Environmental and genetic predictors of whole blood mercury and selenium concentrations in pregnant women in a UK birth cohort.

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.

COVID-19 cluster surveillance using exposure data collected from routine contact tracing: The genomic validation of a novel informatics-based approach to outbreak detection in England.

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.

Genome-Wide Association Study of Blood Mercury in European Pregnant Women and Children.

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.

Maternal vitamin D during pregnancy and offspring autism and autism-associated traits: a prospective cohort study.

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.

Effect of Returning University Students on COVID-19 Infections in England, 2020.

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.

Prenatal Mercury Exposure and Neurodevelopment up to the Age of 5 Years: A Systematic Review.

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.

Public health impact of mass sporting and cultural events in a rising COVID-19 prevalence in England.

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.

Prenatal Mercury Exposure and Infant Weight Trajectories in a UK Observational Birth Cohort.

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 Cigarette Smoking and Cleft Lip and Palate: A Systematic Review and Meta-Analysis.

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.

Was the risk of death among the population of teachers and other school workers in England and Wales due to COVID-19 and all causes higher than other occupations during the pandemic in 2020? An ecological study using routinely collected data on deaths from the Office for National Statistics.

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.

Mercury and Prenatal Growth: A Systematic Review.

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.

Contribution of the BioFire® FilmArray® Meningitis/Encephalitis Panel: Assessing Antimicrobial Duration and Length of Stay.

INTRODUCTION: Traditional evaluation of meningitis includes cerebrospinal fluid (CSF) culture and gram stain to pinpoint specific causal organisms. The BioFire® FilmArray® Meningitis/Encephalitis (ME) Panel has been implemented as a more timely evaluation method. This study sought to assess if the BioFire® ME Panel was associated with a decreased length of stay or decreased antimicrobial duration when used in the diagnosis of meningitis or encephalitis. METHODS: A case, historical-control, chart review was performed on patients admitted to a regional medical center with CSF pleocytosis during Cohort 1 (the year prior to BioFire® ME Panel implementation) and Cohort 2 (the year after BioFire® ME Panel implementation). Length of hospital stay, duration of antimicrobials, and BioFire® ME Panel result were gathered and analyzed. RESULTS: Average length of stay for both cohorts was about four hospital days. Approximately three-fourths of all patients received antibiotic/antiviral treatment with an average of three days duration. No significant differences were observed between groups. The mean (median) duration of antimicrobials in the year prior to and after the BioFire® ME Panel implementation was 3.6 (3) and 3.1 (2) days, respectively (p = 0.835). The mean (median) length of stay in the year prior to and after the BioFire® ME Panel implementation was 5.8 (4) and 5.4 (4) days, respectively (p = 0.941). Among the patients admitted after the implementation of the BioFire® ME Panel, 4.3 % (n = 2) had a positive bacterial result, 38.3% (n = 18) had a positive viral result, and 57.4% (n = 27) had a negative result. Of the 27 negative results, 77.8% (n = 21) were treated with antimicrobial medication. CONCLUSIONS: This study suggested there is no difference between length of stay or antimicrobial duration in presumed meningitis cases assessed with traditional methods as compared to the BioFire® ME Panel.