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BACKGROUND: Experimental animal work shows that prenatal stress has a persisting effect on the hypothalamic-pituitary-adrenal (HPA) axis of offspring. The implications of these findings for human health and development are not yet clear. METHODS: The data are based on the ALSPAC cohort, a prospective longitudinal study of a community sample that has followed mothers and children from pregnancy. When the children were aged 15 years, diurnal cortisol samples were collected at wake-up, 30min post-awakening and at afternoon and evening times on up to three consecutive days on n=889 adolescents. Diurnal cortisol was predicted from prenatal anxiety and depression, obstetric, life-style, socio-demographic, and postnatal covariates. RESULTS: Multilevel model analysis indicated that maternal prenatal anxiety was associated with a modest alteration of diurnal cortisol, indexed by a reduced cortisol awakening response and flatter diurnal slope. The effects were independent of psychosocial and obstetric covariates and measures of maternal postnatal anxiety; effects were similar for prenatal maternal depression. There was no association between adolescent cortisol and paternal prenatal anxiety. CONCLUSIONS: There are small but persisting associations between maternal prenatal mood and diurnal cortisol in the child that persist into adolescence and may constitute a programming effect.