Nutritional programming during pregnancy and in early life

The European Nutrigenomics Organisation, Wageningen, The Netherlands

"Nutritional programming describes the relationship between the nutritional environment during critical windows of time in the development of early life and the occurrence and severity of disease in adult life. The nutritional programming concept derives from two prior hypotheses. The ‘Thrifty Phenotype’ hypothesis (1) proposes that undernourishment in the womb results in permanent detrimental changes leading to the development of diseases later in life.

The effects of maternal under-nutrition on fetal development have been studied extensively in humans. Initial evidence for this was based on epidemiological studies of survivors of the Dutch famine of 1944–1945, where pre-birth exposure to famine conditions resulted in a higher prevalence of overweight adult offspring. Subsequent studies showed that nutritional deficiencies in the womb predispose adult offspring to metabolic syndrome, including obesity, cardiovascular disease, hypertension and type 2 diabetes.

The ‘Predictive Adaptive Response’ (PAR) hypothesis (2, 3) proposes that the fetus makes adaptations based on the predicted environment after birth. The prenatal nutritional environment is the primary source of ‘predicting’ the environment available to the fetus per this hypothesis. When the PAR is balanced the development is normal. However, when there is either a high or low mismatch between the nutritional environment during critical developmental periods and the adult environment, disease will develop. PARs can only be induced during critical windows of development. Thus, the windows of potential induction differ for individual organs, resulting in the extension of the plasticity phase of development until after birth. Understanding and mapping the interaction between micro- and macronutrient imbalance and modification of gene expression have an enormous potential for improving the health of future generations.

Nutritional programming research requires the multidisciplinary approach of nutritional genomics (see also Topic of the Month: ‘Micronutrients and the human genome‘), in relying on the concepts and technologies of genetics, molecular biology, and epidemiology, as well as public health and clinical trials. More studies are required in order to reach a better understanding of the precise types, timing and duration of inappropriate nutrition that result in chronic disease outcome. There are only few data available regarding long-term effects of nutritional programming.

Specific areas of interest are:

• Studying the mechanism and nutrient-gene interactions through which nutritional programming influences various tissues.

• Narrowing and defining critical periods in fetal development and early life after birth that affect specific chronic diseases.

• Specifying the roles of specific nutrients and their interactions in the maternal and infant diet on programming effects on disease and their risk factors.

• Identifying and studying the impact of genetic determinants on early programming effects and subsequent outcomes.

Up till now, very little has been known about the genes involved in the underlying mechanism of programmed nutrition. Furthermore, products of several genes associated with a specific mechanism can interact with other gene products in different pathways. Thus, studies of genes involved in nutritional programming can reach extreme complexity. Several recent studies have begun elucidating genes influenced by programmed nutrition in several tissues (e.g., the placenta, pancreas and adipose tissue) and pathways (e.g., renin-angiotensin system in relation to hypertension). However, this field is only beginning to figure out which genes and molecular mechanisms are involved in nutritional programming.

Different constituents of the mother and child’s diet can be regarded as either positive or negative ‘programmers’, influencing future health either favorably or adversely, respectively (4). For example, the ‘ Mediterranean Diet ‘ can decrease mother’s risk of premature delivery and improve their babies’ immune functions, as well as their children’s IQ at age five. The most important foods in these diets include fish and vegetables. In fish, it appears to be the long chain omega-3 fatty acids which are providing the benefits; in vegetables, it may be folate. In addition, it has been shown that increased sun exposure (and potentially enhanced vitamin D synthesis) during the last trimester of pregnancy is associated with better bone mass at nine years old. On the other hand, high intakes of fat and sugar can act as ‘negative programmers’ and adversely affect the health of mother and child."