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The mechanism by which cranberry-lingonberry juice (CLJ) prevents urinary tract infections (UTI) in children is unknown. We hypothesized that it alters the composition of the gut or urinary microbiome.Altogether 113 children with UTIs were randomly allocated to drink either CLJ or a placebo juice for 6 months. We collected urinary samples at 3 months and fecal samples at 3, 6 and 12 months and used next generation sequencing of the bacterial 16S gene.The children who consumed CLJ had a lower abundance of Proteobacteria (P=0.03) and a higher abundance of Firmicutes phylum (P=0.04) in their urinary microbiome at 3 months than did those in the placebo group. The abundance of Escherichia coli in the urinary microbiome was 6 % in the CLJ group and 13 % in the placebo group (P=0.42). In the gut microbiome the abundance of Actinobacteria at 3 and 12 months was higher in the children receiving CLJ. The diversity of the urinary and gut microbiome did not differ between the groups.The children drinking CLJ had a different urinary and gut microbiome from those receiving a placebo juice. A healthy urinary microbiome may be important in preventing UTIs in children.

Background Bacterial extracellular vesicles (EVs) are more likely to cross biological barriers than whole-cell bacteria. We previously observed EV-sized particles by electron microscopy in the first-pass meconium of newborn infants. We hypothesized that EVs may be of bacterial origin and represent a novel entity in the human microbiome during fetal and perinatal periods. Methods We extracted EVs from first-pass meconium samples of 17 newborn infants and performed bacterial 16S rRNA gene sequencing of the vesicles. We compared the EV content from the meconium samples of infants based on the delivery mode, and in vaginal delivery samples, based on the usage of intrapartum antibiotics. Results We found bacterial EVs in all first-pass meconium samples. All EV samples had bacterial RNA. Most of the phyla present in the samples were Firmicutes (62%), Actinobacteriota (18%), Proteobacteria (10%), and Bacteroidota (7.3%). The most abundant genera were Streptococcus (21%) and Staphylococcus (17%). The differences between the delivery mode and exposure to antibiotics were not statistically significant. Conclusions Bacterial EVs were present in the first-pass meconium of newborn infants. Bacterial EVs may represent an important novel feature of the gut microbiome during fetal and perinatal periods. Impact We show that bacterial extracellular vesicles are present in the microbiome of first-pass meconium in newborn infants. This is a novel finding. To our knowledge, this is the first study to report the presence of bacterial extracellular vesicles in the gut microbiome during fetal and perinatal periods. This finding is important because bacterial extracellular vesicles are more likely to cross biological barriers than whole-cell bacteria. Thus, the early gut microbiome may potentially interact with the host through bacterial EVs.

Abstract: Rhinovirus is one of the two most common viral agents that cause bronchiolitis in young children. During the first 12 months, it is second to the respiratory syncytial virus, but after 12 months, it begins dominating the statistics. Wheezing and dry cough are typical clinical symptoms indicative of rhinovirus-induced bronchiolitis, although overlap of symptoms with other virus infections is common. Several studies have shown that atopic predisposition and reduced interferon responses increase susceptibility to rhinovirus-induced wheezing. More recent studies have found that certain genetic variations at strong asthma loci also increase susceptibility. Rhinovirus-induced wheezing in the early years of life is known to increase the risk of subsequent asthma development and may be associated with airway remodeling. This risk is increased by aeroallergen sensitization. Currently, there are no clinically approved preventive treatments for asthma. However, studies show promising results indicating that children with rhinovirus-affected first-time wheezing respond to bronchodilators in terms of less short-term symptoms and that controlling airway inflammatory responses with anti-inflammatory medication may markedly decrease asthma development. Also, enhancing resistance to respiratory viruses has been a topic of discussion. Primary and secondary prevention strategies are being developed with the aim of decreasing the incidence of asthma. Here, we review the current knowledge on rhinovirus-induced early wheezing as a risk factor for subsequent asthma development and related asthma-prevention strategies.

Objective: To evaluate parents’ ability to accurately assess their child’s heart and respiratory rates (RRs) in the context of potential utility for telehealth visits. Study design: In this controlled study of 203 child-parent pairs, parents measured their child’s heart rate (HR) using 4 methods: palpation, auscultation, and 2 photoplethysmographic smartphone applications. Parents measured RR by inspecting the child and tapping the smartphone application. The gold standards were electrocardiogram for the HR and the child’s breaths measured by a health care professional for 60 seconds for the RR. We plotted the measurements using a Bland-Altman plot with 95% limits of agreement. Results: Parents underestimated HR by palpation with a calculated bias of −18 beats per minute (bpm) (SD, 19), with limits of agreement ranging from −56 to 19 bpm. Parents overestimated and underestimated HR by auscultation with limits of agreement ranging from −53 to 46 bpm. Smartphone applications did not improve the accuracy of measurements. The accuracy of parental RR measurements was low. For young children, bias was −0.8 breaths per minute (brpm) (SD, 9.8) with limits of agreement from −20 to 19 brpm, and for older children, bias was 0.9 brpm (SD 7.4) with limits of agreement from 6 to 15 brpm. The sensitivity of parental subjective opinion to recognize accelerated RR was 37% (95% CI, 25%-51%). Conclusion: Parents were not able to assess their child’s RR or HR accurately. Digital remote assessment of children should not rely on parental measurements of vital signs.

To investigate the social burden of nasopharyngeal detection of various respiratory viruses and the co-detection of viral and bacterial pathogens.This prospective cohort study included 737 children with a suspected respiratory tract infection or fever in a paediatric emergency department during one epidemiological year (2014-2015) in Finland. Nasopharyngeal swab samples were analysed with multiplex polymerase chain reaction for 16 viruses and 7 respiratory bacteria. Parents filled out a questionnaire regarding child's and parents' absence from day care, school, or work at the time of the visit and 14 days afterward.The length of the children's absence from day care or school, or parental absence from work, did not significantly differ between the detected viral pathogens. Co-detection of any respiratory virus and Streptococcus pneumoniae or Haemophilus influenzae in the nasopharynx were associated with a 2.5-day (95% CI of the difference: 0.71 to 4.3) and 3.0-day (95% CI: 0.35 to 5.7) longer parental absence from work, respectively, compared with the detection of viruses alone when adjusted for age.Nasopharyngeal detection of S. pneumoniae or H. influenzae was associated with an increase in the length of parental absence from work when compared with the detection of virus alone.

Background The gut mycobiome may have important effects on health. Yet, there is limited data on the mycobiome. Previously, we have shown that antibiotic exposure at birth markedly alters the gut bacteriome in children. As fungi and bacteria may have important interactions in the gut microbiome, we hypothesized that perinatal antibiotics may influence the composition of the gut mycobiome. Methods For the study, 434 fecal samples were collected at birth, 6 months, and 18 months of age. We extracted DNA from samples using DNeasy PowerSoil Pro kit. We sequenced the ITS2 gene and analyzed the results using QIIME2. The taxonomy was assigned using UNITE database. Results At birth, newborn infants had a low-biomass gut mycobiome, which developed over time until the age of 18 months. At the genus level, there was a transition from Candida to Trichosporon and Saccharomyces at 6 and 18 months respectively. Unidentified fungi were found in greater numbers in 18-month stool samples than in earlier samples. Alpha and beta diversity analyses showed statistically significant differences depending on the age of infants. Both delivery mode and intrapartum antibiotics were associated with significant differences in the gut mycobiome composition. Infants born vaginally had mycobiome with abundant Candida at birth and their mycobiome progressed towards composition dominated by Trichosporon and Saccharomyces. Samples from infants born via C-section had more Malassezia, Hyalotiella and Saccharomyces. Vaginally delivered infants exposed to antibiotics at birth had more Candida sp. in the gut mycobiome than those unexposed to antibiotics. By 18 months of age, half of the fungi in no intrapartum antibiotic group were unidentified fungi, but more than half of the fungi in the intrapartum antibiotic group were of genus Trichosporon.Figure 1.Taxonomic figures of each sample type. Taxa have been drawn from phylum (innermost level) to species (outermost level). Figure 2. Taxonomic figures of each sample type are based on the delivery mode. Taxa have been drawn from phylum (innermost level) to species (outermost level). Figure 3. Taxonomic figures of each vaginal delivery sample are based on the usage of intrapartum antibiotics. Taxa have been drawn from phylum (innermost level) to species (outermost level). Conclusion In this prospective cohort study, the gut mycobiome composition of newborn infants and young children was markedly influenced both by delivery mode and exposure to antibiotics at birth. The effects were observed from birth until 18 months of age. Disclosures All Authors: No reported disclosures.

To investigate duration of clinical symptoms associated with various respiratory viruses and with the co-detection of respiratory viral and bacterial pathogens.This prospective cohort study included 737 acutely ill children treated in a paediatric emergency department prior to the COVID-19 pandemic. Nasal swab samples were analysed with multiplex PCR panels for 16 viral and 7 bacterial respiratory pathogens. Parents filled in a questionnaire about the symptoms at the time of the visit and 14 days afterwards.Persistent symptoms 2 weeks after the onset of acute illness were common: 32% of the patients with a coronavirus 229 E, NL63 or OC43 finding, 31% of those with human metapneumovirus and 25% of those with rhinovirus reported ongoing symptoms. At least one symptom lasting more than 4 weeks was observed in 3-4% of the children. Children with viral and bacterial co-detection had a longer duration of fever than those with only viral detection (3.3 days [SD 2.8] vs. 1.6 days [SD 2.4], p 0.001).Symptoms lasting for more than 2 to 4 weeks appear to be relatively frequent in all respiratory viral infections in children. Viral and bacterial co-detection may increase the duration of illness.

ImportanceAlthough topical antibiotics are often prescribed for treating acute infective conjunctivitis in children, their efficacy is uncertain.ObjectiveTo assess the efficacy of topical antibiotic therapy for acute infective conjunctivitis.Design, Setting, and ParticipantsA randomized clinical trial was conducted in primary health care in Oulu, Finland, from October 15, 2014, to February 7, 2020. Children aged 6 months to 7 years with acute infective conjunctivitis were eligible for enrollment. The participants were followed up for 14 days. A subsequent meta-analysis included the present trial and 3 previous randomized clinical trials enrolling pediatric patients aged 1 month to 18 years with acute infective conjunctivitis.InterventionsParticipants in the present randomized clinical trial were randomized to moxifloxacin eye drops, placebo eye drops, or no intervention.Main Outcomes and MeasuresThe primary outcome in the present randomized clinical trial was time to clinical cure (in days); in the meta-analysis, the primary outcome was the proportion of participants with conjunctival symptoms on days 3 to 6.ResultsThe randomized clinical trial included 88 participants (46 [52%] girls), of whom 30 were randomized to moxifloxacin eye drops (mean [SD] age, 2.8 [1.6] years), 27 to placebo eye drops (mean [SD], age 3.0 [1.3] years), and 31 to no intervention (mean [SD] age, 3.2 [1.8] years). The time to clinical cure was significantly shorter in the moxifloxacin eye drop group than in the no intervention group (3.8 vs 5.7 days; difference, −1.9 days; 95% CI, −3.7 to −0.1 days; P = .04), while in the survival analysis both moxifloxacin and placebo eye drops significantly shortened the time to clinical cure relative to no intervention. In the meta-analysis, a total of 584 children were randomized (300 to topical antibiotics and 284 to a placebo), and the use of topical antibiotics was associated with a significant reduction in the proportion of children who had symptoms of conjunctivitis on days 3 to 6 compared with placebo eye drops (odds ratio, 0.59; 95% CI, 0.39 to 0.91).Conclusions and RelevanceIn this randomized clinical trial and systematic review and meta-analysis, topical antibiotics were associated with significantly shorter durations of conjunctival symptoms in children with acute infective conjunctivitis.Trial RegistrationClinicalTrialsRegister.eu Identifier: 2013-005623-16

Background Hypotonic fluids have been associated with hospital-acquired hyponatremia. The incidence of life-threatening severe hyponatremia associated with hypotonic fluids has not been evaluated. Methods This was a population-based cohort study of 46,518 acutely ill children 15 years of age or under who visited the pediatric emergency department (ED) at Oulu University Hospital, Finland, between 2007 and 2017. We retrieved all electrolyte measurements from the comprehensive electronic laboratory system and reviewed medical records for all patients with severe hyponatremia. Results The overall occurrence of severe hyponatremia (serum sodium Conclusion In this register-based cohort study of children presenting to the ED, severe hyponatremia developed in one of 998 acutely ill children receiving moderately hypotonic fluid therapy. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

Importance: Corticosteroids administered to women at risk of imminent preterm birth is one of the most effective ways to improve the prognosis of infants born preterm. Scant data about long-term neurodevelopmental and neurosensory outcomes among the treatment-exposed children are mixed, suggesting that not all domains of neurodevelopmental and neurosensory function may be equally affected. Moreover, the long-term outcomes may vary according to whether the treatment-exposed children are being born preterm (

Our aim was to synthesize the published literature on factors that potentially affect the delivery of bronchodilators using valved holding chambers (VHC) in preschool children. We also aimed to identify those attributes that are not yet incorporated or clearly stated in the guidelines and those topics that are still lacking sufficient data. There is strong evidence supporting several recommendations in current guidelines. Based on present knowledge, bronchodilators should be delivered by VHC administering each puff separately. Face mask should be omitted as soon as the child can hold the mouthpiece of the VHC tightly between the lips and teeth. Based on the review, we suggest adding a specific note to current guidelines about the effect of chamber volume and the impact of co-operation during drug administration. Calming the child and securing a tight face-to-mask seal is critical for successful drug delivery. There is not enough evidence to make specific recommendations on the most reliable VHC and face mask for children. There is an urgent need for studies that evaluate and compare the effectiveness of VHCs in various clinical settings in wide age-groups and respiratory patterns. In addition, there is insufficient data on ideal chamber volume, material, and effective antistatic treatment. What is Known:• Valved holding chambers (VHC) should not be considered interchangeable when used with pressurized metered dose inhalers (pMDI).• Drug delivery is influenced by VHC volume, aerodynamic and electrostatic properties; mask fit; respiratory pattern and co-operation during inhalation; and the number of puffs actuated.What is New:• The impact of co-operation, VHC volume, and good mask-to-face fit during drug inhalation is not stressed enough in the guidelines.• Studies are urgently needed to evaluate the effectiveness of different VHCs in various clinical settings focusing on VHC electrostatic properties, respiratory patters, face masks, and ideal pMDI+VHC combinations.

Background Intrapartum antibiotic prophylaxis (IAP) is widely used, but the evidence of the long-term effects on the gut microbiota and subsequent health of children is limited. Here, we compared the impacts of perinatal antibiotic exposure and later courses of antibiotic courses on gut microbiota. Methods This was a prospective, controlled cohort study among 100 vaginally delivered infants with different perinatal antibiotic exposures: control (27), IAP (27), postnatal antibiotics (24), and IAP and postnatal antibiotics (22). At 1 year of age, we performed next-generation sequencing of the bacterial 16S ribosomal RNA gene of fecal samples. Results Exposure to the perinatal antibiotics had a clear impact on the gut microbiota. The abundance of the Bacteroidetes phylum was significantly higher in the control group, whereas the relative abundance of Escherichia coli was significantly lower in the control group. The impact of the perinatal antibiotics on the gut microbiota composition was greater than exposure to later courses of antibiotics (28% of participants). Conclusions Perinatal antibiotic exposure had a marked impact on the gut microbiota at the age of 1 year. The timing of the antibiotic exposure appears to be the critical factor for the changes observed in the gut microbiota. Impact Infants are commonly exposed to IAP and postnatal antibiotics, and later to courses of antibiotics during the first year of life. Perinatal antibiotics have been associated with an altered gut microbiota during the first months of life, whereas the evidence regarding the long-term impact is more limited. Perinatal antibiotic exposure had a marked impact on the infant’s gut microbiota at 1 year of age. Impact of the perinatal antibiotics on the gut microbiota composition was greater than that of the later courses of antibiotics at the age of 1 year.

Antimicrobial resistance (AMR) is a major global public health problem. Human gut microbiome plays an important role in modulating AMR. On one hand, the microbiome itself can serve as a reservoir of AMR genes, i.e. resistome. On the other hand, the microbiome performs colonization resistance, preventing invasive microbes from colonizing the gastrointestinal tract. In this study, we investigated how antibiotic treatment affects the resistome and colonization resistance of the gut microbiome in children receiving amoxicillin, amoxicillin-clavulanate, or no treatment for acute otitis media in a randomized clinical trial. Fecal samples from children receiving an antibiotic or no treatment before and after the treatment were analyzed using deep metagenomic sequencing. We used a flow cytometry-based approach to quantify the bacterial load in the fecal samples. Both metagenomic sequencing-based relative abundance and flow cytometry-based absolute abundance of the microbial species were analyzed. We found that the resistome fluctuated over time and in a small fraction (∼10%) of subjects, AMR genes increased rapidly due to colonization by AMR species, even in the control group without any antibiotic treatment. Amoxicillin significantly increased the risk for invasive species, especially pathogenic species carrying AMR genes, to colonize the gut. We also found that children lacking Blautia, Ruminococcus, Faecalibacterium, Roseburia, or Faecalitalea were more vulnerable to colonization by invasive AMR species in their gut microbiome.

Aim: The aim was to evaluate the incidence, hospitalisations and deaths in acutely ill children with dysnatraemias. Methods: This was a register-based cohort study of 46 518 acutely ill children aged

Objectives Inappropriate use of antibiotics is associated with development of antimicrobial resistance. In respiratory infections it is often difficult to differentiate between viral and bacterial infections, and empirical treatment is common. Enhanced viral testing is expected to clarify clinical decision-making and reduce the prescription of antibacterial agents, but the impact of such information on patient care is unclear. Methods We conducted a (1:1) randomized controlled clinical trial involving 998 adults with respiratory symptoms, fever, chest pain or poor general condition in the emergency unit of a tertiary hospital. Multiplex PCR results for 496 patients were available in 24 hours (intervention group) and those for the remaining 502 patients were available in 7 days (control group). Our primary outcome measures were the duration of hospitalization and the consumption of antibiotics within 30 days of enrolment. Results In all, 841 of 998 (84%) patients had respiratory symptoms at study entry. A respiratory virus was detected in 175 (17.5%). The mean duration of hospitalization was 4.2 days (SD 5.4) in the intervention group and 4.1 days (SD 4.9) in the control group (difference 0.1, 95% CI –0.5 to 0.6, p 0.810). The mean days on antibiotics were 11.3 days (SD 12.6) in the intervention group and 10.4 days (SD 11.4) in the control group (difference 0.9, 95% CI –0.6 to 2.4, p 0.235). Conclusions Multiplex PCR testing for respiratory viruses with results available within 24 hours did not reduce the consumption of bacterial antibiotics or the length of hospital stay in adults presenting with respiratory symptoms, fever, chest pain or reduced general condition in acute care.

Recent studies have shown a diverse microbiome in the first stool after birth. The clinical significance of the microbiome of the first stool is not known. Infantile colic has earlier been associated with the composition of the intestinal microbiome. We set out to test whether the microbiome of the first stool is associated with subsequent infantile colic in a prospective, population-based cohort study of 212 consecutive newborn infants. We used next-generation sequencing of the bacterial 16S rRNA gene. The newborns who later developed infantile colic (n = 19) had a lower relative abundance of the genus Lactobacillus and the phylum Firmicutes in the first stool than those who remained healthy (n = 139). By using all microbiome data, random forest algorithm classified newborn with subsequent colic and those who remained healthy with area under the curve of 0.66 (SD 0.03) as compared to that of shuffled samples (P value

Some cohort studies have suggested that gut microbiota composition is associated with allergic diseases in children. The microbiota of the first-pass meconium, which forms before birth, represents the first gut microbiota that is easily available for research and little is known about any relationship with allergic disease development.We investigated whether the bacterial composition of the first-pass meconium is associated with the development of allergic diseases before 4 years of age.Prospective birth cohort study. Bacterial composition of first-pass meconium was analysed using bacterial 16S rRNA gene amplicon sequencing. Atopic and allergic diseases were evaluated via online survey or telephone to age 4 years, based on the International Study of Asthma and Allergies in Childhood questionnaire.During a 6-week period in 2014, 312 children were born at the Central Finland Central Hospital. Meconium was collected from 212 at a mean of 8-hour age. Outcome data at 4 years were available for 177 (83%) children, and 159 of these had sufficient amplification of bacterial DNA in meconium. Meconium microbiota composition, including diversity indices and relative abundances of the main phyla and genera, was not associated with subsequent atopic eczema, wheezing or cow's milk allergy. Principal components analysis did not identify any clustering of the meconium microbiomes of children with respect to wheezing or cow's milk allergy.We found no evidence that gut microbiota composition of first-pass meconium is associated with atopic manifestations to age 4 years. However, larger studies are needed to fully exclude a relationship.

Importance: Limited data are available on the clinical impact of multiplex polymerase chain reaction (PCR) point-of-care testing for respiratory pathogens in acutely ill children. Objective: To evaluate the effect of multiplex PCR point-of-care testing for respiratory pathogens on antibiotic use in acutely ill children. Design, Setting, and Participants: This unblinded, randomized clinical trial was conducted from May 6, 2019, through March 12, 2020. The participants were followed up until hospitalization or discharge from the emergency department (ED) for primary outcome. The study was conducted at the pediatric ED of Oulu University Hospital, Finland. Eligible study participants were children aged 0 to 17 years with fever and/or any respiratory signs or symptoms. Children with underlying medical conditions were included. The statistical analyses were performed between August 11, 2020, and September 14, 2021. Interventions: The participants were randomly assigned in a 2:1 ratio either to undergo multiplex PCR point-of-care testing (18 respiratory viruses and 3 bacteria with results ready within 70 minutes) upon arrival at the ED or to receive routine care. Main Outcomes and Measures: The primary outcome was the proportion of children receiving antibiotic therapy. The secondary outcomes were the numbers of diagnostic tests and radiographic imaging procedures performed and costs. Results: A total of 1417 children were assessed for eligibility. After exclusions, 1243 children (692 boys [56%]) were randomly allocated to either the intervention (829 children) or control (414 children) group. The mean (SD) age of the participants was 3.0 (3.6) years in the intervention group (median [IQR], 1.7 [0.4–4.1] years) and 3.0 (3.5) years (median [IQR], 1.9 [0.4–4.1] years) in the control group. Multiplex PCR point-of-care testing for respiratory pathogens did not reduce the overall prescribing of antibiotics in the emergency department (226 children [27.3%] in the intervention group vs 118 children [28.5%] in the control group; risk ratio, 0.96; 95% CI, 0.79–1.16). Targeted antibiotic therapy was started in 12 children (1.4%) tested with point-of-care multiplex PCR and 2 children (0.5%) in the control group (risk ratio, 3.0; 95% CI, 0.76–11.9). The numbers of diagnostic tests did not differ between the groups, nor did the costs. Conclusions and Relevance: In this randomized clinical trial, point-of-care testing for respiratory pathogens did not reduce the use of antibiotics at the pediatric ED. Testing for respiratory pathogens appears to have a limited impact on clinical decision-making for acutely ill children. Trial Registration: ClinicalTrials.gov Identifier: NCT03932942

Aim: We investigated whether the ongoing COVID-19 pandemic was associated with the occurrence of Kawasaki disease or with multi-inflammatory syndrome in children (MIS-C). Methods: This national Finnish register-based study was based on laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, MIS-C and Kawasaki disease cases. We performed a time series analysis on the occurrence of Kawasaki disease in 2016–2020. Results: In 2020, there were 5170 laboratory-confirmed COVID-19 cases in children under 18 years of age and five fulfilled the MIS-C case definition. The occurrence of MIS-C was 0.97 per 1000 (95% confidence interval: 0.31-2.26) laboratory-confirmed SARS-CoV-2 infections in children. Our time series analysis showed that Kawasaki disease cases decreased during the COVID-19 pandemic. The seasonally adjusted incidence rate ratio was 0.49 (95% confidence interval: 0.32-0.74) when it was compared to pre-pandemic levels. This coincided with a reduced occurrence of respiratory infections, due to social distancing in the population. Conclusion: This nationwide register-based study found that MIS-C was a rare complication of the SARS-CoV-2 infection. The occurrence of Kawasaki disease and respiratory infections decreased during the pandemic. This suggests that transmissible microbes may play an important role in Kawasaki disease and social distancing may have a protective effect. publishedVersion

Objectives/hypothesis Tonsillectomy is an effective treatment for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, but the role of adenoidectomy, as well as later tonsillar regrowth, is unclear. To find out if the volume of lymphoid tissue is pivotal to the efficacy, we analyzed the association between the relapse of the symptoms of PFAPA syndrome and regrowth of tonsillar tissue after tonsillectomy or adenotonsillectomy. Study design Prospective cohort study of operated PFAPA pateints. Methods We invited all patients that had undergone tonsillectomy or adenotonsillectomy due to PFAPA syndrome at the Oulu University Hospital, Oulu, Finland, between the years 1990 and 2007, at the age of ≤12 years, to a follow-up visit, after an average period of 9.8 years after their diagnoses. Out of the 132 invited, 94 (71%) participated in the follow-up study. Results At the follow-up study visit, 5 (5%) of the 94 PFAPA syndrome cases experienced recurrent fevers. The regrowth of palatine tonsillar tissue was seen in four of them (80%) as compared to 19/89 (21%) of symptom-free patients (P = .006). Two of the patients with clear PFAPA relapse at the time of the study visit were reoperated with clear effect on the symptoms. At the time of the study visit, 59/63 (94%) of the patients who had undergone adenotonsillectomy and 30/31 of the patients (97%) who had undergone tonsillectomy earlier were free of fever flares (P = .99). Conclusion Palatine tonsil regrowth was associated with PFAPA syndrome relapse after tonsillectomy. Reoperation might be a treatment option in these patients. Level of evidence 4 Laryngoscope, 2021.

Aim: Our aim was to survey treatment practices used for preschool children with wheezing in emergency rooms (ER) focussing on inhalation device choice and handling, face mask use, salbutamol dosing and written instructions. We sought to assess whether current protocols are in line with published evidence and guidelines. Methods: This is a cross-sectional survey done in paediatric ER units located in Finnish municipalities with more than 10 000 inhabitants. Results: Of the 100 units contacted, 50% responded. More than 50% of the units used nebulisers. Only 13% of the units administered salbutamol in single puffs. More than 30% of the units lacked criteria on face mask use. Poor co-operation had no effect on the dose of salbutamol in 62% of the units. Ensuring tight mask-to-face seal was included in the training in 20% of the units. A written action plan was provided to the caregivers in 28% of the units. Conclusion: ER treatment guidelines for preschool children with wheezing are poorly endorsed. Research is needed to identify approaches to guideline implementation that are specific for primary care. Clinical research should focus on strengthening recommendations that are currently not embraced. ER treatment protocols need to be updated and adherence to guidelines should be re-evaluated. publishedVersion

Vertical transmission of maternal microbes is a major route for establishing the gut microbiome in newborns. The impact of perinatal antibiotics on vertical transmission of microbes and antimicrobial resistance is not well understood. Using a metagenomic approach, we analyzed the fecal samples from mothers and vaginally delivered infants from a control group (10 pairs) and a treatment group (10 pairs) receiving perinatal antibiotics. Antibiotic-usage had a significant impact on the main source of inoculum in the gut microbiome of newborns. The control group had significantly more species transmitted from mothers to infants (P = .03) than the antibiotic-treated group. Approximately 72% of the gut microbial population of infants at 3–7 days after birth in the control group was transmitted from their mothers, versus only 25% in the antibiotic-treated group. In conclusion, perinatal antibiotics markedly disturbed vertical transmission and changed the source of gut colonization towards horizontal transfer from the environment to the infants., Widely used perinatal antibiotics resulted in a significantly decreased vertical transmission of microbes from mothers to infants’ gastrointestinal tract after birth. Infants treated with antibiotics had more microbes deriving from other environmental sources.

Objective There are limited data on the pathogen-related and host-related factors in the pathogenesis of febrile seizures (FS). We designed a controlled study to compare the role of different respiratory viruses and febrile response in FS. Methods In a prospective cohort study of 1899 pediatric emergency room patients aged 6 months-6 years with a positive respiratory virus multiplex PCR, we identified 225 patients with FSs. We first compared the distribution of respiratory viruses in age-stratified patients with FSs with that in other patients. In an embedded case-control study, we compared the febrile response in patients with FSs with that in the controls matched for age, season and the same respiratory virus. Results The relative risk for FS was the highest for coronavirus OC43, 229E, and NL63 infections [RR: 3.2, 95 % confidence interval (CI): 1.4–7.2) and influenza A and B [RR: 2.5, 95 % CI: 1.4–4.7] as compared to those with other respiratory viral infections. The patients with FSs had a stronger febrile response of 39.2 °C (difference: 0.8 °C, 95 % CI: 0.5–1.2) later during hospitalization after acute care than the controls matched for the same respiratory virus. Conclusions Influenza and coronaviruses caused relatively more FS-related emergency room visits than other respiratory viruses. Furthermore, the febrile response was stronger in the patients with FSs than in the controls matched for the same respiratory virus. The results suggest that the pathomechanism of FSs includes modifiable pathogen-related and host-related factors with possible potential in the prevention of FSs.

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.

BACKGROUND AND OBJECTIVES: Long-term outcomes of urinary tract infection (UTI) in childhood are not well known. Pregnancy may reveal latent renal damage caused by a UTI because of stress on the kidneys. METHODS: Our cohort included adult women with an ultrasonography taken because of a childhood UTI in 1981–1991 (N = 1175). Nine women with a severe congenital kidney malformation or urinary tract obstruction were excluded. Altogether, 260 mothers with a childhood UTI and 500 population-based control mothers without a childhood UTI matched for age, and delivery dates were compared. Our primary end point was the proportion of women with essential or gestational hypertension, preeclampsia, proteinuria, or pyelonephritis during the first pregnancy. RESULTS: The pregnancy outcomes of the women with a UTI in childhood did not differ from those of the controls because 105 of 260 (40%) patients met the primary end point compared with 204 of 500 (41%) controls (relative risk [RR] 0.99; 95% confidence interval [CI] 0.82 to 1.2; P = .91). Similarly, there were no significant differences between the 2 groups in essential hypertension (RR 1.0; 95% CI 0.65 to 1.6; P = .92), gestational hypertension (RR 0.93; 95% CI 0.74 to 1.2; P = .54), preeclampsia (RR 1.5; 95% CI 0.91 to 2.5; P = .11), proteinuria (RR 1.2; 95% CI 0.81 to 1.8; P = .36) or pyelonephritis (2 controls and none of the patients; P = .55) during the first pregnancy. CONCLUSIONS: Childhood UTIs did not increase the risk of pregnancy-related complications in this controlled population-based study. Thus, UTIs in childhood without severe urinary tract abnormalities appear to have a minimal effect on kidney health in early adulthood.

Background Several reports have revealed that the first-pass meconium hosts a diverse microbiome, but its clinical significance is not known. Objective We designed a prospective population-based cohort study to evaluate whether the meconium microbiome predicts subsequent growth in children. Methods The study comprised 212 consecutive newborns with a meconium sample and a follow-up sample at 1 year of age. Trained nurses measured the children for weight and length using standardized techniques. We used next-generation sequencing of bacterial 16S rRNA gene and machine-learning approach for the analysis. Results The children with overweight at 3 years of age differed in their meconium microbiome from those with normal weight, having a higher proportion of Bacteroidetes phylum (29% vs 15%, P = .013). Using the machine-learning approach, the gut microbiome at birth predicted subsequent overweight with area under the curve 0.70 (SD 0.04). A lower proportion of Staphylococcus at birth was associated with greater length/height at 1 year (s = -.68, P = .029) and 2 years of age (β = -.74, P = .030). Conclusions The microbiome of the first-pass meconium predicted subsequent overweight at the age of 3 years. The association between the gut microbiome and overweight appears to start already during pregnancy and at birth.

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.

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.

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. 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. 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. 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.