A write- up of Dr Raman Subramaniam (Consultant Obstetrician and Gynaecologist Fetal Medicine and Gynaecological Centre)

Genetics (nature) and environment (nurture) both influence the development of an individual. In the Asian population, which makes up 60% of the world’s population, non-communicable diseases are prevalent. Obesity, for example, has become a major global health problem; for instance, the proportion of adults with a body mass index of 25 or greater has exceeded 40% among men in Singapore, and among both men and women in Malaysia (1).

The thrifty phenotype

Nature vs Nurture – Who Wins? 1Early genetic and environmental influences may be contributing to the occurrence of these disease in the infant’s later life (2).The “developmental origins hypothesis” posits that the foetus make cellular, metabolic, and physiological adaptations in response to its changing environment to prepare it for postnatal life (3). The phenotype of the developing individual has been described as “thrifty”; for example, during periods of starvation, the foetus reduces insulin secretion and increases peripheral insulin resistance, thus directing more glucose to the brain and heart, and less to skeletal muscles (4). Developmental plasticity exists, with a single genotype potentially giving rise to a range of different phenotypes.

Dutch Famine studies

The influence of nature over nurture can be seen in the outcomes from the Dutch famine studies. In the winter of 1944, there were massive food shortages in the Netherlands due to the war. Consequently, calorie consumption dropped from 2,000 to 500 per day. Children born or raised during this time, and who were exposed to famine, were small and short in stature, and had many diseases including, oedema, anaemia, diabetes and depression later in life (5). The risk of having smaller babies persisted for two generations (6). The infants exposed to famine while in utero had increased risk of insulin resistance and metabolic syndrome as adults. Increases in psychiatric disorders (e.g. schizophrenia, major affective disorder) also occurred when these infants later reached adult life (7-8). Even six decades later, these individuals had less DNA methylation of the imprinted insulin-like growth factor II gene compared with their well-fed, same-sex siblings (9). The periconceptional period was identified as being important in the association between famine and DNA methylation. This study provided the first evidence that early-life environmental conditions can cause epigenetic changes in humans that persist throughout life.

Epigenetics in early life and health outcomes in adults

The expression of our genes is not fixed. Epigenetic regulation of the genes can produce stable changes to the DNA and chromatin structure that alter gene expression. Methylation of DNA and modifications of the histones by acetylation/deacetylation are primarily involved (10-12). The epigenetic programming that occurs early in life can influence outcomes later in life (13-14),such as the development of non-communicable disease such as obesity and type 2 diabetes in later life (15). Moreover, it appears that this epigenetic programming may occur across generations (16). For example, malnourishment of a pregnant women may result in suboptimal foetal development, and the birth of an infant at risk of obesity and insulin resistance. Later in life, these individuals may experience gestational diabetes and give birth to large babies, who are themselves at risk of repeating the cycle. (16)

To illustrate, the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study is following a large parent-offspring cohort from Singapore, primarily to evaluate the influences operating during early development, and determine if these influences may affect the infant’s metabolic trajectory during later life (Figure 1). (17)Available data from the trial have illustrated the important influence of maternal nutrition on the risk of preterm birth and birth size of their neonates (18).

These observations highlight that optimal nutrition of infants, and their parents, is essential if children are to reach their full potential in lifelong health (19). Early intervention is associated with good outcomes; late intervention is associated with less favourable outcomes (Figure 1).

Figure 1.Factors related to the development of obesity and associated disorders10


In conclusion

Early intervention may reduce the risk of non-communicable disease. The preconception period is critical; promoting a healthy start to life means that the beneficial effects of intervention can have greater impact.


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