Recurrent febrile seizures and serum cytokines: a controlled follow-up study.

BACKGROUND: The role of cytokines in the pathogenesis of febrile seizures (FSs) is unclear, and information regarding cytokine production outside of FS episodes is scarce. METHODS: In our controlled follow-up study of patients with FSs, we compared the levels of 12 serum cytokines after the patients' first FSs, during febrile episodes without FSs, after recurrent FSs, during healthy periods after FSs, and between patients and controls. RESULTS: Two-hundred fifty-one patients with first FS participated in the study, of whom 17 (mean age 1.6 years, SD 0.7) with recurrent FSs completed the protocol as required by the sample size calculations. The mean IL-1RA level was higher after the first FSs (2580 pg/mL, SD 1516) than during febrile episodes without FSs (1336 pg/mL, SD 1364, P = 0.006) and healthy periods after FSs (474 pg/mL, SD 901, P = 0.001). IL-1RA levels were also higher during first (2580 pg/mL) and recurrent FSs (2666 pg/mL, SD 1747) in comparison with febrile controls (746 pg/mL, SD 551) (P < 0.001 and P = 0.001, respectively), but there was no difference in the IL-1RA between febrile episodes without FSs and febrile controls. CONCLUSIONS: Patients with FSs produce stronger inflammatory reactions during febrile episodes with FSs compared with febrile episodes without FSs and febrile controls. IMPACT: In patients with FSs, IL-1RA was higher following first FS than during febrile episodes without FSs and healthy periods after FSs. IL-1RA was higher in patients with FSs following first and recurrent FSs than in febrile controls. There was no significant difference in IL-1RA between febrile episodes of patients without FSs and febrile controls. Using IL-1RA as a surrogate marker of IL-1 axis activity, our results indicate that patients with FSs produced stronger inflammatory reactions during FS episodes but not during other febrile episodes or healthy periods after FSs. Cytokines may play a role in pathogenesis of FSs.

Efficacy of the implementation of the National Emergency X-Radiography Utilization Study II decision rule to clinical practice for paediatric head injury patients.

AIM: To investigate the usefulness of the National Emergency X-Radiography Utilization Study (NEXUS) II head trauma decision rule in clinical practice for paediatric patients in a tertiary university hospital serving as the only paediatric hospital in the area. METHODS: We compared how doctors evaluated and examined patients with head injury during two time periods, before and after the introduction of NEXUS II decision rule. Multiple implementation strategies were used as follows: education, tutoring and written instructions for the use of NEXUS II. RESULTS: Two hundred and forty-four head injury patients visited the hospital before and 385 after the introduction of the NEXUS II decision rule. The number of hospital admissions (56%) and the mean duration of hospitalisation (2.5 days) remained the same during the two periods. In the NEXUS II evaluated group, there was a decrease of 40% in the number of hospital admissions. NEXUS II was applied in only 62 (16%) cases. The number of head imaging procedures remained the same. No patients with a clinically significant head injury were missed with the NEXUS II evaluation. CONCLUSION: NEXUS II was ineffective as our implementation failed. When used, NEXUS II reduced expenses in our study population by decreasing the number of hospital admissions.

Diaper-embedded urine test device for the screening of urinary tract infections in children: a cohort study.

BACKGROUND: There is a need for an easy and sensitive method for screening of urinary tract infections in young children. We set out to test whether a novel diaper-embedded urine test device is feasible and reliable in screening for urinary tract infections. METHODS: This prospective cohort study consisted of young children examined due to a suspected acute urinary tract infection at the Pediatric Emergency Department of the Oulu University Hospital, Finland. We analyzed the same urine samples using three different methods: 1) a diaper-embedded test device applied to the urine pad within the diaper, 2) a urine sample aspirated from the urine pad for the conventional point-of-care dipstick test, and 3) a urine sample aspirated from the urine pad and analyzed in the laboratory with an automated urine chemistry analyzer. The gold standard for confirming urinary tract infection was quantitative bacterial culture. RESULTS: Urine samples were available from 565 children. Bacterial culture confirmed urinary tract infection in 143 children. Sensitivity of the positive leukocyte screening of the diaper-embedded urine test device was 93.1% (95% CI: 87.4-96.8) and that of the point-of-care urine dipstick analysis was 95.4% (90.3-98.3) in those with both tests results available (n = 528). The sensitivity of the positive leukocyte test of the diaper-embedded test device was 91.4% (85.4-95.5) and that of the automated analysis was 88.5% (82.0-93.3) in those with both tests available (n = 547). The time to the test result after urination was immediate for the diaper-embedded test, 1-5 min for point-of-care dipstick, and 30-60 min for laboratory-based automated urine chemistry analyzer. CONCLUSIONS: In this prospective study, the diaper-embedded urine test device was an easy and sensitive screening method for UTIs in young children. The main clinical benefit of the diaper-embedded urine test device was that the screening test result was available immediately after urination.

Intravenous magnesium sulfate for acute wheezing in young children: a randomised double-blind trial.

Magnesium sulfate has been shown to be an effective treatment in older children with asthma exacerbations, but it has not been investigated in acute severe virus-induced wheezing in young children.The study enrolled 61 children aged 6 months to 4 years. Inclusion criteria were severe wheezing, classified as a score of ≥6 points as assessed by the Respiratory Distress Assessment Instrument (RDAI) after initial treatment with salbutamol, and the symptoms of acute viral infection. The children were randomly allocated to receive either an infusion of magnesium sulfate (40 mg·kg-1) or 0.9% sodium chloride as a placebo infusion for 20 min. Primary outcome measure was mean change in RDAI scores from baseline to 6 h after the treatment.Change in the severity of wheezing from baseline to 6 h after the treatment, as measured by mean±sd RDAI scores, was 4.7±2.6 in the magnesium sulfate group and 4.2±4.2 in the placebo group (difference 0.5, 95% CI -1.3 to 2.3, p=0.594).Intravenous magnesium sulfate was ineffective in treating acute severe virus-induced wheezing in young children, in contrast to the previous efficacy demonstrated in older children.

Maternal influence on the fetal microbiome in a population-based study of the first-pass meconium.

BACKGROUND: Meconium is formed before birth and may reflect the microbiome of the fetus. To test our hypothesis, we investigated whether maternal factors during pregnancy, such as biodiversity of the living environment, influence the microbiome of the first stool more than immediate perinatal factors. METHODS: We recruited 218 consecutive newborn infants from one hospital. Regions of the bacterial 16S rRNA gene were sequenced to characterize the microbiomes of the first-pass meconium samples (N=212). We used a multivariate model to determine both the prenatal and perinatal factors affecting the microbiome. RESULTS: The number of operational taxonomic units ranged from 0 to 448 per newborn. The most abundant phyla were Firmicutes, with a relative abundance of 44%, Proteobacteria, 28%, and Bacteroidetes, 15%. By a multivariate analysis, the biodiversity of the home environment increased the diversity of microbiomes, whereas perinatal factors, such as the delivery mode or exposure to antimicrobials during labor did not have an effect. CONCLUSION: The microbiome of the first-pass meconium was not altered by immediate perinatal factors, but was affected by maternal factors during pregnancy, implying the in utero transfer of microbes and the development of the gut microbiota niche in fetal life.

Intestinal microbiome as a risk factor for urinary tract infections in children.

As urinary tract infection (UTI) pathogens originate from the gut, we hypothesized that the gut environment reflected by intestinal microbiome influences the risk of UTI. Our prospective case-control study compared the intestinal microbiomes of 37 children with a febrile UTI with those of 69 healthy children. We sequenced the regions of the bacterial 16S rRNA gene and used the LefSe algorithm to calculate the size of the linear discriminant analysis (LDA) effect. We measured fecal lactoferrin and iron concentrations and quantitative PCR for Escherichia coli. At the phylum level, there were no significant differences. At the genus level, Enterobacter was more abundant in UTI patients with an LDA score > 3 (log 10), while Peptostreptococcaceae were more abundant in healthy subjects with an LDA score > 3 (log 10). In total, 20 OTUs with significantly different abundances were observed. Previous use of antimicrobials did not associate with intestinal microbiome. The relative abundance of E. coli was 1.9% in UTI patients and 0.5% in controls (95% CI of the difference-0.8 to 3.6%). The mean concentration of E.coli in quantitative PCR was 0.14 ng/µl in the patients and 0.08 ng/µl in the controls (95% CI of the difference-0.04 to 0.16). Fecal iron and lactoferrin concentrations were similar between the groups. At the family and genus level, we noted several differences in the intestinal microbiome between children with UTI and healthy children, which may imply that the gut environment is linked with the risk of UTI in children.

Comorbidity of PFAPA (periodic fever, aphthous stomatitis, pharyngitis and adenitis) patients: a case control study.

OBJECTIVES: To compare the long-term morbidity of patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome treated by tonsillectomy (TE) in childhood to that of matched controls. METHODS: We identified 132 PFAPA patients from the medical records treated by TE in 1987-2007 in Oulu University Hospital, Finland. Altogether 119 patients participated the follow-up study and 94 were clinically examined on average 9.0 years after TE. The controls consisted of 230 randomly selected age-, sex-, and birth place-matched individuals from the Population Register Center of Finland. The patients and controls completed a detailed questionnaire about their current health and the data were compared. RESULTS: Self-estimated general health was good and growth was normal among PFAPA patients and controls at long-term follow-up. There were no between-group differences in the occurrence of autoimmune or other chronic diseases. Thirty percent of the PFAPA patients and 13% of the controls reported infections as causes of hospital visits during their lifetime (p<0.001). Usage of antibiotics during lifetime was reported by 99% of the PFAPA patients and by 88% of the controls (p= 0.009). Twelve percent of PFAPA patients and 0.4% of the controls reported oral thrush in their history (p=0.003). CONCLUSIONS: The health of the PFAPA patients was as good as that of healthy matched controls. Autoimmune or other chronic diseases were not more prevalent among PFAPA patients treated with TE in childhood than among controls. Respiratory infections and oral thrush were more common among the PFAPA patients than controls.

Risk factors for periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: a case-control study.

The etiology and pathogenesis of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome are unclear. We performed a case-control study to evaluate potential environmental or lifestyle factors associated with PFAPA morbidity. We enrolled 119 patients with PFAPA syndrome who had undergone tonsillectomy in Oulu University Hospital between 1987 and 2007. We recruited 230 controls, matched for sex, birth date, and place from the database of the Population Register Center of Finland. All the patients and controls completed a questionnaire regarding exposure to environmental triggers during early childhood. Maternal smoking was more common among PFAPA syndrome patients than controls (23 vs. 14%; P = 0.005). PFAPA patients had lower breastfeeding rates than controls (94 vs. 99%; P = 0.006). No other environmental factors were associated with PFAPA syndrome, except having an aquarium at home (P = 0.007). The patient group also used natural or herbal medicines more often than the controls (P = 0.01). CONCLUSION: Maternal smoking and lack of breastfeeding, known risk factors for common childhood infections, were more common in patients with PFAPA syndrome than in matched controls. Environmental factors may be important in the pathogenesis of PFAPA syndrome and should be evaluated in future studies. What is Known: • The pathogenesis and genetics of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome remain unsolved. • PFAPA syndrome has been shown to cluster in families. What is New: • Maternal smoking and lack of breastfeeding are more common in patients with PFAPA syndrome than in the controls. • Environmental risk factors may be important in the pathogenesis of the syndrome.

Aetiology of neonatal conjunctivitis evaluated in a population-based setting.

AIM: Our aim was to study prospectively the aetiology of neonatal conjunctivitis in a population-based setting. METHODS: Altogether 173 neonates with clinical conjunctivitis aged on average 20 (SD 10) days were recruited from child welfare clinics in Oulu, Finland, in 2010-2015. Conjunctival specimens were collected from 167 neonates for multiplex polymerase chain reaction to detect 16 respiratory viruses, from 163 for polymerase chain reaction to detect Chlamydia trachomatis and Neisseria gonorrhoeae and from 160 for bacterial culture studies. The cases were followed up until the age of 18 months. RESULTS: Viral conjunctivitis was diagnosed in 8/167 (4.8%; 95% CI 2.1-9.2%), chlamydial or gonococcal conjunctivitis in 0/163 cases (0%; 95% CI 0-2.2%) and other bacterial conjunctivitis in 58/160 (36%; 95% CI 29-44%). Rhinovirus was found at the ocular site in 4/167 (2.4%) neonates, adenovirus in 3/167 (1.8%) and bocavirus in 1/167 (0.6%). The most commonly isolated bacteria included Staphylococcus aureus (16%), Moraxella catarrhalis (9.4%) and Streptococcus pneumoniae (3.1%). None of these pathogens was associated with the 4/173 (2.3%) cases later operated on for persistent nasolacrimal duct obstruction. CONCLUSION: Chlamydia trachomatis was a rare pathogen in neonatal conjunctivitis in a population-based setting, but respiratory viruses were detected more frequently than indicated earlier.

Probability of vertical transmission of Chlamydia trachomatis estimated from national registry data.

OBJECTIVES: Chlamydia trachomatis colonisation is common in pregnant women, and it has been claimed that mother-to-child transmission may occur in 10%-70% of deliveries. C. trachomatis infections are nevertheless rarely encountered in infants in clinical practice. In order to evaluate the reason for this discrepancy, we designed a nationwide study of the C. trachomatis vertical transmission. METHODS: Children with a possible C. trachomatis infection were identified from two national health registries in 1996-2011. Copies of the children's medical records were reviewed and maternal serum bank samples obtained during the index pregnancies were analysed for C. trachomatis antibodies. The risk of vertical transmission was calculated using data from two earlier studies in which nucleic acid amplification test (NAAT) positivity and seroconversion rates among women in the general population were reported. RESULTS: Altogether 206 children had a possible C. trachomatis infection, which represents 0.22 per 1000 live births (95% CI 0.19 to 0.25). The risk of vertical transmission among the estimated 24 901 NAAT-positive mothers was 0.8% (95% CI 0.7 to 0.9). Based on the annual seroconversion rate of maternal antitrachomatis antibodies, the risk of vertical transmission was 1.8% (95% CI 1.5 to 2.0). Altogether 35% of the maternal serum samples obtained in the first trimester of a pregnancy leading to a C. trachomatis infection in the infant were negative, implying that the infection was acquired during pregnancy. CONCLUSIONS: C. trachomatis infections in infants were rare, with a population-based occurrence of 0.22 per 1000 live births. The risk of vertical transmission of C. trachomatis in the population was <2%, which is significantly lower than reported earlier.