Maternal Signatures of Cortisol in First Trimester Small-for-Gestational Age

Abstract

Background: Abnormal maternal hypothalamus-pituitary-adrenal axis is associated with fetal growth, and we hypothesized that the alteration in metabolic signatures of cortisol might be detectable during early pregnancy. The objective of this study was to identify predictable maternal serum signatures of cortisol metabolism during the rst trimester of women who are expected to deliver small-for-gestational age (SGA) neonates.Methods: This prospective cohort study included 112 pregnant women (with and without SGA, n = 56 each). Maternal serum samples were collected at 10~14 gestational weeks to quantify the levels of cortisol and its precursors and metabolites by liquid chromatography-mass spectrometry.Results: Increased maternal serum levels of tetrahydrocortisol (THF, 11.82 ± 8.16 ng/mL vs. 7.51 ± 2.90 ng/mL, P < 0.005) and decreased 21-deoxycortisol (21-deoxyF, 2.98 ± 1.36 ng/mL vs. 4.33 ± 2.06 ng/mL, P < 0.0001) were observed in pregnant women carrying SGA fetus. In conjunction with individual steroid levels, metabolic ratios corresponding to the activity of related enzymes were calculated. In addition to increased THF/cortisol ratio (P < 0.006), the SGA group showed a signi cant increase in the two metabolic ratios including cortisol/11-deoxycortisol (F/11-deoxyF; P < 0.03) and cortisol/21-deoxycortisol (F/21-deoxyF; P < 0.0003) indicating cortisol biosynthesis. The ROC curve generated in combination with three variables of 21-deoxyF concentration and two metabolic ratios of F/21-deoxyF and THF/F resulted in AUC = 0.824 (95% con dence interval, 0.713 ~ 0.918).Conclusions: A signi cant decrease in maternal serum levels of 21-deoxyF and an increase in two metabolic ratios of F/21-deoxyF and THF/F, indicating cortisol biosynthetic rate, represent a reliable biomarker for the prediction of SGA in the rst trimester.

Relationship Between Maternal Serum Cortisol and Maternal Insulin Resistance and Fetal Ultrasound Characteristics in Gestational Diabetes Mellitus

“…The consequence of this process leads to increased fetal calorie consumption. 6 Some studies outlined that maternal cortisol levels affect fetal development, such as the effect on fetal weightfor-age development in the first trimester 7 and the third-trimester cortisol levels related to an increase in neonatal adiposity up to 1-6 months postpartum. 8 A study by Braithwaite et al of 1233 first-time mothers (96.1% White British) at 32 weeks gestation found that maternal cortisol levels were positively related to male infant' postpartum weight with β of 0.167 and p of 0.036 9 .…”