Epigenetics in Nursing: Time to start counseling patients Presented by:Leslee FallR. Joe Robinson

Human Genome Project (Olden et al. 2011).Epigenetics (Clark et al. 2013). Prenatal development (Wright et al. 2013).What is the issue?http://www.nature.com/news/2010/101006/images/news467646a-i2.0.jpgThere is more than enough research evidence to justify having nurses counsel patients about epigenetic remodeling processes and the subsequent potential health consequences that can occur during prenatal and infant periods.

How does it involve genetic or genomic health?DNA methylation (Tollefsbol 2014).

Increase in methylation of CpGs affects prenatal and postnatal gene expression (Wright et al. 2013).http://4.bp.blogspot.com/-ACLsfWrTm5Y/Ug6d6SzOGkI/AAAAAAAAELM/4VO3B_-GTNU/s1600/inheritance.png

Impact on Care or HealthPerinatal stress (Dahlen et al. 2013).Prenatal tobacco exposure (Wright et al. 2013).Birth via cesarean section (Clark et al. 2013).Fetal exposure to famine (Wright et al. 2013).Prenatal stress (Portha et al. 2014).Physiologic labor and birth (Clark et al. 2013). http://www.beginbeforebirth.org/wp-content/themes/BBB/images/logo.png

BackgroundEPIIC (Epigenetic Impact of Childbirth) (Clark 2013).Nursing evidence-based practice (Wright et al. 2013)http://www.nature.com/clpt/journal/v92/n6/images/clpt2012141f1.gif

Current State of the ScienceEpigenetics evidence-based care (Clark et al. 2013)

What research has been conducted?Natural experimentsLongitudinal birth cohortsPrenatal cohortsIn vitro fertilization conception cohorts

What is known/unknown?

Most research on DNA methylationLimited knowledge about epigenomeNeed more research on histone modification and non-coding RNA

(Mill & Heijmans 2013)

Ethical, Legal, and Social ImplicationsEnvironmental challenges

Impacts on health across multiple generations

Legal and financial implications are complicated

(Wright et al. 2013)http://www.uic.edu/classes/bms/bms655/gfx/pedigree5.gif

Nursing Practice and RoleAbility to use an individuals epigenome data for clinical practice

Role of the nurse: to extend their knowledge beyond genetics and embrace epigeneticshttps://www.healerslibrary.com/wp-content/uploads/2013/09/Screen-Shot-2013-09-18-at-10.12.14-PM.png

Nursing CompetenciesIdentify patients who may benefit

Family history

Educate patients

Promote disease prevention practices: Prenatal and postnatal development Transgenerational risk factors

Keep current on latest research

Interpret data for patients(American Nurses Association 2008)http://learn.genetics.utah.edu/content/epigenetics/inheritance/images/DirectExposure.jpg

ReferencesClark, A. E., Adamian, M., & Taylor, J. Y. (2013). An Overview of Epigenetics in Nursing. Genomics, 48(4), 649659. doi:10.1016/j.cnur.2013.08.004

Consensus Panel (2008). Essentials of genetic and genomic nursing: competencies, curricula guidelines and outcome indicators. 2nd edition. Silver Spring, MD: American Nurses Association.

Dahlen, H. G., Kennedy, H. P., Anderson, C. M., Bell, A. F., Clark, A., Foureur, M., Downe, S. (2013). The EPIIC hypothesis: Intrapartum effects on the neonatal epigenome and consequent health outcomes. Medical Hypotheses, 80(5), 656662. doi:10.1016/j.mehy.2013.01.017

Feinberg, A. P. (2007). Phenotypic plasticity and the epigenetics of human disease. Nature, 447(7143), 433440. doi:10.1038/nature05919

Consensus Panel (2008). Essentials of genetic and genomic nursing: competencies, curricula guidelines and outcome indicators. 2nd edition. Silver Spring, MD: American Nurses Association.

Mill, J., & Heijmans, B. T. (2013). From promises to practical strategies in epigenetic epidemiology. Nature Reviews Genetics, 14(8), 585594.

Olden, K., Freudenberg, N., Dowd, J., & Shields, A. E. (2011). Discovering how environmental exposures alter genes could lead to new treatments for chronic illnesses. Health Affairs, 30(5), 833841.

Portha, B., Fournier, A., Ah Kioon, M. D., Mezger, V., & Movassat, J. (2014). Early environmental factors, alteration of epigenetic marks and metabolic disease susceptibility. Biochimie, 97(0), 115. doi:10.1016/j.biochi.2013.10.003

Tollefsbol, T. (2014). Dietary Epigenetics in Cancer and Aging. In V. Zappia, S. Panico, G. L. Russo, A. Budillon, & F. Della Ragione (Eds.), Advances in Nutrition and Cancer (Vol. 159, pp. 257267). Springer Berlin Heidelberg. Retrieved from http://dx.doi.org/10.1007/978-3-642-38007-5_15

Wright, M. L., Ralph, J. L., Ohm, J. E., & Anderson, C. M. (2013). DNA methylation in complex disease: Applicationsinnursing research, practice,and policy. Council for the Advancement of Nursing Science, 61(4), 235241.e4. doi:10.1016/j.outlook.2013.04.010

The NIH invested more than $190 million over five years to accelerate the emerging field of epigenetics for biomedical research (2008).The overall hypothesis of the NIH Roadmap Epigenomics Program is that the origins of health and susceptibility to disease are, in part, the result of epigenetic regulation of the genetic blueprint.NIH Director Elias A. Zerhouni, M.D. (2008) stated, "Epigenomics-based research is now a central issue in biology.After the Human Genome Project was completed scientists realized that the information collected did not explain the variance in disease risk. It became important to advance our understanding of environmental and epigenetic contributions to disease and utilize the information in prevention and treatment of disease.

Epigenetic changes include biochemical alterations to DNA molecules that do not change the sequence but do influence gene expression.

The embryologic period is a vulnerable time during which there is a period of rapid cell division and remodeling of the epigenome.DNA methylation is the most studied of the epigenetic remodeling processes and is based on the addition of a methyl group (CH3) donated enzymatically to a cytosine nucleotide base linked to a guanine nucleotide base (CpG) (Tollefsbol 2014).An increase in methylation of CpGs may attenuate or completely silence gene expression whereas demethylation may induce an increase in gene expression (Wright et al. 2013).The prenatal and postnatal altered expression of genes can contribute to the increased susceptibility of complex disease in individuals and the transmission of risk across generations (Wright et al. 2013).Perinatal stress, including poor maternal engagement and separation from the baby immediately after birth have been shown to permanently increase stress sensitivity and alter behavior in offspring and adults later in life (Dahlen et al. 2013).Prenatal tobacco exposure, coupled with unfavorable early-life conditions, triggers aberrant DNA methylation associated with loss of impulse control, including eating disorders, alcoholism, and indiscriminate social behaviors(Wright et al. 2013).Birth via cesarean section can result in increased rates of asthma, eczema, type 1 diabetes, infant bronchiolitis, multiple sclerosis, and obesity (Clark et al. 2013).Fetal exposure to famine in Northern Han Chinese pregnant women was associated with site-specific methylation linked to future development of schizophrenia, providing evidence of prenatal triggers for differential methylation underlying future risk of disease (Wright et al. 2013).Prenatal stress is known to affect the hypothalamic-adrenal-pituitary (HPA) axis and primarily cortisol secretion, which could explain the association between prenatal programming and a higher prevalence of hyperglycemia in adult life (Portha et al. 2014).Physiologic labor and birth have a positive stress, known as eustress, on the fetus and this process has an epigenetic effect on particular genes, specifically those that program immune responses, genes responsible for weight regulation, and specific tumor suppressor genes (Clark et al. 2013). EPIIC (Epigenetic Impact of Childbirth) is an international, interdisciplinary research collaboration where nurse scientists have found, based on years of research, clinical practice, and recent basic science evidence, that events during the intrapartum period of pregnancy, specifically the use of synthetic oxytocin, antibiotics, and cesarean section, affect the epigenetic remodeling processes and subsequent health of the mother and offspring (Clark et al. 2013).Many environmental exposures are modifiable risk factors for disease that are amenable to nursing interventions. Nurses can use epigenomic techniques to better evaluate and address levels of health and disease risk. Nurses are in a position to provide cutting-edge evidence-based care and patient education based on the application of epigenomics in practice to which the competencies and professional development in genetics and genomics can be applied as the foundation for current, evidence-based practice (Wright et al. 2013).What is the current state of the science regarding this issue?Nurses are already providing epigenetic evidence-based care for childbirth but the education and practice is limited (Clark et al. 2013).What research has been conducted?Natural experiments - The Dutch Hunger Winter Families Study, for example, follows individuals who were in utero during the Dutch famine of 1944 and the effects of prenatal famine on DNA methylation associated with imprinted genes such as insulin-like growth factor 2 (IGF2).Longitudinal birth cohorts - analysis of epigenetic changes over time and provide the ability to relate these to specific environmental exposures and the development of disease. Avon Longitudinal Study of Parents and Children (ALSPAC) ~14,000 pregnant women from the south west of England in 1991 and 1992 to assess the health and development of children since birth.Longitudinal twin studies - Peri/Postnatal Epigenetic Twins Study (PETS) to explore the epigenetic variation between twins at birth due to differences in effects of non-shared intrauterine environmental influences and stochastic (random) factors.Prenatal cohorts - Southampton Womens Survey (SWS) in the United Kingdom to measure the pre-pregnant characteristics of 12,500 women aged 2034 years while following them through their subsequent pregnancies.In vitro fertilization conception cohorts - Assisted reproductive technologies (ART), such as in vitro fertilization (IVF) have been linked to epigenetic disruption in the developing embryo, especially at imprinted loci, and studies such as the Danish National IVF Cohort Study are particularly valuable for understanding the epigenetic mechanisms involved in imprinting disorders.What is known? What remains unknown? - We know that epigenetic changes are taking place and the effect processes (DNA methylation, histone modifications, & non-coding RNA). We just dont know how the variation within and between individuals relates to disease risk.Limited basic knowledge about the epigenome - most of the research focused on DNA methylation.More research nees to be conducted - histone modifications and non-coding RNAs.Need much more rigor in designing research studies - The dynamic properties of the epigenome and its sensitivity to environmental exposures

Environmental challenges - epigenetic modifications present a threat to prenatal health.Impacts on health across multiple generations - we need maternal/child health policies that promote optimal maternal, fetal, and infant well-being through avoidance of environmental epigenetic modifiers (no smoking, no alcohol).Legal and financial implications are complicated - Due to the transgenerational effect of some epigenomic modifications resulting from environmental exposures, as first manifestations of disease may occur one or more generations after initial exposure (sue your grandparents?). (Wright et al. 2013)Identify clients who may benefit from specific epigenetic and epigenomic information and/or services based on assessment data, i.e. clients planning a family, pregnant females and partner(s).Provide clients with credible, accurate, appropriate, and current epigenetic and epigenomic information that facilitate decision-making.Use health promotion/disease prevention practices that: Consider epigenetic and epigenomic influences on personal and environmental risk factors that affect prenatal and postnatal development. Incorporate knowledge of transgenerational epigenetic risk factors (e.g., an expecting mother who is around smokers can not only affect the health of the unborn child but also affect the health of her future grandchildren).