Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants.

Early onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection.In this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7-32.2) were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12); presumed sepsis (PS, n = 30); and no sepsis (controls, n = 30). Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™). In addition, placental histopathologic data were linked to biomarker results.cEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01). SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01) and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants.This study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and identification of infants with EOS

Association Between the 7-Day Moving Average for Nutrition and Growth in Very Low Birth Weight Infants.

BACKGROUND: Very low birth weight (VLBW) infants remain at risk for postnatal growth restriction. Clinicians may have difficulty identifying growth patterns resulting from nutrition interventions, impeding prompt management changes intended to increase growth velocity. This study aimed to quantify the association between growth and nutrition intake through 7-day moving averages (SDMAs). METHODS: The first 6 weeks of daily nutrition intake and growth measurements were collected from VLBW infants admitted to a level 4 neonatal intensive care unit (2011-2014). The association between SDMA for energy and macronutrients and subsequent 7-day growth velocities for weight, length, and head circumference were determined using mixed effects linear regression. Analyses were adjusted for fluid intake, infant characteristics, and comorbid conditions. RESULTS: Detailed enteral and parenteral caloric provisions were ascertained for 115 infants (n = 4643 patient-days). Each 10-kcal/kg/d increase over 7 days was independently associated with increased weight (1.7 g/kg/d), length (0.4 mm/wk), and head circumference (0.9 mm/wk; P \u3c .001, for weight and head circumference; P = .041 for length). Each 1 g/kg/d macronutrient increase was also associated with increased weight (protein, P = .027; fat and carbohydrates, P \u3c .001), increased length (fat, P = .032), and increased head circumference (fat and carbohydrates, P \u3c .001). CONCLUSIONS: The SDMA identifies clinically meaningful associations among total energy, macronutrient dosing, and growth in VLBW infants. Whether SDMA is a clinically useful tool for providing clinicians with prompt feedback to improve growth warrants further attention

Acute phase reactant levels in sepsis groups.

<p>Box and whisker plots displaying distribution of 9 APR biomarkers (SAA, CRP, Hp, ferritin, SAP, PCT, tissue plasminogen activator, fibrinogen, α-2-macroglobulin) in each sepsis category. *Indicates significant difference in APR values between cEOS and control groups. **Indicates significant difference in APR values between cEOS and PS groups.</p

Metabolic Uncoupling Following Cardiopulmonary Bypass.

OBJECTIVE: The objective of this study was to characterize the natural history of metabolic uncoupling (type B hyperlactemia and hyperglycemia) following cardiopulmonary bypass (CPB), and to determine the impact of insulin therapy on time to lactate normalization in patients without low cardiac output. DESIGN: The design used was a retrospective cohort study. SETTING: The study was set in a pediatric cardiac intensive care unit in a tertiary-care urban children\u27s hospital. PATIENTS: All patients were aged ≤21 years admitted between 2007 and 2013 following cardiac surgery involving CPB with empiric intraoperative corticosteroids. ELIGIBILITY CRITERIA: simultaneous hyperlactemia (≥3.5 mEq/L) and hyperglycemia (≥200 mg/dL) within 48 hours after bypass. EXCLUSION CRITERIA: Exclusion criteria were evidence of low cardiac output state, diabetes or postoperative steroid administration. INTERVENTIONS: Characteristics were compared between those treated with insulin and those who were not (controls). OUTCOME MEASURES: Outcome measures used were time from admission to onset of hyperglycemia and hyperlactemia and time to resolution. Clinical outcomes included duration of mechanical ventilation, length of stay, unplanned readmission/reoperation, hypoglycemia and death. RESULTS: Of the 1345 patients receiving CPB, 132 (9.8%) met inclusion criteria. Seventy-eight (59%) were treated with insulin, leaving 54 controls. Patient characteristics, surgical complexity and time to onset of hyperglycemia and hyperlactemia were similar between groups. The insulin group had a shorter duration of hyperglycemia. There was no significant difference between groups in time to lactate normalization, ventilator days, length of stay, readmission and reoperation rates. Hypoglycemia (/dL) occurred in three patients. CONCLUSIONS: In children with metabolic uncoupling after CPB, insulin use did not shorten the time to lactate normalization or alter clinical outcomes. These findings suggest that type B hyperlactemia with hyperglycemia after CPB will resolve spontaneously and does not warrant specific treatment

Antibiotic duration and changes in FEV1 are not associated with time until next exacerbation in adult cystic fibrosis: a single center study

Abstract Background Pulmonary exacerbations (PEx) are a major driver of morbidity and mortality in cystic fibrosis and reducing their frequency by extending the time between them is an important therapeutic goal. Although treatment decisions for exacerbations are often made based on dynamic changes in lung function, it is not clear if these changes truly impact future exacerbation risk. We analyzed adults with chronic Pseudomonas aeruginosa infection to determine whether changes in FEV1 or duration of intravenous antibiotic therapy were associated with time to the next pulmonary exacerbation. Methods Medical records and Cystic Fibrosis Foundation Patient Registry data were examined retrospectively to assess whether various patient-specific demographic factors and exacerbation-specific characteristics were associated with time until next exacerbation using the Andersen-Gill model in order to control for previous exacerbation frequency history. Results We examined 59 patients with 221 CF pulmonary exacerbations over a 3-year study period. Mean age was 28.2 years and mean baseline FEV1 was 62% predicted. In our univariable model, fall in FEV1 at onset of exacerbation (median absolute −3% predicted change), recovery of FEV1 with treatment (median absolute +3% predicted change) and duration of IV antibiotics (median 16 days) were not associated with time to next exacerbation (median 93.5 days). Paradoxically each one-year increase in age was associated with a reduction in hazard of PEx by 3% (HR 0.97, P = 0.03, 95% CI 0.95–1.00). Conclusions FEV1 drop and recovery associated with onset and treatment of a CF pulmonary exacerbation or duration of intravenous antibiotics were not predictive of time until next exacerbation. Our finding that older age may be associated with decreased hazard of exacerbation is likely due to a healthy survivor effect and should be controlled for in clinical trials of pulmonary exacerbations

Case definition, demographics and placental histopathology.

<p>Case definition, demographics and placental histopathology.</p

Receiver operating characteristic curves.

<p>ROC curves for serum amyloid A, C-reactive protein, and haptoglobin. The above acute phase reactants had areas under the curve of >95% for prediction of EOS.</p

Linear regression model for sepsis effect on acute phase reactants.

<p>Linear regression model for sepsis effect on acute phase reactants.</p

Receiver operating characteristic analysis: AUC and biomarker cut-offs.

<p>Receiver operating characteristic analysis: AUC and biomarker cut-offs.</p

Cord blood acute phase reactants: comparison of cEOS to other sepsis groups and controls.

<p>Cord blood acute phase reactants: comparison of cEOS to other sepsis groups and controls.</p