BackgroundPrenatal maternal stress (PNMS) predicts a wide variety of behavioral and physical outcomes in the offspring. Although epigenetic processes may be responsible for PNMS effects, human research is hampered by the lack of experimental methods that parallel controlled animal studies. Disasters, however, provide natural experiments that can provide models of prenatal stress.MethodsFive months after the 1998 Quebec ice storm we recruited women who had been pregnant during the disaster and assessed their degrees of objective hardship and subjective distress. Thirteen years later, we investigated DNA methylation profiling in T cells obtained from 36 of the children, and compared selected results with those from saliva samples obtained from the same children at age 8.ResultsPrenatal maternal objective hardship was correlated with DNA methylation levels in 1675 CGs affiliated with 957 genes predominantly related to immune function; maternal subjective distress was uncorrelated. DNA methylation changes in SCG5 and LTA, both highly correlated with maternal objective stress, were comparable in T cells, peripheral blood mononuclear cells (PBMCs) and saliva cells.ConclusionsThese data provide first evidence in humans supporting the conclusion that PNMS results in a lasting, broad, and functionally organized DNA methylation signature in several tissues in offspring. By using a natural disaster model, we can infer that the epigenetic effects found in Project Ice Storm are due to objective levels of hardship experienced by the pregnant woman rather than to her level of sustained distress.

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Prenatal maternal stress (PNMS) can impact a variety of outcomes in the offspring throughout childhood and persisting into adulthood as shown in human and animal studies. Many of the effects of PNMS on offspring outcomes likely reflect the effects of epigenetic changes, such as DNA methylation, to the fetal genome. However, no animal or human research can determine the extent to which the effects of PNMS on DNA methylation in human offspring is the result of the objective severity of the stressor to the pregnant mother, or her negative appraisal of the stressor or her resulting degree of negative stress. We examined the genome-wide DNA methylation profile in T cells from 34 adolescents whose mothers had rated the 1998 Québec ice storm's consequences as positive or negative (that is, cognitive appraisal). The methylation levels of 2872 CGs differed significantly between adolescents in the positive and negative maternal cognitive appraisal groups. These CGs are affiliated with 1564 different genes and with 408 different biological pathways, which are prominently featured in immune function. Importantly, there was a significant overlap in the differentially methylated CGs or genes and biological pathways that are associated with cognitive appraisal and those associated with objective PNMS as we reported previously. Our study suggests that pregnant women's cognitive appraisals of an independent stressor may have widespread effects on DNA methylation across the entire genome of their unborn children, detectable during adolescence. Therefore, cognitive appraisals could be an important predictor variable to explore in PNMS research.