Effects of Neonatal BCG-Japan Versus BCG-Russia Vaccination on Overall Mortality and Morbidity: Randomized Controlled Trial From Guinea-Bissau (BCGSTRAIN II).

Background: Vaccination with the Danish strain of bacille Calmette-Guérin (BCG) has been associated with pronounced reductions in all-cause neonatal mortality and morbidity. Developing a skin reaction postvaccination is associated with markedly reduced mortality risk. It is unknown whether the beneficial nonspecific effects are maintained across different BCG strains. Methods: This was an open-label randomized controlled trial in Guinea-Bissau, comparing BCG-Japan (n = 8754) versus BCG-Russia (n = 8752) for all-cause hospital admission risk by 6 weeks of age (primary outcome) and 6 months of age. Additional secondary outcomes were in-hospital case-fatality risk (CFR), all-cause mortality, and BCG skin reaction prevalence. Participants were followed through telephone calls at 6 weeks and 6 months, with a subgroup also visited at home. We assessed admission and mortality risk in Cox models providing incidence rate ratios (IRRs) and mortality rate ratios. CFR and skin reactions were assessed by binomial regression providing risk ratios. Analyses were done overall and stratified by sex. Results: BCG strain was not associated with admission risk, the BCG-Japan/BCG-Russia IRR being 0.92 (95% confidence interval [CI], .81-1.05) by 6 weeks and 0.92 (95% CI, .82-1.02) by 6 months. By 6 months of age, there were significantly fewer BCG-Japan infants with no skin reaction (1%) than for BCG-Russia (2%), the risk ratio being 0.36 (95% CI, .16-.81). BCG-Japan skin reactions were also larger. Conclusions: Both vaccines induced a skin reaction in almost all participants. The BCG strains had comparable effects on morbidity and mortality, but BCG-Japan was associated with more and larger skin reactions that are indicators of lower mortality risk. Clinical Trials Registration: NCT03400878.

Impact of a National Follow-Up Program on the Age at Diagnosis for Cerebral Palsy.

BACKGROUND: The Danish National Cerebral Palsy Follow-up Program (CPOP) is a nationwide program offering standardized treatment to all children with cerebral palsy (CP) since 2004. We aimed to establish if its implementation had a positive impact on the diagnostic age of CP. METHODS: Children with validated CP diagnoses were identified from the Danish Cerebral Palsy Registry and the CPOP. We then compared the age at diagnosis and the clinical features of children with CP born in 2000 to 2003 with those born in 2010 to 2013. Differences in time to diagnosis were compared using log-rank test. RESULTS: The age at diagnosis was not different in the two periods (P = 0.23), with identical overall median diagnostic ages at 13.0 months. The number of children with severe motor disability decreased markedly from 47.5% in 2000 to 2003 to 32.0% in 2010 to 2013 (P < 0.001). There was increased usage of cerebral magnetic resonance imaging; however, this was not associated with lower diagnostic age. CONCLUSIONS: The diagnostic age of CP did not change after the implementation of a nationwide follow-up program, offering standardized and early assessments. However, central clinical aspects also changed significantly between the periods compared, which possibly affected the diagnostic age.

Cytokine profile of pediatric patients with obsessive-compulsive and/or movement disorder symptoms: A review.

Cytokines are an important modulator of the immune system and have been found to be altered significantly in many neurological and psychiatric disorders, like obsessive compulsive disorder (OCD) and movement disorders. Also, in pediatric autoimmune neuropsychiatric disorders associated with group A streptococcal infections (PANDAS), which are characterized by abrupt debut of symptoms of OCD and /or movement disorder symptoms, alterations in the immune system have been suggested. The aim of this paper was to review the current literature on the cytokine profile of pediatric patients with symptoms of OCD and/or movement disorder symptoms. A search of PubMed and Medline was performed with specific keywords to review studies measuring cytokines in pediatric patients with symptoms of OCD and/or movement disorders. Nineteen studies were found, twelve of which included a healthy control group, while four studies had control groups of children with other disorders, primarily neurological or psychiatric. One study compared cytokines measurements to reference intervals, and two studies had a longitudinal design. Many cytokines were found to have significant changes in patients with symptoms of OCD and/or movement disorders compared to both healthy controls and other control groups. Furthermore, differences were found when comparing cytokines in periods of exacerbation with periods of remission of symptoms in study participants. The cytokines that most studies with healthy control groups found to be significantly altered were TNF-α, IL-1ß and IL-17. Although the exact role of these cytokines in OCD and movement disorder symptoms remains unclear, the available literature suggests a proinflammatory cytokine profile. This offers interesting perspectives on the pathogenesis of OCD and/or movement disorder symptoms in children, and further research into the implications of cytokines in neuropsychiatric disorders is warranted.