Epigenetic signatures of Prenatal stress: FELICITy study.

PETER ZIMMERMANN; RORY WILSON; BAMMLER, THEO K.; ANTONELLI, MARTA C.; RITIKA SHARMA; BERG, G.; MELANIE WALDENBERGER; FRASCH, MARTIN G.; CAMILA ZELGERT; BIBIANA FABRE; MACDONALD, JAMES W.; LOBMAIER, SILVIA M.

Jornada; MGC Science Day. Technical University of Munich.; 2020

Background/Aims: Maternal stress before, during and after pregnancy may program physiological responses of the infant, and epigenetically reprogram its lifelong trajectory. We hypothesize that infants affected by prenatal stress (PS) might show epigenetic alterations of the fetal autonomic nervous system and Hypothalamic-Pituitary axis. This we aimed to develop a biomarker panel from the salivary DNA as an early non-invasive measure of PS exposed infants. Method: In a prospective study, we screened women for chronic stress exposure using the Cohen perceived stress scale (PSS) and were classified into stressed group (SG, PSS-10 ≥ N= 55), the control group (CG, PS-10 > 19, N=55) matched 1:1 for parity, maternal age and gestational age. We analysed coupling between mHR and fHR using bivariate Phase Rectified Signal Averaging that yielded foetal stress index (FSI). On the day of delivery maternal hair was collected to measure cortisol. DNA methylation was measured in saliva samples of the newborn using the EPIC Bead Chip array (758132 CpG). To identify associations between FSI and methylation, linear regression models adjusting for confounders (sex, age and cell types) were run. Results: No difference in the methylation levels was observed in the PS newborns. However two top hits of this association are cg12131093 (p = 4.184e-07) whose gene annotates for the protein RAB27B and cg27133711 (p = 1.66e-06) whose gene annotates NRG1, both involved in neurological pathways. Discussion: We are due to prove that the PS as defined in this study actually results in epigenetic changes postnatally. For this, 24-months measurement will be performed. Meanwhile, based on the observation of differences in the FSI, i.e., differences in the brain development at 34 weeks of gestation due to PS, we can also infer that because the methylation marks due to PS do not appear fixed at birth, this underscores the opportunity to use early enrichment interventions for reversing any functional changes.