TY - JOUR A1 - Gilles, Maria A1 - Otto, Henrike A1 - Wolf, Isabell A. C. A1 - Scharnholz, Barbara A1 - Peus, Verena A1 - Schredl, Michael A1 - Suetterlin, Marc W. A1 - Witt, Stephanie H. A1 - Rietschel, Marcella A1 - Laucht, Manfred A1 - Deuschle, Michael T1 - Maternal hypothalamus-pituitary-adrenal (HPA) system activity and stress measures at birth JF - Psychoneuroendocrinology N2 - Background: Prenatal maternal stress might be a risk for the developing fetus and may have long-lasting effects on child and adult vulnerability to somatic and psychiatric disease. Over-exposure of the unborn to excess glucocorticoids and subsequent alteration of fetal development is hypothesized to be one of the key mechanisms linking prenatal stress with negative child outcome. Methods: In this prospective longitudinal study, mothers-to-be (n = 405) in late pregnancy (36.8 +/- 1.9 weeks of gestational age) and their singleton neonates were studied. We investigated the impact of different prenatal stress indices derived from six stress variables (perceived stress, specific prenatal worries, negative life events, symptoms of depression, trait anxiety, neuroticism) and diurnal maternal saliva cortisol secretion on gestational age and anthropometric measures at birth. KW - Early life stress KW - Gestational age KW - Anthropometric measures at birth KW - Cortisol KW - Prenatal distress KW - Pregnancy Y1 - 2018 U6 - https://doi.org/10.1016/j.psyneuen.2018.04.022 SN - 0306-4530 VL - 94 SP - 152 EP - 161 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Witt, Stephanie H. A1 - Frank, Josef A1 - Gilles, Maria A1 - Lang, Maren A1 - Treutlein, Jens A1 - Streit, Fabian A1 - Wolf, Isabell A. C. A1 - Peus, Verena A1 - Scharnholz, Barbara A1 - Send, Tabea S. A1 - Heilmann-Heimbach, Stefanie A1 - Sivalingam, Sugirthan A1 - Dukal, Helene A1 - Strohmaier, Jana A1 - Sütterlin, Marc A1 - Arloth, Janine A1 - Laucht, Manfred A1 - Nöthen, Markus M. A1 - Deuschle, Michael A1 - Rietschel, Marcella T1 - Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation JF - BMC genomics N2 - Background: Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic "smoking methylation pattern", and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight. The aims of the present study were to replicate previous reports that methylation mediates the effect of maternal smoking on birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific in order to account for known sex-specific differences in methylation levels. Methods: Methylation levels in the cord blood of 313 newborns were determined using the Illumina HumanMethylation450K Beadchip. A total of 5,527 CpG sites selected on the basis of evidence from the literature were tested. To determine whether the observed association between maternal smoking and birth weight was attributable to methylation, mediation analyses were performed for significant CpG sites. Separate analyses were then performed in males and females. Results: Following quality control, 282 newborns eventually remained in the analysis. A total of 25 mothers had smoked consistently throughout the pregnancy. The birthweigt of newborns whose mothers had smoked throughout pregnancy was reduced by >200g. After correction for multiple testing, 30 CpGs showed differential methylation in the maternal smoking subgroup including top "smoking methylation pattern" genes AHRR, MYO1G, GFI1, CYP1A1, and CNTNAP2. The effect of maternal smoking on birth weight was partly mediated by the methylation of cg25325512 (PIM1); cg25949550 (CNTNAP2); and cg08699196 (ITGB7). Sex-specific analyses revealed a mediating effect for cg25949550 (CNTNAP2) in male newborns. Conclusion: The present data replicate previous findings that methylation can mediate the effect of maternal smoking on birth weight. The analysis of sex-dependent mediation effects suggests that the sex of the newborn may have an influence. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the sex of the newborn in mediating the association between maternal smoking during pregnancy and birth weight. KW - DNA methylation KW - Smoking KW - Birth weight KW - Mediation analysis Y1 - 2018 U6 - https://doi.org/10.1186/s12864-018-4652-7 SN - 1471-2164 VL - 19 PB - BMC CY - London ER -