Assessment of prenatal stress-related cortisol exposure: focus on cortisol accumulation in hair and nails

Prenatal stress adversely affects offspring development. Although cortisol is hypothesized to be a key mediator of stress-induced developmental deficits, determining the amount of fetal cortisol exposure produced by maternal stress has proved challenging. Current approaches, such as measuring cortisol concentrations in maternal plasma, saliva, or urine, amniotic fluid, fetal plasma, or cord blood, all have significant limitations for assessing cumulative fetal cortisol exposure over time. A recently emerging approach is to measure cortisol concentrations in maternal hair and/or newborn hair or nail samples. Maternal hair cortisol potentially shows long-term production across each trimester of pregnancy, whereas neonatal hair or nail cortisol is thought to reflect mainly third trimester hormone accumulation. This review first describes fetal adrenocortical development, placental cortisol metabolism, and the various sources of fetal cortisol exposure across pregnancy. We then summarize the results obtained from "classical" methods of assessing prenatal cortisol exposure prior to the advent of hair and nail cortisol measurement. Lastly, we discuss the initial development and validation of the hair cortisol methodology, its subsequent application to studies of chronic stress, and recent findings regarding maternal and neonatal hair or nail cortisol concentrations in relation to prenatal stress and other variables of interest.