Intrapartum azithromycin to prevent maternal and neonatal sepsis and deaths: A systematic review with meta-analysis.

OBJECTIVES: A systematic review with met-analysis was performed to summarise the evidence on the effect of intrapartum azithromycin on maternal and neonatal infections and deaths. SEARCH STRATEGY: PubMed, Scopus and Web of Science databases were searched in March 2023. SELECTION CRITERIA: Randomised controlled trials comparing intrapartum single-dose of azithromycin with placebo. DATA COLLECTION AND ANALYSIS: Maternal infections, maternal mortality, neonatal sepsis, neonatal mortality. We used the random-effects Mantel-Haenszel method to calculate risk ratios (RR) with 95% confidence intervals (95% CI). We assessed risk of bias of the included studies and estimated the evidence certainty using the GRADE approach. MAIN RESULTS: After screening 410 abstracts, five studies with 44 190 women and 44 565 neonates were included. The risk of bias was low in four and had some concerns in one of the studies. The risk of endometritis was 1.5% in the azithromycin group and 2.3% in the placebo group (RR 0.64, 95% CI 0.55-0.75), and the evidence certainty was high. The respective risk for chorioamnionitis was 0.05% and 0.1% (RR 0.50, 95% CI 0.22-1.18; evidence certainty moderate). The wound infection rate was lower in the azithromycin group (1.6%) than in the placebo group (2.5%), RR 0.52 (95% CI 0.30-0.89; moderate certainty evidence). The maternal sepsis rate was 1.1% in the azithromycin group and 1.7% in the placebo group (RR 0.66, 95% CI 0.56-0.77; evidence certainty high). Mortality rates did not show evidence of a difference (0.09% versus 0.08%; RR 1.26, 95% CI 0.65-2.42; moderate certainty evidence). The neonatal mortality rate was 0.7% in the azithromycin group and 0.8% in the placebo group (RR 0.94, 95% CI 0.76-1.16; moderate certainty evidence). The neonatal sepsis rate was 7.6% in the azithromycin group and 7.4% in the placebo group (RR 1.02, 95% CI 0.96-1.09; moderate certainty evidence). CONCLUSIONS: Intrapartum administration of azithromycin to the mother reduces maternal postpartum infections, including sepsis. Impact on maternal mortality remains undecided. Azithromycin does not reduce neonatal sepsis or mortality rates.

Pneumonia, wheezing and asthma were more common in children after thymectomy due to open-heart surgery.

AIM: This nationwide study evaluated the clinical impact that an early thymectomy, during congenital heart defect (CHD) surgery, had on the health of children and adolescents. METHODS: The subjects were patients aged 1-15 years who had undergone CHD surgery at the University Children's Hospital, Helsinki, where all CHD surgery in Finland is carried out, from 2006 to 2018. The parents or the cases and population-based controls, matched for sex, age and hospital district, completed electronic questionnaires. We excluded those with low birth weights or a known immunodeficiency. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated for prespecified outcomes. RESULTS: We received responses relating to 260/450 (58%) cases and 1403/4500 (31%) controls and excluded 73 cases with persistent cardiac or respiratory complaints after surgery. The CHD group reported more recurrent hospitalisations due to infections (aOR 6.3, 95% CI 3.0-13) than the controls and more pneumonia episodes (aOR 3.5, 95% CI 2.1-5.6), asthma (aOR 2.5, 95% CI 1.5-4.1) and wheezing (aOR 2.1, 95% CI 1.5-2.9). CONCLUSION: Hospitalisation due to infections, pneumonia, wheezing and asthma was more common in children after a thymectomy due to open-heart surgery than population-based controls, underlining the importance of immunological follow-ups.

Antibiotic Treatment Duration for Community-Acquired Pneumonia in Outpatient Children in High-Income Countries-A Systematic Review and Meta-Analysis.

BACKGROUND: The optimal treatment duration of community-acquired pneumonia (CAP) in children has been controversial in high-income countries. We conducted a meta-analysis to compare short antibiotic treatment (3-5 days) with longer treatment (7-10 days) among children aged ≥6 months. METHODS: On 31 January 2022, we searched PubMed, Scopus, and Web of Science databases for studies published in English from 2003 to 2022. We included randomized controlled trials focusing on antibiotic treatment duration in children with CAP treated as outpatients. We calculated risk differences (RDs) with 95% confidence intervals and used the fixed-effect model (low heterogeneity). Our main outcome was treatment failure, defined as need for retreatment or hospitalization within 1 month. Our secondary outcome was presence of antibiotic-related harms. RESULTS: A total of 541 studies were screened, and 4 studies with 1541 children were included in the review. Three studies had low risk of bias, and one had some concerns. All 4 studies assessed treatment failures, and the RD was 0.1% (95% confidence interval, -3.0% to 2.0%) with high quality of evidence. Two studies (1194 children) assessed adverse events related to antibiotic treatment, and the RD was 0.0% (-5.0% to 5.0%) with moderate quality of evidence. The diagnostic criteria varied between the included studies. CONCLUSIONS: A short antibiotic treatment duration of 3-5 days was equally effective and safe compared with the longer (current) recommendation of 7-10 days in children aged ≥6 months with CAP. We suggest that short antibiotic courses can be implemented in treatment of pediatric CAP.

Parental Ability to Assess Pediatric Vital Signs.

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.

Azithromycin for acute bronchiolitis and wheezing episodes in children - a systematic review with meta-analysis.

BACKGROUND: The aim of this systematic review and meta-analysis was to analyse the efficacy of azithromycin in acute bronchiolitis and wheezing. METHODS: PubMed, Scopus, and Web of Science databases were searched for randomized controlled trials comparing azithromycin to placebo in children <2 years of age. Main outcomes were progress of acute wheezing episode and recurrence of wheezing. We used random-effects model to calculate mean difference (MD) with 95% confidence interval (CI) or risk ratios (RR) with CI. RESULTS: We screened 1604 abstracts and included 7 studies. Risk of bias was low in three and had some concerns in four studies. Need for intensive care unit treatment was assessed in four studies (446 children) and the risk difference was 0.0% (CI -2.0 to 2.0; low quality evidence). Hospitalization duration was -0.27 days shorter in the azithromycin group (MD-0.27, CI -0.47 to -0.07; three studies; moderate quality evidence). Azithromycin did not prevent recurrence of wheezing (RR 0.84, CI 0.45-1.56; three studies), hospital readmissions (RR 1.14, CI 0.82-1.60; four studies). CONCLUSIONS: We found moderate quality evidence that azithromycin may reduce hospitalization duration. Low certainty evidence suggests that azithromycin does not reduce the need for intensive care unit treatment. Furthermore, azithromycin did not prevent wheezing recurrence. IMPACT: Azithromycin may reduce hospitalization time in acute bronchiolitis and wheezing episodes among children aged less than two. Azithromycin administrated during the acute wheezing period, does not have preventive effect on wheezing recurrence. Azithromycin seemed to have similar adverse event profile than placebo. Future studies with clinically relevant outcomes, and sufficient sample sizes are needed, before implementing azithromycin into clinical use.

Lumbar puncture position in infants-a systematic review and meta-analysis.

To analyze the optimal lumbar puncture position in infants. A systematic review and meta-analysis. Infants (age < 1 year). December 2022 in PubMed, Scopus, and Web of Science. Randomized controlled trials focusing on lumbar puncture positions were included. Other lumbar puncture position than standard lateral decubitus position. First puncture success and overall success rate. Secondary outcome was desaturation during puncture and procedure-related harms. Risk of bias 2.0 assessment was performed. Outcomes are reported as risk ratios (RR) with 95% confidence intervals (CI). We screened 225 abstracts, and six studies were included. Four studies compared sitting position, one study head elevated lateral position, and one study prone position to lateral position. Risk of bias was high in two studies. First puncture success rate in sitting position (RR 1.00, CI: 0.78-1.18; 2 studies) and overall success rate in sitting position were similar to lateral position (RR 0.97, CI: 0.87-1.17; 3 studies). First attempt success rate was higher in elevated lateral position (RR 1.48, CI: 1.14-1.92; 1 study) and in prone position (RR 1.09, CI: 1.00-1.17; 1 study).  Conclusion: Sitting position seems to be equally effective in terms of first attempt and overall success in lumbar puncture than standard lateral position. Elevated lateral position and prone positions had better first attempt success than standard lateral position, but these were assessed only in one study each and thus further studies in these positions are needed.  Trial registration: This review was registered in PROSPERO. ID: CRD42022382953. What is Known: •  Success rate in lumbar puncture has been poor and first attempt success rate has varied between 50 to 80% in literature. •  Optimal lumbar puncture positions for infants have been debated between sitting and lateral decubitus position mostly. What is New: •  This is the first meta-analysis focused on lumbar puncture positions in infants, and it found that sitting position was equal to standard lateral position. • Prone position and head elevated lateral positions had higher first puncture success rates, but these were assessed both only in one study, which creates uncertainty to the finding.

Honey for acute cough in children - a systematic review.

To analyze the efficacy of using honey to treat acute cough in children. Systematic review, synthesis without meta-analysis. We searched PubMed, Scopus, CENTRAL, CINAHL, and Web of Science databases on August 15, 2022, for words honey and cough. Randomized controlled trials conducted in children were included. Risk-of-bias and evidence quality were assessed. Studies were not pooled due to lack of key information. Instead, we provided the range of observed effects for the main outcomes. Three hundred ninety-six papers were screened, and 10 studies were included. Two studies had high risk-of-bias and six had some concerns. Honey seemed to decrease cough frequency more than placebo/no treatment (range of observed effect 0.0-1.1 points) and cough medication (0.2-0.9 points). Sleep improved more often in the honey group (range of effect was 0.0-1.1) compared to placebo/no treatment and (- 0.2-1.1 points) compared to cough medication. Quality of the evidence was low to very low. CONCLUSION: We found low quality evidence that honey may be more effective than cough medication or placebo/no treatment in relieving symptoms and improving sleep in children with acute cough. Better quality randomized, placebo-controlled blinded trials are needed to confirm the effectiveness of honey in treating acute cough in children. TRIAL REGISTRATION: CRD42022369577. WHAT IS KNOWN: • Honey has been suggested to be effective as a symptomatic treatment in acute cough. • Prior randomized trials have had conflicting results and thus an overview of the literature was warranted. WHAT IS NEW: • Based on low quality evidence honey may be more effective than placebo or over-the-counter medications for acute symptom reliwef in cough. • Future studies with better reporting are needed to confirm the results.

Use of antibiotics contrary to guidelines for children's lower respiratory tract infections in different health care settings.

This study aimed to evaluate antibiotic prescriptions for children with lower respiratory tract infection (LRTI) in public and private primary care clinics and in a hospital's pediatric emergency department (PED) in 2012-2013 (pre-guideline) and in 2014-2015 (post-guideline). Special attention was paid to guideline compliance, especially regarding macrolide prescriptions, which the guidelines discourage. Retrospective data of 1431 children with LRTI in November-December 2012-2015 were collected from electronic registers and checked manually. Three diagnostic groups were analyzed: community-acquired pneumonia (CAP), wheezing bronchitis, and non-wheezing bronchitis. A comparison of the pre- and post-guideline periods revealed antibiotic prescription rates of 48.7% and 48.9% (p = 0.955) for all LRTIs, respectively, and 77.6% and 71.0% (p = 0.053) for non-wheezing bronchitis. The prescription rates for all LRTIs were 24.9% in PED and 45.9% in public (p < 0.001 vs. PED) and 75.4% in private clinics (p < 0.001 vs. PED and p < 0.001 vs. public clinics). During post-guideline periods, antibiotics were prescribed for CAP less often in private (56.3%) than in public clinics (84.6%; p = 0.037) or in PED (94.3%; p < 0.001 vs. private and p = 0.091 vs. public primary clinics). Macrolide prescriptions were highest in private clinics (42.8%), followed by public primary care clinics (28.5%; p < 0.05) and PED (0.8%; p < 0.05 vs. both public and private primary care). Amoxicillin was the predominant antibiotic in public primary care and PED and macrolides in private primary care. CONCLUSION:  Antibiotic prescribing for children with LRTI differed significantly between healthcare providers. CAP was undertreated and bronchitis overtreated with antibiotics in primary care, especially in the private clinics. WHAT IS KNOWN: • Clinical Treatment Guidelines tend to have modest effect on physicians' antibiotic prescribing habits. • Pediatric viral LRTIs are widely treated with unnecessary antibiotics. WHAT IS NEW: • Remarkable differences in antibiotic prescriptions in pediatric LRTIs between Finnish private and public providers were observed. • Overuse of macrolides was common especially in private clinics.

Duration of clinical symptoms in children with acute respiratory infection.

AIM: To investigate duration of clinical symptoms associated with various respiratory viruses and with the co-detection of respiratory viral and bacterial pathogens. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Absence from day care or school and parental absence from work during children's respiratory infections.

AIM: To investigate the social burden of nasopharyngeal detection of various respiratory viruses and the co-detection of viral and bacterial pathogens. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Nasopharyngeal detection of atypical bacteria by multiplex polymerase chain reaction panel in acutely ill children was associated with an increased risk of pneumonia.

AIM: We aimed to assess whether detection of respiratory bacteria by multiplex polymerase chain reaction (PCR) testing associates with clinical outcomes in acutely ill children. METHODS: This cross-sectional study enrolled children under the age of 18 with a suspected respiratory infection treated in a paediatric emergency department of Oulu University Hospital, Finland from January 2015 through December 2015. Nasopharyngeal samples were routinely analysed for 16 respiratory viruses and later, after storage, analysed with a multiplex PCR panel for seven respiratory bacteria. RESULTS: At least one bacterial pathogen was detected in 600 out of the 1195 children (50%). The mean age was 3.3 (SD 3.7) years and 54% were boys. Atypical bacteria were associated with a risk of pneumonia (adjusted odds ratio [aOR] 14.1, 95% CI 3.98-50.1). Co-detection of rhinovirus with Streptococcus pneumoniae was not associated with risk of pneumonia (aOR 2.39, 95% CI 0.78-7.30). Detection of Streptococcus pneumoniae, Haemophilus influenzae or both was not associated with the risk of hospital admission or prescription of antibiotics. CONCLUSION: Nasopharyngeal detection of atypical bacteria in acutely ill children was associated with a markedly increased risk of pneumonia. The clinical utility of wide testing for other respiratory bacteria needs further evaluation.

Comparison of remote learning methods to on-site teaching -randomized, controlled trial.

BACKGROUND: In the digitalized world, there is a need for developing new online teaching and learning methods. Although audio and video recordings are increasingly used in everyday learning, little scientific evidence is available on the efficacy of new online methods. This randomized trial was set out to compare the learning outcomes of online and classroom teaching methods in training healthcare students to diagnose breathing difficulties in children. METHODS: In total, 301 students of medicine (N = 166) and nursing (N = 135) volunteered to participate in this total sampling study in 2021-2022. The students were randomized into four groups based on teaching methods: classroom teaching (live, N = 72), streamed classroom teaching (live-stream, N = 77), audio recording (podcast, N = 79) and video recording (vodcast, N = 73). Each 45-minute lesson was taught by the same teachers and used the same protocol. The students participated an online test with their own electronic device at three distinct time points: prior to any teaching (baseline), immediately after teaching (final test), and five weeks later (long-term memory test). The test consisted of 10 multiple-choice questions on recognizing breathing difficulties from real-life videos of breathing difficulties in pre-school age. The test results scale ranged from - 26 to 28 points. Statistical analyses were performed using ANOVA multiple comparison and multiple regression tests. RESULTS: The mean scores (SD) of the final tests were 22.5 (5.3) in the vodcast, 22.9 (6.1) in the live, 20.0 (5.6) in the podcast (p < 0.05 vs. live) and 20.1 (6.8) in the live-stream group. The mean difference of test scores before and after the lesson improved significantly (p < 0.05) in all study groups, with 12.9 (6.5) in the vodcast, 12.6 (5.6) in the live, 10.9 (7.0) in the live-stream and 10.4 (6.9) in the podcast group. The improvement in test scores was significantly higher in the vodcast (p = 0.016) and the live (p = 0.037) groups than in the podcast group. No significant differences were found between the other groups. However, there was a nonsignificant difference towards better results in the vodcast group compared to the live-stream group. CONCLUSIONS: While the new online teaching methods produce learning, only video learning is comparable to team teaching in classrooms.

Microbiota of the first-pass meconium and subsequent atopic and allergic disorders in children.

BACKGROUND: 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. OBJECTIVE: We investigated whether the bacterial composition of the first-pass meconium is associated with the development of allergic diseases before 4 years of age. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Respiratory virus circulation in children after relaxation of COVID-19 restrictions in fall 2021-A nationwide register study in Finland.

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.

Antibiotics at birth and later antibiotic courses: effects on gut microbiota.

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.

Urinary tract infections decreased in Finnish children during the COVID-19 pandemic.

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 < 1 and 7-14. 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.

Pacifier use and breastfeeding in term and preterm newborns-a systematic review and meta-analysis.

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.

Systemic antibiotics and asthma medicines dispensed to 0-12 year olds significantly decreased during the COVID-19 pandemic in 2020.

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.

Loss of DIAPH1 causes SCBMS, combined immunodeficiency, and mitochondrial dysfunction.

BACKGROUND: Homozygous loss of DIAPH1 results in seizures, cortical blindness, and microcephaly syndrome (SCBMS). We studied 5 Finnish and 2 Omani patients with loss of DIAPH1 presenting with SCBMS, mitochondrial dysfunction, and immunodeficiency. OBJECTIVE: We sought to further characterize phenotypes and disease mechanisms associated with loss of DIAPH1. METHODS: Exome sequencing, genotyping and haplotype analysis, B- and T-cell phenotyping, in vitro lymphocyte stimulation assays, analyses of mitochondrial function, immunofluorescence staining for cytoskeletal proteins and mitochondria, and CRISPR-Cas9 DIAPH1 knockout in heathy donor PBMCs were used. RESULTS: Genetic analyses found all Finnish patients homozygous for a rare DIAPH1 splice-variant (NM_005219:c.684+1G>A) enriched in the Finnish population, and Omani patients homozygous for a previously described pathogenic DIAPH1 frameshift-variant (NM_005219:c.2769delT;p.F923fs). In addition to microcephaly, epilepsy, and cortical blindness characteristic to SCBMS, the patients presented with infection susceptibility due to defective lymphocyte maturation and 3 patients developed B-cell lymphoma. Patients' immunophenotype was characterized by poor lymphocyte activation and proliferation, defective B-cell maturation, and lack of naive T cells. CRISPR-Cas9 knockout of DIAPH1 in PBMCs from healthy donors replicated the T-cell activation defect. Patient-derived peripheral blood T cells exhibited impaired adhesion and inefficient microtubule-organizing center repositioning to the immunologic synapse. The clinical symptoms and laboratory tests also suggested mitochondrial dysfunction. Experiments with immortalized, patient-derived fibroblasts indicated that DIAPH1 affects the amount of complex IV of the mitochondrial respiratory chain. CONCLUSIONS: Our data demonstrate that individuals with SCBMS can have combined immune deficiency and implicate defective cytoskeletal organization and mitochondrial dysfunction in SCBMS pathogenesis.

Rhinovirus spread in children during the COVID-19 pandemic despite social restrictions-A nationwide register study in Finland.

Social restrictions during the coronavirus disease 2019 pandemic strongly affected the epidemiology of influenza and respiratory syncytial virus (RSV). As rhinovirus seemed to spread despite the restrictions, we aimed to analyze rhinovirus epidemiology in children during the pandemic. This register-based study used data from the Finnish Infectious Disease Register. Nationwide rhinovirus findings from July 2015 to March 2021 were included and stratified by age (0-4, 5-9, and 10-14). Cumulative 14-day incidence per 100000 children was calculated. Four thousand five hundred and seventy six positive rhinovirus findings were included, of which 3788 (82.8%) were among children aged 0-4. The highest recorded incidence was 36.2 among children aged 0-4 in October 2017. The highest recorded incidence during the pandemic period was 13.6 in November 2020. The impact of the restrictions was mostly seen among children aged 0-4 years of age in weeks 14-22 in 2020. The incidence has since remained near reference levels in all age groups. Strict restrictions temporarily interrupted the circulation of rhinovirus in spring 2020. Rhinovirus incidence returned to normal levels soon after the harsh restrictions were lifted. These looser social restrictions prevented RSV and influenza seasons but failed to prevent the spread of rhinovirus.