title: Maternal stress, preterm birth, and DNA methylation at imprint regulatory sequences in humans.
abstract: In infants exposed to maternal stress in utero, phenotypic plasticity through epigenetic events may mechanistically explain increased risk of preterm birth (PTB), which confers increased risk for neurodevelopmental disorders, cardiovascular disease, and cancers in adulthood. We examined associations between prenatal maternal stress and PTB, evaluating the role of DNA methylation at imprint regulatory regions. We enrolled women from prenatal clinics in Durham, NC. Stress was measured in 537 women at 12 weeks of gestation using the Perceived Stress Scale. DNA methylation at differentially methylated regions (DMRs) associated with H19, IGF2, MEG3, MEST, SGCE/PEG10, PEG3, NNAT, and PLAGL1 was measured from peripheral and cord blood using bisulfite pyrosequencing in a sub-sample of 79 mother-infant pairs. We examined associations between PTB and stress and evaluated differences in DNA methylation at each DMR by stress. Maternal stress was not associated with PTB (OR = 0.98; 95% CI, 0.40-2.40; P = 0.96), after adjustment for maternal body mass index (BMI), income, and raised blood pressure. However, elevated stress was associated with higher infant DNA methylation at the MEST DMR (2.8% difference, P < 0.01) after adjusting for PTB. Maternal stress may be associated with epigenetic changes at MEST, a gene relevant to maternal care and obesity. Reduced prenatal stress may support the epigenomic profile of a healthy infant.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Epidemiology, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Vidal
authors.affiliation: Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Benjamin Neelon
authors.affiliation: Duke University School of Medicine, Durham, NC, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Duke University School of Medicine, Durham, NC, USA.
authors.forename: Abbas M
authors.initials: AM
authors.lastname: Tuli
authors.affiliation: Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA. ; Department of Psychology and Neurosciences, Duke University, Durham, NC, USA.
authors.forename: Bernard F
authors.initials: BF
authors.lastname: Fuemmeler
authors.affiliation: Department of Obstetrics and Gynecology, Division of Epidemiology, Duke University School of Medicine, Durham, NC, USA. ; Duke Comprehensive Cancer Center, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Cathrine
authors.initials: C
authors.lastname: Hoyo
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Murtha
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Psychology and Neurosciences, Duke University, Durham, NC, USA. ; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Joellen
authors.initials: J
authors.lastname: Schildkraut
authors.affiliation: Department of Obstetrics and Gynecology, Division of Epidemiology, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Francine
authors.initials: F
authors.lastname: Overcash
authors.affiliation: Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA. ; Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
authors.affiliation: Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Randy L
authors.initials: RL
authors.lastname: Jirtle
authors.affiliation: Department of Statistical Sciences, Duke University, Durham, NC, USA.
authors.forename: Edwin S
authors.initials: ES
authors.lastname: Iversen
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC, USA. ; Department of Pathology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Murphy
keywords: epigenetics; imprinting; intrauterine growth restriction (IUGR); perceived stress; perinatal; pregnancy