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  1. Soh SE, Chong YS, Kwek K, Saw SM, Meaney MJ, Gluckman PD, et al.
    Ann Nutr Metab, 2014;64(3-4):218-25.
    PMID: 25300263 DOI: 10.1159/000365023
    BACKGROUND: The dramatic emergence of noncommunicable diseases (NCD) in Asia, albeit with ethnic variation, has coincided with the rapid socioeconomic and nutritional transition taking place in the region, with the prevalence of diabetes rising 5-fold in Singapore in less than 4 decades. The Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study recruited 1,247 expectant mothers of Chinese, Malay, or Indian ethnicity in their first trimester, with detailed longitudinal tracking--through the antenatal period, birth, and the child's first 4 years of life--to examine the potential roles of fetal, developmental, and epigenetic factors in early pathways to metabolic and neurodevelopmental outcomes.

    KEY MESSAGES: A number of findings with a translational and clinical focus have already emerged. In the mothers, we found that changes and differences in food consumption varied across ethnic groups, with persistence of traditional beliefs, during pregnancy and the postpartum period. During pregnancy, higher maternal glucose levels, even in the absence of gestational diabetes mellitus, had graded relations with infant adiposity. Relations between maternal emotional health and birth outcomes and neurodevelopment have been identified. Genotype (25%) and in particular gene × environment interactions (75%) shape interindividual variations in the DNA methylome at birth. The complex effects of fixed genetic variations and different in utero environments can influence the epigenetic status at birth and the later-life phenotype.

    CONCLUSIONS: The richness of the clinical data in 3 ethnicities, the extent of the biospecimen collection, and the extensive infancy and preschool follow-up have allowed us to study the biological pathways that link fetal development to health outcomes. In the coming years, more sophisticated analyses of epigenotype-phenotype relationships will become possible as the children grow and develop. Our studies will lead to the development of clinical and population-based interventions to reduce the burden of NCD.

  2. Lim WY, Kwek K, Chong YS, Lee YS, Yap F, Chan YH, et al.
    J Hypertens, 2014 Apr;32(4):857-64.
    PMID: 24390251 DOI: 10.1097/HJH.0000000000000096
    OBJECTIVE: Greater maternal adiposity is a potentially modifiable risk factor for elevated blood pressure during pregnancy; however, the association has been little studied in Asian populations, and no study has evaluated potential differences in the adiposity-blood pressure relation between ethnic groups or interaction with gestational diabetes.

    METHODS: We performed a cross-sectional evaluation of a Singapore mother-offspring cohort comprising 799 pregnant Chinese, Malay and Indian women. Data on body weight, height, skinfold thickness and glycaemia (oral glucose tolerance test) were collected during the 2nd trimester; peripheral SBP and DBP were measured using an oscillometric device and central pressures by noninvasive radial applanation tonometry. The associations between adiposity measures BMI and sum of skinfold thickness and blood pressure outcomes were examined by linear regression with adjustment for potential confounders.

    RESULTS: Higher maternal BMI was associated with elevated peripheral and central pressures: the increases in pressure (mmHg) for each kg/m(2) increase in BMI were 1.19 (95% confidence interval, 1.03-1.36) for peripheral SBP, 0.76 (0.63-0.89) for peripheral DBP, 1.02 (0.87-1.17) for central systolic pressure and 0.26 (0.16-0.37) for central pulse pressure. The associations were generally stronger in Chinese women (P-interaction = 0.03 for central pulse pressure) and individuals with gestational diabetes (P-interaction = 0.03 for DBP and P-interaction = 0.046 for central systolic pressure). Similar patterns of results were found when using skinfold thickness as the measure of adiposity.

    CONCLUSION: Maternal adiposity is associated with higher peripheral and central blood pressures during pregnancy. Stronger associations in Chinese women and individuals with gestational diabetes warrant further investigation.
  3. Yang PL, Lu Y, Khoo CM, Leow MK, Khoo EY, Teo A, et al.
    J Clin Endocrinol Metab, 2013 Nov;98(11):4516-23.
    PMID: 24037892 DOI: 10.1210/jc.2013-2454
    Chinese men in Singapore have a higher incidence of hip fractures than Malay and Indian men. We investigated whether there were corresponding ethnic differences in peak bone mineral density (BMD) in young men and whether differences in body composition influenced peak BMD.
  4. Cai S, Tan S, Gluckman PD, Godfrey KM, Saw SM, Teoh OH, et al.
    Sleep, 2017 Feb 01;40(2).
    PMID: 28364489 DOI: 10.1093/sleep/zsw058
    STUDY OBJECTIVES: To examine the influence of maternal sleep quality and nocturnal sleep duration on risk of gestational diabetes mellitus (GDM) in a multiethnic Asian population.

    METHODS: A cohort of 686 women (376 Chinese, 186 Malay, and 124 Indian) with a singleton pregnancy attended a clinic visit at 26-28 weeks of gestation as part of the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study. Self-reported sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index (PSQI). GDM was diagnosed based on a 75-g oral glucose tolerance test administered after an overnight fast (1999 WHO criteria). Multiple logistic regression was used to model separately the associations of poor sleep quality (PSQI score > 5) and short nocturnal sleep duration (<6 h) with GDM, adjusting for age, ethnicity, maternal education, body mass index, previous history of GDM, and anxiety (State-Trait Anxiety Inventory score).

    RESULTS: In the cohort 296 women (43.1%) had poor sleep quality and 77 women (11.2%) were categorized as short sleepers; 131 women (19.1%) were diagnosed with GDM. Poor sleep quality and short nocturnal sleep duration were independently associated with increased risk of GDM (poor sleep, adjusted odds ratio [OR] = 1.75, 95% confidence interval [CI] 1.11 to 2.76; short sleep, adjusted OR = 1.96, 95% CI 1.05 to 3.66).

    CONCLUSIONS: During pregnancy, Asian women with poor sleep quality or short nocturnal sleep duration exhibited abnormal glucose regulation. Treating sleep problems and improving sleep behavior in pregnancy could potentially reduce the risk and burden of GDM.

  5. Chong YS, Cai S, Lin H, Soh SE, Lee YS, Leow MK, et al.
    BMC Pregnancy Childbirth, 2014 Oct 02;14:345.
    PMID: 25273851 DOI: 10.1186/1471-2393-14-345
    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.

  6. Parvaresh Rizi E, Teo Y, Leow MK, Venkataraman K, Khoo EY, Yeo CR, et al.
    J Clin Endocrinol Metab, 2015 11;100(11):4249-56.
    PMID: 26308293 DOI: 10.1210/jc.2015-2639
    CONTEXT: Among Asian ethnic groups, Chinese or Malays are more insulin sensitive than South Asians, in particular in lean individuals. We have further reported that body fat partitioning did not explain this ethnic difference in insulin sensitivity.

    OBJECTIVE: We examined whether adipocytokines might explain the ethnic differences in the relationship between obesity and insulin resistance among the three major ethnic groups in Singapore.

    DESIGN AND PARTICIPANTS: This was a cross-sectional study of 101 Chinese, 82 Malays, and 81 South Asian men. Insulin sensitivity index (ISI) was measured using hyperinsulinemic euglycemic clamp. Visceral (VAT) and subcutaneous adipose tissue (SAT) volumes were quantified using magnetic resonance imaging.

    MAIN OUTCOME MEASURES: Plasma total and high-molecular-weight adiponectin, leptin, visfatin, apelin, IL-6, fibroblast growth factor 21 (FGF21), retinol binding protein-4 (RBP 4), and resistin were measured using enzyme-linked immunoassays.

    RESULTS: Principle component (PC) analysis on the adipocytokines identified three PCs, which explained 49.5% of the total variance. Adiponectin loaded negatively, and leptin and FGF21 loaded positively onto PC1. Visfatin, resistin, and apelin all loaded positively onto PC2. IL-6 loaded positively and RBP-4 negatively onto PC3. Only PC1 was negatively associated with ISI in all ethnic groups. In the path analysis, SAT and VAT were negatively associated with ISI in Chinese and Malays without significant mediatory role of PC1. In South Asians, the relationship between VAT and ISI was mediated partly through PC1, whereas the relationship between SAT and ISI was mediated mainly through PC1.

    CONCLUSIONS: The relationships between abdominal obesity, adipocytokines and insulin sensitivity differ between ethnic groups. Adiponectin, leptin, and FGF21 play a mediating role in the relationship between abdominal adiposity and insulin resistance in South Asians, but not in Malays or Chinese.

  7. Aris IM, Bernard JY, Chen LW, Tint MT, Pang WW, Lim WY, et al.
    Int J Epidemiol, 2017 04 01;46(2):513-525.
    PMID: 27649801 DOI: 10.1093/ije/dyw232
    Background: : Infant body mass index (BMI) peak has received much interest recently as a potential predictor of future obesity and metabolic risk. No studies, however, have examined infant BMI peak in Asian populations, in whom the risk of metabolic disease is higher.

    Methods: : We utilized data among 1020 infants from a mother-offspring cohort, who were Singapore citizens or permanent residents of Chinese, Malay or Indian ethnicity with homogeneous parental ethnic backgrounds, and did not receive chemotherapy, psychotropic drugs or have diabetes mellitus. Ethnicity was self-reported at recruitment and later confirmed using genotype analysis. Subject-specific BMI curves were fitted to infant BMI data using natural cubic splines with random coefficients to account for repeated measures in each child. We estimated characteristics of the child's BMI peak [age and magnitude at peak, average pre-peak velocity (aPPV)]. Systolic (SBP) and diastolic blood pressure (DBP), BMI, sum of skinfolds (SSF) and fat-mass index (FMI) were measured during a follow-up visit at age 48 months. Weighted multivariable linear regression was used to assess the predictors (maternal BMI, gestational weight gain, ethnicity, infant sex, gestational age, birthweight-for-gestational age and breastfeeding duration) of infant BMI peak and its associations with outcomes at 48 months. Comparisons between ethnicities were tested using Bonferroni post-hoc correction.

    Results: : Of 1020 infants, 80.5% were followed up at the 48-month visit. Mean (SD) BMI, SSF and FMI at 48 months were 15.6 (1.8) kg/m 2 , 16.5 (5.3) mm and 3.8 (1.3) kg/m 2 , respectively. Mean (SD) age at peak BMI was 6.0 (1.6) months, with a magnitude of 17.2 (1.4) kg/m 2 and pre-peak velocity of 0.7 (0.3) kg/m 2 /month. Compared with Chinese infants, the peak occurred later in Malay {B [95% confidence interval (CI): 0.64 mo (0.36, 0.92)]} and Indian infants [1.11 mo (0.76, 1.46)] and was lower in magnitude in Indian infants [-0.45 kg/m 2 (-0.69, -0.20)]. Adjusting for maternal education, BMI, gestational weight gain, ethnicity, infant sex, gestational age, birthweight-for-gestational-age and breastfeeding duration, higher peak and aPPV were associated with greater BMI, SSF and FMI at 48 months. Age at peak was positively associated with BMI at 48 months [0.15 units (0.09, 0.22)], whereas peak magnitude was associated with SBP [0.17 units (0.05, 0.30)] and DBP at 48 months [0.10 units (0.01, 0.22)]. Older age and higher magnitude at peak were associated with increased risk of overweight at 48 months [Relative Risk (95% CI): 1.35 (1.12-1.62) for age; 1.89 (1.60-2.24) for magnitude]. The associations of BMI peak with BMI and SSF at 48 months were stronger in Malay and Indian children than in Chinese children.

    Conclusions: : Ethnic-specific differences in BMI peak characteristics, and associations of BMI peak with early childhood cardio-metabolic markers, suggest an important impact of early BMI development on later metabolic outcomes in Asian populations.

  8. Pang WW, Aris IM, Fok D, Soh SE, Chua MC, Lim SB, et al.
    Birth, 2016 Mar;43(1):68-77.
    PMID: 26643773 DOI: 10.1111/birt.12206
    BACKGROUND: Many countries in Asia report low breastfeeding rates and the risk factors for early weaning are not well studied. We assessed the prevalence, duration, and mode of breastfeeding (direct or expressed) among mothers of three Asian ethnic groups.

    METHODS: Participants were 1,030 Singaporean women recruited during early pregnancy. Data collected included early breastfeeding experiences, breastfeeding duration, and mode of breastfeeding. Full breastfeeding was defined as the intake of breast milk, with or without water. Cox regression models were used to identify factors associated with discontinuation of any and full breastfeeding. Logistic regression analyses assessed the association of ethnicity with mode of breastfeeding.

    RESULTS: At 6 months postpartum, the prevalence of any breastfeeding was 46 percent for Chinese mothers, 22 percent for Malay mothers, and 41 percent for Indian mothers; prevalence of full breastfeeding was 11, 2, and 5 percent, respectively. More Chinese mothers fed their infants expressed breast milk, instead of directly breastfeeding them, compared with the other two ethnic groups. Duration of any and full breastfeeding were positively associated with breastfeeding a few hours after birth, higher maternal age and education, and negatively associated with irregular breastfeeding frequency and being shown how to breastfeed. Adjusting for maternal education, breastfeeding duration was similar in the three ethnic groups, but ethnicity remained a significant predictor of mode of breastfeeding.

    CONCLUSIONS: The low rates and duration of breastfeeding in this population may be improved with breastfeeding education and support, especially in mothers with lower education. Further work is needed to understand the cultural differences in mode of feeding and its implications for maternal and infant health.

  9. Chi C, Loy SL, Chan SY, Choong C, Cai S, Soh SE, et al.
    BMC Pregnancy Childbirth, 2018 03 21;18(1):69.
    PMID: 29562895 DOI: 10.1186/s12884-018-1707-3
    BACKGROUND: We assessed the impact of adopting the 2013 World Health Organization (WHO) diagnostic criteria on the rates of gestational diabetes (GDM), pregnancy outcomes and identification of women at future risk of type 2 diabetes.

    METHODS: During a period when the 1999 WHO GDM criteria were in effect, pregnant women were universally screened using a one-step 75 g 2-h oral glucose tolerance test at 26-28 weeks' gestation. Women were retrospectively reclassified according to the 2013 criteria, but without the 1-h glycaemia measurement. Pregnancy outcomes and glucose tolerance at 4-5 years post-delivery were compared for women with GDM classified by the 1999 criteria alone, GDM by the 2013 criteria alone, GDM by both criteria and without GDM by both sets of criteria.

    RESULTS: Of 1092 women, 204 (18.7%) and 142 (13.0%) were diagnosed with GDM by the 1999 and 2013 WHO criteria, respectively, with 27 (2.5%) reclassified to GDM and 89 (8.2%) reclassified to non-GDM when shifting from the 1999 to 2013 criteria. Compared to women without GDM by both criteria, cases reclassified to GDM by the 2013 criteria had an increased risk of neonatal jaundice requiring phototherapy (relative risk (RR) = 2.78, 95% confidence interval (CI) 1.32, 5.86); despite receiving treatment for GDM, cases reclassified to non-GDM by the 2013 criteria had higher risks of prematurity (RR = 2.17, 95% CI 1.12, 4.24), neonatal hypoglycaemia (RR = 3.42, 95% CI 1.04, 11.29), jaundice requiring phototherapy (RR = 1.71, 95% CI 1.04, 2.82), and a higher rate of abnormal glucose tolerance at 4-5 years post-delivery (RR = 3.39, 95% CI 2.30, 5.00).

    CONCLUSIONS: Adoption of the 2013 WHO criteria, without the 1-h glycaemia measurement, reduced the GDM rate. Lowering the fasting glucose threshold identified women who might benefit from treatment, but raising the 2-h threshold may fail to identify women at increased risk of adverse pregnancy and future metabolic outcomes.

    TRIAL REGISTRATION: NCT01174875 . Registered 1 July 2010 (retrospectively registered).

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