Too much? Mortality and health service utilisation among Danish children 1999-2016:A register-based study

ObjectivesTo describe the temporal development of mortality and health service utilisation defined as in- and outpatient hospital contacts, contacts with general practitioner and specialists, and prescribed dispensed medication among Danish children 0-5 years of age from 1999 to 2016.DesignRegister-based descriptive study.ParticipantsAll children born in Denmark in the period 1994-2016 followed until 5 years of age.Main outcome measuresAnnual incidence rates of mortality and health service utilisation outcomes, and incidence rate ratios compared to the reference calendar year 1999. The new measure of post-discharge mortality is presented.ResultsPost-discharge mortality decreased from 1999 to 2016, IRR2016 = 0.49 (95% CI: 0.36 to 0.66). Total contacts did not change much over time, IRR2016 = 1.02 (1.02 to 1.03), but increased among neonates, IRR2016 = 3.69 (3.63 to 3.75), and decreased among children with chronic disease IRR2016 = 0.94 (0.93 to 0.94). In- and out-patient hospitalisations increased, IRR2016 = 1.26 (1.24-1.27) resp. IRR2016 = 1.62 (1.60-1.63), contacts with medical specialists increased, IRR2016 = 1.43 (1.42 to 1.43), whilst contacts with general practitioner decreased, IRR2016 = 0.91 (0.91 to 0.91). Medication use decreased, IRR2016 = 0.82 (0.82 to 0.82).ConclusionsOur measure of post-discharge mortality was halved during the study period indicating improved health. Overall health service utilisation did not change much, but the type of utilisation changed, and the development over time differed between subgroups defined by age and chronic disease status. Our findings call for considerations about the benefit of increased specialisation and increased use of health services among 'healthy' children not suffering from chronic disease

Risk factors of post-discharge under-five mortality among Danish children 1997-2016:A register-based study

OBJECTIVES:Estimating associations between somatic and socioeconomic risk factors and post-discharge under-five mortality. DESIGN:Register-based national cohort study using multiple Cox regression. PARTICIPANTS:The population of 1,263,795 Danish children live-born 1997-2016 who survived until date of first discharge to the home after birth was followed from that date until death, emigration, 5 years of age or 31 December 2016. MAIN OUTCOME MEASURES:(A) Mortality hazard ratios (HRs) among all children, (B) mortality HRs among children without severe chronic disease, and (C) mortality HRs among children without severe chronic disease or asthma. MAIN RESULTS:In the total population (1,947 deaths) severe chronic disease was associated with mortality HR = 15.28 (95% CI: 13.77-16.95). In children without severe chronic-disease (719 deaths) other somatic risk factors were immature birth HR = 3.40 (1.92-6.02), maternal smoking HR = 1.84 (1.55-2.18) and low birth weight HR = 1.74 (1.21-2.51). Socioeconomic risk factors for mortality included: maternal age 35 years (similar for 30-35 years and 25-29 years), lowest vs. highest family income tertile HR = 1.76 (1.23-2.51), not living with both parents HR = 1.63 (1.25-2.13), maternal unemployment HR = 1.54 (1.12-2.12), presence of siblings HR = 1.44 (1.20-1.71) and secondary vs. tertiary parental education HR = 1.33 (1.07-1.65) for fathers and HR = 1.23 (1.01-1.52) for mothers. Factors not found to be associated with child mortality in this population included presence of asthma HR = 1.29 (0.83-1.98) and non-Danish ethnicity HR = 0.98 (0.70-1.37). CONCLUSIONS:Childhood death after discharge to the home after birth and before 5 years of age is a very rare event in Denmark. This 'post-discharge' mortality was heavily associated with severe chronic disease. In children without severe chronic disease, immature birth, maternal smoking and certain socioeconomic characteristics were noticeable risk factors. Mortality may possibly be decreased by focusing on vulnerable groups

The match between need and use of health services among healthy under-fives in Denmark:A register-based national cohort study

OBJECTIVES:To study a potential positive association (referred to as 'a match') between the need for health service (expressed by a mortality risk score) and observed health service utilisation among healthy Danish under-fives. Further, municipal differences in the match were examined to motivate focused comparisons between the organisation of regional health services. DESIGN:Register-based national cohort study. PARTICIPANTS:The population of 1,246,599 Danish children born 1997-2016 who survived until date of first discharge to the home after birth without a diagnosis of severe chronic disease. MAIN OUTCOME MEASURES:Hazard ratios (HR) for a doubling of the mortality rate were calculated for the following health services: total contacts, inpatient contacts (admission > 1 day), outpatient contacts, general practitioner contacts, specialist contacts, medication use, and vaccinations. RESULTS:The use of total contacts, inpatient contacts (> 1 day) and general practitioner contacts as well as medication matched with the mortality risk score, HRs between 1.027 (1.026 to 1.028) and 1.111 (1.108 to 1.113), whereas outpatient and specialist contacts as well as vaccinations did not, HRs between 0.913 (0.912 to 0.915) and 0.991 (0.991 to 0.991). There were some remarkable differences among the 98 Danish municipalities. CONCLUSIONS:We found some match between need and use for total contacts, inpatient contacts (> 1 day), contacts with general practitioner, and medication use although the associations were relatively weak. For outpatient and specialist contacts, the mismatch may be related to services not addressing potentially fatal disease whereas for vaccination there was a small mismatch. Our results indicate local discrepancies in diagnosis, and a low adjusted utilisation of hospital admissions in Aarhus compared to the other three major cities in Denmark suggests that a comparison of the organisation of services could be useful

Bacille Calmette-Guérin (BCG) vaccination at birth and antibody responses to childhood vaccines. A randomised clinical trial

Contains fulltext : 169904.pdf (publisher's version ) (Open Access)INTRODUCTION: BCG vaccination has been associated with beneficial non-specific effects on child health. Some immunological studies have reported heterologous effects of vaccines on antibody responses to heterologous vaccines. Within a randomised clinical trial of Bacille Calmette-Guerin (BCG) vaccination at birth, The Danish Calmette Study, we investigated the effect of BCG at birth on the antibody response to the three routine vaccines against DiTeKiPol/Act-Hib and Prevenar 13 in a subgroup of participants. METHODS: Within 7days after birth, children were randomised 1:1 to BCG vaccination or to the control group (no intervention). After three routine vaccinations given at age 3, 5 and 12months, antibodies against DiTeKiPol/Act-Hib and Prevenar 13 (Streptococcus pneumoniae serotype type 4, 6B, 9V, 14, 18C, 19F and 23F) were measured 4weeks after the third vaccine dose. RESULTS: Among the 300 included children (178 BCG; 122 controls), almost all children (>96%) had antibody responses above the protective levels. Overall BCG vaccination at birth did not affect the antibody level. When stratifying by 'age at randomisation' we found a possible inducing effect of BCG on antibodies against B. pertussis and all pneumococcal serotypes, when BCG was given after the first day of life. Girls had significantly higher antibody levels for Haemophilus influenza type b and pneumococcus than boys. CONCLUSIONS AND RELEVANCE: Three routine vaccinations with DiTeKiPol/Act-Hib and Prevenar 13 induced sero-protective levels in almost all children. No overall effect of neonatal BCG vaccination was observed

Adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine in new-born infants:an evaluation of the Danish strain 1331 SSI in a randomized clinical trial

AbstractObjectiveTo evaluate adverse reactions of the Bacillus Calmette–Guérin (BCG) Statens Serum Institut (SSI) (Danish strain 1331) used as intervention in a randomized clinical trial.DesignA randomized clinical multicenter trial, The Danish Calmette Study, randomizing newborns to BCG or no intervention. Follow-up until 13 months of age.SettingPediatric and maternity wards at three Danish university hospitals.ParticipantsAll women planning to give birth at the three study sites (n=16,521) during the recruitment period were invited to participate in the study. Four thousand one hundred and eighty four families consented to participate and 4262 children, gestational age 32 weeks and above, were randomized: 2129 to BCG vaccine and 2133 to no vaccine. None of the participants withdrew because of adverse reactions.Main outcome and measureTrial-registered adverse reactions after BCG vaccination at birth. Follow-up at 3 and 13 months by telephone interviews and clinical examinations.ResultsAmong the 2118 BCG-vaccinated children we registered no cases of severe unexpected adverse reaction related to BCG vaccination and no cases of disseminated BCG disease. Two cases of regional lymphadenitis were hospitalized and thus classified as serious adverse reactions related to BCG. The most severe adverse reactions were 10 cases of suppurative lymphadenitis. This was nearly a fivefold increase compared to what was expected based on the summary of product characteristics of the vaccine. All cases were treated conservatively and recovered. Six of 10 (60%) families of children experiencing suppurative lymphadenitis compared to 117/2071 (6%) of those with no lymphadenitis indicated that the vaccine had more adverse effects than expected (p-value <0.001).Conclusions and relevanceBCG vaccination was associated with only mild morbidity and no mortality. A higher incidence of suppurative lymphadenitis than expected was observed. All children were treated conservatively without sequelae or complications.Trial registrationTrial registration number NCT01694108 at www.clinicaltrials.go

BCG vaccination at birth and early childhood hospitalisation:a randomised clinical multicentre trial

BACKGROUND: The BCG vaccine is administered to protect against tuberculosis, but studies suggest there may also be non-specific beneficial effects upon the infant immune system, reducing early non-targeted infections and atopic diseases. The present randomised trial tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalisation in Denmark, a high-income setting. METHODS: Pregnant women planning to give birth at three Danish hospitals were invited to participate. After parental consent, newborn children were allocated to BCG or no intervention within 7 days of age. Randomisation was stratified by prematurity. The primary study outcome was number of all-cause hospitalisations analysed as repeated events. Hospitalisations were identified using The Danish National Patient Register. Data were analysed by Cox proportional hazards models in intention-to-treat and per-protocol analyses. RESULTS: 4184 pregnant women were randomised and their 4262 children allocated to BCG or no intervention. There was no difference in risk of hospitalisation up to 15 months of age; 2129 children randomised to BCG experienced 1047 hospitalisations with a mean of 0.49 hospitalisation per child compared with 1003 hospitalisations among 2133 control children (mean 0.47), resulting in a HR comparing BCG versus no BCG of 1.05 (95% CI 0.93 to 1.18) (intention-to-treat analysis). The effect of BCG was the same in children born at term (1.05 (0.92 to 1.18)) and prematurely (1.07 (0.63 to 1.81), p=0.94). The effect was also similar in the two sexes and across study sites. The results were essentially identical in the per-protocol analysis and after adjustment for baseline characteristics. CONCLUSIONS: BCG vaccination at birth did not reduce the risk of hospitalisation for somatic acquired disease until 15 months of age in this Danish study population. TRIAL REGISTRATION NUMBER: NCT01694108, results