Cortisol metabolism in pregnancies with small for gestational age neonates

Abstract

Small for gestational age (SGA) newborns are often born from hypertensive pregnancies. This study aimed to compare the systemic metabolism of cortisol (F) in pregnancies with SGA and appropriate for gestational age (AGA) infants, considering both the normotensive (NT) and hypertensive patients. We hypothesized that the disturbances in systemic metabolism of F in pre-eclampsia (PE) might be attributed not to hypertension only, but to SGA. The study included 117 pregnants in the third trimester, divided into groups: NT pregnancy and SGA neonate (SGA-NT); NT pregnancy and AGA neonate (AGA-NT; controls), and respective groups with PE: SGA-PE and AGA-PE. We assessed the glucocorticoid balance with the function of enzymes involved in systemic metabolism of F: 11β-hydroxysteroid dehydrogenase type 1 and 2 (11β-HSD1 and 11β-HSD2), 5α- and 5β-reductase. The enzymes’ functions were estimated with the levels of F, cortisone (E), and their metabolites in plasma or urine, which we measured with HPLC-FLD and HPLC-MS/MS. The plasma F/E and urinary free F/E (UFF/UFE) ratios correlated significantly only in patients with the normal function of 5α- and 5β-reductase. The increased function of 11β-HSD2 was noted in all pre-eclamptic pregnancies. Increased function of 5α- and 5β-reductase was specific only for SGA-PE pregnancies, and the function of 5α-reductase was dependent on fetal sex. The SGA-NT pregnancies with male fetuses trended towards the higher function of renal 11β-HSD2 and 5β-reductase; SGA-NT pregnancies with female fetuses lacked any systemic glucocorticoid imbalance. In conclusion, systemic metabolism of F is the most intensive in pre-eclamptic pregnancies complicated by SGA with female fetuses. Our study supports the hypothesis about the different origins of PE and idiopathic intrauterine growth restriction and suggests the sex-specific mechanisms responsible for fetal growth restriction.

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

“…1), while its metabolic ratio relative to cortisol, THF/F, was also higher in women carrying SGA fetus (Fig. 2A), similar to previous ndings in pregnant women in third trimester [13]. Our study demonstrated that these changes may also represent predictive biomarkers in the rst trimester.…”

“…However, the serum levels of cortisol in the SGA group at early stage of the rst trimester were not statistically signi cant (P = 0.337; Fig. 1), consistent with previous studies involving women in the rst and third trimesters [12,13].…”

“…Despite the altered adrenal function of newborns with intrauterine growth restriction (IUGR) within the rst several weeks of life [7], increased cord blood levels of cortisol were detected in SGA fetus and newborn [8,9], while low-birth weight preterm infants had decreased cortisol levels compared with full-term normal babies [10,11]. Cortisol metabolism in pregnant women carrying SGA fetus was altered, but the increased levels of maternal serum cortisol were not statistically signi cant [12,13].…”

Associations Between Maternal Awakening Salivary Cortisol Levels in Mid-Pregnancy and Adverse Birth Outcomes

“…Interestingly, decreased functioning of 11β-HSD2 in SGA infants has only been observed in pregnancies with female fetuses [51]. Recent ndings on sex-speci c differences in systemic glucocorticoid imbalance [52] also strengthen the plausibility of our nding that elevated maternal salivary cortisol increases the risk of SGA among female fetuses only. Likewise, previous research indicated that the effects of depression during pregnancy could have a different impact on the two sexes [53].…”

Steroidomics of Pregnant Women at Advanced Age

“…Cortisol and cortisone also play a vital role in pregnancy ( 12 ). The high concentration of cortisol from the mother needs to be rapidly converted to its inactive metabolite (cortisone) under the actions of the enzyme hydroxysteroid 11β dehydrogenase type 2 ( 13 ). This enzyme is the key to protecting the fetus’s normal growth.…”