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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: 11\u03b2-hydroxysteroid dehydrogenase type 1 and 2 (11\u03b2-HSD1 and 11\u03b2-HSD2), 5\u03b1- and 5\u03b2-reductase. The enzymes\u2019 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 5\u03b1- and 5\u03b2-reductase. The increased function of 11\u03b2-HSD2 was noted in all pre-eclamptic pregnancies. Increased function of 5\u03b1- and 5\u03b2-reductase was specific only for SGA-PE pregnancies, and the function of 5\u03b1-reductase was dependent on fetal sex. The SGA-NT pregnancies with male fetuses trended towards the higher function of renal 11\u03b2-HSD2 and 5\u03b2-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.<\/jats:p>","DOI":"10.1038\/s41598-019-54362-0","type":"journal-article","created":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T11:03:10Z","timestamp":1575025390000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Cortisol metabolism in pregnancies with small for gestational age neonates"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3568-4716","authenticated-orcid":false,"given":"Anna","family":"Siemi\u0105tkowska","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3551-4784","authenticated-orcid":false,"given":"Katarzyna","family":"Kosicka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5546-4799","authenticated-orcid":false,"given":"Agata","family":"Szpera-Go\u017adziewicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariola","family":"Krzy\u015bcin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grzegorz H.","family":"Br\u0119borowicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6611-5789","authenticated-orcid":false,"given":"Franciszek K.","family":"G\u0142\u00f3wka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,11,29]]},"reference":[{"key":"54362_CR1","first-page":"67","volume":"10","author":"D Sharma","year":"2016","unstructured":"Sharma, D., Shastri, S. & Sharma, P. 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