The Human Fetus Preferentially Secretes Corticosterone, Rather than Cortisol, in Response to Intra-Partum Stressors

Abstract

ContextFetal stress is relevant to newborn outcomes. Corticosterone is rarely quantified in human clinical endocrinology and is found at much lower concentrations than cortisol. However, fetal corticosterone is a candidate hormone as a fetal stress signal.ObjectiveTest the hypothesis that preferential fetal corticosterone synthesis occurs in response to fetal intra-partum stress.DesignCross-sectional comparison of paired serum corticosteroid concentrations in umbilical artery and vein from 300 women providing consent at admission to a General Hospital Labor and Delivery unit. Pre-term and multiple births were excluded, leaving 265 healthy deliveries.Main Outcome MeasuresCorticosterone and cortisol concentrations determined by LC-MS/MS for umbilical cord venous (V) and arterial (A) samples and used to calculate fetal synthesis (A−V) and proportional fetal synthesis ([A−V]/V). Chart-derived criteria stratified samples by type of delivery, maternal regional analgesia, augmentation of contractions, and clinical rationale for emergent Caesarian delivery.ResultsCortisol concentrations were higher than corticosterone concentrations; however, the fetus preferentially secretes corticosterone (148% vs 49% proportional increase for cortisol) and differentially secretes corticosterone as fetal stress increases. Fetal corticosterone synthesis is elevated after passage through the birth canal relative to Caesarian deliveries. For vaginal deliveries, augmentation of contractions does not affect corticosteroid concentrations whereas maternal regional analgesia decreases venous (maternal) concentrations and increases fetal synthesis. Fetal corticosterone synthesis is also elevated after C-section indicated by cephalopelvic disproportion after labor, whereas cortisol is not.ConclusionsThe full-term fetus preferentially secretes corticosterone in response to fetal stress during delivery. Fetal corticosterone could serve as a biomarker of fetal stress.

Developmental programming: Sex‐specific programming of growth upon prenatal bisphenol A exposure

“…In general, maternal stress raises corticosterone concentrations during pregnancy with negative effects on a feto‐placental unit (Jafari, Mehla, Afrashteh, Kolb, & Mohajerani, ; Vaughan, Sferruzzi‐Perri, & Fowden, ). Elevations in corticosterone rather than cortisol concentrations strongly correlate with fetal stress in human studies (Wynne‐Edwards, Edwards, & Hancock, ). Despite elevated corticosterone in maternal circulation, corticosterone and DOC, which are both downstream products in the adrenal steroidal pathway leading to aldosterone synthesis, were lower in the D90 BPA‐exposed female fetuses.…”

Glucocorticoids are lower at delivery in maternal, but not cord blood of obese pregnancies

“…where labour had occurred), compared with delivery by elective Caesarean section (i.e. pre-labour) 10 , 12 , 14 . Our finding of higher corticosterone (but not cortisol) in labouring cord samples was in-keeping with a previous study 14 who found highest corticosterone levels in vaginal deliveries, followed by emergency caesarean deliveries (who would have laboured), and lowest levels in elective caesarean deliveries (no labour).…”

“…As offspring born to obese women are more likely to need respiratory support at delivery 9 , it is plausible that exposure to comparatively lower levels of glucocorticoids in utero could limit fetal lung maturation in this group. One previous study reported lower maternal cortisol, but not cord cortisol at delivery in obese compared to normal weight women 4 , but did not adjust for mode of delivery or labour; both factors are known to influence cord cortisol levels 10 – 14 .…”

“…While cortisol is the major circulating glucocorticoid hormone in humans, there is increasing interest in the potential physiological roles of corticosterone, which comprises 5–10% of total plasma glucocorticoids 15 . The observation of proportionally greater increases in cord blood corticosterone than cortisol according to ‘stressful’ labour and mode of delivery has led to the suggestion that the full-term human fetus preferentially secretes corticosterone in response to fetal stress 14 .…”

Is the Correlation between Salivary Cortisol and Serum Cortisol Reliable Enough to Enable Use of Salivary Cortisol Levels in Preterm Infants?

“…Cortisol quantitation by Agilent 1200 Liquid Chromatography (LC) coupled to ABSciex 5500 qTrap Tandem Mass Spectrometry (MS/MS) (atmospheric pressure chemical ionization ¼ APCI source) used the area ratio against an internal deuterated cortisol standard (cortisol d4, D-5280, CDN isotopes, Pointe-Claire, Quebec, Canada). 7 The lower limit of quantitation (LLOQ) with a minimum of 50 µL of sample was 0.075 µg/dL. We measured free cortisol levels in saliva and total cortisol levels in serum.…”