EPIGENETICS AND BIRTH OUTCOMES

MOST MOTHERS have the intention to provide the best life for their expectant baby. Regular exercise, adequate rest, low stress, avoiding smoking and drinking in concert with a well balanced diet and supplementation all contribute to her goal (Inskip et al, 2009). However, new discoveries in the field of epigenetics add even more tools in the new mother's arsenal (Vanhees et al, 2014). The maternal intake of macro and micronutrients can discourage orencourage DNA methylation and therefore predetermining the risk of her child developing chronic illness later in their lifetime. Thisfield of study can perhaps pave the way for a morecustomizedapproached to providing nutrition education and recommendations for the mother of the 21st century.

Compromises to a person’s wellness may in part be due to the ability for genes to be modified by environmental factors such as diet, exercise, smoking, or drugs (Csoka et al, 2014). Human beings are constantly being exposed to these external influences and are vulnerable to change throughout their lifespan (Csoka et al, 2014).

Figure 1 (Csoka et al, 2014,p.2)

This image depicts some of the variables that can affect the way our genes are expressed.

Each human being has a genetic predisposition that has the potential to be influenced by one or more variables, expressed in Figure 1. The genetic code can be altered/modified in response to these insults via two main pathways: DNA methylation and histone modification (Csoka et al, 2014). Studies on DNA methylation are vast and its role in human health has been widely accepted as a primary epigenetic regulator of chromatin structure and function (Markunas et al, 2014). Methylation can turn off the way a gene is expressed if when a methyl group connects to cytosine at the 5-carbon end of the DNA strand (Liu et al, 2003). Histone modification, however, occurs when an acetyl group or other protein is added to the nitrogen or carbon end of the histone thread of chromatin (Csoka et al, 2014). It important to understand that these two

pathways do not affect the DNA nucleotide sequence; only the chromatin is changed (Csoka et al, 2014). The scope of this paper will detail solely the maternal diet and how this non-genetic variable may cause the offspring’s genes to be expressed alternatively.

These nutrients, such as biotin, folate, resveratrol and curcumin, act on the substrates or enzymes within these two pathways and elicit changes in metabolic function (Choi & Friso, 2010). Note that humans are extremely adaptable and rely on the malleability of our genes to adjust to the ever-changing word we live in, throughout our lifespan (Csoka et al, 2014).

1.1 Maternal Diet: Preconception

There are both animal and human studies that provide proof that the maternal diet impacts the life of the fetus. Low birth weight, hormonal dysregulation, fat metabolism, and insulin sensitivity may result from inadequate diets (Hussain, 2013; Liu et al, 2003). One example of this is taken from data collected from the Dutch Hunger Winter at the time of World War II: there is evidence of impacted methylation activity of certain genes in utero (leading to psychiatric and metabolic effects) of the children of cohort of famine- exposed mothers (Liu et al, 2003).

Folic acid has proven capabilities to help prevent neural tube defects. This fact has been so well accepted that the United States Department of Agriculture (USDA) mandated that grain products be fortified with folic acid to help prevent the development of neural tube defects and that a women in their fertile years consume at least 400 mcg of this B vitamin daily via diet or supplementation (Canani et al, 2011). Folic acid can also be fortified in orange juice and found naturally as folate in green

leafy vegetables and broccoli (Evans et al, 2014).

The next example of how a nutrient can alter gene expression involves the mineral zinc. There is evidence on the effects of zinc deficiency and the epigenetic programming of the to-be-fertilized egg (aka antral follicular development.) During the period just before the mother releases her egg (then an oocyte), there is a change in chromatin, preparing it for fertilization (Tian & Diaz, 2013). Zinc is needed for DNA methylation during this integral period when there is a high speed of transcription while the mother’s RNA is being protected until the oocyte is fertilized (Tian & Diaz, 2013).

1.2 Maternal Diet: During Pregnancy

The fetus has little defense against the mother’s lifestyle choices, susceptible to epigenetic modification at this critical time of her life (Csoka et al, 2014). During pregnancy the epigenome is undergoing methylation which is choreographed in such a way to ensure ideal fetal development (Vanhees et al, 2014).

1.2a Macronutrients

In animal studies, a higher protein intake throughout pregnancy has been shown to impact the transcription of genes relating to glucose and fat metabolism and may result in the offspring becoming obese or suffering from metabolic syndrome (Canani et al, 2011). Other studies provide insight as to why poor nutrition in utero can damage islet cells of the pancreas. This can limit the adaptability of b-cells to function optimally later in life, leading to glucose intolerance (Canani et al, 2011). Conversely, an excessive caloric intake especially during the last trimester may result in altered gene expression causing cardio-metabolic complications (King et al, 2013). A higher fat diet has been shown to affect gene transcription and predispose the fetus to chronic illness later in life, such as non-alcoholic-fatty liver disease (Bruce et al, 2009). Similarly, a high fat maternal diet has been linked to her infant’s sustained proclivity for fat and a yearning to consume fatty foods as a child (Bruce et al, 2009). In a study published this month in Nutrition Journal, a direct correlation was drawn between the mother’s fat and sugar intake during pregnancy and the distribution of her neonate’s fat stores: the more fatty and sugary foods mom eats, the higher risk for an excessive abdominal fat in her neonate. (Horan et al, 2014). Lastly, a high fat maternal diet has been shown to negatively affect the development, form, and function of the fetus’ brain (Niculescu & Lupu, 2009).

1.2b Micronutrients

As with the preconception, zinc has been shown to affect the epigenetic pathways during the gestational period. Zinc diminishes histone and methylation of DNA and can result in an underdeveloped embryo/fetus. (Tian & Diaz, 2013). Choline is a second micronutrient that is recommended for its beneficial effects on the baby’s long-term

brain function via its activity in epigenetic communication (Jiang et al, 2014). Generally, women in the developing world do take multivitamin/mineral supplements at this time as it’s accepted that the B vitamins are needed for DNA methylation and vitamin A, C, iron, chromium, zinc and phytonutrients play a role in fetal programming (Vanhees et al, 2014).

1.3 Neonate Nutrition (Post-Pregnancy Maternal Diet)

Breast milk is the preferred choice for infant nutrition. We know that postnatal nutrition will affect the baby’s risk of developing non-communicable diseases (Lillycrop, 2011). Breast milk provides many benefits: immunologic, hormonal, growth promoters, brain health, to name a few (Gibbins et al, 2013). It is important to be aware that the WHO recommends that women breastfed for the first six months due to all its advantages but only about 50% of women worldwide do so (Wöckel et al, 2008).

Protocols using epigenetic markers have been applied in studies observing the impact of infant nutrition (Neu, 2007b). DNA analysis in animal studies revealed a benefit from a B-supplemented diet on the infants central nervous, renal, and hepatic systems (Neu, 2007b). There has also been human observational studies that illustrates a positive correction between early, good infant nutrition (breast milk) and cardiovascular and skeletal health (Koletzko et al, 2011). There was a negative correlation between fast catch –up growth (in premature babies) and future endocrine disruption (Koletzko et al, 2011). Colostrum, the first few days of breast milk, has rich cell diversity and a wide variety of leukocytes that may be a contributor to the advantageous health outcomes of the baby. (Hassiotou et al, 2013).

The gastrointestinal system and the microbiotia is mostly responsible for an individual immune function across the lifespan. Healthy intestinal flora, bacteria that live in the small and large intestines, has been shown to elicit epigenetic modifications, particularly those involving butyrate as well as the bacteria that produce short chain fatty acids (Koletzko et al, 2011). The newborn’s introduction to good bacteria via breast milk will allow him to have continuous life-long immune system advantage over a non-breastfed infant (Koletzko et al, 2011; Neu, 2007a).

Along with immunological effects, breastfeeding may have effect on epigenetic expression relating to psychological wellness of the baby: there is evidence to support that the bonding between infant and mother reflects behavior and the mother’s stress level during feeding correlates with mental health of her offspring (Wöckel et al, 2008).

Conclusion

The field of nutriepigenetics is relatively new and further human studies are certainly essential. Accurately collecting nutritional data has long been a challenge to investigators as reporting/recording methods have many limitations. Insufficient data are available featuring the newborn’s molecular changes with regard to the mother’s intake

but there are hypotheses that this could have implications for chronic illness during their life. Newer technologies, better understanding of food composition, and the ability to modify epigenetic pathways will lead mothers to best nourish theirbabies from preconception through the post-partum period. The evidence-based data available now is enough to make dietary recommendations to women of childbearing age, to pregnant women, and to new mothers. We know that it’s not only a balance of macronutrients that are essential in DNA methylation and thus long-term health of the child, but micronutrients are as critical and have life-long relevance as well (Vanhees et al, 2014).

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