Validation of a laboratory risk index score for the identification of severe bacterial infection in children with fever without source.

OBJECTIVE: The identification of severe bacterial infection (SBI)in children with fever without source (FWS) remains a diagnostic problem. The authors previously developed in their Swiss population a risk index score, called the Lab-score, associating three independent predictors of SBI, namely C reactive protein (CRP), procalcitonin (PCT) and urinary dipstick. The objective of this study was to validate the Lab-score in a population of children with FWS different from the derivation model. METHODS: A prospective study, conducted in Padova, on 408 children aged 7 days to 36 months with FWS was recently published. PCT, CRP, white blood cell count (WBC) and urinary dipstick were determined in all children. The Lab-score was applied to this population and the diagnostic characteristics for the detection of SBI were calculated for the Lab-score and for any single variable used in the Italian study. RESULTS: For the identification of SBI, the sensitivity of a score ≥3 was 86% (95% CI 77% to 92%) and the specificity 83% (95% CI 79% to 87%). The area under the receiver operating characteristic curve for the Lab-score (0.91) was significantly superior to that of any single variable: 0.71 for WBC, 0.86 for CRP and 0.84 for PCT. The Lab-score performed better than other laboratory markers, even when applied to children of different age groups (<3 months, 3-12 months and >12 months). The results obtained in this validation set population were comparable with those of the derivation set population. CONCLUSIONS: This study validated the Lab-score as a valuable tool to identify SBI in children with FWS.

A score identifying serious bacterial infections in children with fever without source.

The objective of the study was to develop a simple clinical tool to identify serious bacterial infection (SBI) in children with fever without a source. For each child, a clinical assessment, a white blood cell count, a urine analysis, a determination of C-reactive protein, procalcitonin, and appropriate cultures were performed. Two hundred two children were studied of whom 54 (27%) had SBI. In the multivariate analysis, only procalcitonin [odds ratio (OR): 37.6], C-reactive protein (OR: 7.8), and urine dipstick (OR: 23.2) remained significantly associated with SBI. The sensitivity of the score for the identification of SBI was 94% and the specificity 81%. In the validation set the sensitivity of the score was 94% and the specificity 78%.

Correlation between specific immunoglobulin E levels and the severity of reactions in egg allergic patients.

Different studies proposed specific immunoglobulin E (IgE) cut-off levels for the diagnosis of egg allergy. Little is known if IgE titres could be helpful for prediction of the severity of the reaction. The aim of this study was to determine whether IgE titres are associated with the severity of the reaction during a standardized egg challenge. We reviewed data obtained during oral challenge tests to egg performed between 2003 and 2005, and attributed a clinical score to the positive reactions. Serum specific IgE levels were analysed in relation with the severity of the reaction. We analysed data from 51 oral food challenges to egg, raw or cooked. Sixteen challenges (31%) were negative and 35 (69%) were positive of which 13 challenges (37% of positive reactions) elicited a severe reaction. IgE levels in our patients ranged from undetectable to 14.90 kU/l. We could determine a cut-off level of 8.20 kU/l for a 90% probability of clinical reactivity. IgE titres were statistically significantly different between the patients with absent, mild and moderate or severe reaction. Patients with negative challenge had IgE levels between 0.35 and 6.41 kU/l (median 1.17), those with mild and moderate reaction had IgE levels ranging from 0.35 to 14.90 (median 2.47) and patients with severe reactions had IgE between 1.18 and 11.00 (median 3.70) (p = 0.006). Our results show a correlation between IgE titres and the severity of the clinical reaction to egg. IgE titres may help to determine the potential risk of a reaction to eggs.

Continuing food-avoidance diets after negative food challenges.

Negative food challenges for follow-up in patients previously diagnosed with food allergy should logically be followed by a normal diet. However, all patients do not reintroduce the food. The aims of the study were to define the proportion of negative food challenge not followed by a normal diet, and to identify possible reasons for not reintroducing the food. Patients with a negative food challenge were sent a questionnaire by mail. Items in the questionnaire included the symptoms at diagnosis, the duration of the diet, the fear of an accidental reaction during the avoidance diet and how it influenced the social life. Patients were also asked if the food was reintroduced after the negative food challenge, and if not, for which reasons. In 25.4% of the questionnaires (18/71) respondents reported that the food was not reintroduced. Patients with a previous diagnosis of peanut allergy tended to reintroduce the food less frequently than patients allergic to other foods. Girls were found to significantly less frequently reintroduce the food than boys. However, neither the severity of the initial reaction, the anxiety of an accidental reaction during the avoidance diet, nor a prolonged avoidance diet did influence the decision to reintroduce the food. Among other reasons listed, fears of persistence of allergies, with recurrent pruritus or non-specific skin rashes after eating the food, were reported in 12.7% of the total number of questionnaires. Patients who reintroduced the food reported that their social life generally improved. One quarter of previously allergic patients continue a food avoidance diet despite a negative challenge. We suggest reassessing food consumption in all patients after a negative food challenge, and in those still avoiding the specific food to consider a repeated challenge test.

24-hour electrocardiogram before and during cisapride treatment in neonates and infants.

We studied prospectively the effects of cisapride on heart rate and rhythm using standard ECG and 24-hour ECG recordings in term and preterm neonates and infants. We studied subjects with gastroesophageal reflux disease (apparent life-threatening events, apneas, bradycardias) before and 3 days after starting cisapride (0.8 mg/kg/day in 4 doses). We performed standard ECGs for determination of corrected Q-T interval (QTc) and Q-T dispersion (QTd) and 24-hour ECG recordings for analysis of heart rate, heart rate variability, and heart rhythm. Fourteen term and 17 preterm subjects (gestational age range 28-36 weeks) were studied at a median chronological age of 29 (range 3-132) days. Cisapride significantly increased the QTc in preterm infants (before vs. after: 408 +/- 7 vs. 433 +/- 7 ms, p = 0.001). Two preterm and 1 term infant had a QTc >450 ms before cisapride. Four preterm (4/15 = 27%) and 2 term (2/13 = 15%) subjects had a QTc >450 ms on cisapride. After cisapride the QTd remained normal, and no relevant arrhythmias were documented on Holter recordings. Cisapride significantly decreased peak and mean heart rates of all study subjects without affecting the heart rate variability, while it increased the minimal heart rate of preterm infants only (before vs. after: 66 +/- 5 vs. 78 +/- 5 bpm, p = 0.02). The maximally measured R-R intervals (pauses) decreased after cisapride in preterm infants (before vs. after: 1.33 +/- 0.2 s vs. 1.05 +/- 0.2 s, p = 0.04). Although cisapride did cause a significant prolongation of the ventricular action potential duration in preterm infants, the QTd remained unaffected, and no clinically relevant arrhythmias were documented in this small sample. On the other hand, cisapride had a direct lowering effect on the maximal and mean heart rates of both term and preterm infants, while the drug increased the minimal heart rate and reduced the severity of bradycardia episodes in preterm infants.

Bedside procalcitonin and C-reactive protein tests in children with fever without localizing signs of infection seen in a referral center.

OBJECTIVE: To assess the value of bedside tests for predicting the occurrence of severe bacterial infections (SBIs) in children with fever without source. METHODS: We conducted a prospective study of 99 children, aged 7 days to 36 months, who were seen for fever >38 degrees C and no localizing sign of infection at the emergency department of the University Children's Hospital of Geneva. Blood procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) values were determined using rapid tests and were compared with the total white blood cell (WBC) count with differential and clinical score. Specificity, sensitivity, predictive values, and multilevel likelihood ratios (LRs) with posttest probabilities of disease were calculated. RESULTS: Twenty-nine (29%) children received a diagnosis of having an SBI. PCT had the best sensitivity (93%) and negative predictive value (96%). Band count had the best specificity (93%), but its positive predictive value was only 38%. Multilevel LRs revealed that a PCT concentration <0.5 ng/mL (LR: 0.093) almost ruled out SBI (posttest probability of disease: 3.7%) in 54 (54%) subjects, whereas a value >2 ng/mL (LR: 5.2) increased the probability of SBI to 68% in 19 (19%) children. For CRP, values <40 mg/L (LR: 0.263) and >100 mg/L (LR: 14.483) generated posttest probabilities for SBI of 9.7% (61 subjects) and 86.5% (14 subjects), respectively. For WBC count, the posttest probabilities of SBI were modestly changed from the pretest prevalence. CONCLUSIONS: PCT and CRP performed better than IL-6, WBC, and/or band count in predicting the occurrence of SBI. PCT and CRP bedside tests may be useful tools for emergency and private practice doctors and should be considered in the initial work-up of children with fever without source.

Arginine supplementation prevents necrotizing enterocolitis in the premature infant.

OBJECTIVES: To determine whether supplementation with L -arginine reduces the incidence of all stages of necrotizing enterocolitis (NEC) in premature infants with birth weight < or =1250 g and gestational age < or =32 weeks. STUDY DESIGN: In a randomized, double-blind, placebo-controlled study, 152 premature infants were prospectively, randomly assigned to receive either supplemental L -arginine (1.5 mmol/kg per day; n =75 [group A]) or placebo (control group; n = 77 [group B]) with oral feeds/parenteral nutrition during the first 28 days of life. Nutrient intake, plasma ammonia, arginine, and amino acid concentrations were measured in all infants at days 3, 14, and 28 and at the time of diagnosis of NEC. RESULTS: NEC developed in 5 infants in group A compared with 21 infants in group B (P <.001). Arginine intake and plasma arginine concentrations were similar in both groups at study entry and (as expected) increased in group A at days 14 and 28. Plasma arginine concentrations were lower in both groups at time of diagnosis of NEC. No significant differences in maternal and neonatal demographics, nutrient intake, plasma ammonia and total and essential amino acid concentrations were present between the two groups. CONCLUSIONS: Arginine supplementation (1.5 mmol/kg per day) in premature infants reduces the incidence of all stages of NEC.

Outcome of children with fetal, neonatal or childhood diagnosis of isolated congenital atrioventricular block. A single institution's experience of 30 years.

OBJECTIVES: We reviewed our institution's experience with isolated (congenital) third-degree atrioventricular block (CAVB) to identify pre- and post-natal predictors of mortality and the requirement for pacemakers in infancy and childhood. BACKGROUND: Because of the relative rarity of the disease, there is a paucity of data concerning the outcome of fetuses and children with isolated CAVB. METHODS: The medical records of all cases of CAVB encountered at our institution from January 1965 to December 1998 were analyzed. RESULTS: Of 102 cases identified, 29 were diagnosed in utero (F) at 26.1 +/- 5.6 weeks gestation, 33 as neonates (N; < or = 28 days), and 40 as children (C) at 5.7 +/- 4.8 years of age. Anti-Ro and/or anti-La were present in 95% of F and 90% of N, but only in 5% of C mothers tested (p < 0.0001). Patients with CAVB having F, N and C diagnosis had a mortality of 43%, 6% and 0%, respectively, in the first two decades of life. Increased mortality risk was associated with a fetal diagnosis of CAVB (13/15 deaths; p < 0.05), fetal hydrops (6/6 cases; p < 0.0001), endocardial fibroelastosis (5/5 cases; p < 0.0001) and delivery at < or = 32 weeks (4/6 cases; p < 0.05). Timing of pacemaker implantation differed significantly among F versus N (p < 0.05) and N versus C (p < 0.001) cases. At 20 years of age only 11% and 12% of CAVB patients with N and C diagnosis, respectively, were not paced. CONCLUSIONS: Pre-natal diagnosis of CAVB is associated with high fetal and neonatal mortality. Among survivors, whether the diagnosis is made before or after birth, most undergo pacemaker implantation by adulthood, with earlier intervention and a significantly greater need for reintervention among those diagnosed in utero.