Jocelyne Cousineau

Markers for bacterial infection in children with fever without source

Objectives To compare the diagnostic properties of procalcitonin (PCT), C reactive protein (CRP), total white blood cells count (WBC), absolute neutrophil count (ANC) and clinical evaluation to detect serious bacterial infection (SBI) in children with fever without source. Design Prospective cohort study. Setting Paediatric emergency department of a tertiary care hospital. Participants Children aged 1–36 months with fever and no identified source of infection. Intervention Complete blood count, blood culture, urine analysis and culture. PCT and CRP were also measured and SBI probability evaluated clinically with a visual analogue scale before disclosing tests results. Outcome measure Area under the curves (AUC) of the receiver operating characteristic curves. Results Among the 328 children included in the study, 54 (16%) were diagnosed with an SBI: 48 urinary tract infections, 4 pneumonias, 1 meningitis and 1 bacteraemia. The AUC were similar for PCT (0.82; 95% CI 0.77 to 0.86), CRP (0.88; 95% CI 0.84 to 0.91), WBC (0.81; 95% CI 0.76 to 0.85) and ANC (0.80; 95% CI 0.75 to 0.84). The only statistically significant difference was between CRP and ANC (Δ AUC 0.08; 95% CI 0.01 to 0.16). It is important to note that all the surrogate markers were statistically superior to the clinical evaluation that had an AUC of only 0.59 (95% CI 0.54 to 0.65). Conclusion The study data demonstrate that CRP, PCT, WBC and ANC had almost similar diagnostic properties and were superior to clinical evaluation in predicting SBI in children aged 1 month to 3 years.

Impact of procalcitonin on the management of children aged 1 to 36 months presenting with fever without source: A randomized controlled trial

OBJECTIVE The aim of the study was to evaluate the impact of procalcitonin (PCT) measurement on antibiotic use in children with fever without source. METHOD Children aged 1 to 36 months presenting to a pediatric emergency department (ED) with fever and no identified source of infection were eligible to be included in a randomized controlled trial. Patients were randomly assigned to 1 of 2 groups as follows: PCT+ (result revealed to the attending physician) and PCT- (result not revealed). Patients from both groups also had complete blood count, blood culture, urine analysis, and culture performed. Chest radiography or lumbar puncture could be performed if required. RESULTS Of the 384 children enrolled and equally randomized into the PCT+ and PCT- groups, 62 (16%) were diagnosed with a serious bacterial infection (urinary tract infection, pneumonia, occult bacteremia, or bacterial meningitis) by primary ED investigation. Ten were also found to be neutropenic (<500 x 10(6)/L). Of the remaining undiagnosed patients, 14 (9%) of 158 received antibiotics in the PCT+ group vs 16 (10%) of 154 in the PCT- group (Delta -2%; 95% confidence interval [CI], -8 to 5). A strategy to treat all patients with PCT of 0.5 ng/mL or greater with prophylactic antibiotic in this group of patients would have resulted in an increase in antibiotic use by 24% (95% CI, 15-33). CONCLUSION Semiquantitative PCT measurement had no impact on antibiotic use in children aged 1 to 36 months who presented with fever without source. However, a strategy to use prophylactic antibiotics in all patients with abnormal PCT results would have resulted in an increase use of antibiotics.

Maternal and Fetal IGF-I and IGF-II Levels, Fetal Growth, and Gestational Diabetes

CONTEXT It remains uncertain whether maternal IGF-I is associated with fetal growth. Little is known about the role of maternal IGF-II in fetal growth and whether IGF-I or IGF-II is implicated in fetal hypertrophy in gestational diabetes. OBJECTIVE The objective of the study was to assess maternal and fetal IGF-I and IGF-II levels in association with fetal growth and gestational diabetes. STUDY DESIGN, POPULATION, AND OUTCOMES: A singleton pregnancy cohort study (n = 307). The primary outcome was birth weight. RESULTS Maternal plasma concentrations increased by an average of 55.4% for IGF-I and 11.8% for IGF-II between 24-28 and 32-35 weeks of gestation. The maternal IGF-I but not IGF-II level was correlated with birth weight and placental weight. Adjusting for maternal and infant characteristics, each SD increase in maternal IGF-I level at 24-28 weeks was associated with a 75-g (95% confidence intervals 29-120) increase in birth weight, a 20-g (7-33) increase in placental weight, and a 1.91-fold (1.28-2.86) higher odds of macrosomia (birth weight > 90th percentile). Similar associations were observed for the maternal IGF-I level at 32-35 weeks. Maternal and fetal IGF-I (but not IGF-II) levels were significantly higher in gestational diabetic than in nondiabetic pregnancies. The significantly higher birth weight z scores in diabetic pregnancies disappeared after adjusting for maternal and fetal IGF-I levels alone. CONCLUSIONS Higher maternal IGF-I (but not IGF-II) levels at mid- and late gestation may indicate greater placental and fetal growth. IGF-I (but not IGF-II) may be implicated in fetal hypertrophy in gestational diabetes.

Point of care testing: Transcutaneous bilirubinometry in neonates

Physicians taking care of infants in the first days of life are often faced with neonatal jaundice, especially in an era where post-partum discharge occurs earlier and assessment of newborn bilirubinemia status is required prior to discharge. The Canadian Pediatric Society and the American Academy of Pediatrics have developed and published guidelines for the diagnosis and management of hyperbilirubinemia in newborns. Point of care testing refers to any test performed outside of laboratory by clinical personnel and close to the site of patient care. Based on a summary of multiple reports during the last twenty years, we realize that devices which provide a non-invasive transcutaneous bilirubin (TcB) measurement have proven to be very useful as screening tools and provide a valid estimate of the total serum bilirubin level (TSB). Published data suggest that these devices provide measurements within 30-50 micromol/L of the TSB levels and can replace laboratory measurement particularly when TSB levels are less than 260 micromol/L. At the present time, in the literature, evidence is insufficient to abandon neonatal serum bilirubin testing and replace it with TcB. Any measurement, TSB or TcB, has potential for error. However, we have evidence that TcB, can help avoiding potential errors associated with even visual assessment of jaundice and may be useful as screening device to detect significant jaundice and decrease a large number of unnecessary skin punctures. The current manuscript is based on a careful comprehensive literature review concerning neonatal hyperbilirubinemia. We consider that this manuscript will help clinicians and laboratory professionals in the management of neonatal jaundice.

Value of amino-terminal pro B-natriuretic peptide in diagnosing Kawasaki disease

Background:  The aim of the present study was to investigate the diagnostic value of the N‐terminal B‐type natriuretic peptide (NT‐proBNP) in acute Kawasaki disease (KD) given that the clinical criteria and the current basic laboratory tests lack the necessary specificity for accurate diagnosis.

Threshold for toxicity from hyperammonemia in critically ill children.

BACKGROUND & AIMS Hyperammonemia results from reduction of hepatocyte function or enzyme of urea cycle deficiency. Hyperammonemia contributes to cerebral edema that may lead to cerebral herniation. The threshold of toxicity of ammonemia is unknown. METHODS We conducted a retrospective observational study in our pediatric intensive care unit. All children who developed hyperammonemia from January 2000 to April 2009 were included. Clinical and laboratory data at admission, specific treatments implemented, and ammonemias the first 7 days after inclusion were collected. The outcome assessed was 28 day mortality. Risk of mortality was estimated by a logistic regression model. RESULTS Ninety patients with liver failure (63.3%) and primary or secondary urea cycle defect (23.3%) were included. Patients with urea cycle defects were more likely to receive ammonia scavengers than patients with liver failure (47.6% versus 3.5%). The 28 day mortality rate was 31.1%. Risk of mortality increased according to the ammonemia within 48 h: odds ratio 1.5, 1.9, 3.3, 2.4 for ammonemia above 100, 150, 200, and 300 μmol/L, respectively. Peak ammonemia ≥200 μmol/L within the first 48 h was an independent risk factor for mortality, with greater risk found in liver failure than in urea cycle defect. CONCLUSIONS Our study identifies a threshold of exposure to ammonia (≥200 μmol/L) above which mortality increases significantly, especially in liver failure. Specific treatments of hyperammonemia are rarely used in liver failure when compared with urea cycle defect even though use of ammonia scavengers may help to decrease ammonemia.

Biological variation of glycated haemoglobin in a paediatric population and its application to calculation of significant change between results

Background To determine precisely the probability that a change between two glycated haemoglobin A1c (HbA1c) results is significant and that clinical actions may be required, the biological variation of HbA1c must be known. However, it has not been evaluated in a paediatric population. We therefore determined the long-term biological variation of HbA1c in a paediatric population and used it to generate a probability curve for significant changes between two consecutive HbA1c measurements. Methods A group of 24 boys and 14 girls with cystic fibrosis (CF) but without diabetes or impaired glucose tolerance has been selected. HbA1c has been measured at least five times over five consecutive years for all subjects. We have used the Fraser and Harris method to calculate within-subject biological variation (CVI), which allowed the determination of the probability that a change is significant between results. Results As within-subject variances are equivalent for girls and boys (P > 0.1), both genders were merged for biological variation analysis. The CVI calculated for HbA1c was 4.8% and the between-subject variation (CVG) was 12.8%. Then, a probability curve based on the CVI found was generated and showed that a change of 14% between two consecutive HbA1c results corresponding to a probability of 95% was significant. Conclusions We determined for the first time the biological variation of HbA1c in a paediatric population, which is higher than the ones found for adult populations. The probability curves generated from these data could be invaluable tools for clinicians to balance HbA1c results with other clinical parameters.

Comparison of procalcitonin measurement by a semi-quantitative method and an ultra-sensitive quantitative method in a pediatric emergency department

OBJECTIVE To compare procalcitonin measurements between semi-quantitative and quantitative assays. METHOD Procalcitonin was measured with the PCT-Q and the Kryptor assays in a pediatric emergency department. RESULTS Among the 359 pairs of results, 103 had discordant results. The linear weighted kappa was 0.44 (95% CI 0.36, 0.51). The concordant/discordant results distribution varied depending on the laboratory technician (p=0.018). CONCLUSION Agreement between procalcitonin measured semi-quantitatively and quantitatively was moderate. This is probably due to a subjective interpretation of the assay result.