Abstract
BackgroundPrenatal stress affects the health of the pregnant woman and the fetus. Cortisol blood levels are elevated in pregnancy, and fetal exposure to cortisol is regulated by the placenta enzyme 11β-HSD2. A decrease in enzyme activity allows more maternal cortisol to pass through the placental barrier. Combining the fetal and maternal cortisol to cortisone ratio into the adjusted fetal cortisol exposure (AFCE) represents the activity of the enzyme 11β-HSD2 in the placenta.AimTo investigate the effect of prenatal maternal stress on the ratio of cortisol and cortisone in maternal and fetal blood at birth in a normal population.MethodMaternal self-reported stress was assessed at one time-point, as late in the pregnancy as convenient for the participant, using the Depression Anxiety Stress Scales (DASS-42), Pregnancy Related Anxiety (PRA), and Major Life Events during pregnancy. The study included 273 participants from Copenhagen University Hospital. Maternal and umbilical cord blood was sampled directly after birth and cortisol and cortisone concentrations were quantified using UPLC chromatography. Data were analyzed in a five-step regression model with addition of possible confounders. The primary outcome was AFCE, and plasma concentrations of maternal and fetal cortisol and cortisone were secondary outcomes.ResultsSignificant associations were seen for the primary outcome AFCE and the plasma concentrations of maternal cortisol and fetal cortisone with exposure to Pregnancy Related Anxiety (PRA), though the associations were reduced when adjusting for birth related variables, especially delivery mode. The weight of the placenta affected the associations of exposures on AFCE, but not plasma concentrations of cortisol and cortisone in mother and fetus. Moreover, the study demonstrated the importance of delivery mode and birth strain on cortisol levels right after delivery.ConclusionOur main finding was associations between PRA and AFCE, which shows the effect of maternal stress on placental cortisol metabolism.
Highlights
The prevalence of psychosocial stress and anxiety during pregnancy is a cause of concern worldwide, and maternal psychosocial stress has been conceptualized as a teratogen [1]
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Our main finding was associations between Pregnancy Related Anxiety (PRA) and adjusted fetal cortisol exposure (AFCE), which shows the effect of maternal stress on placental cortisol metabolism
Summary
The prevalence of psychosocial stress and anxiety during pregnancy is a cause of concern worldwide, and maternal psychosocial stress has been conceptualized as a teratogen [1]. During the first two trimesters of pregnancy, the serum cortisol levels in the fetus are low, except for a peak around gestation week 10 to counteract the effects of hormones from newly formed fetal adrenal tissue. The fetal serum cortisol levels rise, and is at a maximum at term due to a decline in the placental cortisol metabolizing activity, and the production of cortisol by the fetal adrenal glands [17]. Cortisol blood levels are elevated in pregnancy, and fetal exposure to cortisol is regulated by the placenta enzyme 11β-HSD2. Combining the fetal and maternal cortisol to cortisone ratio into the adjusted fetal cortisol exposure (AFCE) represents the activity of the enzyme 11βHSD2 in the placenta
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