Hair cortisol levels as a retrospective marker of hypothalamic–pituitary axis activity throughout pregnancy: Comparison to salivary cortisol
Research Highlights
► Maternal cortisol levels in hair correlated with maternal salivary cortisol levels during pregnancy. ► Both maternal salivary cortisol levels and maternal hair cortisol level displayed the classic increase of cortisol across pregnancy. ► This study supports hair cortisol as a potential proxy measure of long term HPA activation and maternal stress during pregnancy.
Introduction
Maternal stress negatively affects pregnancy outcomes and subsequent child development [1], [2], [3], but the mechanism by which this occurs is not clear. Cortisol, the hormonal product of activation of the hypothalamic–pituitary–adrenal (HPA) axis, has been suggested as a potential mechanism linking maternal stress and perinatal outcomes [4]. Recently, long-term estimates of prenatal HPA activity of the mother have been measured in hair collected in the postpartum period providing a novel retrospective means of assessing stress during pregnancy.
Abnormal patterns of maternal cortisol during pregnancy have been associated with negative perinatal outcomes including miscarriage [5], increased fetal activity [4], premature birth and decreased birth weight [4]. Elevated maternal stress and consequently, cortisol [6], negatively affect long-term HPA-axis regulation of the offspring [3], [7], [8] by reorganizing the offspring's HPA-axis. Dysfunction of peripheral aspects of the HPA-axis and increases in absolute cortisol has been correlated with maternal psychosocial reports of stress, though the results are inconsistent [9], [10]. This suggests that during pregnancy women may have altered physiological stress reactivity with potential consequences for infant outcome. Thus, maternal cortisol is a candidate physiological mediator between prenatal maternal stress and adverse outcome for the offspring.
Cortisol can be measured in a variety of ways. Many studies include single blood and/or saliva samples and, while useful, they are only snapshots of HPA activity. In addition, there is great individual variability of baseline cortisol levels between and within subjects due to circadian rhythms and system fluctuations based on homeostatic regulation [11]. Thus, cortisol level measured in saliva, even repeatedly, may not be the most informative measure to use to evaluate overall or long term HPA activity during the prenatal period. A measure integrating cortisol over a longer time frame may be more useful in quantifying the early perinatal environment of both the mother and her offspring.
Hair cortisol is a reliable measure of overall HPA activity in humans [12]. Cortisol measured from hair collected closest to the scalp estimates cortisol production retrospectively for up to 6 months [13]. It is unclear how cortisol becomes incorporated into the hair shaft, however, cortisol has been determined to be synthesized by the pilosebaceous unit located in the hair follicles in response to adrenocorticotropic hormone [14]. Unbound cortisol may also diffuse from capillaries into the cells of the hair follicle and become deposited within the hair shaft as well [15]. Hair typically grows at a regular rate and cortisol levels in hair are easily measured by standard cortisol assay techniques [12], [13], [16], [17]. Hair and salivary cortisol are highly correlated in non-human primates [16] and significantly increase in response to an extended environmental challenge (Fairbanks, Jorgenson, Bailey, Breidenthal, Grzwya, & Laudenslager, submitted). Thus, hair cortisol has the potential to serve as an integrated measure of HPA activity over an extended period of time of up to 3–6 months.
Hair cortisol has been used to evaluate environmental stress in humans. For example, hair cortisol levels in hospitalized infants are increased compared to their healthy non-hospitalized counterparts. Hair cortisol increased for each additional day an infant was ventilated [17]. Hair cortisol is elevated during the third trimester of pregnancy [13] and is higher in association with stress during the late first trimester of pregnancy [18]. This is the first study to directly compare salivary cortisol and hair cortisol longitudinally from early pregnancy through the postpartum period. The goal of the present study is to compare hair cortisol with diurnal salivary cortisol throughout pregnancy and in the first three months postnatally.
Section snippets
Sample
Twenty one non-smoking pregnant women (ages 18–45), less than 17 weeks gestational age and experiencing non-complicated pregnancies were recruited to participate in the study. The primary exclusion criteria were use of any medications (other than prenatal vitamins) at time of enrollment or having bleached hair or using high-level peroxide products on their hair. All research subjects provided informed consent under the Colorado Multiple Institutional Review Board.
Salivary cortisol collection and analysis
Saliva was collected using
Sample characteristics
The mean age (± standard deviation) of mothers in the study was 30 ± 1 years. All other maternal demographics, including age range, race, education, employment and marital status are included in Table 1.
Pattern of cortisol levels across pregnancy in saliva and hair
Self reported times of daily collection saliva times across pregnancy were not significantly different: wake + 30 min (F (3,20) = 0.365; p = 0.778; RM ANOVA), lunch (F(3,20) = 1.533, p = 0.216; RM ANOVA) and wake + 10 hr (F(3,20) = 2.371, p = 0.08; RM ANOVA). See Table 2 for saliva collection time mean and standard
Discussion
The goal of this study was to investigate maternal hair cortisol as a measure of longer term prenatal cortisol release. In support of this, cortisol levels in hair correlated with contemporaneously collected salivary cortisol. Both salivary and maternal hair cortisol levels also displayed the expected increase across pregnancy followed by a postnatal decline. These findings provide valuable empirical support for the use of hair cortisol as a proxy measure of long term HPA activity during
Acknowledgements
The authors would like to acknowledge Rachel Grzywa and Maribel Perea for their contributions to this research and Gary Zerbe for his assistance in the analysis as well as Angela Goodteacher for her assistance in collecting the hair samples. We would also to thank the mothers for their participation. This work was funded by research grants from the Developmental Psychobiology Endowment Fund (University of Colorado Denver, Department of Psychiatry) and NIH [AA013973 (MLL), CA126971(MLL), MH086383
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