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For a long time, associations have been observed between adverse maternal intrauterine environments and the incidence of non-communicable diseases in later life.
For example, the thrifty phenotype hypothesis studies the link between the epidemiological evidence of poor fetal and infant development with permanent detrimental changes in glucose-insulin metabolism (1). These alterations of glucose metabolism can include insulin resistance. This, in turn, may predispose an individual to develop non-communicable diseases like type 2 diabetes, fibromyalgia, and heart disease.
The usefulness of this information, however, is limited. It is hard to predict future pathologies in an adult from the complex systems that contribute to the maternal intrauterine environment. To put it simply, while the associations exist, the science behind it is too complicated to draw a direct link between time-specific developmental insults and the incidence of disease in adulthood. However, that is now changing.
The fields of nutrition and of systems biology are developing every day. Metabolic programming as a field continues to expand alongside them. Metabolic programming describes metabolic adaptations made by specific tissues and organs in an organism in response to environmental cues during a critical period in development. An example of such adaptations are those made by a developing fetus in response to the mother’s intrauterine environment and nutrient availability during gestation.
An impaired intrauterine environment may result in adverse fetal metabolic adaptations which could contribute to metabolic disorders later in life. For example, maternal obesogenic environments are most associated with altered glucose and lipid metabolism in the fetus (2). There is then an increased risk for the development of chronic diseases. For example, type 2 diabetes or metabolic syndrome may develop later in life.
Non-communicable diseases associate with an immense number of deaths in the U.S. and worldwide. Obesity rates, for example, are at an all-time high and continue to rise. The world health organization (WHO) has declared it a public health crisis (3). Cardiovascular diseases continue to be the leading cause of death in the U.S. and type 2 diabetes is now common in children.
The point here is that there is a deep need for better understanding of non-communicable diseases, and metabolic programming provides an alternate perspective to do that. The concept of metabolic programming alone sheds light on the complexity and interconnectedness of health, but more importantly on the significance of nutritional support during pregnancy.
Epigenetics in Programming:
Epigenetics is the perfect tool for studies in metabolic programming. This field studies the science of gene expression and independent genetic code changes. This allows for analysis of changes in gene expression of specific tissues in relation to impaired nutritional environments. For example, how the intrauterine environment affects the gene-expression of liver tissues, which are metabolically active. Or how does an impaired environment affect the development of neural pathways in charge of homeostatic regulations, like those of the hypothalamus (2)? Such studies are possible because factors like nutrient availability will influence epigenetic changes in DNA and development of tissue-specific abnormalities.
The Current Findings:
While epigenetic changes in response to impaired intrauterine environments are still association based, these associations are much stronger. The following represents a short list of the nutritional impairments and their associated alterations to fetal metabolism:
Gestational Diabetes Mellitus (GDM):
Gestational diabetes comes with a number of risks for both the mother and child. Hyperglycemia (elevated blood glucose) and increased insulin resistance often characterize GDM. Hyperglycemia represents an imparted environment which negatively affects fetal development. For example, infants who develop in a hyperglycemic environment are often large for gestational age. This then represents an increased risk during delivery. Both the infant and mother are put in danger as a result of the increased size.
Offspring from GDM are at a two- to four-time increased risk for becoming overweight or obese (4). GDM is also a good marker for determining an increased mother’s risk for the development of diabetes later in life. Both of these associations are dangerous as in the incidence of GDM and DM (diabetes mellitus) are becoming increasingly common in the population.
The MEST (mesoderm-specific transcript) gene is one example of how epigenetic findings are linked to metabolic phenotypes. This gene was found to be underexpressed in the placentas of GDM babies. When compared to adult data, it was found that this gene is also underexpressed in morbidly obese adults in comparison to adults with a normal BMI (4). The GDM model combined with epigenetic tools represent a good method for the further study of specific mechanisms in metabolic programming.
In-Utero Overnutrition (obesogenic environment):
High-fat diets and an overabundance of nutrients characterize overnutrition during pregnancy. Adverse effects associated with this intrauterine environment deals with alterations to glucose and lipid metabolism (2). The developing fetus will adapt to the impaired environment which can result in liver metabolic programming (like insulin resistance) and organ lipid accumulation (fatty liver). These individuals are therefore at an increased risk for the development of non-communicable and cluster diseases (like metabolic syndrome). Hepatomegaly (enlarged liver) also links to this environment.
Impaired nutrient availability characterizes an undernourished intrauterine environment. Infants who develop in this environment are the most associated with increased cardiovascular morbidity (rate of disease) and mortality (2). This is because the impaired nutrient availability links to effects on cardiovascular development and metabolic functions. These individuals are also more susceptible to the development of cluster diseases like metabolic syndrome and may also suffer from an enlarged liver.
While much of this information can be a little scary, it will prove beneficial for mothers and infants alike. This also reminds us of the importance of healthy living, nutrition, and education when it comes to pregnancy. Visit our nutrition experts for further questions and deeper understanding of the role of nutrients and intrauterine environments of fetal development.
Hales, Nicholas C, and David JP Barker. “The Thrifty Phenotype Hypothesis: Type 2 Diabetes.” Oxford Academic, British Medical Bulletin, 1 Nov. 2001, academic.oup.com/bmb/article/60/1/5/322752.
Sookoian, Silvia, et al. “Fetal Metabolic Programming and Epigenetic Modifications: A Systems Biology Approach.” Nature.com, Pediatric Research, 27 Feb. 2013, www.nature.com/articles/pr20132.
“Controlling the Global Obesity Epidemic.” World Health Organization, World Health Organization, 6 Dec. 2013, www.who.int/nutrition/topics/obesity/en/.
Bouchard, Luigi. “Epigenetics and Fetal Metabolic Programming: A Call for Integrated Research on Larger Cohorts.” Diabetes, American Diabetes Association, 1 Apr. 2013, diabetes.diabetesjournals.org/content/62/4/1026/.