The association between the acute psychobiological stress reactivity in second-trimester pregnant women and amniotic fluid cortisol and cortisone

Rationale/statement of the problem : Scientific evidence indicating that excessive stress during human pregnancy can have long-lasting effects on mother and child is increasing. But the underlying biological mechanisms remain elusive. Recent findings suggest a key role of the hypothalamic–pituitary–adrenal axis and the placental enzyme 11β-hydroxysteroid dehydrogenase Type 2 (11β-HSD2). This enzyme inactivates cortisol (F) to cortisone (E), thereby protecting the foetus from maternal F overexposure. Studies on pregnant rats show that placental 11β-HSD2 is up-regulated following acute maternal stress but impaired after chronic stress. Whether a similar mechanism exists in humans is unclear. Therefore, we investigated the acute stress response of salivary F (SalF) in second-trimester pregnant women undergoing amniocentesis and compared this response with amniotic fluid F, E, and the E/(E + F) ratio as an index of placental 11β-HSD2 activity. Since 11β-HSD2 is also present in the adult salivary glands, we determined salivary E (SalE) and the SalE/(SalE + SalF) ratio, as a marker for salivary 11β-HSD2 activity as well and examined the association of these parameters with the amniotic fluid markers of stress. Methods : Repeated saliva samples and an aliquot of amniotic fluid were collected from 34 healthy pregnant women (mean age = 37.5, SD = 3.9 years) undergoing amniocentesis for karyotyping. Changes in stress perception and state anxiety were monitored using questionnaires. Participants were re-invited for a control condition after receiving the inconspicuous test results of the amniocentesis. Results : Compared to the control condition, the pregnant participants showed significant increases in psychological distress during the amniocentesis. SalF and SalE increased correspondingly while SalE/(SalE + SalF) decreased. SalF correlated positively with amniotic fluid E (r=.38, p=.048), and a stronger decrease in SalE/(SalE + SalF) was associated with increased amniotic fluid E/(E + F) (r=.44, p=.02). Conclusions : The present results further our understanding of the maternal–foetal stress response considerably and suggest that during acute stress, maternal F is converted to E within the foeto-placental unit. This is most probably due to the activity of placental 11β-HSD2. Further investigation of the influence of chronic stress on the enzyme activity is essential