Blood-based genome-wide DNA methylation correlations across body-fat- and adiposity-related biochemical traits.

The recent increase in obesity levels across many countries is likely to be driven by nongenetic factors. The epigenetic modification DNA methylation (DNAm) may help to explore this, as it is sensitive to both genetic and environmental exposures. While the relationship between DNAm and body-fat traits has been extensively studied, there is limited literature on the shared associations of DNAm variation across such traits. Akin to genetic correlation estimates, here, we introduce an approach to evaluate the similarities in DNAm associations between traits: DNAm correlations. As DNAm can be both a cause and consequence of complex traits, DNAm correlations have the potential to provide insights into trait relationships above that currently obtained from genetic and phenotypic correlations. Utilizing 7,519 unrelated individuals from Generation Scotland with DNAm from the EPIC array, we calculated DNAm correlations between body-fat- and adiposity-related traits by using the bivariate OREML framework in the OSCA software. For each trait, we also estimated the shared contribution of DNAm between sexes. We identified strong, positive DNAm correlations between each of the body-fat traits (BMI, body-fat percentage, and waist-to-hip ratio, ranging from 0.96 to 1.00), finding larger associations than those identified by genetic and phenotypic correlations. We identified a significant deviation from 1 in the DNAm correlations for BMI between males and females, with sex-specific DNAm changes associated with BMI identified at eight DNAm probes. Employing genome-wide DNAm correlations to evaluate the similarities in the associations of DNAm with complex traits has provided insight into obesity-related traits beyond that provided by genetic correlations.

Anorectal gonorrhoea and chlamydia among transgender women in Brazil: prevalence and assessment of performance and cost of anorectal infection detection and management approaches.

OBJECTIVES: We aimed to determine the prevalence of anorectal Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) among transgender women in Brazil, and to assess the performance and costs of various approaches for the diagnosis and management of anorectal NG/CT. METHODS: TransOdara was a multicentric, cross-sectional STI prevalence study among 1317 transgender women conducted in five capital cities representing all Brazilian regions. Participants aged >18 years were recruited using respondent-driven sampling (RDS), completed an interviewer-led questionnaire, offered an optional physical examination and given choice between self-collected or provider-collected samples for NG/CT testing. Performance and cost indicators of predetermined management algorithms based on the WHO recommendations for anorectal symptoms were calculated. RESULTS: Screening uptake was high (94.3%) and the estimated prevalence of anorectal NG, CT and NG and/or CT was 9.1%, 8.9% and 15.2%, respectively. Most detected anorectal NG/CT infections were asymptomatic (NG: 87.6%, CT: 88.9%), with a limited number of participants reporting any anorectal symptoms (9.1%). Of those who permitted anal examination, few had clinical signs of infection (13.6%). Sensitivity of the tested algorithms ranged from 1.4% to 5.1% (highest for treatment based on the reported anorectal discharge or ulcer and receptive anal intercourse (RAI) in the past 6 months) and specificity from 98.0% to 99.3% (highest for treatment based on the reported anorectal discharge with clinical confirmation or report of RAI). The estimated cost-per-true case of anorectal NG/CT infection treated varied from lowest providing treatment for anorectal discharge syndrome based on the reported RAI ($2.70-4.28), with algorithms including clinical examinations decreasing cost-effectiveness. CONCLUSIONS: High prevalence of mostly asymptomatic anorectal NG and CT was observed among Brazilian transgender women. Multi-site NG/CT screening should be offered to transgender women. Where diagnostic testing capacity is limited, syndromic management for those presenting with anorectal symptoms is recommended.

Acceptability and Usability of Self-Sampling for the Detection of Sexually Transmitted Infections Among Transgender Women: The TransOdara Multicentric Study in Brazil.

BACKGROUND: The effective testing of sexually transmitted infections (STIs) requires sampling from potential infection sites. This study aimed to assess the choice, satisfaction, and performance of self-collected samples (SCS) from potential infection sites for STI testing among transgender women in Brazil. METHODS: TransOdara was a multicentric, cross-sectional STI prevalence study conducted in 5 Brazilian cities. Using respondent-driven sampling, 1317 transgender women 18 years or older were recruited. Participants completed interviewer-led questionnaires and provided swab samples from multiple sites (anorectal, oropharyngeal, genital) for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and human papillomavirus (HPV) testing. Participants were given a choice of SCS or provider-collected samples (PCS) at each site. RESULTS: Most participants selected SCS for anorectal (74.9%; 95% confidence interval [CI], 72.4-77.3) and genital (72.7%; 95% CI, 70.2-75.1) sites, whereas fewer chose for oropharyngeal samples (49.8%; 95% CI, 47.0-52.6). For future testing, most participants expressed a preference for SCS for genital (72.2%; 95% CI, 69.5-74.7) and anorectal (70.2%; 95% CI, 67.6-72.7) sites. There was no significant difference in the positive test results for CT and NG between SCS and PCS at anorectal and oropharyngeal sites, or for HPV at anorectal and genital (penile or neovaginal) sites. CONCLUSIONS: This study demonstrated a high level of acceptability and usability of self-sampling for STI testing among transgender women. A preference for SCS was evident at the anorectal and genital sites, and the results of SCS were comparable to those of PCS. The findings suggest that multisite STI testing utilizing self-collection methods as a provided option can be effectively integrated into sexual health services for transgender women.

Alzheimer's disease genetic pathways impact cerebrospinal fluid biomarkers and imaging endophenotypes in non-demented individuals.

INTRODUCTION: Unraveling how Alzheimer's disease (AD) genetic risk is related to neuropathological heterogeneity, and whether this occurs through specific biological pathways, is a key step toward precision medicine. METHODS: We computed pathway-specific genetic risk scores (GRSs) in non-demented individuals and investigated how AD risk variants predict cerebrospinal fluid (CSF) and imaging biomarkers reflecting AD pathology, cardiovascular, white matter integrity, and brain connectivity. RESULTS: CSF amyloidbeta and phosphorylated tau were related to most GRSs. Inflammatory pathways were associated with cerebrovascular disease, whereas quantitative measures of white matter lesion and microstructure integrity were predicted by clearance and migration pathways. Functional connectivity alterations were related to genetic variants involved in signal transduction and synaptic communication. DISCUSSION: This study reveals distinct genetic risk profiles in association with specific pathophysiological aspects in predementia stages of AD, unraveling the biological substrates of the heterogeneity of AD-associated endophenotypes and promoting a step forward in disease understanding and development of personalized therapies. HIGHLIGHTS: Polygenic risk for Alzheimer's disease encompasses six biological pathways that can be quantified with pathway-specific genetic risk scores, and differentially relate to cerebrospinal fluid and imaging biomarkers. Inflammatory pathways are mostly related to cerebrovascular burden. White matter health is associated with pathways of clearance and membrane integrity, whereas functional connectivity measures are related to signal transduction and synaptic communication pathways.

Blood-based epigenome-wide analyses of 19 common disease states: A longitudinal, population-based linked cohort study of 18,413 Scottish individuals.

BACKGROUND: DNA methylation is a dynamic epigenetic mechanism that occurs at cytosine-phosphate-guanine dinucleotide (CpG) sites. Epigenome-wide association studies (EWAS) investigate the strength of association between methylation at individual CpG sites and health outcomes. Although blood methylation may act as a peripheral marker of common disease states, previous EWAS have typically focused only on individual conditions and have had limited power to discover disease-associated loci. This study examined the association of blood DNA methylation with the prevalence of 14 disease states and the incidence of 19 disease states in a single population of over 18,000 Scottish individuals. METHODS AND FINDINGS: DNA methylation was assayed at 752,722 CpG sites in whole-blood samples from 18,413 volunteers in the family-structured, population-based cohort study Generation Scotland (age range 18 to 99 years). EWAS tested for cross-sectional associations between baseline CpG methylation and 14 prevalent disease states, and for longitudinal associations between baseline CpG methylation and 19 incident disease states. Prevalent cases were self-reported on health questionnaires at the baseline. Incident cases were identified using linkage to Scottish primary (Read 2) and secondary (ICD-10) care records, and the censoring date was set to October 2020. The mean time-to-diagnosis ranged from 5.0 years (for chronic pain) to 11.7 years (for Coronavirus Disease 2019 (COVID-19) hospitalisation). The 19 disease states considered in this study were selected if they were present on the World Health Organisation's 10 leading causes of death and disease burden or included in baseline self-report questionnaires. EWAS models were adjusted for age at methylation typing, sex, estimated white blood cell composition, population structure, and 5 common lifestyle risk factors. A structured literature review was also conducted to identify existing EWAS for all 19 disease states tested. The MEDLINE, Embase, Web of Science, and preprint servers were searched to retrieve relevant articles indexed as of March 27, 2023. Fifty-four of approximately 2,000 indexed articles met our inclusion criteria: assayed blood-based DNA methylation, had >20 individuals in each comparison group, and examined one of the 19 conditions considered. First, we assessed whether the associations identified in our study were reported in previous studies. We identified 69 associations between CpGs and the prevalence of 4 conditions, of which 58 were newly described. The conditions were breast cancer, chronic kidney disease, ischemic heart disease, and type 2 diabetes mellitus. We also uncovered 64 CpGs that associated with the incidence of 2 disease states (COPD and type 2 diabetes), of which 56 were not reported in the surveyed literature. Second, we assessed replication across existing studies, which was defined as the reporting of at least 1 common site in >2 studies that examined the same condition. Only 6/19 disease states had evidence of such replication. The limitations of this study include the nonconsideration of medication data and a potential lack of generalizability to individuals that are not of Scottish and European ancestry. CONCLUSIONS: We discovered over 100 associations between blood methylation sites and common disease states, independently of major confounding risk factors, and a need for greater standardisation among EWAS on human disease.

Alcohol use disorder is associated with DNA methylation-based shortening of telomere length and regulated by TESPA1: implications for aging.

Chronic heavy alcohol consumption is associated with increased mortality and morbidity and often leads to premature aging; however, the mechanisms of alcohol-associated cellular aging are not well understood. In this study, we used DNA methylation derived telomere length (DNAmTL) as a novel approach to investigate the role of alcohol use on the aging process. DNAmTL was estimated by 140 cytosine phosphate guanines (CpG) sites in 372 individuals with alcohol use disorder (AUD) and 243 healthy controls (HC) and assessed using various endophenotypes and clinical biomarkers. Validation in an independent sample of DNAmTL on alcohol consumption was performed (N = 4219). Exploratory genome-wide association studies (GWAS) on DNAmTL were also performed to identify genetic variants contributing to DNAmTL shortening. Top GWAS findings were analyzed using in-silico expression quantitative trait loci analyses and related to structural MRI hippocampus volumes of individuals with AUD. DNAmTL was 0.11-kilobases shorter per year in AUD compared to HC after adjustment for age, sex, race, and blood cell composition (p = 4.0 × 10-12). This association was partially attenuated but remained significant after additionally adjusting for BMI, and smoking status (0.06 kilobases shorter per year, p = 0.002). DNAmTL shortening was strongly associated with chronic heavy alcohol use (ps < 0.001), elevated gamma-glutamyl transferase (GGT), and aspartate aminotransferase (AST) (ps < 0.004). Comparison of DNAmTL with PCR-based methods of assessing TL revealed positive correlations (R = 0.3, p = 2.2 × 10-5), highlighting the accuracy of DNAmTL as a biomarker. The GWAS meta-analysis identified a single nucleotide polymorphism (SNP), rs4374022 and 18 imputed ones in Thymocyte Expressed, Positive Selection Associated 1(TESPA1), at the genome-wide level (p = 3.75 × 10-8). The allele C of rs4374022 was associated with DNAmTL shortening, lower hippocampus volume (p < 0.01), and decreased mRNA expression in hippocampus tissue (p = 0.04). Our study demonstrates DNAmTL-related aging acceleration in AUD and suggests a functional role for TESPA1 in regulating DNAmTL length, possibly via the immune system with subsequent biological effects on brain regions negatively affected by alcohol and implicated in aging.

Pulmonary Function and Blood DNA Methylation: A Multiancestry Epigenome-Wide Association Meta-analysis.

Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication. Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function. Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV1, FVC, and FEV1/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics. Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery rate, <0.025) in relation to FEV1, FVC, or FEV1/FVC, including 1,240 novel and 73 also related to chronic obstructive pulmonary disease (1,787 cases). We found 294 CpGs unique to European or African ancestry and 395 CpGs unique to never or ever smokers. The majority of significant CpGs correlated with nearby gene expression in blood. Findings were enriched in key regulatory elements for gene function, including accessible chromatin elements, in both blood and lung. Sixty-nine implicated genes are targets of investigational or approved drugs. One example novel gene highlighted by integrative epigenomic and druggable target analysis is TNFRSF4. Mendelian randomization and colocalization analyses suggest that epigenome-wide association study signals capture causal regulatory genomic loci. Conclusions: We identified numerous novel loci differentially methylated in relation to pulmonary function; few were detected in large genome-wide association studies. Integrative analyses highlight functional relevance and potential therapeutic targets. This comprehensive discovery of potentially modifiable, novel lung function loci expands knowledge gained from genetic studies, providing insights into lung pathogenesis.

A comparison of blood and brain-derived ageing and inflammation-related DNA methylation signatures and their association with microglial burdens.

Inflammation and ageing-related DNA methylation patterns in the blood have been linked to a variety of morbidities, including cognitive decline and neurodegenerative disease. However, it is unclear how these blood-based patterns relate to patterns within the brain and how each associates with central cellular profiles. In this study, we profiled DNA methylation in both the blood and in five post mortem brain regions (BA17, BA20/21, BA24, BA46 and hippocampus) in 14 individuals from the Lothian Birth Cohort 1936. Microglial burdens were additionally quantified in the same brain regions. DNA methylation signatures of five epigenetic ageing biomarkers ('epigenetic clocks'), and two inflammatory biomarkers (methylation proxies for C-reactive protein and interleukin-6) were compared across tissues and regions. Divergent associations between the inflammation and ageing signatures in the blood and brain were identified, depending on region assessed. Four out of the five assessed epigenetic age acceleration measures were found to be highest in the hippocampus (ß range = 0.83-1.14, p ≤ 0.02). The inflammation-related DNA methylation signatures showed no clear variation across brain regions. Reactive microglial burdens were found to be highest in the hippocampus (ß = 1.32, p = 5 × 10-4 ); however, the only association identified between the blood- and brain-based methylation signatures and microglia was a significant positive association with acceleration of one epigenetic clock (termed DNAm PhenoAge) averaged over all five brain regions (ß = 0.40, p = 0.002). This work highlights a potential vulnerability of the hippocampus to epigenetic ageing and provides preliminary evidence of a relationship between DNA methylation signatures in the brain and differences in microglial burdens.

An epigenetic predictor of death captures multi-modal measures of brain health.

Individuals of the same chronological age exhibit disparate rates of biological ageing. Consequently, a number of methodologies have been proposed to determine biological age and primarily exploit variation at the level of DNA methylation (DNAm). A novel epigenetic clock, termed 'DNAm GrimAge' has outperformed its predecessors in predicting the risk of mortality as well as many age-related morbidities. However, the association between DNAm GrimAge and cognitive or neuroimaging phenotypes remains unknown. We explore these associations in the Lothian Birth Cohort 1936 (n = 709, mean age 73 years). Higher DNAm GrimAge was strongly associated with all-cause mortality over the eighth decade (Hazard Ratio per standard deviation increase in GrimAge: 1.81, P < 2.0 × 10-16). Higher DNAm GrimAge was associated with lower age 11 IQ (ß = -0.11), lower age 73 general cognitive ability (ß = -0.18), decreased brain volume (ß = -0.25) and increased brain white matter hyperintensities (ß = 0.17). There was tentative evidence for a longitudinal association between DNAm GrimAge and cognitive decline from age 70 to 79. Sixty-nine of 137 health- and brain-related phenotypes tested were significantly associated with GrimAge. Adjusting all models for childhood intelligence attenuated to non-significance a small number of associations (12/69 associations; 6 of which were cognitive traits), but not the association with general cognitive ability (33.9% attenuation). Higher DNAm GrimAge associates with lower cognitive ability and brain vascular lesions in older age, independently of early-life cognitive ability. This epigenetic predictor of mortality associates with different measures of brain health and may aid in the prediction of age-related cognitive decline.

Associations between alcohol use and accelerated biological ageing.

Harmful alcohol use is a leading cause of premature death and is associated with age-related disease. Biological ageing is highly variable between individuals and may deviate from chronological ageing, suggesting that biomarkers of biological ageing (derived from DNA methylation or brain structural measures) may be clinically relevant. Here, we investigated the relationships between alcohol phenotypes and both brain and DNA methylation age estimates. First, using data from UK Biobank and Generation Scotland, we tested the association between alcohol consumption (units/week) or hazardous use (Alcohol Use Disorders Identification Test [AUDIT] scores) and accelerated brain and epigenetic ageing in 20,258 and 8051 individuals, respectively. Second, we used Mendelian randomisation (MR) to test for a causal effect of alcohol consumption levels and alcohol use disorder (AUD) on biological ageing. Alcohol use showed a consistent positive association with higher predicted brain age (AUDIT-C: ß = 0.053, p = 3.16 × 10-13 ; AUDIT-P: ß = 0.052, p = 1.6 × 10-13 ; total AUDIT score: ß = 0.062, p = 5.52 × 10-16 ; units/week: ß = 0.078, p = 2.20 × 10-16 ), and two DNA methylation-based estimates of ageing, GrimAge (units/week: ß = 0.053, p = 1.48 × 10-7 ) and PhenoAge (units/week: ß = 0.077, p = 2.18x10-10 ). MR analyses revealed limited evidence for a causal effect of AUD on accelerated brain ageing (ß = 0.118, p = 0.044). However, this result should be interpreted cautiously as the significant effect was driven by a single genetic variant. We found no evidence for a causal effect of alcohol consumption levels on accelerated biological ageing. Future studies investigating the mechanisms associating alcohol use with accelerated biological ageing are warranted.

Investigation of Surrogate Biomarkers Associated with Macular Pigment Status in a Group of Older Irish Adults.

SIGNIFICANCE: Macular pigment (MP) confers potent antioxidant and anti-inflammatory effects at the macula; however, its optical density in the eye is not routinely measured in clinical practice. PURPOSE: This study explored a range of surrogate biomarkers including anthropometric, clinical, and plasma measures that may be associated with lower MP optical density (MPOD). METHODS: Two thousand five hundred ninety-four subjects completed a full MP assessment as part of wave 1 of The Irish Longitudinal Study of Aging. Macular pigment optical density was measured using customized heterochromatic flicker photometry. Clinical (blood pressure), plasma (lipoproteins, inflammatory markers), and anthropometric (waist, hip, height, weight) biomarkers were measured for each participant. RESULTS: Mean (standard deviation) MPOD for the study group was 0.223 (0.161), with a range of 0 to 1.08. One-way ANOVA revealed that MPOD was significantly lower among participants with low plasma high-density lipoprotein (HDL; P = .04), raised plasma triglyceride-to-HDL ratio (P = .003), and raised total cholesterol-to-HDL ratio (P = .03). Subjects with an elevated waist circumference (WC) had a significantly lower MPOD (mean, 0.216 [0.159]) compared with those with an ideal WC (mean, 0.229 [0.162]; P = .03). Significant correlates of MPOD on mixed linear model analysis included education, smoking status, and WC. CONCLUSIONS: Higher abdominal fat is associated with lower MPOD in this representative sample of older Irish adults. Although altered lipoprotein profiles (low HDL, raised triglyceride-to-HDL ratio, raised total cholesterol-to-HDL ratio) may affect the transport, uptake, and stabilization of carotenoids in the retina, these plasma biomarkers were not predictive of low MPOD after adjustment for abdominal circumference. Although WC emerged as a viable anthropometric predictor of lower MPOD, its effect size seems to be small.

Use of geosocial networking applications is independently associated with diagnosis of STI among men who have sex with men testing for STIs: findings from the cross-sectional MSM Internet Survey Ireland (MISI) 2015.

OBJECTIVES: MSM Internet Survey Ireland (MISI) 2015 was an anonymous, self-completed, cross-sectional internet survey assessing sexual behaviours and health needs among men who have sex with men (MSM) in Ireland. We explored factors associated with self-reported STI diagnosis among MSM who were sexually active and had an STI test in the previous year. METHODS: We compared the study population (n=1158; 37% of total population), with the sexually active MISI population not testing for STIs (n=1620; 52% of total population). Within the study population, we identified sociodemographics and sexual behaviours associated with self-reporting STI diagnosis. We used multivariable logistic regression to estimate adjusted odds ratios (aORs). RESULTS: The sociodemographics, lifestyle and sexual behaviours of the study population differed significantly from the sexually active MISI population who did not test for STIs. Within the study population, 65% met a sexual partner via geosocial networking smartphone application (GSNa) and 21% self-reported an STI diagnosis in the previous year. On univariable analysis, factors associated with STI diagnosis included: older age, identifying as gay, HIV-positive status, increasing number of sexual partners in the previous year, condomless anal intercourse (CAI) with ≥2 non-steady partners and using GSNa to meet a new sexual partner in the previous year or most recent sexual partner. On multivariable analysis, STI diagnosis was associated with: being aged 25-39 years (aOR 1.8, 95% CI 1.04 to 3.15), CAI with ≥2 non-steady partners (aOR 2.8, 95% CI 1.84 to 4.34), total number of sexual partners (aOR 1.02, 95% CI 1.00 to 1.03) and using GSNa to meet a new sexual partner (aOR 1.95, 95% CI 1.12 to 3.39). CONCLUSIONS: STI diagnosis among MSM testing for STIs is associated with GSNa use, as well as sexual behaviours. GSNas are key settings for STI prevention interventions, which should prioritise men with high numbers of sexual partners and those with multiple CAI partners.

A review of the putative causal mechanisms associated with lower macular pigment in diabetes mellitus.

Macular pigment (MP) confers potent antioxidant and anti-inflammatory effects at the macula, and may therefore protect retinal tissue from the oxidative stress and inflammation associated with ocular disease and ageing. There is a body of evidence implicating oxidative damage and inflammation as underlying pathological processes in diabetic retinopathy. MP has therefore become a focus of research in diabetes, with recent evidence suggesting that individuals with diabetes, particularly type 2 diabetes, have lower MP relative to healthy controls. The present review explores the currently available evidence to illuminate the metabolic perturbations that may possibly be involved in MP's depletion. Metabolic co-morbidities commonly associated with type 2 diabetes, such as overweight/obesity, dyslipidaemia, hyperglycaemia and insulin resistance, may have related and independent relationships with MP. Increased adiposity and dyslipidaemia may adversely affect MP by compromising the availability, transport and assimilation of these dietary carotenoids in the retina. Furthermore, carotenoid intake may be compromised by the dietary deficiencies characteristic of type 2 diabetes, thereby further compromising redox homeostasis. Candidate causal mechanisms to explain the lower MP levels reported in diabetes include increased oxidative stress, inflammation, hyperglycaemia, insulin resistance, overweight/obesity and dyslipidaemia; factors that may negatively affect redox status, and the availability, transport and stabilisation of carotenoids in the retina. Further study in diabetic populations is warranted to fully elucidate these relationships.

Association of Total Zinc Intake with Myopia in U.S. Children and Adolescents.

SIGNIFICANCE: This present study advances our knowledge on the role of lifestyle factors in myopia (short-sightedness), specifically dietary factors. It has been suggested in previous studies that lower zinc status is associated with myopia; however, this article shows no relationship between dietary zinc intake and myopia in U.S. adolescents. PURPOSE: It has been suggested that low zinc levels may contribute to the development of myopia. The aim of the present study is to examine, for the first time in a Western population, the association of total dietary and supplement zinc intake with myopia. METHODS: A total of 1095 children/adolescents aged 12 to 19 years who participated in the U.S. National Health and Nutrition Examination Survey from 2007 to 2008 were enrolled in this study. Multivariate logistic regression analysis was performed to examine the relationship between total zinc intake and myopia after adjustment for potential confounders. In addition, the association between total zinc intake and spherical equivalent refractive error was examined in the myopia group through multiple linear regression. RESULTS: Among study participants, 30% were found to be myopic (≤-1.00 D). Although median total daily zinc intake was lower among myopes (10.8 [10.2] mg/d) than among nonmyopes (11.1 [10.8] mg/d), the difference was not statistically significant (P = .11). In multiple logistic regression analyses, zinc and copper intakes were not significantly associated with myopia after adjustment for age, sex, body mass index, ethnicity, family income, recreational activity, copper intake, and daily energy intake (in kilocalories per day). In multiple linear regression, spherical equivalent refractive error was not associated with total zinc intake in the myopic group after adjustment for confounding factors (P = .13). CONCLUSIONS: In contrast to previous Asian studies, total zinc intake is not associated with the presence of myopia in U.S. adolescents/children.

Optimization of folic acid supplementation in the prevention of neural tube defects.

Background: We examined the relationship between timing and duration of folic acid (FA) supplementation in achieving red blood cell (RBC) folate levels in early pregnancy which are optimal (>906 nmol/l) for the prevention of neural tube defects (NTDs). Methods: Clinical, FA supplementation and dietary folate details were computerized at the first antenatal visit. Maternal blood samples were analysed for RBC and serum folate. Results: Of the 502 women, 98.2% (n = 493) reported taking FA. There was a positive correlation between duration of supplementation and both RBC folate (r = 0.43, P < 0.001) and serum folate (rho = 0.29, P < 0.001). The optimal RBC folate level was achieved in 80.4% (n = 46) of women who started FA 400 µg 4-8 weeks before their LMP compared with only 53.6% (n = 153) in women who started 4-8 weeks after their LMP (P < 0.001). Conclusions: This study provides, for the first time, information on both the timing and duration of FA that will achieve the optimum RBC folate levels associated with the prevention of NTDs. Women who are taking FA (400 µg) need to start before they conceive.

Duration of periconceptional folic acid supplementation in women booking for antenatal care.

OBJECTIVE: To provide accurate estimates of the commencement time, duration and dosage of folic acid (FA) supplementation taken by Irish women in the periconceptional period. The study also aimed to establish the factors associated with optimal FA supplementation practices. DESIGN: Cross-sectional observational study. Women's clinical and sociodemographic details were computerised. Maternal weight and height were measured before calculating BMI. Detailed FA supplementation questionnaires were completed under the supervision of a trained researcher. SETTING: A large university maternity hospital, Republic of Ireland, January 2014-April 2016. SUBJECTS: Women (n 856) recruited at their convenience in the first trimester. RESULTS: While almost all of the women (97 %) were taking FA at enrolment, only one in four women took FA for at least 12 weeks preconceptionally (n 208). Among the 44 % of women who were supplementing with FA preconceptionally, 44 % (162/370) reported taking FA for less than the 12 weeks required to achieve optimal red-blood-cell folate levels for prevention of neural tube defects. On multivariate analysis, only planned pregnancy and nulliparity were associated with taking FA for at least 12 weeks preconceptionally. Among women who only took FA postconceptionally, almost two-thirds commenced it after day 28 of their pregnancy when the neural tube had already closed. CONCLUSIONS: As the timing of FA was suboptimal both before and after conception, we recommend that current national FA guidelines need to be reviewed.

Maternal nutrient intakes from food and drinks consumed in early pregnancy in Ireland.

Background: The aim of this observational study was to measure food, macronutrient and micronutrient intakes of women presenting for antenatal care and assess compliance with current nutritional recommendations. Methods: Women were recruited in the first trimester of pregnancy. Maternal weight and height were measured and body mass index (BMI) calculated. Body composition was measured using bioelectrical impedance analysis. Maternal energy and nutrient intakes were estimated using a validated Willett Food Frequency Questionnaire and misreporting of energy intakes (EI) determined. Results: Plausible EIs were reported in 402 women. Mean age, weight and BMI were 30.8 years, 67.1 kg and 24.6 kg/m2 respectively. Median EIs were 2111 kcal, and median protein, carbohydrate and fat intakes were 17.3, 48.1 and 36.2 g/MJ/day, respectively. More than 90% of women exceeded the recommended daily allowance for saturated fat. Nearly all of the women (99%) did not meet estimated average requirements (EAR) for vitamin D. One in three women failed to achieve a dietary folate intake of 400 µg/day. Over one in five women failed to meet the EAR for iron, and 14% failed to achieve the EAR for calcium. Conclusions: Our findings highlight concerning deficits in nutrient intakes among women and will help guide professional dietary advice to women attending for future obstetric care in Ireland.

Breast-feeding and postpartum maternal weight trajectories.

OBJECTIVE: We examined whether breast-feeding, and in particular exclusive breast-feeding, was associated with maternal weight and body composition changes at 4 months postpartum independently of other maternal variables. DESIGN: Prospective longitudinal study. Women were recruited in the first trimester after an ultrasound examination confirmed an ongoing singleton pregnancy. Weight and body composition were measured using advanced bio-electrical impedance analysis at the first antenatal visit and 4 months postpartum. Detailed questionnaires were completed on breast-feeding, socio-economic status, diet and exercise in addition to routine clinical and sociodemographic details. SETTING: Large Irish university maternity hospital. SUBJECTS: Women who delivered a baby weighing ≥500 g between November 2012 and March 2014. RESULTS: At the postpartum visit, the mean weight was 70·9 (sd 14·2) kg (n 470) and the mean BMI was 25·9 (sd 5·0) kg/m2. 'Any breast-feeding' was reported by 65·1 % of women (n 306). Irish nativity (OR=0·085, P<0·001), current smoking (OR=0·385, P=0·01), relative income poverty (OR=0·421, P=0·04) and deprivation (OR=0·458, P=0·02) were negatively associated with exclusive breast-feeding. At 4 months postpartum there was no difference in maternal weight change between women who exclusively breast-fed and those who formula-fed (+2·0 v. +1·1 kg, P=0·13). Women who exclusively breast-fed had a greater increase in percentage body fat at 4 months postpartum compared with women who formula-fed (+1·0 v. -0·03 %, P=0·02), even though their dietary quality was better. Exclusive breast-feeding was not associated with postpartum maternal weight or body fat percentage change after adjusting for other maternal variables. CONCLUSIONS: There are many reasons why breast-feeding should be strongly promoted but we found no evidence to support postpartum weight management as an advantage of breast-feeding.

An analysis of folic acid supplementation in women presenting for antenatal care.

BACKGROUND: Neural tube defects (NTDs) are major congenital malformations that are potentially preventable if the woman takes periconceptional folic acid (FA) supplements. A recent report found that NTD incidence had increased in Ireland. This study examined the usage of FA supplementation in women presenting for antenatal care in a maternity hospital. METHODS: Women were recruited at their convenience in the first trimester. Their clinical and sociodemographic details were computerized. Maternal weight and height were measured before calculating body mass index. Detailed FA questionnaires were completed under supervision of a trained researcher. RESULTS: While 96.1% (n = 564) out of 587 reported that they took FA after they became pregnant, only 24.7% (n = 145) took it for >12 weeks preconceptionally as recommended. Only 5.7% (n = 6) of obese women took high-dose FA as recommended. On univariate analysis, the strongest predictors of preconceptional FA usage were higher maternal age, higher education and income, being married, being nulliparous, not smoking, infertility treatment and planned pregnancy. On multivariate analysis, both planned pregnancy and nulliparity were the most important predictors of preconceptional FA use. CONCLUSIONS: Our study shows that current recommendations to prevent NTDs by FA supplementation pre-pregnancy are not being fully implemented in Ireland. We recommend a review of current public health policies on FA supplementation.

Maternal folic acid supplementation trends 2009-2013.

OBJECTIVE: We analyzed trends in folic acid supplementation among women booking for antenatal care between 2009 and 2013. DESIGN: Prospective observational study. SETTING: Large university teaching hospital. POPULATION: We included all women who delivered an infant ≥500 g from 1 January 2009 to 31 December 2013. METHODS: Body mass index was calculated using early pregnancy weight and height measured at first antenatal visits. Sociodemographic and clinical data were gathered prospectively. Multivariate logistic regression analyses were applied to determine the correlates of periconceptional folic acid supplementation. MAIN OUTCOME MEASURES: Rates and correlates of folic acid supplementation. RESULTS: Of 42 362 women, 99.2% (n = 42 042) were suitable for analysis. The mean age was 30.7 years and mean body mass index was 25.6 kg/m(2) , 40.7% (n = 17 054) were primigravidas and 70.6% (n = 29 741) were Irish-born. Overall, 43.9% (n = 18 473) took periconceptional (preconceptional and postconceptional) folic acid, 49.4% (n = 20 782) took postconceptional folic acid only, and 6.6% (n = 2787) took no folic acid. The women most likely to take folic acid were those who planned their pregnancy and were >30 years old, non-obese, Irish-born and employed professionally. The periconceptional folic acid rate decreased from 45.1% in 2009 to 43.1% in 2013 (p = 0.01). Over five years, periconceptional folic acid supplementation decreased among women who were multiparous (43.8-41.6%, p = 0.02), aged 30-39 years (58.9-55.0%, p < 0.001), Irish-born (50.1-47.1%, p < 0.001) and obese (38.6-36.9%, p = 0.02). CONCLUSION: Overall, the rate of periconceptional folic acid supplementation decreased in the five years 2009-2013, particularly among women who were multiparous, aged 30-39 years, Irish-born and obese.