Early-onset group B streptococcal infections in five Nordic countries with different prevention policies, 1995 to 2019.

BackgroundNeonatal early-onset disease caused by group B Streptococcus (GBS) is a leading cause of infant morbidity. Intrapartum antibiotic prophylaxis (IAP) is effective in preventing early-onset GBS disease, but there is no agreement on the optimal strategy for identifying the pregnant women requiring this treatment, and both risk-based prophylaxis (RBP) and GBS screening-based prophylaxis (SBP) are used.AimThe aim of this study was to evaluate the effect of SBP as a public health intervention on the epidemiology of early-onset GBS infections.MethodsIn 2012, Finland started the universal SBP, while Denmark, Iceland, Norway and Sweden continued with RBP. We conducted an interrupted time series analysis taking 2012 as the intervention point to evaluate the impact of this intervention. The incidences of early- and late-onset GBS infections during Period I (1995-2011) and Period II (2012-2019) were collected from each national register, covering 6,605,564 live births.ResultsIn Finland, a reduction of 58% in the incidence of early-onset GBS disease, corresponding to an incidence rate ratio (IRR) of 0.42 (95% CI: 0.34-0.52), was observed after 2012. At the same time, the pooled IRR of other Nordic countries was 0.89 (95% CI: 0.80-1.0), specifically 0.89 (95% CI: 0.70-1.5) in Denmark, 0.34 (95% CI: 0.15-0.81) in Iceland, 0.72 (95% CI: 0.59-0.88) in Norway and 0.97 (95% CI: 0.85-1.1) in Sweden.ConclusionsIn this ecological study of five Nordic countries, early-onset GBS infections were approximately halved following introduction of the SBP approach as compared with RBP.

The Contribution of Viruses and Bacteria to Childhood Community-acquired Pneumonia: 11-Year Observational Study From Norway.

BACKGROUND: Viruses are associated with pediatric community-acquired pneumonia (CAP) but are also common in the upper airways of healthy children. We have determined the contribution of respiratory viruses and bacteria by comparing children with CAP and hospital controls. METHODS: Children less than 16 years old with radiologically confirmed CAP (n = 715) were enrolled over an 11-year period. Children admitted for elective surgery during the same period served as controls (n = 673). Nasopharyngeal aspirates were tested for 20 respiratory pathogens by semiquantitative polymerase chain reaction tests and cultivated for bacteria and viruses. We used logistic regression to calculate adjusted odds ratios [aOR; 95% confidence intervals (CIs)], and estimated population-attributable fractions (95% CI). RESULTS: At least 1 virus was detected in 85% of cases and 76% of controls, and greater than or equal to 1 bacterium was detected in 70% of cases and controls. The presence of respiratory syncytial virus (RSV) (aOR, 16.6; 95% CI: 9.81-28.2), human metapneumovirus (HMPV) (13.0; 6.17-27.5) and Mycoplasma pneumoniae (27.7; 8.37-91.6) were most strongly associated with CAP. For RSV and HMPV, there were significant trends between lower cycle-threshold values indicating higher viral genomic loads, and higher aORs for CAP. The population-attributable fraction estimates of RSV, HMPV, human parainfluenza virus, influenza virus and M. pneumoniae were 33.3% (32.2-34.5), 11.2% (10.5-11.9), 3.7% (1.0-6.3), 2.3% (1.0-3.6) and 4.2% (4.1-4.4), respectively. CONCLUSIONS: RSV, HMPV and M. pneumoniae were most strongly related to pediatric CAP and accounted for half of all cases. There were positive trends between increasing viral genomic loads of RSV and HMPV, and higher odds for CAP.

Kidney biopsy diagnosis in childhood in the Norwegian Kidney Biopsy Registry and the long-term risk of kidney replacement therapy: a 25-year follow-up.

BACKGROUND: There is scarce information on biopsy-verified kidney disease in childhood and its progression to chronic kidney disease stage 5 (CKD 5). This study aims to review biopsy findings in children, and to investigate risk of kidney replacement therapy (KRT). METHODS: We conducted a retrospective long-term follow-up study of children included in the Norwegian Kidney Biopsy Registry (NKBR) and in the Norwegian Renal Registry (NRR) from 1988 to 2021. RESULTS: In total, 575 children with a median (interquartile range, IQR) age of 10.7 (6.1 to 14.1) years were included, and median follow-up time (IQR) after kidney biopsy was 14.3 (range 8.9 to 21.6) years. The most common biopsy diagnoses were minimal change disease (MCD; n = 92), IgA vasculitis nephritis (IgAVN; n = 76), IgA nephropathy (n = 63), and focal and segmental glomerulosclerosis (FSGS; n = 47). In total, 118 (20.5%) of the biopsied children reached CKD 5, median (IQR) time to KRT 2.3 years (7 months to 8.4 years). Most frequently, nephronophthisis (NPHP; n = 16), FSGS (n = 30), IgA nephropathy (n = 9), and membranoproliferative glomerulonephritis (MPGN; n = 9) led to KRT. CONCLUSIONS: The risk of KRT after a kidney biopsy diagnosis is highly dependent on the diagnosis. None of the children with MCD commenced KRT, while 63.8% with FSGS and 100% with NPHP reached KRT. Combining data from kidney biopsy registries with registries on KRT allows for detailed information concerning the risk for later CKD 5 after biopsy-verified kidney disease in childhood. A higher resolution version of the Graphical abstract is available as Supplementary information.

The burden of hospital-attended influenza in Norwegian children.

Background: Norwegian health authorities do not recommend universal pediatric vaccination against seasonal influenza. We aimed to estimate the incidence of influenza by age and underlying medical conditions in hospitalized Norwegian children aged <18 years. Methods: Active surveillance for influenza in children <18 years was implemented in five hospitals during 2015-18. Children with respiratory symptoms and/or fever were prospectively enrolled and tested for influenza. Surveillance data were linked to health registry data to estimate the national burden of influenza in hospitals. Results: In 309 (10%) out of 3,010 hospital contacts, the child tested positive for influenza, corresponding to an average incidence of 0.96 hospital-attended influenza cases per 1,000 children <18 years of age. Children <1 year of age (3.8 per 1,000 children) and children with underlying medical conditions (17 per 1,000 children with bronchopulmonary dysplasia) had the highest average incidence. Among <1 year old children, 3% tested positive for influenza, compared to 25% for children aged 6-17. Few children were vaccinated against influenza. Conclusions: Children <1 year of age and children with underlying medical conditions had a higher incidence of influenza requiring hospital treatment compared to the general population. Effective interventions against seasonal influenza for children in Norway should be considered.

Parechovirus A in Hospitalized Children With Respiratory Tract Infections: A 10-Year-Long Study From Norway.

BACKGROUND: The role of Parechovirus A (PeV-A) in hospitalized children with respiratory tract infections (RTIs) is unclear. We studied the occurrence and impact of PeV-A over 10 years. METHODS: Children from Sør-Trøndelag County, Norway, hospitalized with RTI and a comparison group of asymptomatic children admitted to elective surgery, were prospectively enrolled from 2006 to 2016. Nasopharyngeal aspirates were cultured and analyzed with polymerase chain reaction tests for PeV-A and 19 other pathogens. The cycle threshold levels of PeV-A were reported as measures of viral genomic loads. Parechovirus A-positive samples were genotyped by amplification and sequencing of the VP3/VP1 junction. RESULTS: Parechovirus A was detected in 8.8% (323/3689) patients with RTI and in 10.1% (45/444) of the children in the comparison group (P = .34). Parechovirus A genotyping (n = 188) revealed PeV-A1 (n = 121), PeV-A3 (n = 15), PeV-A5 (n = 6), and PeV-A6 (n = 46). Viral codetections occurred in 95% of patients and in 84% of the children in the comparison group (P = .016). In multivariable logistic regression analysis, RTI was unrelated to PeV-A genomic loads, adjusted for other viruses and covariates. Similar results were found for PeV-A1 and PeV-A6. CONCLUSIONS: Parechovirus A and viral codetections were common in hospitalized children with RTI and asymptomatic children in a comparison group. Our findings suggest that PeV-A has a limited role in hospitalized children with RTI.

A validity study of the rapid emergency Triage and treatment system for children.

BACKGROUND: The Scandinavian Rapid Emergency Triage and Treatment System-pediatric (RETTS-p) is a reliable triage system that includes both assessment of vital parameters and a systematic approach to history and symptoms. In Scandinavia, the system is used in most pediatric emergency departments (PED). We aimed to study the validity of RETTS-p. METHODS: We conducted a study based on triage priority ratings from all children assessed in 2013 and 2014 to the PED at St. Olavs University Hospital Trondheim, Norway. Patients were assigned one of four priority ratings, based on the RETTS-p systematic evaluation of individual disease manifestations and vital parameter measurements. In the absence of a gold-standard for true disease severity, we assessed whether priority ratings were associated with 3 proxy variables: 1) hospitalization to the wards (yes vs. no), 2) length of hospital stay (≤ mean vs. > mean, and 3) referral to pediatric intensive care (yes vs. no). We further compared priority ratings with selected diagnoses and procedure codes at discharge. RESULTS: Six thousand three hundred sixty-eight children were included in the study. All analyses were performed in the entire population and separately in pediatric sub-disciplines, medicine (n = 4741) and surgery (general and neurosurgery) (n = 1306). In the entire population and the sub-disciplines, a high priority rate was significantly associated with hospitalization to wards, a longer hospital stay and referral to the pediatric intensive care unit compared to patients with low priority. We observed a dose-response relationship between increased triage code level and indicators of more severe disease (p-trend < 0.001). For the same three proxy variables, the sensitivity was 54, 61 and 83%, respectively, and the specificity 66, 62 and 57%, respectively. Subgroup analyzes within the most common complaints, demonstrated that more severe conditions were higher prioritized than less severe conditions for both medical and surgical patients. Overall, children with surgical diagnoses attained lower priority ratings than children with medical diagnoses. CONCLUSIONS: RETTS-p priority ratings varies among a broad spectrum of pediatric conditions and mirror medical urgency in both medical and surgical disciplines. RETTS-p is a valid triage system for children as used in a university hospital setting.

Human adenovirus in nasopharyngeal and blood samples from children with and without respiratory tract infections.

BACKGROUND: Human adenovirus (HAdV) is a double-stranded DNA virus associated with respiratory tract infections (RTI) in children. Using polymerase chain reaction (PCR) tests, HAdV often is detected together with other virus species, even in healthy controls. OBJECTIVES: The aim of this study was to compare molecular detection of HAdV with culture, and to examine the associations of various methods to RTI. STUDY DESIGN: Nasopharyngeal aspirates (NPA) were collected from 4319 children admitted with RTI and from 361 controls. The NPAs were examined for 23 viral and bacterial pathogens, using inhouse real-time PCR-assays based on TaqMan probes, in addition to bacterial and viral culture. HAdV concentration was evaluated semi-quantitatively from the Ct-value and quantitatively by use of ADENOVIRUS R-gene®. RESULTS: HAdV-DNA was detected in 6.1% patient samples and in 10.5% controls (p< 0.001). Compared to controls, patients had an OR of 3.8 (95% CI 1.4-10.3) for mono-detection of HAdV DNA, and an OR of 5.1 (95% CI 2.0-13.4) for HAdV-positive samples grew adenovirus by culture. HAdV DNA loads from children with RTI consisted of two clusters: one cluster with high viral loads (Ct < 30 and >106 copies/ml) and one cluster with low viral loads, whereas among the controls, nearly all had low viral loads (OR 7.8, 95% CI 2.2-27.1). In 61 available plasma samples, 16.4% were positive for HAdV DNA, all were from patients. CONCLUSION: The detection of HAdV DNA per se by qualitative PCR is not useful as a diagnostic test. Detection of HAdV by use of viral culture and a high viral HAdV DNA load are the two methods most strongly associated with RTI in children.

Characterization of signaling pathways regulating the expression of pro-inflammatory long form thymic stromal lymphopoietin upon human metapneumovirus infection.

Thymic stromal lymphopoietin (TSLP) is associated with several allergic diseases including asthma. Two isoforms of TSLP exist in humans, a long form (lfTSLP) and a short form (sfTSLP), displaying distinct immunological functions. Recently, TSLP was found to be upregulated in human airway cells upon human metapneumovirus (hMPV) infection, yet it remains unclear if the two isoforms are regulated differently during hMPV infection. Importantly, the molecular mechanisms underlying hMPV-mediated TSLP induction remain undescribed. In this study, we characterized the expression and regulation of TSLP in hMPV-infected human airway cells. We demonstrated that hMPV strongly induced the expression of pro-inflammatory lfTSLP in human airway epithelial cells and lung fibroblasts. Further, knockdown of pattern recognition receptors retinoic acid-inducible gene I (RIG-I) or Toll-like receptor 3 (TLR3), as well as downstream signal transducers, abrogated hMPV-mediated lfTSLP induction. Importantly, silencing of TANK-binding kinase 1 (TBK1) also impaired hMPV-mediated lfTSLP induction, which could be attributed to compromised NF-κB activation. Overall, these results suggest that TBK1 may be instrumental for hMPV-mediated activation of NF-κB downstream RIG-I and TLR3, leading to a specific induction of lfTSLP in hMPV-infected human airway cells.

Development of cystic periventricular leukomalacia in newborn infants after rotavirus infection.

We describe 5 preterm and 3 term infants who presented with seizures during rotavirus infection within 6 weeks after birth. Six of these infants developed late-onset cystic periventricular leukomalacia. Four of the preterm infants had neurodevelopmental delay, and 4 (near) term infants had normal early outcome.

Human bocavirus in children: mono-detection, high viral load and viraemia are associated with respiratory tract infection.

BACKGROUND AND OBJECTIVES: Human bocavirus 1 (HBoV1) has recently been detected in children with respiratory tract infections (RTI). In order to study whether HBoV1 can cause RTI, we investigated its presence in children with upper RTI (URTI), lower RTI (LRTI) and a control group of children without RTI. STUDY DESIGN: Nasopharyngeal aspirates (NPA) and blood samples were collected from children admitted to hospital with RTI from 6 June 2007 to 28 February 2009 (n=1154), and from children admitted for elective surgery who had no RTI (n=162). Using polymerase chain reaction (PCR), the NPAs were examined for 17 infectious agents including HBoV1. Blood samples were tested with HBoV1-PCR only. RESULTS: HBoV1 was detected in NPAs from 10% of patients and 17% of controls. Adjusted for age, gender and the presence of other viruses, HBoV1 was not associated with RTI. In the HBoV1-positive NPAs, at least one other virus was detected in 75% and the virus appeared alone in 25%. Adjusted for age and gender, the detection of HBoV1 as the sole virus was associated with RTI, but not with LRTI. Viraemia was found only in children with RTI. The study showed that it was associated with RTI and LRTI. A high HBoV1-load was associated with LRTI, but not with RTI. No interactions between HBoV1 and other infectious agents were found. CONCLUSIONS: Our data support the hypothesis that HBoV1 causes RTI in children, because detection of HBoV1 alone, viraemia and high viral load are associated with RTI and/or LRTI in this age group. However, HBoV1 is common in healthy children.

Radiation dose and relapse are predictors for development of second malignant solid tumors after cancer in childhood and adolescence: a population-based case-control study in the five Nordic countries.

The aim of the study was to assess the risk with radiation therapy and chemotherapy of the first cancer in childhood and adolescence for the development of a second malignant solid tumor (SMST). Also, the role of relapse of the primary tumor was studied. It is a nested case-control study within a Nordic cohort of patients less than 20 years of age at first diagnosis 1960-1987. SMSTs were diagnosed in 1960-1991. There were 196 cases and 567 controls. The risk was increased only for radiotherapy given more than five years before the development of the SMST. A significantly increased relative risk of 1.8 was found already at doses below 1 Gy. The risk increased rapidly up to a maximum of 18.3 for doses above 30 Gy. Chemotherapy alone did not increase the risk to develop an SMST. However, in combination with radiotherapy, chemotherapy showed a significant potentiating effect. Relapse was found to be an independent risk factor for development of an SMST, with a higher relative risk for females than for males.

Outbreak of human metapneumovirus infection in norwegian children.

INTRODUCTION: Human metapneumovirus (hMPV) was recently discovered in children with acute respiratory tract infection. We have studied the occurrence of hMPV and report clinical findings of 50 hMPV-infected children who were hospitalized during an outbreak in Norway. METHODS AND POPULATION: During 5 months from November 15, 2002 to April 14, 2003 we collected nasopharyngeal aspirate specimens from 236 children admitted because of respiratory tract infection (RTI). Samples were analyzed for influenza virus A/B, parainfluenza viruses 1, 2 and 3 and respiratory syncytial virus by direct immunofluorescence assays and cell culture. Rhinovirus, adenovirus and hMPV were identified by polymerase chain reaction. RESULTS: Human metapneumovirus was identified in 50 of 236 children (21%). Most (41 of 50) hMPV-infected children were hospitalized between November 15 and January 15, and during these 2 months hMPV was the most common isolate (41 of 72 isolates; 57%). Respiratory syncytial virus was identified in 36 children (15%), among whom 34 were admitted after the hMPV outbreak. The median age of hMPV-infected children was 12 months (range, 1 to 115 months), and one-half of the children had an underlying chronic disease. The most common symptoms were fever (86%), cough (90%), dyspnea (80%), wheezing (56%), rhinorrhea (44%), anorexia (48%) and vomiting (36%). Eight (16%) had an upper respiratory tract infection (rhinopharyngitis, n = 6; laryngitis, n = 2), 24 (48%) had bronchiolitis and 17 (34%) had pneumonia. Two-thirds with a lower RTI also had signs of upper RTI. Fourteen (28%) children needed supplemental oxygen, 1 was treated with continuous positive airway pressure and 2 were ventilated mechanically. CONCLUSION: Human metapneumovirus was the most common virus isolate during the winter season 2002 to 2003 in children hospitalized for respiratory tract infection. Upper respiratory tract infections and mild to severe bronchiolitis were most common, but a relatively high proportion of hospitalized children developed severe pneumonia.

Histologic chorioamnionitis and umbilical serum levels of pro-inflammatory cytokines and cytokine inhibitors.

OBJECTIVE: To study 1. whether leucocyte infiltration in placenta tissues is associated with elevated umbilical serum levels of inflammatory mediators, and 2. whether leucocyte infiltration in the presence of neonatal disease is associated with additional increase in mediator levels. SETTING: University hospital. POPULATION: Two groups of women with either normal delivery (n = 82) or delivery complicated by prolonged rupture of the membranes, clinical signs of intrauterine infection or preterm labour (n = 139). METHODS: Umbilical cord blood and placenta tissues were collected after delivery. Placentas were classified as non-inflamed (i.e. without leucocyte infiltration, n = 74), or as mild (n = 84), or severe chorioamnionitis (n = 63). Mediator levels were compared between groups. RESULTS: Severe chorioamnionitis was associated with elevated levels of tumour necrosis factor (TNF)alpha, interleukin (IL)-1beta, IL-6, IL-8, soluble TNF receptor p55 and p75, IL-1 receptor antagonist (IL-IRA), and C-reactive protein compared with non-inflamed placentas (all P < 0.05). No differences were found between mild chorioamnionitis and placentas without infiltration. In all, 49 babies suffered from various perinatal diseases, such as clinical sepsis, respiratory distress and asphyxia, and 172 were healthy. Severe chorioamnionitis with subsequent neonatal disease (n = 23) had higher levels of all mediators, except IL-1beta and C-reactive protein, than severe chorioamnionitis without neonatal disease (n = 40, all P < 0.01), but severe chorioamnionitis was also accompanied by a more intense and widely distributed leucocyte infiltration when neonatal disease developed. CONCLUSION: High grade leucocyte infiltration in placenta tissues is associated with elevated levels of TNFalpha, IL-1beta, IL-6, IL-8, p55, p75, IL-IRA and C-reactive protein in umbilical serum. The presence of neonatal disease is associated with advanced chorioamnionitis, and highly elevated levels of both pro- and antiinflammatory mediators in umbilical serum.