Abstract
Maternal stress during pregnancy is linked to several negative birth outcomes. The placenta, a unique pregnancy-specific organ, not only nourishes and protects the fetus but is also the major source of progesterone and estrogens. As the placenta becomes the primary source of maternal progesterone (P4) and estradiol between 6–9 weeks of gestation, and these hormones are critical for maintaining pregnancy, maternal stress may modulate levels of these steroids to impact birth outcomes. The objective was to test whether maternal perceived stress crosses the placental barrier to modulate fetal steroids, including cortisol, which is a downstream indicator of maternal hypothalamic–pituitary–adrenal (HPA) axis regulation and is associated with negative fetal outcomes. Nulliparous women, 18 years or older, with no known history of adrenal or endocrine illness were recruited during their third trimester of pregnancy at the University of California San Francisco (UCSF) Mission Bay hospital obstetrics clinics. Simultaneous measurement of 10 steroid metabolites in maternal (plasma and hair) and fetal (cord blood and placenta) samples was performed using tandem mass spectrometry along with assessment of the perceived stress score and sociodemographic status. While the maternal perceived stress score (PSS) and sociodemographic status were positively associated with each other and each with the body mass index (BMI) (r = 0.73, p = 0.0008; r = 0.48, p = 0.05; r = 0.59, p = 0.014, respectively), PSS did not correlate with maternal or fetal cortisol, cortisone levels, or fetal birth weight. Regardless of maternal PSS or BMI, fetal steroid levels remained stable and unaffected. Progesterone was the only steroid analyte quantifiable in maternal hair and correlated positively with PSS (r = 0.964, p = 0.003), whereas cord estradiol was negatively associated with PSS (r = −0.94, p = 0.017). In conclusion, hair progesterone might serve as a better marker of maternal stress than cortisol or cortisone and maternal PSS negatively impacts fetal estradiol levels. Findings have implications for improved biomarkers of stress and targets for future research to identify factors that buffer the fetus from adverse effects of maternal stress.
Highlights
Experiencing too much stress from negative life events or other stressors during pregnancy can have serious consequences for the pregnant mother and the developing fetus, including higher risk of preterm birth and low birth weight [1,2,3]
Mass spectrometry is a sensitive and reliable method to detect and differentiate between different steroid metabolites simultaneously in a sample; it is well established that the steroid concentrations reported using mass spectrometry are lower than those reported with traditional ELISA
We were able to ascertain levels of glucocorticoids, progesterone, and estrogen steroid metabolites and their precursors in maternal and fetal samples; several of these metabolites levels were below levels of detection (LOD) in maternal and fetal samples (Table 2)
Summary
Experiencing too much stress from negative life events or other stressors during pregnancy can have serious consequences for the pregnant mother and the developing fetus, including higher risk of preterm birth and low birth weight [1,2,3]. The placenta forms during pregnancy from fetal trophoblasts and serves as a temporary organ that creates the link between mother and fetus, providing the fetus with oxygen and nutrients necessary for survival. The placenta is a complex vascular, endocrine, and immune organ that supports fetal growth, removes waste products from the fetus, acts as a barrier to prevent infections reaching the fetus, and maintains maternal health [4,5]. The placenta is crucial for the development of the fetal pituitary–adrenocortical axis, responds to maternal cortisol levels, and forms part of the body’s stress response system. The mechanisms responsible for healthy versus problematic outcomes from stress are not completely understood
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