The influence of the environment and lifestyle on myopia.

BACKGROUND: Myopia, commonly known as near-sightedness, has emerged as a global epidemic, impacting almost one in three individuals across the world. The increasing prevalence of myopia during early childhood has heightened the risk of developing high myopia and related sight-threatening eye conditions in adulthood. This surge in myopia rates, occurring within a relatively stable genetic framework, underscores the profound influence of environmental and lifestyle factors on this condition. In this comprehensive narrative review, we shed light on both established and potential environmental and lifestyle contributors that affect the development and progression of myopia. MAIN BODY: Epidemiological and interventional research has consistently revealed a compelling connection between increased outdoor time and a decreased risk of myopia in children. This protective effect may primarily be attributed to exposure to the characteristics of natural light (i.e., sunlight) and the release of retinal dopamine. Conversely, irrespective of outdoor time, excessive engagement in near work can further worsen the onset of myopia. While the exact mechanisms behind this exacerbation are not fully comprehended, it appears to involve shifts in relative peripheral refraction, the overstimulation of accommodation, or a complex interplay of these factors, leading to issues like retinal image defocus, blur, and chromatic aberration. Other potential factors like the spatial frequency of the visual environment, circadian rhythm, sleep, nutrition, smoking, socio-economic status, and education have debatable independent influences on myopia development. CONCLUSION: The environment exerts a significant influence on the development and progression of myopia. Improving the modifiable key environmental predictors like time spent outdoors and engagement in near work can prevent or slow the progression of myopia. The intricate connections between lifestyle and environmental factors often obscure research findings, making it challenging to disentangle their individual effects. This complexity underscores the necessity for prospective studies that employ objective assessments, such as quantifying light exposure and near work, among others. These studies are crucial for gaining a more comprehensive understanding of how various environmental factors can be modified to prevent or slow the progression of myopia.

Identifying Content for an Item Bank to Measure the Quality-of-Life Impact of Myopia Refractive Interventions.

Purpose: To report on the content generation and item refinement phases for a myopia refractive intervention-specific quality-of-life (QoL) item bank that will be operationalized using computerized adaptive testing. Methods: Myopia refractive intervention-specific QoL domains and items were generated from (1) a literature search of existing refractive-intervention QoL questionnaires; (2) semistructured interviews with myopic patients corrected using spectacles, contact lenses and/or refractive surgery (n = 32); (3) and myopia experts (n = 9) recruited from the Singapore National Eye Centre. After a thematic analysis, items were systematically refined and tested using cognitive interviews with 24 additional patients with corrected myopia. Results: Of the 32 participants with myopia interviewed (mean ± standard deviation age, 35.6 ± 9.0 years; 71.9% female; 78.1% Chinese), 12 (37.5%) wore spectacles, 7 (21.9%) used contact lenses, and 20 (62.5%) had undergone laser refractive surgery. Initially, 912 items within 7 independent QoL domains were identified. After refinement, 204 items were retained, including those relating to mobility challenges and work-related difficulties that are not well-represented in current refractive intervention-specific questionnaires. Conclusions: Through a rigorous item generation and selection process, we have developed a 204-item and 7-domain myopia refractive intervention-specific item bank that will now undergo rigorous psychometric testing to generate item calibrations for the validation of a novel computerized adaptive testing instrument designed for use in research and routine clinical practice. Translational Relevance: Once psychometrically validated and operationalized using computerized adaptive testing, this myopia refractive intervention-specific instrument will enable researchers and clinicians to quickly and comprehensively assess the impact of myopic refractive interventions across seven QoL domains.

Family-focused contextual factors associated with lifestyle patterns in young children from two mother-offspring cohorts: GUSTO and EDEN.

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.

Incidence and Progression of Myopia in Early Adulthood.

IMPORTANCE: Myopia incidence and progression has been described extensively in children. However, few data exist regarding myopia incidence and progression in early adulthood. OBJECTIVE: To describe the 8-year incidence of myopia and change in ocular biometry in young adults and their association with the known risk factors for childhood myopia. DESIGN, SETTING, AND PARTICIPANTS: The Raine Study is a prospective single-center cohort study. Baseline and follow-up eye assessments were conducted from January 2010 to August 2012 and from March 2018 to March 2020. The data were analyzed from June to July 2021. A total of 1328 participants attended the baseline assessment, and 813 participants attended the follow-up assessment. Refractive information from both visits was available for 701 participants. Participants with keratoconus, previous corneal surgery, or recent orthokeratology wear were excluded. EXPOSURES: Participants' eyes were examined at ages 20 years (baseline) and 28 years. MAIN OUTCOMES AND MEASURES: Incidence of myopia and high myopia; change in spherical equivalent (SE) and axial length (AL). RESULTS: A total of 516 (261 male [50.6%]) and 698 (349 male [50.0%]) participants without myopia or high myopia at baseline, respectively, were included in the incidences analyses, while 691 participants (339 male [49%]) were included in the progression analysis. The 8-year myopia and high myopia incidence were 14.0% (95% CI, 11.5%-17.4%) and 0.7% (95% CI, 0.3%-1.2%), respectively. A myopic shift (of 0.50 diopters [D] or greater in at least 1 eye) occurred in 261 participants (37.8%). Statistical significance was found in longitudinal changes in SE (-0.04 D per year; P < .001), AL (0.02 mm per year; P <.001), and lens thickness (0.02 mm per year; P < .001). Incident myopia was associated with self-reported East Asian vs White race (odds ratio [OR], 6.13; 95% CI, 1.06-35.25; P = .04), female vs male sex (OR, 1.81; 95% CI, 1.02-3.22; P = .04), smaller conjunctival ultraviolet autofluorescence area (per 10-mm2 decrease, indicating less sun exposure; OR, 9.86; 95% CI, 9.76-9.97; P = <.009), and parental myopia (per parent; OR, 1.57; 95% CI, 1.03-2.38; P = <.05). Rates of myopia progression and axial elongation were faster in female participants (estimate: SE, 0.02 D per year; 95 % CI, 0.01-0.02 and AL, 0.007 mm per year, 95 % CI, 0.00.-0.011; P ≤ .001) and those with parental myopia (estimate per parent: SE, 0.01 D per year; 95% CI, 0.00-0.02 and AL, 95% CI, 0.002-0.008; P ≤ .001). Education level was not associated with myopia incidence or progression. CONCLUSIONS AND RELEVANCE: These findings suggest myopia progression continues for more than one-third of adults during the third decade of life, albeit at lower rates than during childhood. The protective effects of time outdoors against myopia may continue into young adulthood.

Prevalence, Characteristics, and Risk Factors of Moderate or High Hyperopia among Multiethnic Children 6 to 72 Months of Age: A Pooled Analysis of Individual Participant Data.

PURPOSE: To describe the prevalence, ocular characteristics, and associated risk factors of moderate to high hyperopia in early childhood. DESIGN: Pooled analysis of individual participant data from population-based studies. PARTICIPANTS: Six- to 72-month-old multiethnic children who participated in 4 population-based studies of pediatric eye diseases. METHODS: The pooled studies conducted comparable parental interviews and ocular examinations including cycloplegic autorefraction. Presence of hyperopia was defined based on cycloplegic refractive error in the worse eye. Multivariate analyses were performed to evaluate the association of potential risk factors with hyperopia risk. MAIN OUTCOME MEASURES: Prevalence and odds ratios of moderate to high hyperopia (≥4.0 diopters [D]). RESULTS: Cycloplegic refraction was completed in 15 051 children 6 to 72 months of age. Among these children, the overall prevalence of moderate to high hyperopia (≥4.0 D) in the worse eye was 3.2% (95% confidence interval, 2.9%-3.5%), accounting for 15.6% of all hyperopia (≥2.0 D). Among children with moderate to high hyperopia, both eyes were affected in 64.4%, 28.9% showed spherical anisometropia of 1.0 D or more, and 19.5% showed astigmatism of 1.5 D or more. Among 36- to 72-month-old children with moderate to high hyperopia, 17.6% wore glasses. Prevalence of moderate to high hyperopia was slightly less in 12- to 23-month-old children and was relatively stable in children 24 months of age and older. Non-Hispanic and Hispanic white race and ethnicity, family history of strabismus, maternal smoking during pregnancy, and being a participant in the United States studies were associated with a higher risk of moderate to high hyperopia (P < 0.05). CONCLUSIONS: By assembling similarly designed studies, our consortium provided robust estimates of the prevalence of moderate to high hyperopia in the general population and showed that in 6- to 72-month-old children, moderate to high hyperopia is not uncommon and its prevalence does not decrease with age. Risk factors for moderate to high hyperopia differ from those for low to moderate hyperopia (2.0-<4.0 D) in preschool children, with family history of strabismus and maternal smoking during pregnancy more strongly associated with moderate to high hyperopia than low to moderate hyperopia.

HOXA9 is a novel myopia risk gene.

PURPOSE: A recent meta-analysis revealed PAX6 as a risk gene for myopia. There is a link between PAX6 and HOXA9. Furthermore, HOXA9 has been reported to activate TGF-ß that is a risk factor for myopia. We speculate HOXA9 may participate in myopia development. METHODS: The Singapore GUSTO birth cohort provides data on children's cycloplegic refraction measured at age of 3 years and their methylation profile based on the umbilical cord DNA. The HOXA9 expression levels were measured in the eyes of mono-ocular form deprivation myopia in mice. The plasmid with the mouse HOXA9 cDNA was constructed and then transfected to mouse primary retinal pigment epithelial (RPE) cells. The expression levels of myopia-related genes and cell proliferation were measured in the HOXA9-overexpressed RPE cells. RESULTS: A total of 519 children had data on methylation profile and cycloplegic refraction. The mean spherical equivalent refraction (SE) was 0.90D. Among 8 SE outliers (worse than -2D), 7 children had HOXA9 hypomethylation. The HOXA9 levels in the retina of myopic eyes was 2.65-fold (p = 0.029; paired t-test) higher than the uncovered fellow eyes. When HOXA9 was over-expressed in the RPE cells, TGF-ß, MMP2, FGF2 and IGF1R expression levels were dose-dependently increased by HOXA9. However, over-expression of HOXA9 had no significant influence on IGF1 or HGF expression. In addition, HOXA9 also increased RPE proliferation. CONCLUSION: Based on the human, animal and cellular data, the transcription factor HOXA9 may promote the expression of pro-myopia genes and RPE proliferation, which eventually contribute to myopia development.

Longitudinal Changes in Disc and Retinal Lesions Among Highly Myopic Adolescents in Singapore Over a 10-Year Period.

OBJECTIVES: To examine the progression pattern of disc and retinal lesions in highly myopic Chinese adolescents over a 10-year period in Singapore. METHODS: This longitudinal study included Chinese participants who showed high myopia (spherical equivalent [SE] worse than or equal to -5 diopters [D]), no history of refractive surgery, and available fundus photographs at both 2006 (baseline) and 2016 (10-year follow-up) visits. Forty-four adolescents (aged 12-16 years at baseline) who were re-examined later at follow-up were included. Cycloplegic refraction, biometry, and fundus photography were performed at both visits. A trained grader classified myopic macular degeneration (MMD) based on the Meta-pathologic myopia classification and disc lesions from fundus photographs. Choroidal thickness (CT) measurements were performed at 10-year follow-up using swept-source optical coherence tomography. The ocular parameters and lesions were compared between baseline and follow-up. RESULTS: There was a significant worsening of high myopia at follow-up to -7.5±1.8 D (mean SE±SD) in 2016 versus -6.2±1.3 D in 2006; (P<0.001). The 10-year changes included increased degree of tessellation (26 eyes, 29.5%), development of new tessellated fundus (19 eyes, 21.6%), disc tilt (7 eyes, 8.0%), and expansion of peripapillary atrophy size (33 eyes, 37.5%). Eyes with early-onset tessellation (present at baseline, 48 eyes) showed significantly thinner CT (P<0.05), compared with eyes with late-onset tessellation (incident at 10-year follow-up, 19 eyes). No cases of MMD were recorded at baseline or 10-year follow-up. CONCLUSIONS: Although there was no incident MMD, the retinal and disc lesions worsened over the follow-up period. Early-onset fundus tessellation was associated with thinner CT.

Maternal choline status during pregnancy, but not that of betaine, is related to antenatal mental well-being: The growing up in Singapore toward healthy outcomes cohort.

BACKGROUND: Choline and betaine status have previously been associated with symptoms of depression. However, the relation of maternal plasma choline and betaine concentrations in pregnancy to peripartum maternal mood is unknown. METHODS: Maternal plasma choline and betaine concentrations (µmol/L) were measured at 26-28 weeks gestation in the Growing Up in Singapore Toward healthy Outcomes (GUSTO) mother-offspring cohort. Participants completed the State-Trait Anxiety Inventory (STAI) and Edinburgh Postnatal Depression Scale (EDPS) at 26-28 weeks gestation (n = 949) and at 3 months postnatal (n = 689): higher scores are indicative of more symptoms of anxiety and depression. Multivariate linear regression models were used to estimate the association of choline and betaine with ante- and postnatal mental well-being adjusting for covariates. RESULTS: Mean (SD) antenatal plasma choline and betaine concentrations were 9.2 µmol/L (1.6) and 13.1 µmol/L (2.7), respectively. Plasma choline concentrations were positively associated with antenatal depressive (ß = .24 EPDS score [95% CI: 0.05-0.43] per µmol/L] and anxiety symptoms (ß = .46 STAI-state score [95% CI: 0.03-0.88] per µmol/L) adjusting for covariates. Plasma betaine concentrations were not associated with antenatal depression or anxiety symptoms. No associations were observed between pregnancy choline or betaine and postnatal mental well-being. CONCLUSION: This study suggests that higher maternal plasma choline status during pregnancy is associated with more symptoms of antenatal depression and anxiety, whereas plasma betaine concentrations showed no associations. No associations were observed for postnatal mental well-being. Prospective studies are required to replicate these findings and further examine the direction of causality and possible biological mechanisms.

Developmental pathways to adiposity begin before birth and are influenced by genotype, prenatal environment and epigenome.

BACKGROUND: Obesity is an escalating health problem worldwide, and hence the causes underlying its development are of primary importance to public health. There is growing evidence that suboptimal intrauterine environment can perturb the metabolic programing of the growing fetus, thereby increasing the risk of developing obesity in later life. However, the link between early exposures in the womb, genetic susceptibility, and perturbed epigenome on metabolic health is not well understood. In this study, we shed more light on this aspect by performing a comprehensive analysis on the effects of variation in prenatal environment, neonatal methylome, and genotype on birth weight and adiposity in early childhood. METHODS: In a prospective mother-offspring cohort (N = 987), we interrogated the effects of 30 variables that influence the prenatal environment, umbilical cord DNA methylation, and genotype on offspring weight and adiposity, over the period from birth to 48 months. This is an interim analysis on an ongoing cohort study. RESULTS: Eleven of 30 prenatal environments, including maternal adiposity, smoking, blood glucose and plasma unsaturated fatty acid levels, were associated with birth weight. Polygenic risk scores derived from genetic association studies on adult adiposity were also associated with birth weight and child adiposity, indicating an overlap between the genetic pathways influencing metabolic health in early and later life. Neonatal methylation markers from seven gene loci (ANK3, CDKN2B, CACNA1G, IGDCC4, P4HA3, ZNF423 and MIRLET7BHG) were significantly associated with birth weight, with a subset of these in genes previously implicated in metabolic pathways in humans and in animal models. Methylation levels at three of seven birth weight-linked loci showed significant association with prenatal environment, but none were affected by polygenic risk score. Six of these birth weight-linked loci continued to show a longitudinal association with offspring size and/or adiposity in early childhood. CONCLUSIONS: This study provides further evidence that developmental pathways to adiposity begin before birth and are influenced by environmental, genetic and epigenetic factors. These pathways can have a lasting effect on offspring size, adiposity and future metabolic outcomes, and offer new opportunities for risk stratification and prevention of obesity. CLINICAL 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 .

Validation of the Children's Eating Behavior Questionnaire in 3 year old children of a multi-ethnic Asian population: The GUSTO cohort study.

The Children's Eating Behaviour Questionnaire (CEBQ) was developed to measure eating behaviors related to obesity risk in children. However, this questionnaire has not been validated for use in South East Asia, where parenting practices are different from those in western countries and child obesity rates are increasing. The aim of this study was to examine the validity of the CEBQ administered to mothers of children aged 3 years in Singapore. Confirmatory factor analysis (CFA) was used to examine if the original 35-item, 8-factor model was supported in our cohort. Participants were 636 mother-child dyads (mean (SD) child age = 36.7 (1.6) months), from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort in which the mothers were characterized in pregnancy and children were followed up to age 3 years. The CFA showed a poor model fit; RMSEA = 0.072 (PCLOSE<0.001), SRMR = 0.094, CFI = 0.826, and TLI = 0.805. Exploratory factor analysis revealed a 35 item, 7-factor structure (factor loadings ≥ 0.35): enjoyment of food, food fussiness, emotional overeating, desire to drink, emotional under eating, satiety responsiveness and slowness in eating. Cronbach's alpha estimates ranged from 0.70 to 0.88 for the 7 subscales. Convergent validity tests via correlation analysis revealed that emotional under eating (r = -0.14), slowness in eating (r = -0.16) and satiety responsiveness (r = -0.11) were negatively correlated with BMI z-score at 3 years, while enjoyment of food (r = 0.12) was positively correlated, p < 0.05. In conclusion, we found a revised 7-factor structure of the CEBQ more appropriate for examining eating behavior in 3 year old children in the Singapore setting. Further replication studies in a separate cohort study are warranted before further use of these factor structures generated.

Prospective associations of maternal betaine status with offspring weight and body composition at birth: the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study.

BACKGROUND: Betaine supplementation results in lower body weight and fat mass and higher lean mass in animals and adult humans. However, the relation between maternal betaine status and offspring birth weight and body composition is less known. OBJECTIVE: The aim was to examine the association between maternal betaine status and neonatal birth size and adiposity in an Asian mother-offspring cohort. DESIGN: We included 955 pregnant women whose plasma betaine concentrations were measured at 26-28 wk of gestation. Neonatal anthropometric values were measured at birth, and abdominal adipose tissue compartments were assessed by MRI in a subset of infants (n = 307) in the first 14 d after birth. Multivariate general linear models were used to adjust for gestational age; fetal sex; and maternal age, height, education, ethnicity, prepregnancy body mass index, and plasma folate, vitamin B-12, and choline concentrations. RESULTS: The mean ± SD plasma concentration of betaine was 13.2 ± 2.7 µmol/L (range: 5.3-25.0 µmol/L). After adjustment for covariates, higher maternal plasma betaine was associated with lower birth weight (ß: -57.6 g; 95% CI: -109.9, -5.3 g), shorter birth length (ß: -0.29 cm per 5-µmol/L increment; 95% CI: -0.55, -0.03 cm), smaller head circumference (-0.20 cm; 95% CI: -0.38, -0.02 cm), smaller midupper arm circumference (-0.16 cm; 95% CI: -0.30, -0.03 cm), lower volumes of abdominal superficial subcutaneous adipose tissue (-4.53 mL; 95% CI: -8.70, -0.36 mL), and a higher risk of small-for-gestational-age birth (OR: 1.57; 95% CI: 1.05, 2.35). CONCLUSIONS: Higher maternal betaine status was generally associated with smaller infant birth size and less abdominal fat mass. Further studies are needed to replicate these findings and to understand their biological mechanisms. This study was registered at clinicaltrials.gov as NCT01174875.

Demographic Characteristics, Health Behaviors Before and During Pregnancy, and Pregnancy and Birth Outcomes in Mothers with Different Pregnancy Planning Status.

Studies on pregnancy intentions and their consequences have yielded mixed results. Here, we comprehensively analyzed the maternal characteristics, health behaviors before and during pregnancy, as well as pregnancy and birth outcomes, across three different pregnancy planning status in 861 women participating in an ongoing Asian mother-offspring cohort study. At 26-28 weeks' gestation, the women's intention and enthusiasm toward their pregnancy were used to classify their pregnancy into planned or unplanned, and unplanned pregnancy was further subdivided into mistimed or unintended. Data on maternal characteristics, health behaviors, and pregnancy outcomes up to that stage were recorded. After delivery, birth outcomes of the offspring were recorded. Linear and logistic regression analyses were performed. Overall, 56 % had a planned pregnancy, 39 % mistimed, and 5 % unintended. Compared to women who planned their pregnancy, women with mistimed pregnancy had higher body mass index and were more likely to have cigarette smoke exposure and less likely to have folic acid supplementation. At 26-28 weeks' gestation, unintended pregnancy was associated with increased anxiety. Neonates of mistimed pregnancy had shorter birth length compared to those of planned pregnancy, even after adjustment for maternal baseline demographics. These findings suggest that mothers who did not plan their pregnancy had less desirable characteristics or health behaviors before and during pregnancy and poorer pregnancy and birth outcomes. Shorter birth length in mistimed pregnancy may be attributed to maternal behaviors before or in the early stages of pregnancy, therefore highlighting the importance of preconception health promotion and screening for women of child-bearing age.

Is there a link between passive smoke exposure and early-onset myopia in preschool Asian children?

PURPOSE: To investigate the association of passive tobacco smoke exposure with early-onset myopia among three-year-old children in Singapore. METHODS: Pregnant mothers who attended their first trimester clinic at two major maternity units were recruited into the GUSTO birth cohort. The current analysis comprised 572 three-year-old children, who underwent cycloplegic autorefraction and axial length (AL) measurements. Myopia was defined as spherical equivalent (SE) of ≤-0.50 dioptres (D). Either parent completed questionnaires describing their child's exposure to passive smoke at six months, one and two years of age. RESULTS: There were 197 children (36.2%) who were exposed to passive smoke from birth to before six months. Compared to non-exposed children, children exposed to any passive smoke from birth to before six months experienced greater myopia prevalence (adjusted OR = 2.79; 95% CI: 1.24-6.29; p = 0.01). The odds of myopia in a child was greater if a smoker smokes at home, in the family car, or in the presence of the child (adjusted OR = 3.95; 95% CI: 1.41-11.09; p < 0.01) compared to non-exposed child. In contrast to myopia, childhood exposure to passive smoke did not systematically shift mean values for SE or AL. CONCLUSIONS: In this prospective birth cohort study, we found that childhood exposure to passive smoke from birth to before six months slightly increased the risk of early-onset myopia. This may indicate a delayed response to passive smoke exposure before six months and the development of myopia at three years of age. Our study is limited by the small number of myopic children at this young age. Thus, larger prospective studies using more objective cotinine level measures are required to fully establish and understand the influence of tobacco smoke on refractive development in older children.

Incremental Cost-Effectiveness Analysis of Gestational Diabetes Mellitus Screening Strategies in Singapore.

The objective of this study was to conduct an incremental cost-effectiveness analysis from the payer's perspective in Singapore of 3 gestational diabetes mellitus screening strategies: universal, targeted, or no screening. A decision tree model assessed the primary outcome: incremental cost per quality-adjusted life year (QALY) gained. Probabilities, costs, and utilities were derived from the literature, the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study, and the KK Women's and Children's Hospital's database. Relative to targeted screening using risk factors, universal screening generates an incremental cost-effectiveness ratio (ICER) of $USD10,630/QALY gained. Sensitivity analyses show that disease prevalence rates and intervention effectiveness of glycemic management have the biggest impacts on the ICERs. Based on the model and best available data, universal screening is a cost-effective approach for reducing the complications of gestational diabetes mellitus in Singapore as compared with the targeted screening approach or no screening.

Early-life factors affect risk of pain and fever in infants during teething periods.

AIM: This longitudinal study aimed to investigate the prevalence of teething-related pain and fever and the early-life factors that may affect the risk of experiencing these disturbances within the first 1.5 years of life. MATERIALS AND METHODS: Participants were recruited (n = 1033) through the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort (n = 1237). Interviews were performed tri-monthly regarding the prevalence of teething pain and fever in children from 6 to 18 months of age. Crude and multivariable analyses were conducted using Poisson-log regression models. RESULTS: Prevalence rates for teething pain and fever were 35.5 and 49.9 % respectively. Multivariable Poisson regression analysis showed maternal second-hand tobacco smoke (SHS) exposure to increase the risk of both pain (mean ratio = 1.35; p = 0.006) and fever (mean ratio = 1.22; p = 0.025), whereas SHS exposure plus active smoking further increased risk of teething pain in the children (mean ratio = 1.89; p = 0.029). Delivery via Caesarean section increased risk of teething pain (mean ratio = 1.27; p = 0.033), while prenatal plasma vitamin D insufficiency lowered such a risk (mean ratio = 0.62; p = 0.012). Compared to Chinese infants, Indian babies exhibited lower risk of teething pain and fever (both p ≤ 0.001). CONCLUSIONS: Early-life factors such as tobacco smoke exposure and vitamin insufficiency during pregnancy, ethnicity and childbirth via Caesarean section may significantly affect the child's susceptibility to teething-related pain and fever. CLINICAL RELEVANCE: Knowledge of prevalence and risk factors of teething disturbances may better equip primary caregivers and healthcare professionals to accurately detect teething-related local and/or systemic signs/symptoms and effectively facilitate tobacco cessation among pregnant women.

Maternal Blood Pressure During Pregnancy and Early Childhood Blood Pressures in the Offspring: The GUSTO Birth Cohort Study.

Although epidemiological studies suggest that offspring of women with preeclampsia are at increased risk to higher blood pressures and cardiovascular disease, little is known about the nature of blood pressures between the mother and her offspring. As blood pressures comprise of both pulsatile (systolic blood pressure [SBP] and pulse pressure [PP]) and stable (diastolic blood pressure [DBP]) components, and they differ between central and peripheral sites, we sought to examine maternal peripheral and central blood pressure components in relation to offspring early childhood blood pressures. A prospective birth cohort of 567 Chinese, Malay, and Indian mother-offspring with complete blood pressure information were studied. Maternal brachial artery SBP, DBP, and PP were measured at 26 to 28 weeks gestation; and central SBP and PP were estimated from radial artery waveforms. Offspring brachial artery SBP, DBP, and PP were measured at 3 years of age. Associations between continuous variables of maternal blood pressures (peripheral SBP, DBP, PP, central SBP, and PP) and offspring blood pressures (peripheral SBP, DBP, and PP) were examined using multiple linear regression with adjustment for maternal characteristics (age, education level, parity, smoking status, alcohol consumption and physical activity during pregnancy, and pre-pregnancy BMI) and offspring characteristics (sex, ethnicity, BMI, and height at 3 years of age). In the multivariate models, offspring peripheral SBP increased by 0.08 (95% confidence interval 0.00-0.17, P = 0.06) mmHg with every 1-mmHg increase in maternal central SBP, and offspring peripheral PP increased by 0.10 (0.01-0.18, P = 0.03) mmHg for every 1-mmHg increase in maternal central PP. The relations of maternal-offspring peripheral blood pressures (SBP, DBP, and PP) were positive but not statistically significant, and the corresponding values were 0.05 (-0.03 to 0.13; P = 0.21), 0.03 (-0.04 to 0.10; P = 0.35), and 0.05 (-0.02 to 0.13; P = 0.14), respectively. Maternal central pulsatile blood pressure components (SBP and PP) during pregnancy are associated with higher blood pressures in the offspring. This positive correlation is already evident at 3-years old. Studies are needed to further evaluate the effects of maternal central pulsatile blood pressure components during pregnancy and long-term cardiovascular health in the offspring.

A review of environmental risk factors for myopia during early life, childhood and adolescence.

Myopia is a significant public health problem worldwide, particularly in East Asian countries. The increasing prevalence of myopia poses a huge socio-economic burden and progressive high myopia can lead to sight-threatening ocular complications. Hence, the prevention of early-onset myopia progressing to pathological high myopia is important. Recent epidemiological studies suggest that increased outdoor time is an important modifiable environmental factor that protects young children from myopia. This protective effect may be due to high light intensity outdoors, the chromaticity of daylight or increased vitamin D levels. This review summarises the possible underlying biological mechanisms for the protective association between time outdoors and myopia, including the potential role of nicotinic acetylcholine receptors in refractive error development. Recent evidence for the role of other environmental risk factors such as near work, birth seasons, parental smoking and birth order are also summarised.

Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia.

Myopia can cause severe visual impairment. Here, we report a two-stage genome-wide association study for three myopia-related traits in 9,804 Japanese individuals, which was extended with trans-ethnic replication in 2,674 Chinese and 2,690 Caucasian individuals. We identify WNT7B as a novel susceptibility gene for axial length (rs10453441, Pmeta=3.9 × 10(-13)) and corneal curvature (Pmeta=2.9 × 10(-40)) and confirm the previously reported association between GJD2 and myopia. WNT7B significantly associates with extreme myopia in a case-control study with 1,478 Asian patients and 4,689 controls (odds ratio (OR)meta=1.13, Pmeta=0.011). We also find in a mouse model of myopia downregulation of WNT7B expression in the cornea and upregulation in the retina, suggesting its possible role in the development of myopia.

Ethnic differences translate to inadequacy of high-risk screening for gestational diabetes mellitus in an Asian population: a cohort study.

BACKGROUND: Universal and high-risk screening for gestational diabetes mellitus (GDM) has been widely studied and debated. Few studies have assessed GDM screening in Asian populations and even fewer have compared Asian ethnic groups in a single multi-ethnic population. METHODS: 1136 pregnant women (56.7% Chinese, 25.5% Malay and 17.8% Indian) from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study were screened for GDM by 75-g oral glucose tolerance test (OGTT) at 26-28 weeks of gestation. GDM was defined using the World Health Organization (WHO) criteria. High-risk screening is based on the guidelines of the UK National Institute for Health and Clinical Excellence. RESULTS: Universal screening detected significantly more cases than high-risk screening [crude OR 2.2 (95% CI 1.7-2.8)], particularly for Chinese women [crude OR = 3.5 (95% CI 2.5-5.0)]. Pre-pregnancy BMI > 30 kg/m2 (adjusted OR = 3.4, 95% CI 1.5-7.9) and previous GDM history (adjusted OR = 6.6, 95% CI 1.2-37.3) were associated with increased risk of GDM in Malay women while GDM history was the only significant risk factor for GDM in Chinese women (adjusted OR = 4.7, 95% CI 2.0-11.0). CONCLUSION: Risk factors used in high-risk screening do not sufficiently predict GDM risk and failed to detect half the GDM cases in Asian women. Asian women, particularly Chinese, should be screened to avoid under-diagnosis of GDM and thereby optimize maternal and fetal outcomes.

Meta-analysis of genome-wide association studies in multiethnic Asians identifies two loci for age-related nuclear cataract.

Age-related cataract is a leading cause of blindness worldwide, especially in developing countries where access to cataract surgery remains limited. Previous linkage and candidate gene studies suggested genetic influences on age-related nuclear cataract but few genetic markers have been identified thus far. We conducted genome-wide association studies on 4569 Asians (including 2369 Malays and 2200 Indians), and replicated our analysis in 2481 Chinese from two independent cohorts (1768 Chinese in Singapore and 803 Chinese in Beijing). We confirmed two genome-wide significant loci for nuclear cataract in the combined meta-analysis of four cohorts (n = 7140). The first locus was at chromosome 3q25.31 in KCNAB1 (rs7615568, fixed-effect Pmeta = 2.30 × 10(-8); random-effect Pmeta = 1.08 × 10(-8)). The second locus was at chromosome 21 in the proximity of CRYAA (rs11911275, fixed-effect Pmeta = 2.77 × 10(-8); random-effect Pmeta = 1.98 × 10(-9)), a major protein component of eye lens. The findings were further supported by up-regulation and down-regulation of KCNAB1 and CRYAA in human lens capsule, respectively, as the severity of nuclear cataract increases. The results offer additional insights into the pathogenesis of nuclear cataract in Asians.