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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.

The purpose of this study is to assess whether pacifier use is associated with breastfeeding success in term and preterm newborns and whether it influences hospitalization time in preterm newborns. Four databases were searched for randomized controlled trials (RCTs), and a systematic review and meta-analysis were conducted. The risk of bias and evidence quality, according to the GRADE methodology, were analyzed. Risk ratios with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) for continuous outcomes were used. The random effect model was used if heterogeneity was high (I2 over 40%). We screened 772 abstracts, assessed 44 full texts, and included 10 studies, of which 5 focused on term and 5 on preterm newborns. There were a few concerns about the risk of bias in 9 of the 10 studies. Breastfeeding rates were analyzed at 2, 3, 4, and 6 months, and the success rates were similar between the restricted and free pacifier use groups (evidence quality was moderate to high). In preterm neonates, the use of a pacifier shortened the duration of hospitalization by 7 days (MD 7.23, CI 3.98–10.48) and the time from gavage to total oral feeding by more than 3 days (MD 3.21 days, CI 1.19–5.24) (evidence quality was ranked as moderate). Conclusions: Based on our meta-analysis, pacifier use should not be restricted in term newborns, as it is not associated with lower breastfeeding success rates. Furthermore, introducing pacifiers to preterm newborns should be considered, as it seems to shorten the time to discharge as well as the transition time from gavage to total oral feeding. What is Known:• Observational studies show that infants who use a pacifier are weaned from breastfeeding earlier.• Previous randomized studies have not presented such results, and there have been no differences in the successful breastfeeding rates regardless of the use of pacifier. What is New:• Term and preterm newborns do not have worse breastfeeding outcomes if a pacifier is introduced to them, and additionally preterm newborns have shorter hospitalization times.• The decision to offer a pacifier should depend on the caregivers instead of hospital policy or staff recommendation, as there is no evidence to support the prohibition or restriction.

Social restrictions interrupted the normal respiratory virus circulation in Spring 2020. This report describes virus circulation in the pediatric population before and after the restrictions ended in Finland in September 2021. ​​​​​​We used data from the Finnish Infectious Disease Register. Nationwide influenza A and B, rhinovirus, severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), and respiratory syncytial virus (RSV) findings from January 2018 to December 2021. Age stratified (0–4, 5–9, and 10–14 years) weekly incidences per 100 000 children were calculated. ​School and day-care closures interrupted completely the circulation of all other respiratory viruses than rhinovirus in spring 2020. After restrictions were relaxed in September 2021, SARS-Cov-2 detections increased majorly. We observed high RSV season atypically early. SARS-Cov-2 was detected in older children whereas RSV season peaked especially among children aged under 5. Influenza seemed to return to normal circulation. ​In conclusion, we report that the ending of social restrictions in September 2021 led to an increase in SARS-Cov-2 detections and high epidemic peaks of RSV and parainfluenza in atypical timing in children. Our results highlight the importance of continuous pathogen surveillance during the pandemic, as atypical surges of non-COVID-19 respiratory viruses were observed. publishedVersion

Bronchiolitis is common reason for infant hospitalization. The aim of our systematic review and meta-analysis was to evaluate helium-oxygen (heliox) in bronchiolitis.We screened 463 studies, assessed 22 of them, and included six randomized controlled trials. Primary outcomes were the need for continuous positive airway pressure (CPAP) or intubation, hospitalization duration, and change in the modified Woods Clinical Asthma Scale (M-WCAS). We calculated mean differences with 95% confidence intervals (CIs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes.Six studies (five double- and one single-blinded) with 560 infants were included. The risk of bias was high in one, moderate in four, and low in one. The RR for the need for CPAP (three studies) was 0.87 (CI: 0.56-1.35), and for intubation (four studies) was 1.39 (CI: 0.53-3.63), heliox compared to air-oxygen. The hospital stay (four studies) was 0.25 days longer (CI: -0.22 to 0.71) in the heliox group. The mean decrease in M-WCAS from the baseline (three studies) was 1.90 points (CI: 1.46-2.34) greater in the heliox group.We found low-quality evidence that heliox does not reduce the need for CPAP, intubation, or length of hospitalization for bronchiolitis. Based on the M-WCAS scores, heliox seems to relieve respiratory distress symptoms rapidly after its initiation. The included studies had high heterogeneity in their methods and included relatively mild cases of bronchiolitis. A larger randomized controlled trial with more severe cases of bronchiolitis with enough power to analyze the need for intubation is needed in the future.

Social restrictions interrupted the circulation of common respiratory viruses among children in spring 2020. In the winter season 2020–2021, only rhinovirus spread in Finland. As the restrictions were ended in September 2021, we saw record high epidemic peak of parainfluenza. Typically, the epidemic peak is in springtime, but now, it started in the early fall 2021. The monthly incidence among children aged 0–4 years (120 per 100,000 children) was six times higher than the second highest reported monthly incidence (21 per 100,000 children) during the last 10 years. Our finding highlights the importance of active surveillance of viral respiratory pathogens during the pandemic. publishedVersion

Background Acute pyelonephritis is a common infection in children that may cause renal scarring. The aim of this systematic review and meta-analysis was to analyse the use of corticosteroid treatment to prevent renal scarring. Methods We searched the PubMED, SCOPUS, Cochrane CENTRAL and Web of Science databases in June 2022 for (corticosteroid* or dexamethasone or prednisolone* or prednisone* or hydrocortisone*) AND pyelonephritis. Randomised controlled trials focusing on children were included. The intervention was corticosteroid treatment with antibiotics compared to antibiotics with or without a placebo. The main outcome was the presence of renal scars on dimercaptosuccinic acid scanning at follow-up. The evidence quality was assessed using the GRADE methodology and risk of bias 2.0 tool. We calculated the risk ratio (RR), absolute risk difference (RD) with 95% confidence intervals (CI) and the number needed to treat (NNT). We applied a fixed effects model due to low heterogeneity. Results We screened 872 abstracts and included five full texts. Renal scarring at follow-up was found in 31/220 (14.1%) patients in the corticosteroid groups and 76/278 (27.3%) in the control groups (RR 0.65, CI 0.44–0.96, RD − 13.2%, NNT 8). The evidence quality was moderate. Two studies reported adverse events with no differences between the groups. The risk of bias analysis showed some concerns in four studies. Conclusion We found moderate quality evidence that adjuvant corticosteroid treatment could prevent renal scarring. Adverse events were insufficiently reported, and more research on their effectiveness and harm is therefore needed before using corticosteroids in clinical settings.

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.

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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 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.

Polymerase chain reaction (PCR)-based diagnostics for Mycoplasma pneumoniae (M. pneumoniae) from the respiratory tract has become widely available, but the interpretation of the results remains unclear. M. pneumoniae has been suggested to cause mainly mild and self-limiting infections or asymptomatic carriage. However, systematic analyses of the association between PCR results and clinical findings are scarce. This study aimed to clarify the clinical features of PCR-positive M. pneumoniae infections in a hospital setting. We reviewed 103 PCR-positive patients cared for in a university hospital during a 3-year period. Data on age, sex, health condition, acute symptoms, other pathogens found, laboratory and X-ray results and treatments were collected. Over 85% of the patients had a triad of typical symptoms: fever, cough and shortness of breath. Symptoms in the upper respiratory tract were rare. In 91% of the cases, M. pneumoniae was the only pathogen found. The highest incidence was found in the age group of 30–40 years, and 68% of the patients did not have any underlying diseases. Most patients were initially empirically treated with beta-lactam antibiotics and needed 2–4 changes in their treatment. Only 6% were discharged without an antibiotic effective against M. pneumoniae. This study shows that M. pneumoniae often led to hospitalisation and that patients needed appropriate antimicrobial treatment to recover. Mixed infections were rare, and situations that could be interpreted as carriage did not occur.

Aim Our aim was to evaluate the impact of the 2014 Finnish Current Care Guidelines for paediatric lower respiratory tract infections (LRTIs), particularly on taking of chest radiographs. Methods This study used official national data and regional (Pirkanmaa) data on children aged 0-16 years who underwent chest radiographs in 2011 and 2015. We also collected data for LRTI diagnoses from local registers, including prescribed antibiotics and taking of chest radiographs. The local cohort comprised children aged 0-15 who presented to the primary care emergency room or to the hospital emergency department (Tampere university hospital) in November-December 2012-2015. Results Chest radiographs for Finnish children aged 0-16 fell from 2011 to 2015: by 15.9% nationally and by 16.9% in Pirkanmaa. When asylum seekers with chest radiographs for tuberculosis screening were excluded, the estimated national reduction was 29.9%. In the local cohort, chest radiographs increased from 82 to 139 (69.5%) between 2012/2013 and 2014/2015 as the occurrence of community-acquired pneumonia (CAP) increased. However, the proportion of patients with CAP who had chest radiograph taken tended to decrease from 84.6% to 71.3% (p = 0.078). Conclusion Decreases in national and regional chest imaging trends were observed after the 2014 guidance for children`s LRTI was introduced.

BACKGROUND: Social distancing measures are used to reduce the spreading of infection. Our aim was to assess the immediate effects of national lockdown orders due to coronavirus disease 2019 (COVID-19) on pediatric emergency room (ER) visits and respiratory tract infections in hospitals and nationwide in Finland. METHODS: This register-based study used hospital patient information systems and the Finnish national infectious disease register. The participants were all patients visiting pediatric ER in 2 Finnish hospitals (Kuopio University Hospital, Mikkeli Central Hospital) covering 1/5th of the Finnish children population, 4 weeks before and 4 weeks after the start of the nationwide lockdown on March 16, 2020. Nationwide weekly numbers of influenza (A + B) and respiratory syncytial virus (RSV) in children were assessed from the infectious disease register from 2015 to 2020. RESULTS: A major decrease in the rate of daily median pediatric ER visits was detected in both hospitals in the study during the nationwide lockdown compared with the study period before the lockdown (Mikkeli, 19 vs. 7, P < 0.001; Kuopio, 9 vs. 2,5, P < 0.001). The influenza season was shorter (8 weeks from peak to no cases), and the weekly rate of new cases decreased faster compared with the previous 4 influenza seasons (previously 15-20 weeks from peak to no cases). A similar decrease was also seen in RSV cases. No pediatric cases of COVID-19 were found in participating hospitals during the study period. CONCLUSION: These results strongly suggest that social distancing and other lockdown strategies are effective to slow down the spreading of common respiratory viral diseases and decreasing the need for hospitalization among children.

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.

Social restrictions reduced the rates of respiratory infections in 2020, but studies on the rates of urinary tract infections (UTIs) during lockdown have had conflicting results. This study aimed to report UTI incidence during the first and second waves of COVID-19 pandemic in Finland. We conducted a retrospective register-based cohort study. The whole Finnish pediatric population (children under the age of 15 years, N = 860,000) was included. The yearly and monthly incidences of UTIs per 100,000 children in 2020 were compared to that of three previous years (2017–2019) by incidence rate ratios (IRRs) with 95% confidence intervals (CIs). A total of 10,757 cystitis and 4873 pyelonephritis cases were included. The yearly incidence of cystitis was 12% lower (IRR 0.88, CI 0.83–0.94) among children aged 1–6 in 2020 and 11% (IRR 0.89, CI 0.83–0.95) lower among children aged 7–14 in 2020 compared with previous years. The yearly incidence of pyelonephritis was 16% lower (IRR 0.84, CI 0.76–0.94) among children aged 1–6. No significant decrease were observed among children aged Conclusion: The incidence of cystitis and pyelonephritis during a period of social restrictions was lower than during 2017–2019, especially in children aged 1–6 years. These results raise the possibility of reducing the occurrence of urinary tract infections in children by improving hygiene measures. What is known:• Social restrictions have reduced the rate of common respiratory infections globally.• Previous studies have presented a decreased or unchanged incidence of urinary tract infections during the COVID-19 pandemic. What is new:• During the pandemic, there was a decrease in the incidence of urinary tract infections in Finnish children and the most prominent decrease was in daycare-aged children.• Improved hygiene measures and social restrictions may have influenced the transmission of uropathogens.

Zoonotic infections are difficult to recognize in children. The age distributions and seasonal occurrences of these infections vary substantially, even among those transmitted by the same vectors, and their epidemiology may change over time. The aim was to report the incidences and trends of Borrelia burgdorferi, Puumala virus, Francisella tularensis and tick-borne encephalitis (TBE) virus infections in the pediatric population (age 0-19) of Finland.A nationwide survey based on the National Infectious Disease Register was conducted from 1996 to 2019 and all laboratory-confirmed cases were included. Age-stratified incidences per 100,000 person-years were calculated.Cumulative incidences were B. burgdorferi 11.2, TBE 0.4, Puumala virus 6.4 and F. tularensis 2.5 per 100,000 person-years. An increasing trend in the incidences of B. burgdorferi and TBE was observed. Borrelia expanded geographically northward and inland. Tularemia follows a 2-4-year epidemic cycle and rates are similar across age groups. Puumala incidences are highest in the older children.Borrelia infections increased most rapidly in children 5-9 years of age and overall expanded geographically in Finland. Tularemia epidemic cycles were shorter than those previously reported. These results will help clinicians to identify these infections in different geographic areas and age groups in Finland.

To the Editor,In a recent report in this journal, the lockdown in the Emilia-Romagna Region of Italy in March and April 2020 was found to be associated with a decrease of overrall antibiotic consum...

Background Neonatal hyperbilirubinemia is observed in most newborns, and 5–15% of neonates require phototherapy. Phototherapy is effective but often prolongs hospitalization and has both short-term and potential long-term harms. The aim of this systematic review and meta-analysis was to evaluate the role of ursodeoxycholic acid (UDCA) combined with phototherapy in neonatal hyperbilirubinemia. Methods A literature search was conducted on September 1, 2021; 590 studies were screened, and 17 full texts were assessed by two authors. We included randomized controlled trials with or without placebo intervention. Primary outcomes were changes in total bilirubin levels at 24 hours and phototherapy duration. We calculated mean differences with 95% confidence intervals (CI). Results Six studies with 880 neonates were included. Of these studies, only two used a placebo-controlled double-blinded design. The overall risk of bias was high in one and moderate in four of the included studies. The mean decrease in the total bilirubin level during the first 24 hours was 2.06 mg/dL (95% CI 0.82–3.30; six studies) greater in the UDCA treatment group. The phototherapy duration was 19.7 hours (95% CI 10.4–29.1; five studies) shorter in the UDCA treatment group. Conclusions We found low-quality evidence that UDCA as an adjuvant to phototherapy seems to decrease total bilirubin faster and shorten phototherapy duration compared to standard treatment. Further studies are needed to confirm the efficacy, acute and long-term outcomes, and safety before implementing UDCA as an adjuvant to phototherapy in neonatal hyperbilirubinemia.

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

Aim Nationwide lockdowns and social restrictions during the COVID‐19 pandemic have reduced childhood infections. We assessed how many items of systemic antibiotics and asthma medicines were dispensed to children aged 0−12 years in Finland before and during the pandemic and analysed the reimbursement costs. Methods The data came from the national Finnish register of reimbursable prescriptions, which is maintained by the country's Social Insurance Institution. It included all prescriptions for antibiotics and asthma medicines dispensed to children aged 0−12 years in 2019 and 2020. Prescription rates per 1000 children were calculated for each quarter and compared using rate ratios and 95% confidence intervals (95% CI). Results Overall dispensing for antibiotics decreased by 55.3% and was most prominent for macrolides for children aged 0−5 years (59.6%, 95% CI 60.9%−58.2%). Asthma medicines decreased by 19.8%, and the most prominent reduction was in short‐acting beta‐agonists for children aged 0−5 years (35.2%, 95% CI 36.1%−34.2%). These reduced reimbursement costs by 3.4 million Euros from 2019 to 2020. Conclusion This nationwide study showed that the number of antibiotics and asthma medicines decreased by 59.6% and 19.8% respectively from 2019 to 2020, generating a cost saving of 3.4 million Euros.

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Introduction The aim of this study was to evaluate the effect of increasing screening-to-labor interval on the performance of group B streptococcus (GBS) screening by late-pregnancy enriched culture compared with intrapartum real-time polymerase chain reaction (RT-PCR). Material and methods Group B streptococcus colonization was determined in 2624 women with singleton pregnancies by culture at 35-37 weeks of gestation and at the beginning of labor by culture and RT-PCR from recto-vaginal swab samples. Results Group B streptococcus colonization rates were 29.0% in late-pregnancy culture, 29.7% in intrapartum culture and 28.2% in intrapartum PCR. Intrapartum culture was used as a reference, the late-pregnancy culture had an overall sensitivity of 89.2% (95% CI 88.0%-90.4%) and specificity of 96.5% (95% CI 95.8%-97.2%), and intrapartum PCR had sensitivity of 91.5% (95% CI 90.4%-92.6%) and specificity of 98.5% (95% CI 98.0%-99.0%). However, up to 4 weeks after screening, the sensitivity of late-pregnancy culture was equivalent to or higher than that of RT-PCR. The RT-PCR was invalid in 0.9% of the women. Between late-pregnancy screening and labor, GBS colonization changed from negative to positive in 3.2% and from positive to negative in 2.5% of the women. Conclusions The late-pregnancy enriched culture and intrapartum RT-PCR have comparable sensitivities in the detection of GBS when culture screening is conducted no more than 4 weeks before labor. Late-pregnancy culture sampling should be postponed to at least 37 weeks of gestation.

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.

Objective To assess the impact of social restrictions due to COVID‐19 on the number of tympanostomies and tonsillar surgeries in children. Methods Incidences were calculated per 100 000 children for tonsillar surgery and tympanostomies in 2020 and compared to the mean incidence of referral years 2017 to 2019 by incidence rate ratios (IRR) with 95% confidence intervals (CIs). Median waiting times were also compared. Results Before the lockdown, tonsillar surgery incidence was 33.4/100000 (IRR 1.14, CI 0.76‐1.71) in February 2020. After the lockdown began, the incidence of tonsillar surgery was 1.4/100000 (IRR 0.04, CI 0.01‐0.15) in April. In June, tonsillar operation incidence started to increase (20.4 per 100 000). The incidence of tympanostomies was 81% lower (IRR 0.19, CI 0.09‐0.39) in April 2020 and 61% lower (IRR 0.39, CI 0.22‐0.69) in August 2020 than in 2017‐2019. These incidence rates remained lower all year (December 2020 IRR 0.13, CI 0.05‐0.33). Median waiting time for tonsillar surgery was 3.3 months in 2020 and 1.6 months in 2017 to 2019; P, We assessed the impact of social restrictions due to COVID‐19 on the number of tympanostomies and tonsillar surgeries in children. Our findings suggest that the restrictions against COVID‐19 reduced the incidence rates of tonsil surgery and tympanostomies in children. Also, the lockdown and cancellations of elective operations in spring 2020 led to increased waiting times.

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.