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Many additives, some of which have no nutritional value, can be legally used in processed foods. They intensify colour, thicken, increase shelf life and enhance flavour. Regulatory authorities issue approvals as safe within acceptable quantitative limits. Ultra-processed foods (UPFs) contain combinations of all these additives and are particularly attractive to children.Many publications suggest that artificial colourants, benzoate preservatives, non-caloric sweeteners, emulsifiers and their degradation derivatives have adverse effects by increasing risks of mental health disorders, attention deficit hyperactivity disorder, cardiovascular disease, metabolic syndrome and potential carcinogenic effects.A systematic review has established that artificial azo dye food colourants (AFCs) and sodium benzoate preservative cause disturbed behaviour in children. AFCs and benzoates in animal models have neurotoxic properties through gut microbial generation of toxic metabolites. Observational studies show associations between high emulsifier intake and cardiovascular disease. Animal models and in vitro studies have highlighted neurotoxic, cytotoxic, genotoxic and carcinogenic effects. High intake of non-caloric sweeteners has been linked to cardiovascular disease and depression in adults and is linked to childhood obesity.Little research has focused on children who are the largest consumers of UPFs. Potentially, they are a ticking time bomb for adult obesity, metabolic syndrome, cardiovascular diseases, mental health disorders and cancers. Based on risk/benefit analysis, azo dye AFCs should be banned. Benzoates, emulsifiers and sweeteners require assessment of quantitative limits and cumulative effects of combinations. Consumers purchasing UPFs require information through ingredient health warnings and recommendations to use natural unprocessed foods which have well-described health-promoting properties.

Observational studies suggest high prenatal vitamin D intake may be associated with reduced childhood wheezing. We examined the effect of prenatal vitamin D on childhood wheezing in an interventional study. We randomised 180 pregnant women at 27 weeks gestation to either no vitamin D, 800 IU ergocalciferol daily until delivery or single oral bolus of 200,000 IU cholecalciferol, in an ethnically stratified, randomised controlled trial. Supplementation improved but did not optimise vitamin D status. Researchers blind to allocation assessed offspring at 3 years. Primary outcome was any history of wheeze assessed by validated questionnaire. Secondary outcomes included atopy, respiratory infection, impulse oscillometry and exhaled nitric oxide. Primary analyses used logistic and linear regression. We evaluated 158 of 180 (88%) offspring at age 3 years for the primary outcome. Atopy was assessed by skin test for 95 children (53%), serum IgE for 86 (48%), exhaled nitric oxide for 62 (34%) and impulse oscillometry of acceptable quality for 51 (28%). We found no difference between supplemented and control groups in risk of wheeze [no vitamin D: 14/50 (28%); any vitamin D: 26/108 (24%) (risk ratio 0.86; 95% confidence interval 0.49, 1.50; P = 0.69)]. There was no significant difference in atopy, eczema risk, lung function or exhaled nitric oxide between supplemented groups and controls. Prenatal vitamin D supplementation in late pregnancy that had a modest effect on cord blood vitamin D level, was not associated with decreased wheezing in offspring at age three years. Controlled-Trials.com ISRCTN68645785.

We undertook a randomised, double-blinded, placebo-controlled, crossover trial to test whether intake of artificial food colour and additives (AFCA) affected childhood behaviour. 153 3-year-old and 144 8/9-year-old children were included in the study. The challenge drink contained sodium benzoate and one of two AFCA mixes (A or B) or a placebo mix. The main outcome measure was a global hyperactivity aggregate (GHA), based on aggregated z-scores of observed behaviours and ratings by teachers and parents, plus, for 8/9-year-old children, a computerised test of attention. This clinical trial is registered with Current Controlled Trials (registration number ISRCTN74481308). Analysis was per protocol. 16 3-year-old children and 14 8/9-year-old children did not complete the study, for reasons unrelated to childhood behaviour. Mix A had a significantly adverse effect compared with placebo in GHA for all 3-year-old children (effect size 0·20 [95% CI 0·01–0·39], p=0·044) but not mix B versus placebo. This result persisted when analysis was restricted to 3-year-old children who consumed more than 85% of juice and had no missing data (0·32 [0·05–0·60], p=0·02). 8/9-year-old children showed a significantly adverse effect when given mix A (0·12 [0·02–0·23], p=0·023) or mix B (0·17 [0·07–0·28], p=0·001) when analysis was restricted to those children consuming at least 85% of drinks with no missing data. Artificial colours or a sodium benzoate preservative (or both) in the diet result in increased hyperactivity in 3-year-old and 8/9-year-old children in the general population.

Background Young people’s experiences of healthcare as they move into adult services can have a major impact on their health, and the transition period for young people with sickle cell disease (SCD) needs improvement. In this study, we explore how young people with SCD experience healthcare during this period of transition. Methods We conducted a co-produced longitudinal qualitative study, including 80 interviews in 2016–2017 with young people with SCD aged 13–21 (mean age 16.6) across two cities in England. We recruited 48 participants (30 female, 18 male): 27 interviews were one-off, and 53 were repeated 2–3 times over approximately 18 months. We used an inductive analytical approach, combining elements of Grounded Theory and thematic analysis. Results Participants reported significant problems with the care they received in A&E during painful episodes, and in hospital wards as inpatients during unplanned healthcare. They experienced delays in being given pain relief and their basic care needs were not always met. Participants said that non-specialist healthcare staff did not seem to know enough about SCD and when they tried to work with staff to improve care, staff often seemed not prepared to listen to them or act on what they said. Participants said they felt out of place in adult wards and uncomfortable with the differences in adult compared with paediatric wards. Because of their experiences, they tried to avoid being admitted to hospital, attempting to manage their painful episodes at home and accessing unplanned hospital care only as a last resort. By contrast, they did not report having problems within SCD specialist services during planned, routine care. Conclusions Our study underscores the need for improvements to make services youth-friendly and youth-responsive, including training staff in SCD-specific care, compassionate care and communication skills that will help them elicit and act on young people’s voices to ensure they are involved in shaping their own healthcare. If young people are prevented from using transition skills (self-management, self-advocacy), or treated by staff who they worry do not have enough medical competency in their condition, they may well lose their trust in services, potentially compromising their own health.

Avoidance of allergens in the treatment of asthma has hitherto not achieved significant benefit despite the strong evidence that allergy both increases severity and contributes to exacerbations of asthma. House dust mite, cat and dog allergens are the most common perennial allergic triggers and most avoidance strategies have focused on reducing exposures in bedrooms. Cochrane reviews have suggested that they neither significantly reduce allergen levels nor improve asthma. While the lack of efficacy may be assumed to be a consequence of exposures occurring outside the bedroom, prolonged sleep is associated with increased susceptibility to bronchospasm and airway inflammation. Thus, if efficient reductions in allergen exposure could be achieved during sleep, it might be expected that this would result in significant improvements in control of asthma. The temperature-controlled laminar airflow (TLA) is a system which can be employed over beds in a domestic environment and results in massive reductions in particulate exposure of recumbent subjects, including highly respirable allergens such as Fel. D1 from cats. Trials of TLA have demonstrated highly significant improvements in asthma quality of life and reductions on airway inflammation as monitored by exhaled nitric oxide levels. Furthermore, in patients with the worst disease, severe exacerbation frequency was significantly reduced. Based on UK health-service costs, the use of TLA falls well below the National Institute for Health and Care Excellence (NICE) threshold for the incremental cost effectiveness ratio (ICER) per quality adjusted life year (QALY). Indeed, for those with frequent exacerbations, it is cost saving and should be prescribed for such allergic asthmatic patients.

Correspondence to Professor John O Warner, Paediatrics, Imperial College London National Heart and Lung Institute, London, UK; j.o.warner@imperial.ac.uk The medical research cycle is often initiated by clinical observation and epidemiological study which identify associations between clinical manifestations and biological or environmental factors. Subsequent controlled intervention trials, despite being published in high-impact journals with evidence which should have modified clinical practice for patient benefit, did not improve patient outcomes. Successive reports on the parlous state of care for patients with allergic diseases were not followed by meaningful Department of Health (DH) action other than to commission Royal College of Paediatrics and Child Health to produce guidance on integrated care pathways. Studies showed that genetic variation (such as filaggrin gene polymorphisms) and inflammation disrupt the epidermal skin barrier, increasing the risk of eczema and allergic sensitisation through the skin.10 Trials targeting the skin barrier defect using emollients were disappointing.11 However, lower peanut allergy prevalence associated with earlier peanut complementary feeding in Israel compared with UK led to the LEAP and EAT trials.

The first nine months from conception to birth involves greater changes than at any other time in life, affecting organogenesis, endocrine, metabolic and immune programming. It has led to the concept that the “first 1000 days” from conception to the second birthday are critical in establishing long term health or susceptibility to disease. Immune ontogeny is predominantly complete within that time and is influenced by the maternal genome, health, diet and environment pre-conception and during pregnancy and lactation. Components of the immunological protection of the pregnancy is the generation of Th-2 and T-regulatory cytokines with the consequence that neonatal adaptive responses are also biased towards Th-2 (allergy promoting) and T-regulatory (tolerance promoting) responses. Normally after birth Th-1 activity increases while Th-2 down-regulates and the evolving normal human microbiome likely plays a key role. This in turn will have been affected by maternal health, diet, exposure to antibiotics, mode of delivery, and breast or cow milk formula feeding. Complex gene/environment interactions affect outcomes. Many individual nutrients affect immune mechanisms and variations in levels have been associated with susceptibility to allergic disease. However, intervention trials employing single nutrient supplementation to prevent allergic disease have not achieved the expected outcomes suggested by observational studies. Investigation of overall dietary practices including fresh fruit and vegetables, fish, olive oil, lower meat intake and home cooked foods as seen in the Mediterranean and other healthy diets have been associated with reduced prevalence of allergic disease. This suggests that the “soup” of overall nutrition is more important than individual nutrients and requires further investigation both during pregnancy and after the infant has been weaned. Amongst all the potential factors affecting allergy outcomes, modification of maternal and infant nutrition and the microbiome are easier to employ than changing other aspects of the environment but require large controlled trials before recommending changes to current practice.

Some observational studies have suggested that higher prenatal Vitamin D intake may be associated with improved health outcomes in childhood. However there have been mixed results in this area with some negative studies, especially for effects on atopic and respiratory outcomes. We examined the effect of prenatal Vitamin D on healthcare utilisation in the first three years of life. In an ethnically stratified randomised controlled trial conducted at St Mary's Hospital London, 180 women at 27 weeks gestation were allocated to no Vitamin D, 800 IU ergocalciferol daily until delivery, or a single oral bolus of 200,000 IU cholecalciferol. Participants were randomised in blocks of 15 using computer-generated numbers and investigators were blinded to group assignment. Supplementation increased maternal and cord blood 25(OH) vitamin D concentrations, but levels remained lower than current recommendations. Primary health economic outcome was overall cost of unscheduled healthcare utilisation in the first three years of life as documented in the child's electronic health record. Secondary outcomes included cost attributable to: primary and secondary healthcare visits, respiratory and atopic complaints, cost in years 1, 2 and 3 of life and cost and frequency of prescribed medication. All costs were calculated as pounds sterling. Differences between groups were analysed using unpaired t-test or Mann-Whitney U test, and analysis of variance for adjusted analyses. We assessed 99/180 (55%) complete electronic health records, control (n = 31), daily (n = 36) and bolus (n = 32). We found no difference in total healthcare utilisation costs between the control and daily (mean difference in costs in pounds sterling 1.02, 95%CI -1.60, 1.65; adjusted 1.07, 95%CI -1.62, 1.86) or control and bolus groups (mean difference -1.58, 95%CI -2.63, 1.06; adjusted -1.40, 95%CI -2.45, 1.24). There were no adverse effects of supplementation reported during the trial. We found no evidence that prenatal vitamin D supplementation from 27 weeks gestation to delivery, at doses which failed to completely correct maternal vitamin D deficiency, influence overall healthcare utilisation in children in the first 3 years. Controlled-Trials.com ISRCTN68645785.

The COVID-19 pandemic has potentially had a negative impact on the mental health and well-being of individuals and families. Anxiety levels and risk factors within particular populations are poorly described. This study aims to evaluate confidence, understanding, trust, concerns, and levels of anxiety during the COVID-19 pandemic in the general population and assess risk factors for increased anxiety. We launched a cross-sectional online survey of a large Russian population between April 6 and 15, 2020, using multiple social media platforms. A set of questions targeted confidence, understanding, trust, and concerns in respondents. The State-Trait Anxiety Inventory was used to measure anxiety. Multiple linear regressions were used to model predictors of COVID-19-related anxiety. The survey was completed by 23,756 out of 53,966 (44.0% response rate) unique visitors; of which, 21,364 were residing in 62 areas of Russia. State Anxiety Scale (S-Anxiety) scores were higher than Trait Anxiety Scale scores across all regions of Russia (median S-Anxiety score 52, IQR 44-60), exceeding published norms. Time spent following news on COVID-19 was strongly associated with an increased S-Anxiety adjusted for baseline anxiety level. One to two hours spent reading COVID-19 news was associated with a 5.46 (95% CI 5.03-5.90) point difference, 2-3 hours with a 7.06 (95% CI 6.37-7.74) point difference, and more than three hours with an 8.65 (95% CI 7.82-9.47) point difference, all compared to less than 30 minutes per day. Job loss during the pandemic was another important factor associated with higher S-Anxiety scores (3.95, 95% CI 3.31-4.58). Despite survey respondents reporting high confidence in information regarding COVID-19 as well as an understanding of health care guidance, they reported low overall trust in state and local authorities, and perception of country readiness. Among Russian respondents from multiple social media platforms, there was evidence of higher levels of state anxiety associated with recent job loss and increased news consumption, as well as lower than expected trust in government agencies. These findings can help inform the development of key public health messages to help reduce anxiety and raise perceived trust in governmental response to this current national emergency. Using a similar methodology, comparative surveys are ongoing in other national populations.