Growing Up in Singapore Towards Healthy Outcomes

Study Overview
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Brief Summary
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This study aims to test the following hypotheses in women recruited in early pregnancy and whose children will be followed up till at least 14 years of age. Epigenetic changes in conceptual tissues obtained at birth reflect the environment that the fetus was exposed to during development. The pattern of epigenetic marks in gene promoters obtained from DNA in birth tissues, together with genotype, phenotype, and environmental exposures, can be utilized to assess how the perinatal environment affects subsequent metabolic, neurodevelopmental and other phenotypes.

Detailed Description
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The dramatic emergence of non-communicable diseases (NCDs) in Asia has coincided with the rapid socioeconomic and nutritional transition taking place in the region, with the prevalence of diabetes rising five-fold in Singapore in less than four decades. One unique aspect of the epidemic has been the significant ethnic differences in predisposition to diabetes among Asians and in the ethnic variation between BMI and the risk of developing insulin resistance, a precursor to type 2 diabetes. Apart from genetic factors, dietary, lifestyle and cultural factors might have influenced the developmental programming through effects on the mechanisms associated with developmental plasticity. A center piece of this study is to examine how epigenetic changes at birth both reflects past developmental influences and, in association with other factors, influences future trajectories of development and its relationship to NCDs. Also factors active during childhood - especially the first 1000 days of life - will be focused upon. The longitudinal GUSTO birth cohort study allows us to examine associations among genetic, environmental and lifestyle interactions in the three distinct ethnic groups, Chinese, Malays and Indians, present in the Singaporean population. Participants have been followed up for their pregnancy outcome, fetal growth and offspring development for over a decade. Participants will continue to be followed up as the children enter into the pubertal phase from the age of 10 to 14 years. Data will be collected through questionnaires and clinical measurements. The questionnaires include socio-economic factors, maternal and child's diet, medical histories, behavioural, cognition, lifestyle factors, health status, and home environment. Bio-physical measurements will be obtained from anthropometric measurements of participants, human biological materials such as blood, buccal swabs, saliva, hair, urine, stool, oral specimen such as exfoliated milk teeth, dental plaque and tongue biofilms are collected from the participants (mother / father / child where applicable) at their follow-up time points with the GUSTO cohort upon their consent.

Official Title
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Metabolic Health in Asian Women and Their Children

Conditions
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Metabolic Diseases, Neurological and Mental Health Conditions

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women 18 years and above Pregnant women attending the first visit (< 14 weeks GA) at the maternity units of KKH and NUH Singapore citizens or Singapore Permanent Residents Currently resident in mainland Singapore Intention to eventually deliver in KKH or NUH Intention to reside in Singapore for the next 5 years Intention to donate cord, cord blood and placenta The fetus should be racially homogenous with both sets of grandparents of the same ethnicity Exclusion Criteria: Women whose pregnancies end in miscarriages will be excluded Pregnant women on chemotherapy Exclude women with significant medical conditions e.g. Type 1 diabetes mellitus, psychosis etc. Exclude women on certain medications - e.g. psychotropic drugs. Mixed marriages will be excluded

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pregnant mothers, infants and children<br>Women in their early pregnancy who are attending the first trimester antenatal ultrasound scan at the public maternity units at KK Women's and Children's Hospital (KKH) and National University Hospital (NUH). Only women age 18 years and above who are Singapore Citizens or Singapore Permanent Residents. Participants have to intend to eventually deliver in NUH or KKH and to reside in Singapore for the next 5 years. Willingness to donate cord, cord blood and placenta. The fetus should be racially homogenous with both sets of grandparents of the same ethnicity. Babies born from these mothers will be followed up until the child is at least 14 years of age. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Roles of fetal, developmental and epigenetic factors in pathways to disease | To evaluate the role of fixed genetic risk variants, modifiable epigenetic markers, circulating metabolites and hormones in blood, and host-microbe interactions which can reflect past developmental influences, and in association with other factors, affect future trajectories of development and its relationship to NCDs. | Perinatal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Influence of prenatal and early postnatal factors on child health | To examine the role of maternal nutrition, lifestyle, emotional health, and other environmental factors in infancy that can influence the development of phenotypes in childhood which confer risk for later metabolic and mental disorders. | During pregnancy and infancy period | 
| Effect of factors in pregnancy and early postpartum period on maternal health | To examine the role of maternal nutrition, lifestyle, emotional health, and other environmental factors in pregnancy or postpartum period that can influence future maternal risk of metabolic disorders, including body weight changes. | During pregnancy and postpartum period | 
| Influence genetic and epigenetics factors in combination with lifestyle on child health | To examine the role of genetic and epigenetic factors, lifestyle (physical activity and dietary intake), growth trajectories and other environmental factors that can influence the development of phenotypes in childhood which confer risk for later metabolic and mental disorders. | Childhood and Adolescence up to age 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epigenetics, Development, Metabolic, Neurodevelopment