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Offspring born preterm (ie, before 37 weeks of gestation) are more likely to die or experience long-standing illness than full-term offspring. Maternal genetic variants (ie, heritable, stable variations in the genetic code) and epigenetic modifications (ie, chemical modifications to the genetic code that can affect which genes are turned on or off) in response to stress have been implicated in preterm birth. Fetal genetic variants have been linked to preterm birth though the role of offspring epigenetics in preterm birth remains understudied. This systematic review synthesizes the literature examining associations among stress during pregnancy and epigenetic modifications to offspring DNA, with 25 reports identified. Ten reports examined DNA methylation (ie, addition/removal of methyl groups to/from DNA) across the epigenome. The remainder examined DNA methylation near genes of interest, primarily genes linked to hypothalamic-pituitary-adrenal axis function (NR3C1, FKBP51), growth/immune function (IGF2), and socioemotional regulation (SLC6A4, OXTR). The majority of reports noted associations among stress and offspring DNA methylation, primarily when perceived stress, anxiety, or depression served as the predictor. Findings suggest that differences in offspring epigenetic patterns may play a role in stress-associated preterm birth and serve as targets for novel interventions.

Background: A rapidly expanding literature suggests that individuals of the same chronological age show significant variation in biological age., Purpose: The purpose of this article is to review the literature surrounding epigenetic age as estimated by DNA methylation, involving the addition or removal of methyl groups to DNA that can alter gene expression without changing the DNA sequence., Methods: This state of the science literature review summarizes current approaches in epigenetic age determination and applications of aging algorithms., Findings: A number of algorithms estimate epigenetic age using DNA methylation markers, primarily among adults. Algorithm application has focused on determining predictive value for risk of disease and death and identifying antecedents to age acceleration. Several studies have incorporated epigenetic age to evaluate intervention effectiveness., Discussion: As the research community continues to refine aging algorithms, there may be opportunity to promote health from a precision health perspective., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Exposure to chronic stress such as living in disadvantaged neighborhoods has been related to cardiovascular disease (CVD). Chronic stress may increase the risk for CVD by increasing levels of systemic inflammation (e.g., higher levels of pro-inflammatory cytokines). Differential DNA methylation of inflammation-related candidate genes is also related to higher risk for CVD. Thus, the purpose of this review was to examine the association of neighborhood disadvantage with DNA methylation. A search of literature was conducted using Scopus, CINAHL, PubMed, Medline, and Embase databases. The keywords neighborhood, neighborhood disorder, neighborhood crime, neighborhood violence, neighborhood safety, built environment, and housing vacancy were combined with the keywords DNA methylation and epigenetics. Five studies were included in this review (n = 3 adult blood samples and n = 2 fetal blood samples). Four of the five studies reported an association of neighborhood socioeconomic status, social environment, and crime with either global or gene-specific DNA methylation. Only two studies examined the association of neighborhood disadvantage with inflammation-related candidate genes. One of these studies found a significant association of neighborhood socioeconomic disadvantage and social environment with DNA methylation in inflammation-related candidate genes. Thus, data are limited on the association between neighborhood disadvantage and DNA methylation of inflammation-related candidate genes, as well as genes in other potential mechanistic pathways including psychosocial stress, toxin response, and adiposity. Future studies should examine these associations and the potential epigenetic mechanisms by which neighborhood disadvantage increases the risk for CVD.

Introduction: Mothers and infants are at high risk for inadequate vitamin D status. Mechanisms by which vitamin D may affect maternal and infant DNA methylation are poorly understood., Objective: This study quantified the effects of vitamin D 3 supplementation on DNA methylation in pregnant and lactating women and their breastfed infants., Materials and Methods: In this randomized controlled pilot study, pregnant women received vitamin D 3 400 international units (IU) (n = 6; control) or 3,800 IU (n = 7; intervention) daily from late second trimester through 4-6 weeks postpartum. Epigenome-wide DNA methylation was quantified in leukocytes collected from mothers at birth and mother-infant dyads at 4-6 weeks postpartum., Results: At birth, intervention group mothers showed DNA methylation gain and loss at 76 and 89 cytosine-guanine (CpG) dinucleotides, respectively, compared to controls. Postpartum, methylation gain was noted at 200 and loss at 102 CpGs. Associated gene clusters showed strongest biologic relevance for cell migration/motility and cellular membrane function at birth and cadherin signaling and immune function at postpartum. Breastfed 4-6-week-old infants of intervention mothers showed DNA methylation gain and loss in 217 and 213 CpGs, respectively, compared to controls. Genes showing differential methylation mapped most strongly to collagen metabolic processes and regulation of apoptosis., Conclusions: Maternal vitamin D supplementation during pregnancy and lactation alters DNA methylation in mothers and breastfed infants. Additional work is needed to fully elucidate the short- and long-term biologic effects of vitamin D supplementation at varying doses, which could hold important implications for establishing clinical recommendations for prenatal and offspring health promotion.

Aims: As maternal vitamin D status has been associated with preeclampsia, the purpose of this study was to determine variations in DNA methylation patterns and associated protein expression in placental genes regulating vitamin D metabolism., Main Methods: A convenience sample of 48 pregnant nulliparous women, including 11 later diagnosed with preeclampsia, were recruited in this prospective study. Using a case-control design in two groups of women, we administered a food frequency questionnaire to determine vitamin D dietary intake. Laboratory measures included serum vitamin D levels (25[OH]D), DNA methylation patterns and protein expression in placental genes regulating vitamin D metabolism (1α-hydroxylase, CYP27B1; vitamin D receptor, VDR; retinoid X receptor, RXR) from placental tissue collected at delivery among those diagnosed with preeclampsia and those who remained normotensive throughout pregnancy., Key Findings: There were no significant differences in vitamin D dietary intake or mean serum 25[OH]D levels, although the proportion of women with deficient 25[OH]D levels was higher in the preeclampsia group (46%) than the normotensive group (20%). Placenta samples from women with preeclampsia also had increased DNA methylation of CYP27B1, VDR and RXR genes with lower protein expression levels limited to RXR., Significance: Hypermethylation of key placental genes involved in vitamin D metabolism suggests uncoupling of processes that may interfere with placentation and availability of vitamin D at the maternal-fetal interface., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Preeclampsia contributes significantly to pregnancy-associated morbidity and mortality as well as future risk of cardiovascular disease in mother and offspring, and preeclampsia in offspring. The lack of reliable methods for early detection limits the opportunities for prevention, diagnosis, and timely treatment., Purpose: The purpose of this study was to explore distinct DNA methylation patterns associated with preeclampsia in both maternal cells and fetal-derived tissue that represent potential biomarkers to predict future preeclampsia and inheritance in children., Method: A convenience sample of nulliparous women (N = 55) in the first trimester of pregnancy was recruited for this prospective study. Genome-wide DNA methylation was quantified in first-trimester maternal peripheral white blood cells and placental chorionic tissue from normotensive women and those with preeclampsia (n = 6/group)., Results: Late-onset preeclampsia developed in 12.7% of women. Significant differences in DNA methylation were identified in 207 individual linked cytosine and guanine (CpG) sites in maternal white blood cells collected in the first trimester (132 sites with gain and 75 sites with loss of methylation), which were common to approximately 75% of the differentially methylated CpG sites identified in chorionic tissue of fetal origin., Conclusion: This study is the first to identify maternal epigenetic targets and common targets in fetal-derived tissue that represent putative biomarkers for early detection and heritable risk of preeclampsia. Findings may pave the way for diagnosis of preeclampsia prior to its clinical presentation and acute damaging effects, and the potential for prevention of the detrimental long-term sequelae., (© The Author(s) 2013.)

DNA methylation is an epigenomic modification that is essential to normal human development and biological processes. DNA methylation patterns are heritable and dynamic throughout the life span. Environmental exposures can alter DNA methylation patterns, contributing to the development of complex disease. Identification and modulation of environmental factors influencing disease susceptibility through alterations in DNA methylation are amenable to nursing intervention and form the basis for individualized patient care. Here we describe the evidence supporting the translation of DNA methylation analyses as a tool for screening, diagnosis, and treatment of complex disease in nursing research and practice. The ethical, legal, social, and economic considerations of advances in genomics are considered as a model for epigenomic policy. We conclude that contemporary and informed nurse scientists and clinicians are uniquely poised to apply innovations in epigenomic research to clinical populations and develop appropriate policies that guide equitable and ethical use of new strategies to improve patient care., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: In the United States, Black women experience preterm birth (PTB; <37 weeks gestation) at more than 1.5 times the rate of non-Hispanic White women. Social determinants of health including the neighborhood environment have been recognized as contributing to the risk of PTB. Due to historical segregation, Black women are more likely to live in neighborhoods with higher levels of neighborhood disorder compared with White women. Perceived neighborhood disorder appears to be a risk factor for maternal psychological distress in Black women and psychological distress has mediated the association between neighborhood disorder and the risk for PTB. However, the biological pathways underpinning these associations are not clear. Objective: We examined the associations among neighborhood disorder; psychological distress; DNA methylation of six stress-related, glucocorticoid candidate genes (AVP, CRH, CRHBP, FKBP5, HSD11B2, NR3C1); and gestational age at birth among 44 Black pregnant women. Methods: Women who were 18–45 years old and 8–18 weeks gestation had blood drawn and completed questionnaires measuring perceived neighborhood disorder, neighborhood crime, and psychological distress. Results: Three CpG sites were associated with neighborhood disorder (cg03405789 [ CRH ], cg14939152 and cg15910486 [ NR3C1 ]). One CpG site, cg03098337 (FKBP5) was associated with psychological distress. Three of the identified CpG sites were located within gene CpG islands or shores—areas at which DNA methylation is known to affect gene transcription. Conclusion: These findings warrant further research to clarify intermediate biological pathways and potential biomarkers to identify women at risk for PTB. Identification of PTB risk early in pregnancy would allow for interventions to prevent PTB. [ABSTRACT FROM AUTHOR]

Preterm birth (PTB; <37 weeks gestation) rates have increased for 5 of the last 6 consecutive years in the United States. These rates are particularly alarming for U.S. non-Hispanic Black women who give birth prematurely at 1.5 times the rate of non-Hispanic White women. Previous research suggests that psychological stress is associated with PTB in Black women. However, the biological pathways by which stress alters birth timing are not clear. We examined DNA methylation (DNAm) in peripheral blood leukocytes in 6 glucocorticoid, stress-related genes in 44 (22 PTB; 22 term birth) pregnant Black women. Four cytosine-phosphate-guanine (CpG) sites were identified as differentially methylated (p < 0.05) between women with PTB and women with term births. The ability to identify stress-related biological markers that are associated with PTB among Black women would provide a critical step toward decreasing the PTB disparity among these women. Future studies should include larger sample sizes and gene expression analyses of the stress-related biological pathways to PTB. [ABSTRACT FROM AUTHOR]

Epigenetic modifications are chemical changes that can modify gene expression without changing the sequence of the gene. These modifications are potentially identifiable and reversible, making the epigenome an important area of research for discovering biomarkers to identify those who may be at risk and providing therapeutic interventions to prevent adverse health outcomes. African Americans bear a disproportionate risk of adverse health outcomes (e.g., hypertension, cancer). Indeed, African American women experience preterm birth (PTB; <37 completed weeks gestation) at more than twice the rate of non-Hispanic White women. Research suggests that environmental influences may play a significant role in PTB outcomes for this population. However, the biological pathways by which these influences contribute to PTB are poorly understood. This paper describes research methods and ethical considerations for the collection and analysis of biological samples based on our study examining the epigenetic regulation of stress pathways in PTB in pregnant African American women. [ABSTRACT FROM AUTHOR]

Objective: We compared blood-based DNA methylation levels of endoglin (ENG) and transforming growth factor beta receptor 2 (TGFβR2) gene promoter regions between women with clinically-overt preeclampsia and women with uncomplicated, normotensive pregnancies. Methods: We used EpiTect Methyl II PCR Assays to evaluate DNA methylation of CpG islands located in promoter regions of ENG (CpG Island 114642) and TGFβR2 (CpG Island 110111). Preeclampsia was diagnosed based on blood pressure, protein, and uric acid criteria. N = 21 nulliparous preeclampsia case participants were 1:1 frequency matched to N = 21 nulliparous normotensive control participants on gestational age at sample collection (±2 weeks), smoking status, and labor status at sample collection. Methylation values were compared between case and control participant groups [(ENG subset: n = 20 (9 cases, 11 controls); TGFβR2 subset: n = 28 (15 cases, 13 controls)]. Results: The majority of the preeclampsia cases delivered at ⩾34 weeks' gestation (83%). Average methylation levels for ENG ([M ± (SD)]; Case Participant Group = 6.54% ± 4.57 versus Control Participant group = 4.81% ± 5.08; P =.102) and TGFβR2 (Case Participant Group = 1.50% ± 1.37 vs Control Participant Group = 1.70% ± 1.40; P =.695) promoter CpG islands did not differ significantly between the participant groups. Removal of 2 extreme outliers in the ENG analytic subset revealed a trend between levels of ENG methylation and pregnancy outcome (Case Participant Group = 5.17% ± 2.16 vs Control Participant Group = 3.36% ± 1.73; P =.062). Conclusion: Additional epigenetic studies that include larger sample sizes, investigate preeclampsia subtypes, and capture methylation status of CpG island shores and shelves are needed to further inform us of the potential role that ENG and TGFβR2 DNA methylation plays in preeclampsia pathophysiology. [ABSTRACT FROM AUTHOR]