Costs of vitamin D testing and prescribing among children in primary care.

Vitamin D has attracted considerable interest in recent years, with a marked increase in diagnosis of vitamin D deficiency seen among children in clinical practice in the UK. The economic implications of this change in diagnostic behaviour have not been explored. We performed a cohort study to examine longitudinal trends in healthcare expenditure arising from vitamin D testing and prescribing for children in primary care in England, using the electronic healthcare records of 722,525 children aged 0-17 years held in The Health Improvement Network database. Combined costs of vitamin D tests and prescriptions increased from £1647 per 100,000 person-years in 2008 (95% CI, £934 to £3007) to £28,913 per 100,000 person-years in 2014 (95% CI, £26,361 to £31,739). The total cost of vitamin D prescriptions and tests for children in primary care at the national level in England in 2014 was estimated to be £4.31 million (95% CI, £2.96-£6.48 million). CONCLUSION: There has been a marked increase in healthcare expenditure on vitamin D tests and prescriptions for children in primary care over the past decade. Future research should explore the drivers for this change in diagnostic behaviour and the reasons prompting investigation of vitamin D status in clinical practice. What is Known: • Vitamin D deficiency has attracted considerable interest in recent years, with a marked increase in diagnosis seen in children. • The economic implications of this change in diagnostic behaviour have not been explored. What is New: • There has been a large increase in healthcare expenditure on vitamin D tests and prescriptions for children in primary care in England over the past decade (> 15 fold between 2008 and 2013). • Screening of vitamin D status in children without specific risk factors or clinical features of deficiency may represent avoidable healthcare expenditure.

Bibliography of published COVID-19 in children literature.

BACKGROUND: The COVID-19 pandemic is the biggest worldwide health challenge in this century. Research concerning the role of children in the spread of SARS-CoV-2, and investigating the clinical effects of infection in children, has been vital. This paper describes the publication trend for pertinent scientific literature relating to COVID-19 in children during the first 6 months of the pandemic. METHODS: A comprehensive search of preprint and published literature was conducted daily across four databases (PubMed, Scopus, Ovid-Embase and MedRXiv) between 1 January 2020 and 30 June 2020. Titles and abstracts were screened against predefined inclusion and exclusion criteria. FINDINGS: Over the study period, a total of 45 453 papers were retrieved, of which 476 met our inclusion criteria. The cumulative number of children described in included publications totalled (at most) 41 396. The median number of children per paper was 6 (IQR 1-33). Nearly one-third of papers (30.2%) reported on a single child, and a further 28.3% reported on between 1 and 9 children. Half of all the publications originated from Asia. INTERPRETATION: Our prospective bibliographic analysis of paediatric COVID-19 publications demonstrated a steady increase in the number of papers over time. Understanding and policy evolved with new information that was gathered over the course of the study period. However, over half of publications were individual case reports or small case series, which may have had a limited contribution to advancement of knowledge. During a pandemic, literature should be interpreted with great caution, and clinical/policy decisions should be continually reviewed in light of emerging evidence.

Association Between Severity of Diabetic Ketoacidosis at Diagnosis and Multiple Autoimmunity in Children With Type 1 Diabetes Mellitus: A Study From a Greek Tertiary Centre.

OBJECTIVES: Type 1 diabetes mellitus is a chronic disorder associated with development of autoimmunity. In this work, we studied the relationship between severity of acidosis at diagnosis and future risk for autoimmunity development in children with type 1 diabetes. METHODS: We investigated the presence of associated autoimmunity in 144 children with type 1 diabetes (mean ± standard deviation: age, 12.44±4.76 years; diabetes duration, 4.41±3.70 years). We identified the presence of thyroid disease, celiac disease, autoimmune gastritis and adrenal autoimmunity, and retrospectively reviewed the files for presence of diabetic ketoacidosis at diagnosis. RESULTS: Autoimmunity prevalence was 16.7% for thyroid autoimmunity, 9.5% for celiac disease, 5% for gastric autoimmunity and 8.0% for multiple autoimmunities. There were strong associations between severe acidosis at diabetes diagnosis (pH<7.10) and development of thyroid autoimmunity (odds ratio [OR], 5.34; 95% confidence interval [CI], 1.90‒15.1; p<0.001), celiac disease (OR, 5.83; 95% CI, 1.19‒28.6; p=0.013), gastric autoimmunity (OR, 13.1; 95% CI, 1.22‒140; p=0.006) and multiple autoimmunity (OR, 26.7; 95% CI, 2.36‒301; p<0.01). The associations persisted after adjustment for sex, age at diabetes diagnosis, age at assessment, time since diabetes diagnosis and antiglutamic acid decarboxylase autoantibody status. CONCLUSIONS: The severity of acidosis at diagnosis is strongly associated with the development of associated autoimmune diseases in children with type 1 diabetes and could act as a predictive factor for multiple autoimmunity development. This association can be either due to effect of acidosis on immune system or to the presence of a more aggressive diabetes endotype.

Growth of children conceived by IVF and ICSI up to 12years of age.

Recent studies have given conflicting results regarding growth in children born following assisted reproductive treatments up to the age of 18years. It has been suggested that children conceived via IVF may be taller than naturally conceived children and that this may due to subtle epigenetic alteration of imprinted genes as a result of the IVF process. A prospective match-controlled study was performed to investigate the growth of children born in the UK following standard IVF and intracytoplasmic sperm injection (ICSI) up to the age of 12years. The study assessed 143 IVF and 166 ICSI children with 173 matched naturally conceived controls. Primary end-points were height and weight at various time points: birth, 5years, 7-9years and 10-12years. In addition, head circumference was assessed at birth. No significant differences were observed regarding head circumference, height and weight between the three groups at any of the time points. In conclusion, this preliminary study provides reassuring information regarding the growth of IVF and ICSI children up to 12years. Further studies must continue to investigate the growth and other outcomes in assisted-conception children as they develop through puberty into early adulthood.

Vitamin D prescribing in children in UK primary care practices: a population-based cohort study.

OBJECTIVE: To examine temporal changes in the incidence and patterns of vitamin D supplementation prescribing by general practitioners (GPs) between 2008 and 2016. DESIGN: Population-based cohort study. SETTING: UK general practice health records from The Health Improvement Network. PARTICIPANTS: Children aged 0 to 17 years who were registered with their general practices for at least 3 months. OUTCOME MEASURES: Annual incidence rates of vitamin D prescriptions were calculated, and rate ratios were estimated using multivariable Poisson regression to explore differences by sociodemographic factors. Data on the type of supplementation, dose, dosing schedule, linked 25-hydroxyvitamin D (25(OH)D) laboratory test results and clinical symptoms suggestive of vitamin D deficiency were analysed. RESULTS: Among 2 million children, the crude annual incidence of vitamin D prescribing increased by 26-fold between 2008 and 2016 rising from 10.8 (95% CI: 8.9 to 13.1) to 276.8 (95% CI: 264.3 to 289.9) per 100 000 person-years. Older children, non-white ethnicity and general practices in England (compared with Wales/Scotland/Northern Ireland) were independently associated with higher rates of prescribing. Analyses of incident prescriptions showed inconsistent supplementation regimens with an absence of pre-supplementation 25(OH)D concentrations in 28.7% to 56.4% of prescriptions annually. There was an increasing trend in prescribing at pharmacological doses irrespective of 25(OH)D concentrations, deviating in part from UK recommendations. Prescribing at pharmacological doses for children with deficient status increased from 3.8% to 79.4%, but the rise was also observed in children for whom guidelines recommended prevention doses (0% to 53%). Vitamin D supplementation at pharmacological doses was also prescribed in at least 40% of children with no pre-supplementation 25(OH)D concentrations annually. CONCLUSIONS: There has been a marked and sustained increase in vitamin D supplementation prescribing in children in UK primary care. Our data suggests that national guidelines on vitamin D supplementation for children are not consistently followed by GPs.

Trends in the Diagnosis of Vitamin D Deficiency.

BACKGROUND: Vitamin D has attracted considerable interest in recent years, and health care providers have reported large increases in vitamin D test requests. However, rates of diagnosis of vitamin D deficiency in clinical practice have not been investigated. We examined trends in diagnosis of vitamin D deficiency in children in England over time, and by sociodemographic characteristics. METHODS: Cohort study using primary care records of 711 788 children aged 0 to 17 years, from the Health Improvement Network database. Incidence rates for diagnosis of vitamin D deficiency were calculated per year between 2000 and 2014. Rate ratios exploring differences by age, sex, ethnicity, and social deprivation were estimated using multivariable Poisson regression. RESULTS: The crude rate of vitamin D deficiency diagnosis increased from 3.14 per 100 000 person-years in 2000 (95% confidence interval [CI], 1.31-7.54) to 261 per 100 000 person-years in 2014 (95% CI, 241-281). After accounting for changes in demographic characteristics, a 15-fold (95% CI, 10-21) increase in diagnosis was seen between 2008 and 2014. Older age (≥10 years), nonwhite ethnicity, and social deprivation were independently associated with higher rates of diagnosis. In children aged <5 years, diagnosis rates were higher in boys than girls, whereas in children aged ≥10 they were higher in girls. CONCLUSIONS: There has been a marked increase in diagnosis of vitamin D deficiency in children over the past decade. Future research should explore the drivers for this change in diagnostic behavior and the reasons prompting investigation of vitamin D status in clinical practice.

Incidence of hypocalcemic seizures due to vitamin D deficiency in children in the United Kingdom and Ireland.

CONTEXT: Anecdotal reports suggest that increasing numbers of children in the UK are presenting with clinical manifestations of vitamin D deficiency (VDD). However, the epidemiology of symptomatic VDD is largely undetermined; existing studies are limited to local case series, and national incidence estimates of disease burden are lacking. OBJECTIVE: To estimate the incidence of hypocalcaemic seizures secondary to VDD in children in the UK and Ireland, and describe the demographic and clinical features of cases. DESIGN AND SETTING: Prospective, population-based active surveillance study using the established British Paediatric Surveillance Unit (BPSU) methodology. POPULATION: Children aged 0-15 years, resident in the UK and Ireland, who developed a hypocalcaemic seizure due to VDD between September 2011 and September 2013. MAIN OUTCOME MEASURE: Overall incidence of hypocalcaemic seizures due to VDD in children age 0-15, and incidence stratified by age, sex, and ethnicity. RESULTS: Ninety one confirmed or probable cases were reported, equating to an overall annual incidence of 3.49 per million children age 0-15 years (95% CI: 2.81-4.26). Incidence was significantly greater in males compared to females, in infants compared to older children, and in children of South Asian or Black ethnicity compared to children from white ethnic backgrounds. CONCLUSIONS: Current implementation of public health policy in the UK is not successful in preventing children from developing one of the severe manifestations of VDD. Further studies are required to evaluate the epidemiology of symptomatic VDD more broadly in order to guide future public health policy decisions.

Maternal prepregnancy BMI and child cognition: a longitudinal cohort study.

OBJECTIVE: To examine the association between maternal prepregnancy BMI and cognitive performance in children at 5 and 7 years of age. METHODS: This is a secondary analysis of data from the Millennium Cohort Study, a prospective population based cohort of 19,517 children in the United Kingdom. Standardized cognitive assessments of children, involving components of the British Ability Scales, second edition and a number skills test, were performed at 5 and 7 years of age. Principal components analysis was used to identify a general cognitive ability factor (g) from individual test scores. Maternal prepregnancy BMI was retrospectively self-reported when children were 9 months old. Mixed-effects linear regression models were fitted, controlling for multiple socio-demographic factors, child's birth weight, child's BMI, maternal smoking, and maternal diabetes. Complete data were available for 11,025 children at 5 years, and 9882 children at 7 years. RESULTS: Maternal prepregnancy BMI was negatively associated with children's cognitive performance (g) at age 5 (P = .0069) and age 7 (P < .0001). The overall effect size was modest: a 10-point increase in maternal BMI was associated with a decrease in cognitive performance of ~1/10th of an SD at age 7. CONCLUSIONS: Maternal prepregnancy BMI is negatively associated with children's cognitive performance, even after adjusting for multiple socio-demographic confounders and children's BMI. The relationship appears to become stronger as children get older, although the overall effect size is modest. In utero fetal programming or residual confounding may explain these findings.