrophil value score. Alternative biomarkers are needed.

Biomarkers for severity of neonatal hypoxic-ischemic encephalopathy and outcomes in newborns receiving hypothermia therapy.

OBJECTIVE: To evaluate serum neuronal and inflammatory biomarkers to determine whether measurements of umbilical cords at birth can stratify severity of hypoxic-ischemic encephalopathy (HIE), whether serial measurements differ with hypothermia-rewarming, and whether biomarkers correlate with neurological outcomes. STUDY DESIGN: This is a prospective cohort of inborn term newborns with varying degrees of HIE by neurological assessment. Neuronal glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1, and inflammatory cytokines were measured in serum from umbilical artery at 6-24, 48, 72, and 78 hours of age. Neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development-III scales) were performed at 15-18 months. RESULTS: Twenty neonates had moderate (n = 17) or severe (n = 3) HIE and received hypothermia; 7 had mild HIE and were not cooled. At birth, serum GFAP and ubiquitin carboxyl-terminal hydrolase L1 increased with the severity of HIE (P < .001), and serial GFAP remained elevated in neonates with moderate to severe HIE. Interleukin (IL)-6, IL-8, and vascular endothelial growth factor were greater at 6-24 hours in moderate to severe vs mild HIE (P < .05). The serial values were unaffected by hypothermia-rewarming. Elevated GFAP, IL-1, IL-6, IL-8, tumor necrosis factor, interferon, and vascular endothelial growth factor at 6-24 hours were associated with abnormal neurological outcomes. CONCLUSIONS: The severity of the hypoxic-ischemic injury can be stratified at birth because elevated neuronal biomarkers in cord serum correlated with severity of HIE and outcomes.

Serial neutrophil values facilitate predicting the absence of neonatal early-onset sepsis.

OBJECTIVE: To validate established neonatal neutrophil reference ranges (RRs) and determine the utility of serial measurements of neutrophil values in the first 24 hours to predict the absence of neonatal early-onset sepsis (EOS). STUDY DESIGN: Retrospective study of 2073 admissions to the neonatal intensive care unit (2009-2011). Neonates were classified as blood culture-positive, proven EOS (n = 9), blood culture-negative but clinically suspect EOS (n = 292), and not infected (n = 1292). Neutrophil values from 745 not-infected neonates without perinatal complications were selected to validate RR distributions. Positive and negative predictive values were calculated; area under receiver operating characteristic curves (AUCs) were constructed to predict the presence or absence of EOS. Neutrophil value scores were established to determine whether serial neutrophil values predict the absence of EOS. RESULTS: Seventy-seven percent of admissions to the neonatal intensive care unit were evaluated for EOS: 9 (0.56%) had proven EOS with positive blood culture ≤ 37 hours; 18% had clinically suspect EOS. Neutropenia occurred in preterm neonates, and nonspecific neutrophilia was common in uninfected neonates. The distribution of neutrophil values differed significantly between study groups. The specificity for absolute total immature neutrophils and immature to total neutrophil proportions was 91% and 94%, respectively, with negative predictive value of 99% for proven and 78% for proven plus suspect EOS. Absolute total immature neutrophils and immature to total neutrophil proportions had the best predictability for EOS >6 hours postnatal with an AUC ∼ 0.8. Neutrophil value scores predicted the absence of EOS with AUC of 0.9 and 0.81 for proven and proven plus suspect EOS, respectively. CONCLUSION: Age-dependent neutrophil RRs remain valid. Serial neutrophil values at 0, 12, and 24 hours plus blood culture and clinical evaluation can be used to discontinue antimicrobial therapy at 36-48 hours.