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Abstract Background Myopia affects 1.4 billion individuals worldwide. Notably, there is increasing evidence that choroidal thickness plays an important role in myopia and risk of developing myopia-related conditions. With the advancements in artificial intelligence (AI), choroidal thickness segmentation can now be automated, offering inherent advantages such as better repeatability, reduced grader variability, and less reliance for manpower. Hence, we aimed to evaluate the agreement between AI-automated and manual segmented measurements of subfoveal choroidal thickness (SFCT) using two swept-source optical coherence tomography (OCT) systems. Methods Subjects aged ≥ 16 years, with myopia of ≥ 0.50 diopters in both eyes, were recruited from the Prospective Myopia Cohort Study in Singapore (PROMYSE). OCT scans were acquired using Triton DRI-OCT and PLEX Elite 9000. OCT images were segmented both automatically with an established SA-Net architecture and manually using a standard technique with adjudication by two independent graders. SFCT was subsequently determined based on the segmentation. The Bland–Altman plot and intraclass correlation coefficient (ICC) were used to evaluate the agreement. Results A total of 229 subjects (456 eyes) with mean [± standard deviation (SD)] age of 34.1 (10.4) years were included. The overall SFCT (mean ± SD) based on manual segmentation was 216.9 ± 82.7 µm with Triton DRI-OCT and 239.3 ± 84.3 µm with PLEX Elite 9000. ICC values demonstrated excellent agreement between AI-automated and manual segmented SFCT measurements (PLEX Elite 9000: ICC = 0.937, 95% CI: 0.922 to 0.949, P

Summary: Genomic researchers increasingly utilize commercial cloud service providers (CSPs) to manage data and analytics needs. CSPs allow researchers to grow Information Technology (IT) infrastructure on demand to overcome bottlenecks when combining large datasets. However, without adequate security controls, the risk of unauthorized access may be higher for data stored on the cloud. Additionally, regulators are mandating data access patterns and specific security protocols for the storage and use of genomic data. While CSP provides tools for security and regulatory compliance, building the necessary controls required for cloud solutions is not trivial. Research Assets Provisioning and Tracking Online Repository (RAPTOR) by the Genome Institute of Singapore is a cloud-native genomics data repository and analytics platform that implements a “five-safes” framework to provide security and governance controls to data contributors and users, leveraging CSP for sharing and analysis of genomic datasets without the risk of security breaches or running afoul of regulations.

Abstract Background Integrated patterns of energy balance-related behaviours of preschool children in Asia are sparse, with few comparative analyses. Purpose Using cohorts in Singapore (GUSTO) and France (EDEN), we characterized lifestyle patterns of children and investigated their associations with family-focused contextual factors. Methods Ten behavioural variables related to child’s diet, walking, outdoor play and screen time were ascertained by parental questionnaires at age 5–6 years. Using principal component analysis, sex-specific lifestyle patterns were derived independently for 630 GUSTO and 989 EDEN children. Contextual variables were organised into distal (family socio-economics, demographics), intermediate (parental health, lifestyle habits) and proximal (parent-child interaction factors) levels of influence and analysed with hierarchical linear regression. Results Three broadly similar lifestyle patterns were identified in both cohorts: “discretionary consumption and high screen time”, “fruit, vegetables, and low screen time” and “high outdoor playtime and walking”. The latter two patterns showed small differences between cohorts and sexes. The “discretionary consumption and high screen time” pattern was consistently similar in both cohorts; distal associated factors were lower maternal education (EDEN boys), no younger siblings (GUSTO boys) and Malay/Indian ethnicity (GUSTO), while intermediate and proximal associated factors in both cohorts and sexes were poor maternal diets during pregnancy, parents allowing high child control over food intake, snacking between meals and having television on while eating. Conclusions Three similar lifestyle patterns were observed among preschool children in Singapore and France. There were more common associated proximal factors than distal ones. Cohort specific family-focused contextual factors likely reflect differences in social and cultural settings. Findings will aid development of strategies to improve child health.

BackgroundExisting modes of collecting self-reported 24-hour movement information from children, including digital assessments, have not been demonstrated to be of acceptable validity when compared to objective measurements. My E-Diary for Activities and Lifestyle (MEDAL) is an interactive web-based diary developed to collect time-use information from children aged 10 years and older. ObjectiveThis study evaluated the validity of MEDAL for assessing children’s movement behaviors by comparing self-reported and accelerometer-measured time spent in movement behavior among children in Singapore aged 10-11 years. MethodsFunding for this study was obtained in October 2017, and data were collected between April and August 2020. Participants recorded their daily activities using MEDAL over 2 specified weekdays and 2 weekend days and wore an Actigraph accelerometer on their nondominant wrist throughout the study to objectively assess movement behaviors. Spearman correlation coefficient and intraclass correlation coefficient (ICC) were used to compare the accelerometer measurements and self-reports for each movement behavior. Bland-Altman plots were generated to investigate trends of bias in the self-reports. ResultsAmong the participants aged 10-11 years (29/49, 59% boys), we observed that children reported lower light physical activity (LPA) and higher moderate-to-vigorous physical activity (MVPA), inactivity, and night sleep than that measured by the accelerometer. There was a moderate-to-strong correlation between self-reported and accelerometer-measured MVPA (r=0.37; 95% CI 0.20-0.54), inactivity (r=0.36; 95% CI 0.18-0.54), and night sleep (r=0.58; 95% CI 0.43-0.74); the correlation for LPA was poor (r=0.19; 95% CI 0.02-0.36). Agreement was poor for all behaviors (MVPA: ICC=0.24, 95% CI 0.07-0.40; LPA: ICC=0.19, 95% CI 0.01-0.36; inactivity: ICC=0.29, 95% CI 0.11-0.44; night sleep: ICC=0.45, 95% CI 0.29-0.58). There was stronger correlation and agreement on weekdays for inactivity and night sleep; conversely, there was stronger correlation and agreement for MVPA and LPA on weekend days. Finally, based on Bland-Altman plots, we observed that with increasing MVPA, children tended to report higher MVPA than that measured by the accelerometer. There were no clear trends for the other behaviors. ConclusionsMEDAL may be used to assess the movement behaviors of children. Based on self-reports, the children are able to estimate their time spent in MVPA, inactivity, and night sleep although actual time spent in these behaviors may differ from accelerometer-derived estimates; self-reported LPA warrant cautious interpretation. Observable differences in reporting accuracy exist between weekdays and weekend days.

Abstract Dental caries, although preventable, remains one of the most prevalent chronic disease worldwide. Most studies focused on the relationship between sugar intake and caries. However, examining multidimensional dietary patterns is becoming increasingly important. Here, we examined the relationship between dietary patterns from ages 6 to 12 months and early childhood caries (ECC) at age 2 to 3-years. Infant dietary data was collected from caregivers and dietary pattern trajectories from 6 to 12 months derived. Oral examinations were carried out by trained calibrated dentists at ages 2 and 3 years. Associations between dietary pattern and ECC were estimated using generalized estimating equation. We found a 3.9 fold lower prevalence of decayed surfaces among children with high Guidelines dietary pattern scores at 6-months (IRR 0.26; CI [0.12–0.53]; p-value

Myopic maculopathy is a complication of myopia that often progresses to blindness. Here, in a genome-wide association study, Hosoda et al. find that rs11873439 intronic to CCDC102B is associated with myopic maculopathy, but not with myopia, thus representing a risk factor independent of myopia.

My E-Diary for Activities and Lifestyle (MEDAL), a web-based application, was developed to assess the diets of children. This study examined the validity of school recess meals reported by children on MEDAL, using meal photography as the reference. Recess meals were photographed by trained researchers, and food items and portion sizes of recess meals reported on MEDAL were compared to recess meal photos. Validity was assessed by percentages of match, omission and intrusion for food items and percentages of the match, underestimation and overestimation for portion sizes. The Mann–Whitney test and the Wilcoxon matched-pairs signed-rank test examined if sex, school and day of recording influenced the validity of food item reporting. We found that participants (n = 33, aged 10–11 years) recalled 60.2% of food items consumed at recess accurately (matches); omissions (24.6%) were more common than intrusions (15.2%). Omissions tended to be side dishes, and intrusions tended to be high-calorie items. Sex, school and day of recording did not influence validity. For food portion sizes, 58.3% of items were accurately reported. Overestimations (33.3%) were more common than underestimations (8.3%). In conclusion, these children were able to report food items consumed during school recess meals using MEDAL, albeit with limitations on the degree of accuracy.

Abstract Background Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. Methods In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Results Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. Conclusions The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. Trial registration This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 .

Abstract Background Few studies have investigated physical activity (PA) and sedentary behavior (SB) in relation to fasting (FG) and 2-h postprandial plasma glucose (2hPG) levels and gestational diabetes mellitus (GDM); we investigated these associations among Asian pregnant women. Methods As part of the Growing Up in Singapore Towards healthy Outcomes cohort study, PA and SB (sitting and television times) were assessed by interviewer-administered questionnaire. During 75 g oral glucose tolerance tests at 26–28 weeks’ gestation we measured FG, 2hPG levels and GDM (FG ≥ 7.0 mmol/L and/or 2hPG ≥ 7.8 mmol/L). Associations were analysed by multiple linear and logistic regression. Results Among the 1083 women studied, 18.6% had GDM. SB was not associated with FG, 2hPG and GDM. Higher categories of PA were associated with lower 2hPG and a lower likelihood of GDM (p-trend

Abstract Background Higher screen viewing time (SVT) in childhood has been associated with adverse health outcomes, but the predictors of SVT in early childhood are poorly understood. We examined the sociodemographic and behavioral predictors of total and device-specific SVT in a Singaporean cohort. Methods At ages 2 and 3 years, SVT of 910 children was reported by their parents. Interviewer-administered questionnaires assessed SVT on weekdays and weekends for television, computer, and hand-held devices. Multivariable linear mixed-effect models were used to examine the associations of total and device-specific SVT at ages 2 and 3 with predictors, including children’s sex, ethnicity, birth order, family income, and parental age, education, BMI, and television viewing time. Results At age 2, children’s total SVT averaged 2.4 ± 2.2 (mean ± SD) hours/day, including 1.6 ± 1.6 and 0.7 ± 1.0 h/day for television and hand-held devices, respectively. At age 3, hand-held device SVT was 0.3 (95% CI: 0.2, 0.4) hours/day higher, while no increases were observed for other devices. SVT tracked moderately from 2 to 3 years (r = 0.49, p

ObjectivesTo assess whether epigenetic mechanisms affecting gene expression may be involved in the pathogenesis of early-onset myopia, we performed genome-wide DNA methylation analyses of umbilical cord tissues, and assessed any associations between CpG site-specific methylation and the development of the disorder when the children were 3 years old.MethodsGenome-wide DNA methylation profiling of umbilical cord samples from 519 Singaporean infants involved in a prospective birth cohort 'Growing Up in Singapore Towards healthy Outcomes' (GUSTO) was performed using the Illumina Infinium HumanMethylation450K chip microarray. Multivariable logistic regression models were used to assess any associations between site-specific CpG methylation of umbilical cord tissue at birth and myopia risk in 3 year old children, adjusting for potential confounders. Gene expression of genes located near CpG sites that demonstrated statistically significant associations were measured in relevant ocular tissues using human and mouse fetal and adult eye samples.ResultsWe identified statistically significant associations between DNA methylation levels at five CpG sites and early-onset myopia risk after correcting for multiple comparisons using a false discovery rate of 5%. Two statistically significant CpG sites were identified in intergenic regions: 8p23(p = 1.70×10-7) and 12q23.2(p = 2.53×10-7). The remaining 3 statistically significant CpG sites were identified within the following genes: FGB (4q28, p = 3.60×10-7), PQLC1 (18q23, p = 8.9×10-7) and KRT12 (17q21.2, p = 1.2×10-6). Both PQLC1 and KRT12 were found to be significantly expressed in fetal and adult cornea and sclera tissues in both human and mouse.ConclusionsWe identified five CpG methylation sites that demonstrate a statistically significant association with increased risk of developing early-onset myopia. These findings suggest that variability in the neonatal cord epigenome may influence early-onset myopia risk in children. Further studies of the epigenetic influences on myopia risk in larger study populations, and the associations with adulthood myopia risk are warranted.

Imbalanced macronutrient intakes can induce impairment of endothelial and vascular function, and further lead to metabolic and cardiovascular disease. However, little is known about the influence of such diets on endothelial and vascular dysfunction in pregnant women, even though high-fat diet is a known risk for pregnancy complications such as gestational diabetes and pre-eclampsia.We aimed to assess the association between maternal macronutrient intakes (protein, fat and carbohydrates), dietary quality and retinal microvascular changes in a multi-ethnic Asian mother-offspring cohort.Pregnant women (n = 614) with singleton pregnancies were recruited during their first trimester from June 2009 to Sep 2010. Maternal diet quality and macronutrient intakes, expressed as a percentage of total energy during pregnancy, were ascertained using 24 hr recalls and 3 d food diaries at 26-28 weeks gestation. Retinal examination was completed at the same clinic visit. Dietary quality was assessed and scored using the Health Eating Index in Asian Pregnant women (HEI-AP), while macronutrients intakes ware expressed as percentages of total energy and further log transformed for analysis. Associations were examined cross-sectionally by substitution models with the use of multiple linear regression.In adjusted model, each 20 points decrease in HEI-AP score was associated with a significant increase of 1.70 μm (p

OBJECTIVE:Inaccurate parental perception of their child's weight status is commonly reported in Western countries. It is unclear whether similar misperception exists in Asian populations. This study aimed to evaluate the ability of Singaporean mothers to accurately describe their three-year-old child's weight status verbally and visually. METHODS:At three years post-delivery, weight and height of the children were measured. Body mass index (BMI) was calculated and converted into actual weight status using International Obesity Task Force criteria. The mothers were blinded to their child's measurements and asked to verbally and visually describe what they perceived was their child's actual weight status. Agreement between actual and described weight status was assessed using Cohen's Kappa statistic (κ). RESULTS:Of 1237 recruited participants, 66.4% (n = 821) with complete data on mothers' verbal and visual perceptions and children's anthropometric measurements were analysed. Nearly thirty percent of the mothers were unable to describe their child's weight status accurately. In verbal description, 17.9% under-estimated and 11.8% over-estimated their child's weight status. In visual description, 10.4% under-estimated and 19.6% over-estimated their child's weight status. Many mothers of underweight children over-estimated (verbal 51.6%; visual 88.8%), and many mothers of overweight and obese children under-estimated (verbal 82.6%; visual 73.9%), their child's weight status. In contrast, significantly fewer mothers of normal-weight children were inaccurate (verbal 16.8%; visual 8.8%). Birth order (p

OBJECTIVE:Analyze the relation of gestational diabetes and maternal blood glucose levels to early cognitive functions in the first two years of life. METHODS:In a prospective Singaporean birth cohort study, pregnant women were screened for gestational diabetes at 26-28 weeks gestation using a 75-g oral glucose tolerance test. Four hundred and seventy three children (n = 74 and n = 399 born to mothers with and without gestational diabetes respectively) underwent neurocognitive assessments at 6, 18, and/or 24 month, including electrophysiology during an attentional task and behavioral measures of attention, memory and cognition. RESULTS:Gestational diabetes is related to left hemisphere EPmax amplitude differences (oddball versus standard) at both six (P = 0.039) and eighteen months (P = 0.039), with mean amplitudes suggesting offspring of mothers with gestational diabetes exhibit greater neuronal activity to standard stimuli and less to oddball stimuli. Associations between 2-hour maternal glucose levels and the difference in EPmax amplitude were marginal at 6 months [adjusted β = -0.19 (95% CI: -0.42 to +0.04) μV, P = 0.100] and significant at 18 months [adjusted β = -0.27 (95% CI: -0.49 to -0.06) μV, P = 0.014], and the EPmax amplitude difference (oddball-standard) associated with the Bayley Scales of Infant and toddler Development-III cognitive score at 24 months [β = 0.598 (95% CI: 0.158 to 1.038), P = 0.008]. CONCLUSION:Gestational diabetes and maternal blood glucose levels are associated with offspring neuronal activity during an attentional task at both six and eighteen months. Such electrophysiological differences are likely functionally important, having been previously linked to attention problems later in life.

[This corrects the article DOI: 10.1371/journal.pone.0160704.].

We conducted a cross-sectional study of Malay participants aged 40–80 years (n = 2,932) to examine the associations between polymorphisms at newly identified, lipid-associated loci with blood lipid levels and prevalent cardiovascular disease (CVD) in a Malay population in Asia. A polymorphism adjacent to the TRIB1 locus (rs17321515) was associated with elevated total cholesterol and LDL-cholesterol (LDL-C) after adjustment for age and sex (both P values

Epidemiological studies relating maternal 25-hydroxyvitamin D (25OHD) with gestational diabetes mellitus (GDM) and mode of delivery have shown controversial results. We examined if maternal 25OHD status was associated with plasma glucose concentrations, risks of GDM and caesarean section in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study.Plasma 25OHD concentrations, fasting glucose (FG) and 2-hour postprandial glucose (2HPPG) concentrations were measured in 940 women from a Singapore mother-offspring cohort study at 26-28 weeks' gestation. 25OHD inadequacy and adequacy were defined based on concentrations of 25OHD ≤75nmol/l and >75nmol/l respectively. Mode of delivery was obtained from hospital records. Multiple linear regression was performed to examine the association between 25OHD status and glucose concentrations, while multiple logistic regression was performed to examine the association of 25OHD status with risks of GDM and caesarean section.In total, 388 (41.3%) women had 25OHD inadequacy. Of these, 131 (33.8%), 155 (39.9%) and 102 (26.3%) were Chinese, Malay and Indian respectively. After adjustment for confounders, maternal 25OHD inadequacy was associated with higher FG concentrations (β = 0.08mmol/l, 95% Confidence Interval (CI) = 0.01, 0.14), but not 2HPPG concentrations and risk of GDM. A trend between 25OHD inadequacy and higher likelihood of emergency caesarean section (Odds Ratio (OR) = 1.39, 95% CI = 0.95, 2.05) was observed. On stratification by ethnicity, the association with higher FG concentrations was significant in Malay women (β = 0.19mmol/l, 95% CI = 0.04, 0.33), while risk of emergency caesarean section was greater in Chinese (OR = 1.90, 95% CI = 1.06, 3.43) and Indian women (OR = 2.41, 95% CI = 1.01, 5.73).25OHD inadequacy is prevalent in pregnant Singaporean women, particularly among the Malay and Indian women. This is associated with higher FG concentrations in Malay women, and increased risk of emergency caesarean section in Chinese and Indian women.

Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10(-8)), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10(-11)) and 8q12 (minimum p value 1.82×10(-11)) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.

Understanding healthy brain development in utero is crucial in order to detect abnormal developmental trajectories due to developmental disorders. However, in most studies neuroimaging was done after a significant postnatal period, and in those studies that performed neuroimaging on fetuses, the quality of data has been affected due to complications of scanning during pregnancy. To understand healthy brain development between 37-41 weeks of gestational age, our study assessed the in utero growth of the brain in healthy term born babies with DTI scanning soon after birth.A cohort of 93 infants recruited from maternity hospitals in Singapore underwent diffusion tensor imaging between 5 to 17 days after birth. We did a cross-sectional examination of white matter microstructure of the brain among healthy term infants as a function of gestational age via voxel-based analysis on fractional anisotropy.Greater gestational age at birth in term infants was associated with larger fractional anisotropy values in early developing brain regions, when corrected for age at scan. Specifically, it was associated with a cluster located at the corpus callosum (corrected p

Little is known about the dietary patterns of Asian infants in the first year of life, nor of their associations with maternal socio-demographic factors. Based on the Growing Up in Singapore towards healthy Outcomes (GUSTO) mother-offspring cohort, cross-sectional dietary patterns were derived by factor analysis using 24-h recalls and food diaries of infants at 6-, 9- and 12-months of age. Dietary pattern trajectories were modeled by mapping similar dietary patterns across each age using multilevel mixed models. Associations with maternal socio-demographic variables, collected through questionnaires during pregnancy, were assessed using general linear models. In n = 486 infants, four dietary pattern trajectories were established from 6- to 12-months. Predominantly breastmilk: mainly breastmilk and less formula milk, Guidelines: rice porridge, vegetables, fruits and low-fat fish and meat, Easy-to-prepare foods: infant cereals, juices, cakes and biscuits and Noodles (in soup) and seafood: noodle and common accompaniments. In adjusted models, higher maternal education attainment was correlated with higher start scores on Predominantly breastmilk, but lowest education attainment increased its adherence over time. Older mothers had higher start scores on Easy-to-prepare foods, but younger mothers had increased adherence over time. Chinese mothers had higher start scores on Predominantly breastmilk but greater adherence to Guidelines over time, while Indian mothers had higher start scores on Easy-to-prepare foods but greater adherence to Predominantly breastmilk with time (p < 0.05 for all). Changes in trajectories over time were small. Hence, dietary patterns established during weaning are strongly influenced by maternal socio-demographic factors and remain stable over the first year of life.

BackgroundBabies born at lower gestational ages or smaller birthweights have a greater risk of poorer health in later life. Both the causes of these sub-optimal birth outcomes and the mechanism by which the effects are transmitted over decades are the subject of extensive study. We investigated whether a transcriptomic signature of either birthweight or gestational age could be detected in umbilical cord RNA.MethodsThe gene expression patterns of 32 umbilical cords from Singaporean babies of Chinese ethnicity across a range of birthweights (1698-4151 g) and gestational ages (35-41 weeks) were determined. We confirmed the differential expression pattern by gestational age for 12 genes in a series of 127 umbilical cords of Chinese, Malay and Indian ethnicity.ResultsWe found that the transcriptome is substantially influenced by gestational age; but less so by birthweight. We show that some of the expression changes dependent on gestational age are enriched in signal transduction pathways, such as Hedgehog and in genes with roles in cytokine signalling and angiogenesis. We show that some of the gene expression changes we report are reflected in the epigenome.ConclusionsWe studied the umbilical cord which is peripheral to disease susceptible tissues. The results suggest that soma-wide transcriptome changes, preserved at the epigenetic level, may be a mechanism whereby birth outcomes are linked to the risk of adult metabolic and arthritic disease and suggest that greater attention be given to the association between premature birth and later disease risk.

Aims To determine axial length (AL) elongation profiles in children aged 3-6 years in an Asian population. Methods Eligible subjects were recruited from the Growing Up in Singapore Towards Healthy Outcomes birth cohort. AL measurement was performed using IOLMaster (Carl Zeiss Meditec, Jena, Germany) at 3 and 6 years. Anthropometric measurements at birth, cycloplegic refraction at 3 and 6 years, questionnaires on the children's behavioural habits at 2 years and parental spherical equivalent refraction were performed. Multivariable linear regression model with generalised estimating equation was performed to determine factors associated with AL elongation. Results 273 eyes of 194 children were included. The mean AL increased from 21.72±0.59 mm at 3 years to 22.52±0.66 mm at 6 years (p<0.001). Myopic eyes at 6 years had greater AL elongation (1.02±0.34 mm) compared with emmetropic eyes (0.85±0.25 mm, p=0.008) and hyperopic eyes (0.74±0.16 mm, p<0.001). The 95th percentile limit of AL elongation was 1.59 mm in myopes, 1.34 mm in emmetropes and 1.00 mm in hyperopes. Greater birth weight (per 100 g, ß=0.010, p=0.02) was significantly associated with greater AL elongation from 3 to 6 years, while parental and other behavioural factors assessed at 2 years were not (all p=0.08). Conclusion In this preschool cohort, AL elongates at an average length of 0.80 mm from 3 to 6 years, with myopes demonstrating the greatest elongation. The differences in 95th percentile limits for AL elongation between myopes, emmetropes and hyperopes can be valuable information in identifying myopia development in preschool children. [ABSTRACT FROM AUTHOR]

Purpose To evaluate factors influencing stabilisation of myopia in the Singapore Cohort of Risk factors for Myopia. Methods We evaluated the longitudinal natural history of 424 myopic participants from 1999 to 2022. The outcome was the change in myopia from the adolescence follow-up visit (aged 12-19 years) to the adulthood follow-up visit (aged 26-33 years). Association of predictive factors, including baseline spherical error, gender, ethnicity, parental myopia, time outdoor, near work and age at adolescence, was examined with the dichotomous outcome of adult myopia progression (= -1.00 dioptres (D) over 10 years) using multiple logistic regression and progression in linear regression models. Results For the primary outcome, the mean rate of progression of the outcome was found to be -0.04±0.09 D per year from the adolescent to the adulthood follow-up visits. 82.3% (95% CI 78.3% to 85.8%) had myopia stabilisation, with progression of less than 1.00 D over 10 years while 61.3% (95% CI 56.5% to 66.0%) of the subjects had progression of less than 0.50 D. In logistic regression models, both male gender (p=0.035) and non-Chinese ethnicity (p=0.032) were more likely to achieve myopia stabilisation while in linear multivariate regression models, males had a significantly slower degree of myopia progression (p=0.021). Conclusion 5 in 6 Singaporean young adults had myopia stabilisation. Male gender is 2 times and non-Chinese ethnicities are 2.5 times more likely to achieve myopia stabilisation. However, a proportion of myopes continue to exhibit a clinically significant degree of progression in adulthood. [ABSTRACT FROM AUTHOR]

PurposeTo evaluate the associations of sleep factors with myopia, spherical equivalent (SE), and axial length (AL) in elementary school-aged children from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort.MethodsThis cross-sectional study included multi-ethnic children who participated in the GUSTO prospective birth cohort and were delivered in two major tertiary hospitals in Singapore (2009–2010). Sleep factors and myopia outcomes were assessed at the 8- and 9-year study visits, respectively. Parent-reported sleep quality was assessed with the Children's Sleep Habits Questionnaire (CSHQ) total scores. Additionally, each child's sleep duration, timing (bedtime; waketime), and the consistency of sleep duration or timing (i.e., the difference between weekends and weekdays) were parent-reported. Outcomes included cycloplegic SE, myopia (SE ≤ −0.5 D) and AL. Eye measurements from both eyes were included in the analyses. Multivariable linear or logistic regression with Generalized Estimating Equations were used to account for the correlation between paired eyes and confounders in the associations of sleep factors at age 8 and myopia at age 9.ResultsA total of 572 multi-ethnic children (49.5% boys; 56.1% Chinese) aged 9 years were included in the analyses. Overall, 37.3% of eyes were myopic. Children reported a mean total CSHQ score of 46 [standard deviation (SD) = 6]. The mean duration of sleep was 9.2 (SD = 1.0) hours per day (h/day), with 59.9% of children reporting sufficient sleep (≥9 h/day) based on guidelines recommended by the National Sleep Foundation, USA. The mean bedtime and wake time were 22:00 (SD = 00:53) and 07:08 (SD = 00:55), respectively. In multivariable regression models, total CSHQ scores, the duration of sleep, bedtime and wake time were not significantly associated with myopia, SE, or AL (p ≥ 0.05 for all), adjusting for gender, ethnicity, time outdoors, near-work, parental myopia, maternal education levels (and additionally the child's height when the outcome was AL). Similarly, the consistency of both the duration and timing of sleep (across weekends and weekdays) were not significantly associated with myopia, SE, or AL (p ≥ 0.05 for all).ConclusionIn this cross-sectional study, sleep quality, duration, timing, and the consistency of specific sleep factors were not independently associated with myopia, SE, or AL among elementary school-aged children in Singapore. Large longitudinal studies are warranted to corroborate these results.

Purpose To investigate the predictive factors for myopic macular degeneration (MMD) and progression in adults with myopia. Methods We examined 828 Malay and Indian adults (1579 myopic eyes) with myopia (spherical equivalent (SE) ≤-0.5 dioptres) at baseline who participated in both baseline and 12-year follow-up visits of the Singapore Malay Eye Study and the Singapore Indian Eye Study. Eye examinations, including subjective refraction and axial length (AL) measurements, were performed. MMD was graded from fundus photographs following the Meta-Analysis for Pathologic Myopia classification. The predictive factors for MMD development and progression were assessed in adults without and with MMD at baseline, respectively as risk ratios (RR) using multivariable modified Poisson regression models. The receiver operating characteristic curve was used to visualise the performance of the predictive models for the development of MMD, with performance quantified by the area under the curve (AUC). Results The 12-year cumulative MMD incidence was 10.3% (95% CI 8.9% to 12.0%) among 1504 myopic eyes without MMD at baseline. Tessellated fundus was a major predictor of MMD (RR=2.50, p<0.001), among other factors including age, worse SE and longer AL (all p<0.001). The AUC for prediction of MMD development was found to be 0.78 (95% CI 0.76 to 0.80) for tessellated fundus and increased significantly to an AUC of 0.86 (95% CI 0.84 to 0.88) with the combination of tessellated fundus with age, race, gender and SE (p<0.001). Older age (p=0.02), worse SE (p<0.001) and longer AL (p<0.001) were found to be predictors of MMD progression. Conclusions In adults with myopia without MMD, tessellated fundus, age, SE and AL had good predictive value for incident MMD. In adults with MMD, 1 in 10 eyes experienced progression over the same period. Older age, more severe myopia and longer AL were independent risk factors for progression. [ABSTRACT FROM AUTHOR]

Background/aims To evaluate the association of reported time outdoors and light exposure patterns with myopia among children aged 9 years from the Growing Up in Singapore Towards Healthy Outcomes birth cohort. Methods We assessed reported time outdoors (min/day), light exposure patterns and outdoor activities of children aged 9 years (n=483) with a questionnaire, the FitSight watch and a 7-day activity diary. Light levels, the duration, timing and frequency of light exposure were assessed. Cycloplegic spherical equivalent (SE), myopia (SE≤-0.5 D) and axial length (AL) of paired eyes were analysed using generalised estimating equations. Results In this study, 483 (966 eyes) multiethnic children (50.0% boys, 59.8% Chinese, 42.2% myopic) were included. Reported time outdoors (mean±SD) was 100±93 min/day, and average light levels were 458±228 lux. Of the total duration children spent at light levels of ≥1000 lux (37±19 min/day), 76% were spent below 5000 lux. Peak light exposure occurred at mid-day. Children had 1.7±1.0 light exposure episodes/day. Common outdoor activities were walks, neighbourhood play and swimming. Greater reported time outdoors was associated with lower odds of myopia (OR=0.82, 95% CI 0.70 to 0.95/hour increase daily; p=0.009). Light levels, timing and frequency of light exposures were not associated with myopia, SE or AL (p>0.05). Conclusion Reported time outdoors, light levels and number of light exposure episodes were low among Singaporean children aged 9 years. Reported time outdoors was protective against myopia but not light levels or specific light measures. A multipronged approach to increase time outdoors is recommended in the combat against the myopia epidemic. [ABSTRACT FROM AUTHOR]