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

Abstract

BackgroundNormal pregnancy depends on pronounced adaptations in steroid hormone concentrations. Although in recent years, the understanding of these hormones in pregnancy has improved, the interpretation is hampered by insufficient reference values. Our aim was to establish gestation-specific reference intervals for spot urinary steroid hormone levels in normal singleton pregnancies and 6 weeks postpartum.MethodsCross-sectional multicentre observational study. Women recruited between 2008 and 2013 at 3 University Hospitals in Switzerland (Bern), Scotland (Glasgow) and Austria (Graz). Spot urine was collected from healthy women undergoing a normal pregnancy (age, 16–45 years; mean, 31 years) attending routine antenatal clinics at gestation weeks 11, 20, and 28 and approximately 6 weeks postpartum. Urine steroid hormone levels were analysed using gas-chromatography mass spectrometry. Creatinine was also measured by routine analysis and used for normalisation.ResultsFrom the results, a reference interval was calculated for each hormone metabolite at each trimester and 6 weeks postpartum. Changes in these concentrations between trimesters and postpartum were also observed for several steroid hormones and followed changes proposed for index steroid hormones.ConclusionsNormal gestation-specific reference values for spot urinary steroid hormones throughout pregnancy and early postpartum are now available to facilitate clinical management and research approaches to steroid hormone metabolism in pregnancy and the early postpartum period.

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

“…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.…”

Increased cortisol metabolism in women with pregnancy-related hypertension

“…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 ].…”

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

“…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.…”

“…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.…”

“…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].…”