Maternal stress and placental function, a study using questionnaires and biomarkers at birth

Abstract

Background: Prenatal 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.

Aim: To 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.

Method: Maternal 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.

Results: Significant 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.

Conclusion: Our main finding was associations between PRA and AFCE, which shows the effect of maternal stress on placental cortisol metabolism.

Fig 1. Fetal and maternal cortisone and cortisol.

The y-axis is log-scale. Both fetal and maternal plasma cortisone (blue circle) and fetal and maternal cortisol (orange square) values correlate.

Fig 2. Categorical distribution of the study population based on DASS scores, Major Life Events and PRA.

The study population divided into groups according to severeness of maternal (A) Depression, (B) Anxiety and (C) Stress based on the Depression Anxiety and Stress Scales, (D) Major Life events and (E) Pregnancy related anxiety (PRA).