A little over a decade ago, a team of intrepid researchers from the National University Health System, KK Women’s and Children’s Hospital, and A*STAR’s Singapore Institute for Clinical Sciences set up one of the world’s largest birth cohorts. Working with partners from research institutions in New Zealand, the UK and other countries, they set out to understand how conditions in pregnancy and early childhood influence the health and development of mothers and their children. Dr Khor Ing Wei, Dean's Office, reports. 


Ten years on, the Growing Up in Singapore Towards healthy Outcomes (GUSTO) continues to yield a treasure trove of information that is helping scientists and doctors understand how the health and potential of Singaporeans can be improved. It has amassed clinical data and samples from more than 1,200 mothers and their children since 2009. More than 15,000 variables relevant to diverse disease areas have been collected, making GUSTO the most deeply phenotyped and sampled cohort in the world.


The impetus to embark on this enormous project was to understand how fetal development and prenatal influences are linked to future health and disease, especially neurodevelopmental diseases and non-communicable illnesses such as obesity and metabolic disease. Ultimately, the goal is to use the deep understanding of the underlying mechanisms acquired through the study to develop clinical and public health interventions.


The school of thought that biological and environmental factors in early life affect health throughout an individual’s lifetime has gained ground in recent years. These ideas form the basis of a relatively new field of research called Developmental Origins of Health and Disease (DOHaD).


Maternal mental health affects foetal brain development


Some of the largest influences on our health could happen even before we are born. Led by Professor Chong Yap Seng, senior consultant in obstetrics and gynaecology and Dean-Designate of the NUS Yong Loo Lin School of Medicine, GUSTO has already revealed some important findings about the effect of foetal life factors on later health and disease. For example, researchers in the programme showed that anxiety and depression in the mother around the time of birth was linked to reduced brain size and changes in brain structure in their babies, and affected the children’s reactivity to stress and mood disorders later on.


Based on these findings, the National University Hospital (NUH) implemented systematic surveillance and support for expectant mothers with mental health concerns in 2014. GUSTO researchers also presented a paper to the Singapore Ministry of Health (MOH) in September 2015 that recommended routine screening for anxiety and depression for all women during pregnancy and the postnatal period, as well as follow-up and intervention for those who screen positive for the conditions. GUSTO was recently awarded $200,000 through the President’s Challenge programme, “Promoting Parental emotional health to Enhance child Learning (ProPEL),” to study the effects of a mother’s mental health on her children.


Diabetes in pregnant women common


Another finding from GUSTO that has had a large clinical impact was the discovery that gestational diabetes (GDM) was much more common in Singapore than doctors had

suspected. GUSTO researchers showed that screening of only high-risk pregnant women (the previous standard practice in Singapore) missed as much as 50% of all cases. GDM is usually discovered during the late second trimester of pregnancy in women who did not have diabetes beforehand. Although the condition usually goes away after delivery of the baby, GUSTO found that nearly half of the women with GDM developed prediabetes/diabetes within five years post-delivery. Their children are also at higher risk for obesity, type 2 diabetes and neurodevelopmental disorders.


The researchers submitted another paper to MOH in September 2015 to change the screening policy. In an inspiring example of the impact of science upon changing clinical practice, the three public maternity units in Singapore (KK Women’s and Children’s Hospital, Singapore General Hospital and NUH) implemented universal screening for GDM in February 2017.


The researchers hope to continue following the mothers and children in the study for a full generational cycle, until the children reach young adulthood. This will provide an unfolding picture of the effects of early life factors on health and disease as these children literally “grow up in Singapore.”


A globally recognised programme


Like the other NUS Medicine Summit Research Programmes, GUSTO has a strong global reputation and is well poised to keep growing in recognition and stature. Although the decade-old GUSTO is the “new kid” in the DOHaD field, the programme has already attracted interest and admiration from leaders of global organisations. One of these leaders, Dr Tadataka Yamada, Executive Vice President of Takeda Pharmaceuticals and former President of the Bill & Melinda Gates Foundation Global Health Program, hailed GUSTO as “truly world-class and best-in-class.” Among its many collaborations, GUSTO is working with the Gates Foundation to provide a reference data set for Asian populations.

GUSTO is also partnering with similar cohorts in Europe (Generation R and Southampton’s Women’s Survey) and Canada (MAVAN), and collaborating with many institutions in Singapore and globally to facilitate replication of findings and broaden the scope of future research directions. GUSTO is also partnered with companies in the nutrition space, such as Abbott, Danone and Nestle to translate the work into clinical and commercial applications.


Sustaining the momentum


Since DOHaD is quite a young field, nurturing upcoming researchers to continue the work is especially important. To achieve this goal, the GUSTO programme is training and mentoring early-career clinician scientists through regular investigator meetings and discussions with established clinician scientists and basic scientists.


Prof Chong expressed his sense of gratification about how GUSTO has evolved. “GUSTO is truly an amazing study! There is so much richness in the data and bio-samples we have collected that I am constantly surprised at what we are able to study. The findings are not just interesting scientifically but have been incredibly relevant in guiding policy and practice changes in Singapore. Every time the GUSTO research fellows present their work, I am thrilled as their findings are so obviously translational,” he said.