Overview of GUSTO

The Study Population consists of all pregnant women attending the first trimester antenatal dating ultrasound scan clinic at the 2 major public maternity units (National University Hospital and KK Women's and Children's Hospital) who are Singapore citizens or Singapore Permanent Residents, intending to eventually deliver in NUH or KKH and to reside in Singapore for the next 5 years. Only women who agree to donate birth tissues such as cord, cord blood and placenta at delivery will be included. We expect to recruit 1200 pregnant women from June 2009 to Aug 2010. Informed written consent are obtained from each participant either on the day the study staff first approach the subject or a few days later if she prefers to consult her spouse. Dedicated, trained staff will explain the nature of the study, including benefits and risks, and confidentiality of the data.

Maternal and intrauterine factors that might influence epigenetic change at birth include intrauterine growth measures, maternal diet and lifestyle, and metabolic predictors. Fetal growth is assessed by ultrasonography (e.g. crown-rump length, head circumference) at the first dating scan, and at 19-21, 26-28 and 32-34 weeks gestation. Scans are conducted in a standard manner at both hospitals by trained ultrasonographers. Ductus venosus flow (by Doppler), a sensitive measure of altered fetal nutrition (note: fetal nutrition is not only a measure of maternal nutrition but a reflection of the delivery of nutrients across the placenta to the fetus) is measured at 32 weeks.









Detailed interviews are conducted in the clinic during the first visit (<14 weeks) and at 26-28 weeks gestation. A 3-day dietary diary developed for use based on the Singapore national food composition database will assess maternal nutrition between 26 and 32 weeks. The mother’s antenatal diet may have an effect on birth size, growth trajectories, and later health of the offspring. Questionnaires are administered to capture maternal smoking, alcohol, drug use, medical history, physical activity, and use of traditional medicines and supplements. Maternal well-being are assessed using Edinburgh Postnatal Depression Scale (EPDS) which has been validated in Singapore women. State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory will also be administered in conjunction with Pittsburgh Sleep Quality Index. LYDON questionnaire to assess pregnancy anxiety and social support in addition to Questionnaire on Domestic Helper which is relevant to the Singaporean context are also in place. Anthropometry measures including skin fold thickness, height, weight, and waist-hip ratio are performed at the visits. At the routine 26-28 week antenatal visit, oral glucose tolerance tests and other biochemical markers will be measured. Hair sample are collected for toxicology screening (exposure to lead, metals etc) and determine levels of drugs (e.g. steroids) in hair. Buccal swab are collected for DNA. Pulse wave velocity is measured to derive the central aortic systolic pressure, radial augmentation index (rAI) and a range of other pulse wave indices from the radial pulse. Autorefraction and Fundus photography are conducted to assess retinal vessel diameters’ changes during pregnancy, and to study the risk factors such as hypertension, obesity, alcohol consumption and smoking habit for retinopathy. The pregnancies will be categorised according to standard criteria as normal, growth restricted, gestational diabetes, etc. Routine antenatal clinical and laboratory data (e.g. weight, blood pressure, full blood count, urine dipstick) for all visits will be captured from hospital case notes.

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