Background Maternal vitamin-D and omega-3 fatty acid (DHA) deficiencies during pregnancy have previously been associated with offspring neurodevelopmental traits. However, observational study designs cannot distinguish causal effects from confounding.Methods First, we conducted Mendelian randomisation (MR) using genetic instruments for vitamin-D and DHA identified in independent genome-wide association studies (GWAS). Outcomes were (1) GWAS for traits related to autism and ADHD, generated in the Norwegian mother, father, and child cohort study (MoBa) from 3 to 8 years, (2) autism and ADHD diagnoses. Second, we used mother-father-child trio-MR in MoBa (1) to test causal effects through maternal nutrient levels, (2) to test effects of child nutrient levels, and (3) as a paternal negative control.Results Associations between higher maternal vitamin-D levels on lower ADHD related traits at age 5 did not remain after controlling for familial genetic predisposition using trio-MR. Furthermore, we did not find evidence for causal maternal effects of vitamin-D/DHA levels on other offspring traits or diagnoses. In the reverse direction, there was evidence for a causal effect of autism genetic predisposition on lower vitamin-D levels and of ADHD genetic predisposition on lower DHA levels.Conclusions Triangulating across study designs, we did not find evidence for maternal effects. We add to a growing body of evidence that suggests that previous observational associations are likely biased by genetic confounding. Consequently, maternal supplementation is unlikely to influence these offspring neurodevelopmental traits. Notably, genetic predisposition to ADHD and autism was associated with lower DHA and vitamin-D levels respectively, suggesting previous associations might have been due to reverse causation.

Contact tracing was used globally to prevent onwards transmission of COVID-19. Tracing contacts alone is unlikely to be sufficient in controlling community transmission, due to the pre-symptomatic, overdispersed and airborne nature of COVID-19 transmission. We describe and demonstrate the validity of a national enhanced contact tracing programme for COVID-19 cluster surveillance in England. Data on cases occurring between October 2020 and September 2021 were extracted from the national contact tracing system. Exposure clusters were identified algorithmically by matching ≥2 cases attending the same event, identified by matching postcode and event category within a 7-day rolling window. Genetic validity was defined as exposure clusters with ≥2 cases from different households with identical viral sequences. Exposure clusters were fuzzy matched to the national incident management system (HPZone) by postcode and setting description. Multivariable logistic regression modelling was used to determine cluster characteristics associated with genetic validity. Over a quarter of a million (269,470) exposure clusters were identified. Of the eligible clusters, 25% (3,306/13,008) were genetically valid. 81% (2684/3306) of these were not recorded on HPZone and were identified on average of one day earlier than incidents recorded on HPZone. Multivariable analysis demonstrated that exposure clusters occurring in workplaces (aOR = 5·10, 95% CI 4·23-6·17) and education (aOR = 3·72, 95% CI 3·08-4·49) settings were those most strongly associated with genetic validity. Cluster surveillance using enhanced contact tracing in England was a timely, comprehensive and systematic approach to the detection of transmission events occurring in community settings. Cluster surveillance can provide intelligence to stakeholders to support the assessment and management of clusters of COVID-19 at a local, regional, and national level. Future systems should include predictive modelling and network analysis to support risk assessment of exposure clusters to improve the effectiveness of enhanced contract tracing for outbreak detection.

Mercury is highly toxic metal found in trace quantities in common foods. There is concern that exposure during pregnancy could impair infant development. Epidemiological evidence is mixed, but few studies have examined postnatal growth. Differences in nutrition, exposures, and the living environment after birth may make it easier to detect a negative impact from mercury toxicity on infant growth. This study includes 544 mother–child pairs from the Avon Longitudinal Study of Parents and Children. Blood mercury was measured in early pregnancy and infant weight at 10 intervals between 4 and 61 months. Mixed-effect models were used to estimate the change in infant weight associated with prenatal mercury exposure. The estimated difference in monthly weight gain was −0.02 kg per 1 standard deviation increase in Hg (95% confidence intervals: −0.10 to 0.06 kg). When restricted to the 10th decile of Hg, the association with weight at each age level was consistently negative but with wide confidence intervals. The lack of evidence for an association may indicate that at Hg levels in this cohort (median 1.9 µg/L) there is minimal biological impact, and the effect is too small to be either clinically relevant or detectable.

Maternal vitamin-D and omega-3 fatty acid (DHA) deficiencies during pregnancy have previously been associated with offspring neurodevelopmental traits. Observational study designs cannot distinguish causal intrauterine effects from unmeasured confounding. First, we conducted Mendelian randomisation (MR) using genetic instruments for vitamin-D and DHA identified in independent genome-wide association studies (GWAS). Outcomes were 1) GWAS for autism and ADHD traits, generated in the Norwegian Mother, Father and Child cohort study (MoBa) from 3-8 years, 2) PGC GWAS of autism and ADHD diagnoses. Second, we used mother-father-child trio-MR in MoBa 1) to estimate causal effects through maternal intrauterine exposure, 2) to estimate effects of child nutrient levels, and 3) as a paternal negative control. Using MR, our findings did not support causal intrauterine effects of vitamin-D or DHA levels on offspring traits nor diagnoses. In the reverse direction, there was evidence for a causal effect of autism genetic liability on lower Vitamin-D levels and of ADHD genetic liability on lower DHA levels. In trio-MR, there was evidence for an effect of higher maternal Vitamin-D levels on reduced ADHD traits at age 5. However, these effects attenuated after controlling for familial polygenic risk, suggesting that these associations are unlikely intrauterine. Triangulating across study designs, we did not find evidence for intrauterine effects. We add to a growing body of evidence which suggests that previous observational associations are likely biased by genetic confounding. Consequently, supplementation in pregnancy is unlikely to influence the neurodevelopmental traits included in this study.

Mercury has high industrial utility and is present in many products, and environmental contamination and occupational exposure are widespread. There are numerous biological systems involved in the absorption, metabolism, and excretion of Hg, and it is possible that some systems may be impacted by genetic variation. If so, genotype may affect tissue concentrations of Hg and subsequent toxic effects. Genome-wide association testing was performed on blood Hg samples from pregnant women of the Avon Longitudinal Study of Parents and Children (n = 2893) and children of the Human Early Life Exposome (n = 1042). Directly-genotyped single-nucleotide polymorphisms (SNPs) were imputed to the Haplotype Reference Consortium r1.1 panel of whole genotypes and modelled againstlog-transformed Hg. Heritability was estimated using linkage disequilibrium score regression. The heritability of Hg was estimated as 24.0% (95% CI: 16.9% to 46.4%) in pregnant women, but could not be determined in children. There were 16 SNPs associated with Hg in pregnant women above a suggestive p-value threshold (p < 1 × 10−5), and 21 for children. However, no SNP passed this threshold in both studies, and none were genome-wide significant (p < 5 × 10−8). SNP-Hg associations were highly discordant between women and children, and this may reflect differences in metabolism, a gene–age interaction, or dose–response effects. Several suggestive variants had plausible links to Hg metabolism, such as rs146099921 in metal transporter SLC39A14, and two variants (rs28618224, rs7154700) in potassium voltage-gated channel genes. The findings would benefit from external validation, as suggestive results may contain both true associations and false positives.

There is evidence that tissue concentrations of mercury (Hg) and selenium (Se) are predicted by numerous dietary, sociodemographic, environmental, and genetic factors. This study aimed to estimate the relative importance of predictors of Hg and Se concentrations in blood samples taken from pregnant women. The Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK measured whole blood Hg and Se concentrations in 3,972 pregnant women. We identified 30 potential predictors of Hg and 24 of Se, which were evaluated using cross-validated random forests to identify the optimal models for predictive power. The relative importance of individual variables was estimated by averaging the added-R2 per predictor. Linkage disequilibrium score regression was used to estimate the variance explained by genotype. A multivariable model of 14 predictors explained 22.4% of Hg variance (95% CI: 13.0 to 37.1), including 6.9% from blood Se and 3.2% from white fish consumption. There were 11 predictors which explained 15.3% of Se variance (CI: 8.9 to 25.9), including 6.4% from blood Hg, 1.3% from blood lead, and 1.3% from oily fish. Measured genetic variation explained 30% of Hg variance (CI: 8.4 to 51.5) and 37.5% of Se (CI: 10.4 to 64.5). A high proportion of Hg and Se variance could be explained from dietary, sociodemographic, metabolic, and genetic factors. Seafood consumption was less predictive of Hg than may be expected and other factors should be considered when determining risk of exposure. There was tentative evidence that genotype is a major contributor to Hg and Se variation, possibly by modifying the efficacy of internal metabolism.

Each September in England, ≈1 million students relocate to study at universities. To determine COVID-19 cases and outbreaks among university students after their return to university during the COVID pandemic in September 2020, we identified students with COVID-19 (student case-patients) by reviewing contact tracing records identifying attendance at university and residence in student accommodations identified by matching case-patients’ residential addresses with national property databases. We determined COVID-19 rates in towns/cities with and without a university campus. We identified 53,430 student case-patients during September 1–December 31, 2020, which accounted for 2.7% of all cases during this period. Student case-patients increased rapidly after the start of the term, driven initially by cases and outbreaks in student accommodations. Case rates among students 18–23 years of age doubled at the start of term in towns with universities. Our findings highlight the need for face-to-face and control measures to reduce virus transmission.

Abstract Background There has been a growing interest in the association between maternal levels of vitamin D during pregnancy and offspring autism. However, whether any associations reflect causal effects is still inconclusive. Methods We used data from a UK-based pregnancy cohort study (Avon Longitudinal Study of Parents and Children) comprising 7689 births between 1991 and 1992 with maternal blood vitamin D levels recorded during pregnancy and at least one recorded outcome measure, including autism diagnosis and autism-associated traits. The association between each outcome with seasonal and gestational age-adjusted maternal serum 25-hydroxyvitamin D during pregnancy was estimated using confounder-adjusted regression models. Multiple imputation was used to account for missing data, and restricted cubic splines were used to investigate nonlinear associations. Mendelian randomization was used to strengthen causal inference. Results No strong evidence of an association between maternal serum 25-hydroxyvitamin D during pregnancy and any offspring autism-associated outcome was found using multivariable regression analysis (autism diagnosis: adjusted OR = 0.98, 95% CI = 0.90–1.06), including with multiple imputation (autism diagnosis: adjusted OR = 0.99, 95% CI = 0.93–1.06), and no evidence of a causal effect was suggested by Mendelian randomization (autism diagnosis: causal OR = 1.08, 95% CI = 0.46–2.55). Some evidence of increased odds of autism-associated traits at lower levels of maternal serum 25-hydroxyvitamin D was found using spline analysis. Limitations Our study was potentially limited by low power, particularly for diagnosed autism cases as an outcome. The cohort may not have captured the extreme lows of the distribution of serum 25-hydroxyvitamin D, and our analyses may have been biased by residual confounding and missing data. Conclusions The present study found no strong evidence of a causal link between maternal vitamin D levels in pregnancy and offspring diagnosis or traits of autism.

Neurodevelopmental delays can interfere with children’s engagement with the world and further development, and may have negative consequences into adulthood. Mercury is highly toxic and may negatively influence neurodevelopment because it can freely cross the placenta and accumulate in the fetal brain. We searched four publication databases (Embase, PsycINFO, PubMed/MEDLINE, Scopus) for studies examining the relationship between early life mercury exposure and scores on neurodevelopmental performance measures in children aged 0 to 5 years old. Study quality was assessed using the National Institutes of Health (NIH) Quality Assessment Tool. Thirty-two prospective studies were included in the review. Neurodevelopmental performance was measured using 23 different scales, most commonly the Bayley Scales of Infant and Toddler Development (BSID). In most cases, the evidence for an association between mercury and neurodevelopment was weak. There did not appear to be exceptions for particular childhood ages, outcome scales, or mercury levels. The small number of results to the contrary were more likely to be studies which did not meet our high-quality criteria, and could be a consequence of multiple testing, selection bias, or incomplete confounder adjustment. Based on current evidence, dietary mercury exposure during pregnancy is unlikely to be a risk factor for low neurodevelopmental functioning in early childhood.

A subset of events within the UK Government Events Research Programme (ERP), developed to examine the risk of transmission of COVID-19 from attendance at events, was examined to explore the public health impact of holding mass sporting events. We used contact tracing data routinely collected through telephone interviews and online questionnaires, to describe the potential public health impact of the large sporting and cultural events on potential transmission and incidence of COVID-19. Data from the EURO 2020 matches hosted at Wembley identified very high numbers of individuals who tested positive for COVID-19 and were traced through NHS Test & Trace. This included both individuals who were potentially infectious (3036) and those who acquired their infection during the time of the Final (6376). This is in contrast with the All England Lawn Tennis Championships at Wimbledon, where there were similar number of spectators and venue capacity but there were lower total numbers of potentially infectious cases (299) and potentially acquired cases (582). While the infections associated with the EURO 2020 event may be attributed to a set of socio-cultural circumstances which are unlikely to be replicated for the forthcoming sporting season, other aspects may be important to consider including mitigations for spectators to consider such as face coverings when travelling to and from events, minimising crowding in poorly ventilated indoor spaces such as bars and pubs where people may congregate to watch events, and reducing the risk of aerosol exposure through requesting that individuals avoid shouting and chanting in large groups in enclosed spaces.

A systematic review and meta-analysis to determine the association between active maternal smoking and cleft lip and palate etiology. Medline, Embase, Web of Science and the Cochrane Library from inception to November, 2020. Observational studies of cigarette smoking habits in pregnant women. Outcomes included cleft lip and/or palate, cleft lip ± palate and cleft palate only. Publication bias analyses were performed and the Newcastle Ottawa scales were used to assess study quality. Fixed or random effect models were used in the meta-analysis, dependent on risk of statistical heterogeneity. Forty-five studies were eligible for inclusion of which 11 were cohort and 34 were case–control studies. Sixteen studies were of sufficient standard for inclusion in the meta-analysis. The summary odds ratio for the association between smoking and cleft lip and/or palate was 1.42 (95%CI 1.27-1.59) with a population attributable fraction of 4% (95%CI 3%-5%). There was limited evidence to show a dose–response effect of smoking. This review reports a moderate association between maternal smoking and orofacial cleft but the overall quality of the conventional observational studies included was poor. There is a need for high quality and novel research strategies to further define the role of smoking in the etiology of cleft lip and palate.

Objectives To estimate occupation risk from COVID-19 among teachers and others working in schools using publicly available data on mortality in England and Wales. Design Analysis of national death registration data from the Office for National Statistics. Setting England and Wales, 8 March-28 December 2020, during the COVID-19 pandemic. Participants The total working age population in England and Wales plus those still working aged over 65 years. Primary and secondary outcomes Death with COVID-19 as a primary outcome and death from all causes as a secondary outcome. Results Across occupational groups, there was a strong correlation between COVID-19 mortality and both non-COVID-19 and all-cause mortality. The absolute mortality rates for deaths with COVID-19 were low among those working in schools (from 10 per 100 000 in female primary school teachers to 39 per 100 000 male secondary school teachers) relative to many other occupations (range: 9-50 per 100 000 in women; 10-143 per 100 000 in men). There was weak evidence that secondary school teachers had slightly higher risks of dying with COVID-19 compared with the average for all working-aged people, but stronger evidence of a higher risk compared with the average for all professionals; primary school teachers had a lower risk. All-cause mortality was also higher among all teachers compared with all professionals. Teaching and lunchtime assistants were not at higher risk of death from COVID-19 compared with all working-aged people. Conclusion There was weak evidence that COVID-19 mortality risk for secondary school teachers was above expectation, but in general school staff had COVID-19 mortality risks which were proportionate to their non-COVID-19 mortality risk.

Background: Universities in England returned to in–person teaching in September 2020, requiring a large migration of students across the country. To understand the impact this had on COVID–19 transmission, we identified and described student cases during the 2020 autumn term. Methods: Student COVID–19 cases were identified from two sources: contact tracing records identifying attendance at university prior to onset and residence in student accommodation identified from matching cases' residential addresses against national property databases. Residential outbreaks were defined as ≥2 cases with specimen dates within 14 days residing in the same property. A matched analysis of COVID–19 rates and trends in towns/cities with and without a university campus was undertaken. Findings: We identified 53,430 student cases between 1 September and 31 December 2020, constituting 2·7% of all cases (n=1,999,180) in this time period; 39,032 reported attendance at a university during contact tracing; 19,901 resided in student accommodation premises. Cases increased rapidly following the start of term driven initially by cases in student accommodation. Over two thirds (72·2% n=14,375) of cases in student accommodation were part of a residential outbreak.Towns/cities with universities saw a threefold increase in rates amongst 18–23 year olds compared to non–university towns. Interpretation: This study suggests that the return to university teaching and associated movement of students in England was linked to large increases in SARS–CoV–2 transmission amongst this population and potentially contributing to subsequent large increases in the wider population surrounding a campus. Funding Information: No funding was received for this work. Declaration of Interests: None of the authors declare any conflicts of interest.Ethics Approval Statement: UKHSA has legal permission, provided by Regulation 3 of The Health Service (Control of Patient Information) Regulations 2002, to process patient confidential information for national surveillance of communicable diseases and as such, individual patient consent is not required.

The intrauterine environment is critical for healthy prenatal growth and affects neonatal survival and later health. Mercury is a toxic metal which can freely cross the placenta and disrupt a wide range of cellular processes. Many observational studies have investigated mercury exposure and prenatal growth, but no prior review has synthesised this evidence. Four relevant publication databases (Embase, MEDLINE/PubMed, PsycINFO, and Scopus) were systematically searched to identify studies of prenatal mercury exposure and birth weight, birth length, or head circumference. Study quality was assessed using the NIH Quality Assessment Tool, and results synthesised in a narrative review. Twenty-seven studies met the review criteria, these were in 17 countries and used 8 types of mercury biomarker. Studies of birth weight (total = 27) involving populations with high levels of mercury exposure, non-linear methods, or identified as high quality were more likely to report an association with mercury, but overall results were inconsistent. Most studies reported no strong evidence of association between mercury and birth length (n = 14) or head circumference (n = 14). Overall, our review did not identify strong evidence that mercury exposure leads to impaired prenatal growth, although there was some evidence of a negative association of mercury with birth weight.

Coatings deposited by cladding serve multiple purpose, ranging from hard, wear and corrosion-resistant layers to fully functional optical and spectral selective coating materials. This paper is aimed at assessing the occupational health issues arising during preplaced cladding of several metallic powders (based on nickel, iron and aluminum) on carbon steel substrates, having as purpose the obtaining of hard and corrosion-resistant coatings. The emissions formed during the cladding process are analyzed, and their composition is expressed in terms of airborne metal species per unit volume of air.The toxic emissions are correlated to the parameters of the laser cladding process, such as for example the deposition speed or laser power, as well to the performance of the material (hardness, microstructure, etc.), concluding on the best working conditions for the analyzed cases

AbstractObjectivesTo estimate occupation risk from Covid19 among teachers and others working in schools using publicly available data on mortality in England and Wales.DesignAnalysis of national death registration data from the Office for National Statistics.SettingEngland and Wales, March 20th to 28th December 2020, during the Covid19 pandemic.ParticipantsThe total working age population in England and Wales plus those still working aged over 65.Primary and Secondary outcomesDeath with Covid19 as a primary outcome and death from all causes as a secondary outcome.ResultsAcross occupational groups there was a strong correlation between Covid19 mortality and both non-Covid19 and all-cause mortality. The absolute mortality rates for deaths with Covid19 were low amongst those working in schools (from 10 per 100,000 in female primary school teachers to 39 per 100,000 male secondary school teachers) relative to many other occupations (range: 10 to 143 per 100,000 in men; 9 to 50 per 100,000 in women).There was weak evidence that secondary school teachers had slightly higher risks of dying with Covid19 compared to the average for all working aged people, but stronger evidence of a higher risk compared to the average for all professionals; primary school teachers had a lower risk. All-cause mortality was also higher amongst all teachers compared to all professionals. Teaching and lunchtime assistants were not at higher risk of death from Covid19 compared with all working aged people.ConclusionThere was weak evidence that Covid19 mortality risk for secondary school teachers was above expectation, but in general school staff had Covid19 mortality risks which were proportionate to their non-covid mortality risk.Strengths and limitations of this studyWe used routinely collected data on all deaths in England and Wales;, which are near-complete and not susceptible to serious ascertainment biases.We were able to compare mortality data for teachers and other school workers with all other occupational groups and with the working-age population.The number of deaths due to Covid19 were small and thus differences between the specific occupational groups were imprecisely estimated.We did not have access to individual level mortality data so were not able to account for potential confounders such as comorbidities or household size.For those working in school aged over 65 we had neither mortality rates per 100,000 nor total numbers within the group; we only had number of deaths and a 5-year average and we do not know whether the denominators have changed for this group over the last 5 years.