Bibian van der Voorn

37 INTERPRETATION OF GC LEVELS IN NEONATAL HAIR INTRODUCTION Prenatal exposure to excessive glucocorticoids (GCs) has been associated with an increased risk of cardiovascular diseases and depressive disorders 1,2 . This might be due to permanent alterations in the settings of the fetal HPA axis, which are protective in the short term, but might pose a risk in the long term 3 . The development of the fetal HPA axis is, among other factors, influenced by the placental transfer of maternal GCs throughout pregnancy 4 . During early gestation, maternal GCs are the main supply. By the second half of gestation, the fetal adrenal starts producing its own steroids, predominantly sex steroids (which serve as a substrate for the placental production of estriol) and precursor GCs, since the adrenocortical enzymes are not fully matured yet 5 . Subsequently, during the last 6-8 wks of pregnancy, the more matured fetal adrenal produces increasing amounts of cortisol and cortisone under the control of CRH production in the placenta, which – in contrast to the negative feedback loop between cortisol and CRH under non- pregnant conditions – establishes a positive feedback loop 6 . This increase in cortisol concentration promotes maturation of the fetal lungs as well as of other organs 7 . Knowledge on the fetal HPA axis development is mainly based on animal studies 5,8 , as it is difficult to measure fetal HPA axis activity in humans. Up till now, amniotic fluid GC levels and umbilical cord GC levels have been used to assess intrauterine GC regulation. Cortisol in amniotic fluid has previously been correlated with maternal cortisol levels 9 and onset of labor 10 . However, the source of amniotic fluid cortisol remains uncertain, although findings point toward fetal production 11,12 . In addition, sampling of amniotic fluid is a stressful occasion and only provides cross-sectional information. Alternatively, umbilical cord blood can be drawn non-invasively, but GC levels are influenced by delivery 13 and might not reflect normal intrauterine HPA axis activity. GCs measured in scalp hair might offer a solution, as it is used as a measure for HPA axis activity over time without the disturbing influence of the circadian rhythm. The hair GC concentrations reflect the exposure in the time frame during which the hair grows 14 . Maternal hair GC levels seem to reflect HPA axis activity during pregnancy 15-17 . Neonatal hair GC levels have also been associated with pre- and perinatal factors. A recent study by Hoffman et al. (2017) 18 has shown that gestational age as well as birth weight had a positive association with cortisol levels in neonatal hair. Neonatal hair GC levels were also significantly higher than maternal hair GC levels. This study suggests that features of the fetal adrenal development are represented in neonatal hair GC levels, although these findings are limited due to the fact that this has only