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1.
EBioMedicine ; 88: 104441, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36696816

RESUMO

BACKGROUND: Amino acids are key to protein synthesis, energy metabolism, cell signaling and gene expression; however, the contribution of specific maternal amino acids to fetal growth is unclear. METHODS: We explored the effect of maternal circulating amino acids on fetal growth, proxied by birthweight, using two-sample Mendelian randomisation (MR) and summary data from a genome-wide association study (GWAS) of serum amino acids levels (sample 1, n = 86,507) and a maternal GWAS of offspring birthweight in UK Biobank and Early Growth Genetics Consortium, adjusting for fetal genotype effects (sample 2, n = 406,063 with maternal and/or fetal genotype effect estimates). A total of 106 independent single nucleotide polymorphisms robustly associated with 19 amino acids (p < 4.9 × 10-10) were used as genetic instrumental variables (IV). Wald ratio and inverse variance weighted methods were used in MR main analysis. A series of sensitivity analyses were performed to explore IV assumption violations. FINDINGS: Our results provide evidence that maternal circulating glutamine (59 g offspring birthweight increase per standard deviation increase in maternal amino acid level, 95% CI: 7, 110) and serine (27 g, 95% CI: 9, 46) raise, while leucine (-59 g, 95% CI: -106, -11) and phenylalanine (-25 g, 95% CI: -47, -4) lower offspring birthweight. These findings are supported by sensitivity analyses. INTERPRETATION: Our findings strengthen evidence for key roles of maternal circulating amino acids during pregnancy in healthy fetal growth. FUNDING: A full list of funding bodies that contributed to this study can be found under Acknowledgments.

2.
Wellcome Open Res ; 7: 26, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466951

RESUMO

The richness of linked population data provides exciting opportunities to understand local health needs, identify and predict those in most need of support and evaluate health interventions. There has been extensive investment to unlock the potential of clinical data for health research in the UK. However, most of the determinants of our health are social, economic, education, environmental, housing, food systems and are influenced by local authorities. The Connected Bradford Whole System Data Linkage Accelerator was set up to link health, education, social care, environmental and other local government data to drive learning health systems, prevention and population health management. Data spanning a period of over forty years has been linked for 800,000 individuals using the pseudonymised NHS number and other data variables. This prospective data collection captures near real time activity. This paper describes the dataset and our Connected Bradford Whole System Data Accelerator Framework that covers public engagement; practitioner and policy integration; legal and ethical approvals; information governance; technicalities of data linkage; data curation and guardianship; data validity and visualisation.

3.
Nat Commun ; 13(1): 7024, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36411288

RESUMO

Environmental exposures during early life play a critical role in life-course health, yet the molecular phenotypes underlying environmental effects on health are poorly understood. In the Human Early Life Exposome (HELIX) project, a multi-centre cohort of 1301 mother-child pairs, we associate individual exposomes consisting of >100 chemical, outdoor, social and lifestyle exposures assessed in pregnancy and childhood, with multi-omics profiles (methylome, transcriptome, proteins and metabolites) in childhood. We identify 1170 associations, 249 in pregnancy and 921 in childhood, which reveal potential biological responses and sources of exposure. Pregnancy exposures, including maternal smoking, cadmium and molybdenum, are predominantly associated with child DNA methylation changes. In contrast, childhood exposures are associated with features across all omics layers, most frequently the serum metabolome, revealing signatures for diet, toxic chemical compounds, essential trace elements, and weather conditions, among others. Our comprehensive and unique resource of all associations ( https://helixomics.isglobal.org/ ) will serve to guide future investigation into the biological imprints of the early life exposome.


Assuntos
Expossoma , Gravidez , Feminino , Humanos , Exposição Ambiental/efeitos adversos , Estudos de Coortes , Metaboloma , Transcriptoma
4.
Clin Epigenetics ; 14(1): 130, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-36243740

RESUMO

Ethnic differences in non-communicable disease risk have been described between individuals of South Asian and European ethnicity that are only partially explained by genetics and other known risk factors. DNA methylation is one underexplored mechanism that may explain differences in disease risk. Currently, there is little knowledge of how DNA methylation varies between South Asian and European ethnicities. This study characterised differences in blood DNA methylation between individuals of self-reported European and South Asian ethnicity from two UK-based cohorts: Southall and Brent Revisited and Born in Bradford. DNA methylation differences between ethnicities were widespread throughout the genome (n = 16,433 CpG sites, 3.4% sites tested). Specifically, 76% of associations were attributable to ethnic differences in cell composition with fewer effects attributable to smoking and genetic variation. Ethnicity-associated CpG sites were enriched for EWAS Catalog phenotypes including metabolites. This work highlights the need to consider ethnic diversity in epigenetic research.


Assuntos
Metilação de DNA , /genética , Humanos , Fatores de Risco , Reino Unido , /genética
5.
Br J Gen Pract ; 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35817584

RESUMO

BACKGROUND: Antibiotic prescribing during childhood, most commonly for respiratory tract infections (RTIs), contributes to antimicrobial resistance, which is a major public health concern. AIM: To identify factors associated with amoxicillin prescribing and RTI consultation attendance in young children in primary care. DESIGN AND SETTING: Cohort study in Bradford spanning pregnancy to age 24 months, collected 2007-2013, linked to electronic primary care and air pollution data. METHOD: Amoxicillin prescribing and RTI consultation rates/1000 child-years were calculated. Mixed-effects logistic regression models were fitted with general practice (GP) surgery as the random effect. RESULTS: The amoxicillin prescribing rate among 2493 children was 710/1000 child-years during year 1 (95% confidence interval [CI] = 677 to 744) and 780/1000 (95% CI = 745 to 816) during year 2. During year 1, odds of amoxicillin prescribing were higher for boys (adjusted odds ratio [aOR] 1.36, 95% CI = 1.14 to 1.61), infants from socioeconomically deprived households (aOR 1.36, 95% CI = 1.00 to 1.86), and infants with a Pakistani ethnic background (with mothers born in the UK [aOR 1.44, 95% CI = 1.06 to 1.94] and outside [aOR 1.42, 95% CI = 1.07 to 1.90]). During year 2, odds of amoxicillin prescribing were higher for infants with a Pakistani ethnic background (with mothers born in the UK [aOR 1.46, 95% CI = 1.10 to 1.94] and outside [aOR 1.56, 95% CI = 1.19 to 2.04]) and those born <39 weeks gestation (aOR 1.20, 95% CI = 1.00 to 1.45). Additional risk factors included caesarean delivery, congenital anomalies, overcrowding, birth season, and childcare attendance, with GP surgery explaining 7%-9% of variation. CONCLUSION: Socioeconomic status and ethnic background were associated with amoxicillin prescribing during childhood. Efforts to reduce RTI spread in household and childcare settings may reduce antibiotic prescribing in primary care.

6.
Elife ; 112022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35302492

RESUMO

Background: The identification of expression quantitative trait methylation (eQTMs), defined as associations between DNA methylation levels and gene expression, might help the biological interpretation of epigenome-wide association studies (EWAS). We aimed to identify autosomal cis eQTMs in children's blood, using data from 832 children of the Human Early Life Exposome (HELIX) project. Methods: Blood DNA methylation and gene expression were measured with the Illumina 450K and the Affymetrix HTA v2 arrays, respectively. The relationship between methylation levels and expression of nearby genes (1 Mb window centered at the transcription start site, TSS) was assessed by fitting 13.6 M linear regressions adjusting for sex, age, cohort, and blood cell composition. Results: We identified 39,749 blood autosomal cis eQTMs, representing 21,966 unique CpGs (eCpGs, 5.7% of total CpGs) and 8,886 unique transcript clusters (eGenes, 15.3% of total transcript clusters, equivalent to genes). In 87.9% of these cis eQTMs, the eCpG was located at <250 kb from eGene's TSS; and 58.8% of all eQTMs showed an inverse relationship between the methylation and expression levels. Only around half of the autosomal cis-eQTMs eGenes could be captured through annotation of the eCpG to the closest gene. eCpGs had less measurement error and were enriched for active blood regulatory regions and for CpGs reported to be associated with environmental exposures or phenotypic traits. In 40.4% of the eQTMs, the CpG and the eGene were both associated with at least one genetic variant. The overlap of autosomal cis eQTMs in children's blood with those described in adults was small (13.8%), and age-shared cis eQTMs tended to be proximal to the TSS and enriched for genetic variants. Conclusions: This catalogue of autosomal cis eQTMs in children's blood can help the biological interpretation of EWAS findings and is publicly available at https://helixomics.isglobal.org/ and at Dryad (doi:10.5061/dryad.fxpnvx0t0). Funding: The study has received funding from the European Community's Seventh Framework Programme (FP7/2007-206) under grant agreement no 308333 (HELIX project); the H2020-EU.3.1.2. - Preventing Disease Programme under grant agreement no 874583 (ATHLETE project); from the European Union's Horizon 2020 research and innovation programme under grant agreement no 733206 (LIFECYCLE project), and from the European Joint Programming Initiative "A Healthy Diet for a Healthy Life" (JPI HDHL and Instituto de Salud Carlos III) under the grant agreement no AC18/00006 (NutriPROGRAM project). The genotyping was supported by the projects PI17/01225 and PI17/01935, funded by the Instituto de Salud Carlos III and co-funded by European Union (ERDF, "A way to make Europe") and the Centro Nacional de Genotipado-CEGEN (PRB2-ISCIII). BiB received core infrastructure funding from the Wellcome Trust (WT101597MA) and a joint grant from the UK Medical Research Council (MRC) and Economic and Social Science Research Council (ESRC) (MR/N024397/1). INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66). The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. The Rhea project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009- single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EU- FP7- HEALTH-2012 Proposal No 308333 HELIX), and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011-2014; "Rhea Plus": Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012-15). We acknowledge support from the Spanish Ministry of Science and Innovation through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. MV-U and CR-A were supported by a FI fellowship from the Catalan Government (FI-DGR 2015 and #016FI_B 00272). MC received funding from Instituto Carlos III (Ministry of Economy and Competitiveness) (CD12/00563 and MS16/00128).


Cells can fine-tune which genes they activate, when and at which levels using a range of chemical marks on the DNA and certain proteins that help to organise the genome. One well-known example of such 'epigenetic tags' is DNA methylation, whereby a methyl group is added onto particular positions in the genome. Many factors ­ including environmental effects such as diet ­ control DNA methylation, allowing an organism to adapt to ever-changing conditions. An expression quantitative trait methylation (eQTM) is a specific position of the genome whose DNA methylation status regulates the activity of a given gene. A catalogue of eQTMs would be useful in helping to reveal how the environment and disease impacts the way cells work. Yet, currently, the relationships between most epigenetic tags and gene activity remains unclear, especially in children. To fill this gap, Ruiz-Arenas et al. studied DNA methylation in blood samples from over 800 healthy children across Europe. Amongst all tested DNA methylation sites, 22,000 (5.7% of total) were associated with the expression of a gene ­ and therefore were eQTMs; reciprocally, 9,000 genes (15.3% of all tested genes) were linked to at least one methylation site, leading to a total of 40,000 pairs of DNA methylation sites and genes. Most often, eQTMs regulated the expression of nearby genes ­ but only half controlled the gene that was the closest to them. Age and the genetic background of the individuals influenced the nature of eQTMs. This catalogue is a useful resource for the scientific community to start understanding the relationship between epigenetics and gene activity. Similar studies are now needed for other tissues and age ranges. Overall, extending our knowledge of eQTMs may help reveal how life events lead to illness, and could inform prevention efforts.


Assuntos
Metilação de DNA , Epigenoma , Adulto , Pré-Escolar , Estudos de Coortes , Europa (Continente) , Humanos , Fenótipo
7.
BMC Med ; 20(1): 34, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35101027

RESUMO

BACKGROUND: Greater maternal adiposity before or during pregnancy is associated with greater offspring adiposity throughout childhood, but the extent to which this is due to causal intrauterine or periconceptional mechanisms remains unclear. Here, we use Mendelian randomisation (MR) with polygenic risk scores (PRS) to investigate whether associations between maternal pre-/early pregnancy body mass index (BMI) and offspring adiposity from birth to adolescence are causal. METHODS: We undertook confounder adjusted multivariable (MV) regression and MR using mother-offspring pairs from two UK cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) and Born in Bradford (BiB). In ALSPAC and BiB, the outcomes were birthweight (BW; N = 9339) and BMI at age 1 and 4 years (N = 8659 to 7575). In ALSPAC only we investigated BMI at 10 and 15 years (N = 4476 to 4112) and dual-energy X-ray absorptiometry (DXA) determined fat mass index (FMI) from age 10-18 years (N = 2659 to 3855). We compared MR results from several PRS, calculated from maternal non-transmitted alleles at between 29 and 80,939 single nucleotide polymorphisms (SNPs). RESULTS: MV and MR consistently showed a positive association between maternal BMI and BW, supporting a moderate causal effect. For adiposity at most older ages, although MV estimates indicated a strong positive association, MR estimates did not support a causal effect. For the PRS with few SNPs, MR estimates were statistically consistent with the null, but had wide confidence intervals so were often also statistically consistent with the MV estimates. In contrast, the largest PRS yielded MR estimates with narrower confidence intervals, providing strong evidence that the true causal effect on adolescent adiposity is smaller than the MV estimates (Pdifference = 0.001 for 15-year BMI). This suggests that the MV estimates are affected by residual confounding, therefore do not provide an accurate indication of the causal effect size. CONCLUSIONS: Our results suggest that higher maternal pre-/early-pregnancy BMI is not a key driver of higher adiposity in the next generation. Thus, they support interventions that target the whole population for reducing overweight and obesity, rather than a specific focus on women of reproductive age.


Assuntos
Adiposidade/genética , Obesidade/genética , Adolescente , Alelos , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Estudos Longitudinais , Obesidade/etiologia , Gravidez , Fatores de Risco , Reino Unido
8.
Bioinformatics ; 38(7): 1980-1987, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35134881

RESUMO

MOTIVATION: Metabolomics is an increasingly common part of health research and there is need for preanalytical data processing. Researchers typically need to characterize the data and to exclude errors within the context of the intended analysis. Whilst some preprocessing steps are common, there is currently a lack of standardization and reporting transparency for these procedures. RESULTS: Here, we introduce metaboprep, a standardized data processing workflow to extract and characterize high quality metabolomics datasets. The package extracts data from preformed worksheets, provides summary statistics and enables the user to select samples and metabolites for their analysis based on a set of quality metrics. A report summarizing quality metrics and the influence of available batch variables on the data are generated for the purpose of open disclosure. Where possible, we provide users flexibility in defining their own selection thresholds. AVAILABILITY AND IMPLEMENTATION: metaboprep is an open-source R package available at https://github.com/MRCIEU/metaboprep. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Metabolômica , Software , Humanos , Fluxo de Trabalho , Pesquisadores
9.
J Clin Med ; 11(2)2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35054050

RESUMO

Modern approaches to resuscitation seek to bring patient interventions as close as possible to the initial trauma. In recent decades, fresh or cold-stored whole blood has gained widespread support in multiple settings as the best first agent in resuscitation after massive blood loss. However, whole blood is not a panacea, and while current guidelines promote continued resuscitation with fixed ratios of blood products, the debate about the optimal resuscitation strategy-especially in austere or challenging environments-is by no means settled. In this narrative review, we give a brief history of military resuscitation and how whole blood became the mainstay of initial resuscitation. We then outline the principles of viscoelastic hemostatic assays as well as their adoption for providing goal-directed blood-component therapy in trauma centers. After summarizing the nascent research on the strengths and limitations of viscoelastic platforms in challenging environmental conditions, we conclude with our vision of how these platforms can be deployed in far-forward combat and austere civilian environments to maximize survival.

10.
Platelets ; 33(4): 520-530, 2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34369848

RESUMO

We carried out a literature search in MEDLINE (PubMed) and EMBASE literature databases to provide a concise review of the role of viscoelastic testing in assessing peri-interventional platelet function and coagulation. The search identified 130 articles that were relevant for the review, covering the basic science of VHA and VHA in clinical settings including cardiac surgery, cardiology, neurology, trauma, non-cardiac surgery, obstetrics, liver disease, and COVID-19. Evidence from these articles is used to describe the important role of VHAs and platelet function testing in various peri-interventional setups. VHAs can help us to comprehensively assess the contribution of platelets and coagulation dynamics to clotting at the site-of-care much faster than standard laboratory measures. In addition to standard coagulation tests, VHAs are beneficial in reducing allogeneic transfusion requirements and bleeding, in predicting ischemic events, and improving outcomes in several peri-interventional care settings. Further focused studies are needed to confirm their utility in the peri-interventional case.


Assuntos
Transtornos da Coagulação Sanguínea , COVID-19 , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Hemostasia , Humanos , Tromboelastografia
11.
Hum Mol Genet ; 31(11): 1762-1775, 2022 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34897462

RESUMO

BACKGROUND: Higher birthweight is associated with higher adult body mass index (BMI). Alleles that predispose to greater adult adiposity might act in fetal life to increase fetal growth and birthweight. Whether there are fetal effects of recently identified adult metabolically favorable adiposity alleles on birthweight is unknown. AIM: We aimed to test the effect on birthweight of fetal genetic predisposition to higher metabolically favorable adult adiposity and compare that with the effect of fetal genetic predisposition to higher adult BMI. METHODS: We used published genome wide association study data (n = upto 406 063) to estimate fetal effects on birthweight (adjusting for maternal genotype) of alleles known to raise metabolically favorable adult adiposity or BMI. We combined summary data across single nucleotide polymorphisms (SNPs) with random effects meta-analyses. We performed weighted linear regression of SNP-birthweight effects against SNP-adult adiposity effects to test for a dose-dependent association. RESULTS: Fetal genetic predisposition to higher metabolically favorable adult adiposity and higher adult BMI were both associated with higher birthweight (3 g per effect allele (95% CI: 1-5) averaged over 14 SNPs; P = 0.002; 0.5 g per effect allele (95% CI: 0-1) averaged over 76 SNPs; P = 0.042, respectively). SNPs with greater effects on metabolically favorable adiposity tended to have greater effects on birthweight (R2 = 0.2912, P = 0.027). There was no dose-dependent association for BMI (R2 = -0.0019, P = 0.602). CONCLUSIONS: Fetal genetic predisposition to both higher adult metabolically favorable adiposity and BMI is associated with birthweight. Fetal effects of metabolically favorable adiposity-raising alleles on birthweight are modestly proportional to their effects on future adiposity, but those of BMI-raising alleles are not.


Assuntos
Adiposidade , Estudo de Associação Genômica Ampla , Adiposidade/genética , Adulto , Alelos , Peso ao Nascer/genética , Índice de Massa Corporal , Predisposição Genética para Doença , Humanos , Obesidade/genética , Polimorfismo de Nucleotídeo Único/genética
12.
Nat Commun ; 12(1): 7189, 2021 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-34893604

RESUMO

Previous genetic and public health research in the Pakistani population has focused on the role of consanguinity in increasing recessive disease risk, but little is known about its recent population history or the effects of endogamy. Here, we investigate fine-scale population structure, history and consanguinity patterns using genotype chip data from 2,200 British Pakistanis. We reveal strong recent population structure driven by the biraderi social stratification system. We find that all subgroups have had low recent effective population sizes (Ne), with some showing a decrease 15‒20 generations ago that has resulted in extensive identity-by-descent sharing and homozygosity, increasing the risk of recessive disorders. Our results from two orthogonal methods (one using machine learning and the other coalescent-based) suggest that the detailed reporting of parental relatedness for mothers in the cohort under-represents the true levels of consanguinity. These results demonstrate the impact of cultural practices on population structure and genomic diversity in Pakistanis, and have important implications for medical genetic studies.


Assuntos
/genética , Consanguinidade , Genética Populacional , /genética , Estudos de Coortes , Demografia , Genótipo , Homozigoto , Humanos , Casamento , Modelos Genéticos , Paquistão , Pais , Densidade Demográfica , Status Social
13.
Genome Biol ; 22(1): 194, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187551

RESUMO

BACKGROUND: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. RESULTS: Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. CONCLUSION: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.


Assuntos
Envelhecimento/genética , Metilação de DNA , Epigênese Genética , Loci Gênicos , Herança Multifatorial , Adiposidade/genética , Adiposidade/imunologia , Envelhecimento/imunologia , Biomarcadores/metabolismo , Proteína C-Reativa/genética , Proteína C-Reativa/imunologia , Ilhas de CpG , Escolaridade , Marcadores Genéticos , Genoma Humano , Estudo de Associação Genômica Ampla , Granulócitos/citologia , Granulócitos/imunologia , Humanos , Imunidade Inata , Metabolismo dos Lipídeos/genética , Metabolismo dos Lipídeos/imunologia , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/imunologia
14.
J Am Heart Assoc ; 10(11): e020051, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34039012

RESUMO

Background Congenital heart diseases (CHDs) are the most common congenital anomaly. The causes of CHDs are largely unknown. Higher prenatal body mass index (BMI), smoking, and alcohol consumption are associated with increased risk of CHDs. Whether these are causal is unclear. Methods and Results Seven European birth cohorts, including 232 390 offspring (2469 CHD cases [1.1%]), were included. We applied negative exposure paternal control analyses to explore the intrauterine effects of maternal BMI, smoking, and alcohol consumption during pregnancy, on offspring CHDs and CHD severity. We used logistic regression, adjusting for confounders and the other parent's exposure and combined estimates using a fixed-effects meta-analysis. In adjusted analyses, maternal overweight (odds ratio [OR], 1.15 [95% CI, 1.01-1.31]) and obesity (OR, 1.12 [95% CI, 0.93-1.36]), compared with normal weight, were associated with higher odds of CHD, but there was no clear evidence of a linear increase in odds across the whole BMI distribution. Associations of paternal overweight, obesity, and mean BMI were similar to the maternal associations. Maternal pregnancy smoking was associated with higher odds of CHD (OR, 1.11 [95% CI, 0.97-1.25]) but paternal smoking was not (OR, 0.96 [95% CI, 0.85-1.07]). The positive association with maternal smoking appeared to be driven by nonsevere CHD cases (OR, 1.22 [95% CI, 1.04-1.44]). Associations with maternal moderate/heavy pregnancy alcohol consumption were imprecisely estimated (OR, 1.16 [95% CI, 0.52-2.58]) and similar to those for paternal consumption. Conclusions We found evidence of an intrauterine effect for maternal smoking on offspring CHDs, but no evidence for higher maternal BMI or alcohol consumption. Our findings provide further support for the importance of smoking cessation during pregnancy.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Índice de Massa Corporal , Pai/estatística & dados numéricos , Cardiopatias Congênitas/etiologia , Mães/estatística & dados numéricos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/efeitos adversos , Adulto , Europa (Continente)/epidemiologia , Feminino , Cardiopatias Congênitas/epidemiologia , Humanos , Incidência , Masculino , Gravidez , Fatores de Risco
15.
Euro Surveill ; 26(6)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33573711

RESUMO

BackgroundBronchiolitis caused by respiratory syncytial virus (RSV) is a major cause of mortality and morbidity in infants.AimTo describe RSV epidemiology in children in the community in a high-income setting.MethodsWe used stored blood samples from the United Kingdom Born in Bradford cohort study that had been collected at birth, age 1 and 2 years old, tested for IgG RSV postfusion F antibody and linked to questionnaires and primary and hospital care records. We used finite mixture models to classify children as RSV infected/not infected according to their antibody concentrations at age 1 and 2 years. We assessed risk factors for primary RSV infection at each age using Poisson regression models.ResultsThe study cohort included 700 children with cord blood samples; 490 had additional blood samples taken at both ages 1 and 2 years old. Of these 490 children, 258 (53%; 95% confidence interval (CI): 48-57%) were first infected with RSV at age 1, 99 of whom (38%; 95% CI: 33-43%) had been in contact with healthcare during peak RSV season (November-January). Having older siblings, birth in October-June and attending formal childcare were associated with risk of RSV infection in infancy. By age 2, a further 164 of 490 children (33%; 95% CI: 29-38%) had been infected.ConclusionOver half of children experienced RSV infection in infancy, a further one third had evidence of primary RSV infection by age 2, and one in seven remained seronegative by their second birthday. These findings will inform future analyses to assess the cost-effectiveness of RSV vaccination programmes in high-income settings.


Assuntos
Registros Eletrônicos de Saúde , Infecções por Vírus Respiratório Sincicial , Criança , Pré-Escolar , Estudos de Coortes , Inglaterra/epidemiologia , Hospitalização , Humanos , Lactente , Recém-Nascido , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/epidemiologia , Fatores de Risco , Inquéritos e Questionários , Reino Unido
16.
Diagnostics (Basel) ; 11(2)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530346

RESUMO

Coronavirus disease 2019 (COVID-19)-associated coagulopathy (CAC), characterized by hypercoagulability and an increased risk of thrombotic complications, is an important consideration in the management of patients with COVID-19. As COVID-19 is a new disease, no standard of care for the diagnosis or management of its associated coagulopathy is yet established. Whole blood viscoelastic tests, such as thromboelastography (TEG® hemostasis analyzer), analyze whole blood to provide a complete overview of the coagulation status. We conducted a systematic review of thromboelastography for management of patients with COVID-19, using MEDLINE (PubMed) and Cochrane databases. TEG® parameter measurements and clinical outcomes data were extracted for analysis. Our review found 15 publications, with overall results showing thromboelastography can identify and assess a hypercoagulable state in patients with COVID-19. Furthermore, utilization of thromboelastography in this patient population was shown to predict thrombotic complications. The benefits of thromboelastography presented here, in addition to advantages compared with laboratory coagulation tests, position thromboelastography as an important opportunity for optimizing diagnosis of CAC and improving patient management in COVID-19. Given that the benefits of thromboelastography have already been demonstrated in several other clinical applications, we anticipate that clinical data from future studies in patients with COVID-19 will further elucidate the optimal use of thromboelastography in this patient population.

17.
Nutrients ; 13(1)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466826

RESUMO

Iodine is essential for normal thyroid function, supporting healthy fetal and child development. Iodine requirements increase in pregnancy, but many women in regions without salt iodization have insufficient intakes. We explored associations between iodide intake and urinary iodine concentration (UIC), urinary iodine/creatinine ratio (I/Cr), thyroid stimulating hormone, thyroglobulin, free triiodothyronine, free thyroxine and palpable goiter in a region of mild-to-moderate iodine insufficiency. A total of 246 pregnant women aged 18-40 in Bradford, UK, joined the Health and Iodine in Babies (Hiba) study. They provided detailed information on diet and supplement use, urine and serum samples and were assessed for goiter at around 12, 26 and 36 weeks' gestation, and 6, 18 and 30 weeks postpartum. Dietary iodide intake from food and drink was estimated using six 24 h recalls. During pregnancy, median (IQR) dietary iodide intake was 101 µg/day (54, 142), with 42% from dairy and 9% from white fish. Including supplements, intake was 143 µg/day (94, 196), with 49% < UK reference nutrient intake (140 µg/day). Women with Pakistani heritage had 129 µg/day (87, 190) median total intake. Total intake during pregnancy was associated with 4% (95% CI: 1%, 7%) higher UIC, 5% (3%, 7%) higher I/Cr, 4% (2%, 6%) lower thyroglobulin and 21% (9%, 32%) lower odds of palpable goiter per 50 µg/day. This cohort consumed less iodide in pregnancy than UK and World Health Organization dietary recommendations. UIC, I/Cr and thyroglobulin were associated with intake. Higher intake was associated with fewer goiters. Because dairy was the dominant source of iodide, women following plant-based or low-dairy diets may be at particular risk of iodine insufficiency.


Assuntos
Deficiências Nutricionais , Iodetos/análise , Iodo , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Hormônios Tireóideos/sangue , Adolescente , Adulto , Deficiências Nutricionais/sangue , Deficiências Nutricionais/epidemiologia , Deficiências Nutricionais/urina , Dieta/estatística & dados numéricos , Suplementos Nutricionais/estatística & dados numéricos , Feminino , Humanos , Iodo/deficiência , Iodo/urina , Período Pós-Parto/fisiologia , Gravidez/estatística & dados numéricos , Reino Unido , Adulto Jovem
18.
Paediatr Perinat Epidemiol ; 35(2): 236-246, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32870514

RESUMO

BACKGROUND: Maternal iodine requirements increase during pregnancy to supply thyroid hormones critical for fetal neurodevelopment. Iodine insufficiency may result in poorer cognitive or child educational outcomes but current evidence is sparse and inconsistent. OBJECTIVES: To quantify the association between maternal iodine status and child educational outcomes. METHODS: Urinary iodine concentrations (UIC) and iodine/creatinine ratios (I:Cr) were measured in 6971 mothers at 26-28 weeks' gestation participating in the Born in Bradford cohort. Maternal iodine status was examined in relation to child school achievement (early years foundation stage (EYFS), phonics, and Key Stage 1 (KS1)), other learning outcomes, social and behavioural difficulties, and sensorimotor control in 5745 children aged 4-7 years. RESULTS: Median (interquartile range) UIC was 76 µg/L (46, 120), and I:Cr was 83 µg/g (59, 121). Overall, there was no strong or consistent evidence to support associations between UIC or I:Cr and neurodevelopmental outcomes. For instance, predicted EYFS and phonics scores (primary outcomes) at the 25th vs 75th I:Cr percentiles (99% confidence intervals) were similar, with no evidence of associations: EYFS scores were 32 (99% CI 31, 33) and 33 (99% CI 32, 34), and phonics scores were 34 (99% CI 33, 35) and 35 (99% CI 34, 36), respectively. CONCLUSIONS: In the largest single study of its kind, there was little evidence of detrimental neurodevelopmental outcomes in children born to pregnant women with iodine insufficiency as defined by World Health Organization-outlined thresholds. Alternative functional biomarkers for iodine status in pregnancy and focused assessment of other health outcomes may provide additional insight.


Assuntos
Iodo , Criança , Cognição , Feminino , Idade Gestacional , Humanos , Estado Nutricional , Gravidez , Gravidez Múltipla , Reino Unido/epidemiologia
19.
Diabetologia ; 64(12): 2790-2802, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34542646

RESUMO

AIMS/HYPOTHESIS: Higher maternal BMI during pregnancy is associated with higher offspring birthweight, but it is not known whether this is solely the result of adverse metabolic consequences of higher maternal adiposity, such as maternal insulin resistance and fetal exposure to higher glucose levels, or whether there is any effect of raised adiposity through non-metabolic (e.g. mechanical) factors. We aimed to use genetic variants known to predispose to higher adiposity, coupled with a favourable metabolic profile, in a Mendelian randomisation (MR) study comparing the effect of maternal 'metabolically favourable adiposity' on offspring birthweight with the effect of maternal general adiposity (as indexed by BMI). METHODS: To test the causal effects of maternal metabolically favourable adiposity or general adiposity on offspring birthweight, we performed two-sample MR. We used variants identified in large, published genetic-association studies as being associated with either higher adiposity and a favourable metabolic profile, or higher BMI (n = 442,278 and n = 322,154 for metabolically favourable adiposity and BMI, respectively). We then extracted data on the metabolically favourable adiposity and BMI variants from a large, published genetic-association study of maternal genotype and offspring birthweight controlling for fetal genetic effects (n = 406,063 with maternal and/or fetal genotype effect estimates). We used several sensitivity analyses to test the reliability of the results. As secondary analyses, we used data from four cohorts (total n = 9323 mother-child pairs) to test the effects of maternal metabolically favourable adiposity or BMI on maternal gestational glucose, anthropometric components of birthweight and cord-blood biomarkers. RESULTS: Higher maternal adiposity with a favourable metabolic profile was associated with lower offspring birthweight (-94 [95% CI -150, -38] g per 1 SD [6.5%] higher maternal metabolically favourable adiposity, p = 0.001). By contrast, higher maternal BMI was associated with higher offspring birthweight (35 [95% CI 16, 53] g per 1 SD [4 kg/m2] higher maternal BMI, p = 0.0002). Sensitivity analyses were broadly consistent with the main results. There was evidence of outlier SNPs for both exposures; their removal slightly strengthened the metabolically favourable adiposity estimate and made no difference to the BMI estimate. Our secondary analyses found evidence to suggest that a higher maternal metabolically favourable adiposity decreases pregnancy fasting glucose levels while a higher maternal BMI increases them. The effects on neonatal anthropometric traits were consistent with the overall effect on birthweight but the smaller sample sizes for these analyses meant that the effects were imprecisely estimated. We also found evidence to suggest that higher maternal metabolically favourable adiposity decreases cord-blood leptin while higher maternal BMI increases it. CONCLUSIONS/INTERPRETATION: Our results show that higher adiposity in mothers does not necessarily lead to higher offspring birthweight. Higher maternal adiposity can lead to lower offspring birthweight if accompanied by a favourable metabolic profile. DATA AVAILABILITY: The data for the genome-wide association studies (GWAS) of BMI are available at https://portals.broadinstitute.org/collaboration/giant/index.php/GIANT_consortium_data_files . The data for the GWAS of body fat percentage are available at https://walker05.u.hpc.mssm.edu .


Assuntos
Adiposidade , Estudo de Associação Genômica Ampla , Adiposidade/genética , Peso ao Nascer , Índice de Massa Corporal , Feminino , Humanos , Recém-Nascido , Gravidez , Reprodutibilidade dos Testes
20.
Obstet Gynecol ; 138(4): 633-646, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34623076

RESUMO

OBJECTIVE: To evaluate the associations of depressive symptoms and antidepressant use during pregnancy with the risks of preterm birth, low birth weight, small for gestational age (SGA), and low Apgar scores. DATA SOURCES: MEDLINE, EMBASE, ClinicalTrials.gov, and PsycINFO up to June 2016. METHODS OF STUDY SELECTION: Data were sought from studies examining associations of depression, depressive symptoms, or use of antidepressants during pregnancy with gestational age, birth weight, SGA, or Apgar scores. Authors shared the raw data of their studies for incorporation into this individual participant data meta-analysis. TABULATION, INTEGRATION, AND RESULTS: We performed one-stage random-effects meta-analyses to estimate odds ratios (ORs) with 95% CIs. The 215 eligible articles resulted in 402,375 women derived from 27 study databases. Increased risks were observed for preterm birth among women with a clinical diagnosis of depression during pregnancy irrespective of antidepressant use (OR 1.6, 95% CI 1.2-2.1) and among women with depression who did not use antidepressants (OR 2.2, 95% CI 1.7-3.0), as well as for low Apgar scores in the former (OR 1.5, 95% CI 1.3-1.7), but not the latter group. Selective serotonin reuptake inhibitor (SSRI) use was associated with preterm birth among women who used antidepressants with or without restriction to women with depressive symptoms or a diagnosis of depression (OR 1.6, 95% CI 1.0-2.5 and OR 1.9, 95% CI 1.2-2.8, respectively), as well as with low Apgar scores among women in the latter group (OR 1.7, 95% CI 1.1-2.8). CONCLUSION: Depressive symptoms or a clinical diagnosis of depression during pregnancy are associated with preterm birth and low Apgar scores, even without exposure to antidepressants. However, SSRIs may be independently associated with preterm birth and low Apgar scores. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42016035711.


Assuntos
Antidepressivos/efeitos adversos , Depressão/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Resultado da Gravidez/epidemiologia , Adulto , Antidepressivos/uso terapêutico , Índice de Apgar , Peso ao Nascer , Depressão/epidemiologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Gravidez , Complicações na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , /efeitos adversos
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