Gestation-specific reference intervals for comprehensive spot urinary steroid hormone metabolite analysis in normal singleton pregnancy and 6 weeks postpartum

Mistry, Hiten D.; Eisele, Nicole; Escher, Geneviève; Dick, Bernhard; Surbek, Daniel; Delles, Christian; Currie, Gemma; Schlembach, Dietmar; Mohaupt, Markus; Gennari-Moser, Carine

doi:10.1186/s12958-015-0100-6

Cited by 11 publications

(7 citation statements)

References 35 publications

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“…Early in previous research, it has been detected that steroid hormones, including estradiol, hydroxyprogesterone cortisol and androstenedione in serum and urine were increasing with pregnancy progression using target LC-MS method 14 . In urine, metabolites of steroid hormones, such as 17-hydroxypregnenolone and deoxycorticosterone, were found to be up-regulated during pregnancy 15 . These researches showed consistent results with ours that during normal pregnancy, function of steroid hormones biosynthesis was more activated.…”

Section: Discussionmentioning

confidence: 99%

Urinary metabolic variation analysis during pregnancy and application in Gestational Diabetes Mellitus and spontaneous abortion biomarker discovery

Liu

Wang

Sun

et al. 2019

Sci Rep

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Pregnancy is associated with the onset of many adaptation processes that are likely to change over the course of gestation. Understanding normal metabolites’ variation with pregnancy progression is crucial for gaining insights of the key nutrients for normal fetal growth, and for comparative research of pregnancy-related complications. This work presents liquid chromatography-mass spectrum-based urine metabolomics study of 50 health pregnant women at three time points during pregnancy. The influence of maternal physiological factors, including age, BMI, parity and gravity to urine metabolome was explored. Additionally, urine metabolomics was applied for early prediction of two pregnancy complications, gestational diabetes mellitus and spontaneous abortion. Our results suggested that during normal pregnancy progression, pathways of steroid hormone biosynthesis and tyrosine metabolism were significantly regulated. BMI is a factor that should be considered during cross-section analysis. Application analysis discovered potential biomarkers for GDM in the first trimester with AUC of 0.89, and potential biomarkers for SA in the first trimester with AUC of 0.90. In conclusion, our study indicated that urine metabolome could reflect variations during pregnancy progression, and has potential value for pregnancy complications early prediction. The clinical trial number for this study is NCT03246295.

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Section: Discussionmentioning

confidence: 99%

Urinary metabolic variation analysis during pregnancy and application in Gestational Diabetes Mellitus and spontaneous abortion biomarker discovery

Liu

Wang

Sun

et al. 2019

Sci Rep

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“…There are limited data reporting levels of F and E metabolites in pregnant women [ 13 – 15 ], some of which refers to spot urine only [ 14 ]. Others include women in the first weeks of pregnancy [ 15 ] or—like the study from 1980—concern only the tetrahydrometabolites of F and E assessed in samples from 6 patients [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Increased cortisol metabolism in women with pregnancy-related hypertension

et al. 2018

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PurposeThe diminished function of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) was found in placentae from preeclamptic pregnancies. Here, we examine the overall maternal glucocorticoid balance in pregnancy-related hypertension. We aim to answer the question if the functions of primary enzymes involved in cortisol metabolism: 11β-HSD1 and 11β-HSD2 and 5-reductases (both 5α- and 5β) are altered in the course of hypertensive pregnancy.MethodsWe determined plasma and urinary cortisol and cortisone as well as their urinary tetrahydro- and allo-tetrahydrometabolites, both in free and conjugated forms in samples obtained from 181 Polish women in the third trimester of pregnancy. We compared steroid profiles in women with preeclampsia (PE), gestational hypertension (GH), chronic hypertension (CH) and in normotensives (controls).ResultsWe found significant differences in glucocorticoid balance in pregnancy-related hypertension. Plasma cortisol to cortisone was significantly lower in PE than in controls (3.00 vs. 4.79; p < 0.001). Increased function of renal 11β-HSD2 in PE and GH was manifested by significantly lower urinary free cortisol to cortisone ratio (0.169 and 0.206 vs. 0.277 in controls; p < 0.005). Markedly enhanced metabolism of cortisol was observed in pregnancy-related hypertension, with no significant alterations in CH, and the changes were more clearly expressed in PE than in GH.ConclusionsThe glucocorticoid balance in PE and GH is shifted towards decreasing cortisol concentration either due to intensified conversion to cortisone or enhanced production of tetrahydro and allo-tetrahydrometabolites.

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“…Our finding that urinary TH-aldo: creatinine ratios are also lower in SPE compared with women with CKD who did not develop SPE further suggests that this finding is a PE-specific alteration. It is important to highlight that previous measurements of plasma aldosterone using radioimmunoassays or ELISA are hampered by high cross-reactivity with other metabolites, especially progesterone [30], whereas the validated, highly sensitive GC-MS of the major metabolite, TH-aldo, used in this study resolves such issues. In addition, urinary excretion must be considered a better representation of the overall temporal exposure to aldosterone and AGT.…”

Section: Discussionmentioning

confidence: 99%

“…Urinary TH-aldo was analysed by gas chromatography-mass spectrometry (GC-MS) according to a modified method, originally described by Shackleton [29] and applied by us as reported earlier [30]. Measurement of TH-aldo rather the aldosterone was conducted as we used the mass spectrometry-based assays that are able to accurately measure individual steroid hormone concentrations.…”

Section: Methodsmentioning

confidence: 99%

“…Measurement of TH-aldo rather the aldosterone was conducted as we used the mass spectrometry-based assays that are able to accurately measure individual steroid hormone concentrations. Many of the conventional assays for aldosterone, such as the radioimmunoassays and ELISAs, are compromised by significant cross-reactivity and lack of specificity [30].…”

Section: Methodsmentioning

confidence: 99%

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Responses of the renin–angiotensin–aldosterone system in pregnant chronic kidney disease patients with and without superimposed pre-eclampsia

Kurlak

Pipkin

Mohaupt

et al. 2019

Clinical Kidney Journal

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BackgroundWomen with chronic kidney disease (CKD) are at increased risk of superimposed pre-eclampsia (SPE). Accurate identification of SPE is challenging. We hypothesized that specific components of the renin–angiotensin–aldosterone system (RAAS) would discriminate between CKD and SPE. The aim of the study was to establish differences in circulating and intrarenal RAAS in women with CKD with and without SPE and compare these to normotensive controls (NCs) and women with pre-eclampsia (PE).MethodsWhite European NC women (n = 20), women with PE (n = 9), normotensive CKD without SPE (n = 8) and with SPE (n = 11) were recruited in the third trimester. Plasma renin, plasma and urine total angiotensinogen (AGT) concentrations were quantified by enzyme-linked immunosorbent assay, urinary tetrahydroaldosterone (TH-aldo) concentration by gas chromatography-mass spectrometry and placental growth factor (PlGF) by immunoassay.ResultsUrinary TH-aldo:creatinine ratios were lower in women with PE or SPE compared with NC or women with CKD (P < 0.05 for all). The same group differences were observed for plasma active renin and PlGF concentrations (P < 0.05 for all). Urine total AGT was higher in women with PE compared with NC (P < 0.05) and urine TH-aldo:urine AGT was lower (P < 0.05). However, women with SPE had lower urinary AGT concentrations compared with women with PE (P < 0.05). No differences in plasma total AGT were observed between groups.ConclusionsWomen with SPE have a lower urinary TH-aldo:creatinine ratio, lower plasma active renin and lower PlGF concentrations than women with CKD, comparable to women with PE without pre-existing disease, suggestive of similar pathophysiology. These data suggest disruption of the RAAS pathway in SPE similar to PE. Exploration of the predictive value of RAAS components for adverse pregnancy events in women with CKD is required.

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Gestation-specific reference intervals for comprehensive spot urinary steroid hormone metabolite analysis in normal singleton pregnancy and 6 weeks postpartum

Cited by 11 publications

References 35 publications

Urinary metabolic variation analysis during pregnancy and application in Gestational Diabetes Mellitus and spontaneous abortion biomarker discovery

Urinary metabolic variation analysis during pregnancy and application in Gestational Diabetes Mellitus and spontaneous abortion biomarker discovery

Increased cortisol metabolism in women with pregnancy-related hypertension

Responses of the renin–angiotensin–aldosterone system in pregnant chronic kidney disease patients with and without superimposed pre-eclampsia

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