Bibian van der Voorn

44 CHAPTER 3 neonatal hair GC levels are associated with other perinatal factors such as perinatal infection, although to a lesser degree than gestational age. In our study, we could confirm the association described by Hoffmann et al. 18 between neonatal hair cortisol levels and both gestational age and birth weight directly postpartum. However, we did not find an association with birth weight SDS. Since birth weight and gestational age are correlated, the association with birth weight probably reflects the effect of gestational age rather than of intrauterine growth. The association with gestational age might be indicative of several mechanisms. First, adrenal maturation occurs throughout pregnancy, resulting in increased cortisol production by the fetal adrenal 5 . A higher concentration of GCs in hair might therefore reflect a longer exposure to the maturing HPA axis. However, since the association between gestational age and neonatal hair GCs is also still present in term neonates, another mechanism appears to be present as well. Induction of labor has been suggested to be partly due to an increase in cortisol, which promotes fetal organ maturation 7,24 . This increase in cortisol is thought to originate from a positive feedback loop established between placenta-derived CRH and cortisol originating from the fetal adrenals 6,24 , which can only be broken by the severance of the umbilical cord. Fetal distress may accelerate this feedback loop 8 , which might explain the increased hair GC levels in neonates who are treated for a perinatal infection. It is as of yet unknown whether neonatal hair GC levels fully result from fetal cortisol production or whether the transplacental supply of cortisol might also contribute to neonatal GC levels in hair. Previous research has suggested that cortisol is transferred via the placenta to the fetus, although most cortisol is inactivated to cortisone by placental 11βHSD type 2 8 . However, as maternal serum cortisol levels are 10 times higher than fetal serum levels, even small amounts of cortisol could account for about 40% of the variance in fetal concentrations 4 . In our study, we found a positive correlation betweenmaternal and neonatal hair cortisol levels, but not with cortisone. The positive correlation between neonatal and maternal hair cortisol levels might therefore be a reflection of placental transfer. However, this does not explain why the neonatal hair GC levels were much higher compared to maternal levels. We speculate that this may be due to differences in hair growth and structure between the fetus and its mother. While it is feasible that cortisol in neonatal hair is derived from hair follicles, where it is incorporated after diffusion from blood 14 , cortisol in amniotic fluid might contribute to the GC concentrations measured in hair. Moreover, although hair growth in utero is roughly known, the specifics are still unclear. The first stage of hair growth starts during the 15 th week of gestation, and by week 18 to 20 the entire scalp is covered with hair in the primary, anagen stage. Next, between week 24 and