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Background Measles is a highly contagious viral disease. Vaccinated mothers transfer fewer antibodies during pregnancy, resulting in shortened infant immunity. Earlier primary vaccination might avert the gap in protection. Methods Healthy 5–7-month-old Danish infants were assigned in a 1:1 ratio to M-M-RVaxPro or placebo (solvent) in a double-blind, randomized trial between April 15, 2019 and November 1, 2021 (ClinicalTrials.gov NCT03780179, EudraCT 2016-001901-18). Eligibility criteria were birth weight >1000 g and gestational age ≥32 weeks. Immunogenicity was measured by plaque reduction neutralization test (PRNT) and IgG ELISA before intervention, four weeks after intervention and routine MMR. Reactogenicity data were collected for six weeks and measured by hazard ratios (HR). Findings 647 and 6540 infants participated in the immunogenicity and reactogenicity study, respectively; 87% and 99% completed follow-up. After early MMR, seroprotection rates (SPRs) were 47% (13%) in measles PRNT; 28% (2%), 57% (8%) in mumps and rubella IgG (placebo). For measles PRNT, geometric mean ratio was 4.3 (95% CI: 3.4–5.3) between randomization groups after intervention and 1.5 (95% CI: 1.3–1.9) after routine MMR. Reactogenicity was independent of randomization (HR, 1.0; 95% CI: 0.9–1.1). Severe adverse events occurred in 25 infants (HR, 1.8; 95% CI: 0.8–4.0); none deemed vaccine related. Interpretation Early MMR elicited low SPRs but did not negatively impact short-term responses to a subsequent MMR. MMR at 5–7 months was safe and not associated with higher rates of reactogenicity than placebo., Background: Measles is a highly contagious viral disease. Vaccinated mothers transfer fewer antibodies during pregnancy, resulting in shortened infant immunity. Earlier primary vaccination might avert the gap in protection. Methods: Healthy 5–7-month-old Danish infants were assigned in a 1:1 ratio to M-M-RVaxPro or placebo (solvent) in a double-blind, randomized trial between April 15, 2019 and November 1, 2021 (ClinicalTrials.gov NCT03780179, EudraCT 2016-001901-18). Eligibility criteria were birth weight >1000 g and gestational age ≥32 weeks. Immunogenicity was measured by plaque reduction neutralization test (PRNT) and IgG ELISA before intervention, four weeks after intervention and routine MMR. Reactogenicity data were collected for six weeks and measured by hazard ratios (HR). Findings: 647 and 6540 infants participated in the immunogenicity and reactogenicity study, respectively; 87% and 99% completed follow-up. After early MMR, seroprotection rates (SPRs) were 47% (13%) in measles PRNT; 28% (2%), 57% (8%) in mumps and rubella IgG (placebo). For measles PRNT, geometric mean ratio was 4.3 (95% CI: 3.4–5.3) between randomization groups after intervention and 1.5 (95% CI: 1.3–1.9) after routine MMR. Reactogenicity was independent of randomization (HR, 1.0; 95% CI: 0.9–1.1). Severe adverse events occurred in 25 infants (HR, 1.8; 95% CI: 0.8–4.0); none deemed vaccine related. Interpretation: Early MMR elicited low SPRs but did not negatively impact short-term responses to a subsequent MMR. MMR at 5–7 months was safe and not associated with higher rates of reactogenicity than placebo. Funding: Innovation Fund Denmark.

Objective: To test for potential non-specific effects of an additional, early measles, mumps, and rubella (MMR) vaccine at age 5-7 months on risk of infection related hospitalisation before age 12 months. Design: Randomised, double blinded, placebo controlled trial. Setting: Denmark, a high income setting with low exposure to MMR. Participants: 6540 Danish infants aged 5 to 7 months. Interventions: Infants were randomly allocated 1:1 to intramuscular injection with standard titre MMR vaccine (M-M-R VaxPro) or placebo (solvent only). Main outcome measures: Hospitalisations for infection, defined as all hospital contacts of infants referred from primary care for hospital evaluation and with an infection diagnosed, analysed as recurrent events, from randomisation to 12 months of age. In secondary analyses implications of censoring for date of subsequent diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type B, and immunisation with pneumococci conjugate vaccine (DTaP-IPV-Hib+PCV), potential effect modification by sex, prematurity (<37 weeks' gestation), season, and age at randomisation were tested, and the secondary outcomes of hospitalisations ≥12 hours and antibiotic use were evaluated. Results: 6536 infants were included in the intention-to-treat analysis. 3264 infants randomised to MMR vaccine experienced 786 hospitalisations for infection before age 12 months compared with 762 for the 3272 infants randomised to placebo. In the intention-to-treat analysis the rate of hospitalisations for infection did not differ between the MMR vaccine and placebo groups (hazard ratio 1.03, 95% confidence interval 0.91 to 1.18). For infants randomised to MMR vaccine compared with those randomised to placebo, the hazard ratio of hospitalisations for infection with a duration of at least 12 hours was 1.25 (0.88 to 1.77), and for prescriptions of antibiotics was 1.04 (0.88 to 1.23). No significant effect modifications were found by sex, prematurity, age at randomisat

Objective To assess if the overall utilisation of surgery in Danish children 0–5 years of age increased in the period 1999–2018 in line with the development within specialised medical services. The epidemiology on surgical procedures is scarce. Methods National register-based cohort study of all Danish children born 1994–2018 (n = 1,599,573) using data on surgery in public and private hospitals from The National Patient Register and data on surgery in private specialist practice from The Health Service Register. Incidence rate ratios were calculated using Poisson regression with 1999 as the reference year. Results During the study period 115,573 different children (7.2% of the cohort) underwent surgery. The overall incidence of surgical procedures was stable, but the use of surgery increased in neonates mainly due to an increase in frenectomy. Boys underwent more surgery than girls. In children with severe chronic disease the rate of surgery decreased in public hospitals and increased in private specialist practices. Conclusion The utilisation of surgical procedures in Danish children 0–5 years of age did not increase from 1999 to 2018. The use of available register data in the present study may inspire surgeons to conduct further studies to enhance the knowledge within the area of surgical procedures.

Play is a non-invasive, safe, and inexpensive intervention that can help children and adolescents better manage difficult aspects of hospitalisation. Play has existed in hospitals for decades but is emerging as an interdisciplinary scientific field. The field concerns all medical specialties and healthcare professionals working with children. In this review, we describe play within different clinical contexts and recommend that directed and non-directed play activities should be prioritised in future paediatric departments. We also emphasise the need for professionalisation and research in the area.

Declining levels and duration of passively acquired maternal antibodies prompted a Danish trial to test the feasibility of advancing administration of the first measles, mumps, and rubella vaccine (MMR1) from 15 to 6 months of age. A trial-embedded qualitative study aimed to understand parents’ (N = 24) and health professionals’ (N = 11) attitudes about the measles, mumps, and rubella vaccine (MMR) in general and about advancing MMR1 administration. Overly positive parent attitudes were contrasted by members of a vaccine-skeptical organization including parents considering that their child was seriously vaccine-injured long ago. Parents’ attitudes to advancing MMR1 mirrored their attitudes about the MMR vaccine in general, with four positions along a continuum of trust in the healthcare system: unquestioning trust, acceptance after careful consideration, challenging indecisiveness, and defensive rejection. Low tolerance was identified between vaccine supporters and vaccine opponents. Parents of children with perceived serious vaccine-related injuries described lifelong unresolved feelings of guilt. Supporters of advanced MMR1 saw it as a timely and convenient administration of a well-known vaccine, whereas opponents feared it would disturb the children’s immature immune systems and emphasized difficulties in recognizing side effects so early in life. Health professionals were supportive of advancing the MMR1 vaccine and they carefully challenged the parents. Current MMR vaccine supporters show readiness to advance MMR1 administration.

BACKGROUND: It has been suggested that the transiently increased infection risk following childcare enrolment is compensated by decreased infection risk later in childhood and adolescence. We investigated how childcare enrolment affected rates of antimicrobial-treated infections during childhood and adolescence.METHODS: In a register-based cohort study of all children born in Denmark 1997-2014 with available exposure information (n = 1 007 448), we assessed the association between childcare enrolment before age 6 years and infection risks up to age 20 years, using antimicrobial exposure as proxy for infections. Nationwide childcare and prescription data were used. We estimated infection rates and the cumulative number of infections using adjusted Poisson regression models.RESULTS: We observed 4 599 993 independent episodes of infection (antimicrobial exposure) during follow-up. Childcare enrolment transiently increased infection rates; the younger the child, the greater the increase. The resulting increased cumulative number of infections associated with earlier age at childcare enrolment was not compensated by lower infection risk later in childhood or adolescence. Accordingly, children enrolled in childcare before age 12 months had experienced 0.5-0.7 more infections at age 6 years (in total 4.5-5.1 infections) than peers enrolled at age 3 years, differences that persisted throughout adolescence. The type of childcare had little impact on infection risks.CONCLUSIONS: Early age at childcare enrolment is associated with a modest increase in the cumulative number of antimicrobial-treated infections at all ages through adolescence. Emphasis should be given to disrupting infectious disease transmission in childcare facilities through prevention strategies with particular focus on the youngest children.

Background Scant evidence exists on the real-world effectiveness of quadrivalent live attenuated influenza vaccines (LAIV-4) in younger children. We aimed to assess the real-world effectiveness of LAIV-4 against influenza-related hospital contacts and admission and morbidity. Methods Using nationwide Danish health-care registries, we designed a cohort study that emulates a target trial, comparing LAIV-4 to no vaccination in children aged 2–6 years. Eligible children vaccinated from Oct 1, 2021, to Jan 15, 2022, were matched to unvaccinated controls in a 1:1 ratio according to demographic characteristics and risk groups for influenza, and followed-up until May 31, 2022. Primary study outcomes any hospital contact for influenza and influenza-related hospital admissions more than 12 h in duration, while hospital admission for respiratory tract infections, or for wheezing or asthma, and antibiotic prescriptions were evaluated as secondary outcomes. We estimated incidence rate ratios (IRRs) and 95% CIs using Poisson regression for each outcome. Vaccine effectiveness was calculated as 1 – IRR. Findings Among 308 520 Danish children aged 2–6 years, 95 434 vaccinated children were matched with 95 434 unvaccinated children who acted as controls. Receipt of LAIV-4 compared with no vaccination was associated with a reduced IRR of 0·36 (95% CI 0·27 to 0·46) and estimated vaccine effectiveness of 64·3% (53·6 to 72·6) against influenza-related hospital contacts (76 vs 210 events). The corresponding IRR and vaccine effectiveness against influenza-related hospital admissions were 0·63 (0·38 to 1·05) and 36·9% (–5·2 to 62·1; 24 vs 38 events), respectively. LAIV-4 was not associated with reductions in admission rates for respiratory tract infections (IRR 1·14, 95% CI 0·94 to 1·38), wheezing or asthma (1·04, 0·83 to 1·31), or antibiotic prescriptions for respiratory tract infections (0·97, 0·93 to 1·00). Vaccine effectiveness assessed across risk groups f, Background: Scant evidence exists on the real-world effectiveness of quadrivalent live attenuated influenza vaccines (LAIV-4) in younger children. We aimed to assess the real-world effectiveness of LAIV-4 against influenza-related hospital contacts and admission and morbidity. Methods: Using nationwide Danish health-care registries, we designed a cohort study that emulates a target trial, comparing LAIV-4 to no vaccination in children aged 2–6 years. Eligible children vaccinated from Oct 1, 2021, to Jan 15, 2022, were matched to unvaccinated controls in a 1:1 ratio according to demographic characteristics and risk groups for influenza, and followed-up until May 31, 2022. Primary study outcomes any hospital contact for influenza and influenza-related hospital admissions more than 12 h in duration, while hospital admission for respiratory tract infections, or for wheezing or asthma, and antibiotic prescriptions were evaluated as secondary outcomes. We estimated incidence rate ratios (IRRs) and 95% CIs using Poisson regression for each outcome. Vaccine effectiveness was calculated as 1 – IRR. Findings: Among 308 520 Danish children aged 2–6 years, 95 434 vaccinated children were matched with 95 434 unvaccinated children who acted as controls. Receipt of LAIV-4 compared with no vaccination was associated with a reduced IRR of 0·36 (95% CI 0·27 to 0·46) and estimated vaccine effectiveness of 64·3% (53·6 to 72·6) against influenza-related hospital contacts (76 vs 210 events). The corresponding IRR and vaccine effectiveness against influenza-related hospital admissions were 0·63 (0·38 to 1·05) and 36·9% (–5·2 to 62·1; 24 vs 38 events), respectively. LAIV-4 was not associated with reductions in admission rates for respiratory tract infections (IRR 1·14, 95% CI 0·94 to 1·38), wheezing or asthma (1·04, 0·83 to 1·31), or antibiotic prescriptions for respiratory tract infections (0·97, 0·93 to 1·00). Vaccine effectiveness assessed across risk groups for influenza showed simi

Aim To assess the association between socioeconomic factors and mortality in Danish children diagnosed with different types of severe chronic disease, including cancer. Methods National cohort study 1994-2020 including Danish children with chronic disease. Inclusion was based on diagnoses in The National Patient Register, socioeconomic information was obtained from Statistics Denmark and mortality was ascertained from the Cause of Death Register. Hazard ratios (HR) with 95% confidence intervals (CIs) were based on Cox regression. The factors were combined in one common risk score and the association with disease-specific mortality was analysed overall and by ethnicity status. Results Overall, non-Danish ethnicity (HR = 1.96 (95% CI 1.69-2.28)) was associated with all-cause mortality in 128 129 children (69 435 male and 58 694 female) with chronic disease. Median age at first diagnosis was 1.42 years (range 0-18 years). Low family income was associated with mortality regardless of ethnicity status, and young maternal age was also a notable risk factor across ethnicities. The socioeconomic association was more pronounced in children with cancer. Conclusion In the high-income setting of Denmark, ethnicity and differences in socioeconomic background were associated with child mortality even among children with severe chronic disease. The pattern was more pronounced in paediatric cancer patients.

Objectives: To assess the risk of acute and post-acute adverse events after SARS-CoV-2 infection in children and adolescents in Denmark and to evaluate the real world effectiveness of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) among adolescents. Design: Cohort study. Setting: Nationwide Danish healthcare registers. Participants: All Danish people younger than 18 years who were either tested for SARS-CoV-2 using reverse transcriptase polymerase chain reaction (RT-PCR) or vaccinated with BNT162b2 to 1 October 2021. Main outcome measures: Risk of hospital admissions (any hospital contact of ≥12 hours); intensive care unit (ICU) admissions; serious complications, including multisystem inflammatory syndrome in children (MIS-C), myocarditis, and neuroimmune disorders; and initiating drug treatment and health service use up to six months after being tested. Vaccine effectiveness in vaccine recipients compared with unvaccinated peers was evaluated as one minus the risk ratio at 20 days after the first dose and 60 days after the second dose. Results: Of 991 682 children and adolescents tested for SARS-CoV-2 using RT-PCR in Denmark, 74 611 (7.5%) were positive. The risk of hospital admission with any variant for ≥12 hours was 0.49% (95% confidence interval 0.44% to 0.54%; 361/74 350), and 0.01% (0.01% to 0.03%; 10/73 187) of participants were admitted to an ICU within 30 days of testing positive. The risk of MIS-C within two months of SARS-CoV-2 infection was 0.05% (0.03% to 0.06%; 32/70 666), whereas no participants had myocarditis outside of MIS-C or encephalitis and fewer than five had Guillain-Barré syndrome. In the post-acute phase (1-6 months after infection), participants who tested positive for SARS-CoV-2 showed a 1.08-fold (95% confidence interval 1.06-fold to 1.10-fold) increase in rate of contacts with general practitioners compared with a reference cohort sampled among all children tested for SARS-CoV-2 during the study period. Overall, 278 649 adolescents rec