We will build a prediction model for estimation of optimal pregnancy termination in women with intrahepatic cholestasis (ICP). For the construction of this model the steroid metabolome (about 100 steroids and related substances), some bile acids and further markers of ICP will be used. We will attempt to find common components of steroidogenesis and synthesis of bile acids in pregnancy using the multivariate regression. We will verify our hypothesis regarding the influence of ICP on the syncytium isoforms of oxidoreductases which would result in alterations in levels of sex hormones and neuroactive steroids. These substances are known to influence pregnancy sustaining and mother’s mood.

Sestavíme predikční model pro stanovení optimálního ukončení těhotenství u žen s intrahepatální cholestázou (ICP). K sestavení tohoto modelu použijeme steroidní metabolom (kolem 100 steroidů a příbuzných látek), některé žlučové kyseliny a další ukazatele ICP. Pokusíme se o nalezení společných prvků steroidogenezy a tvorby žlučových kyselin v těhotenství s využitím vícerozměrné regrese. Ověříme naší hypotézu o vlivu ICP na syncytiální izoformy oxidoreduktáz které by měly způsobit změny hladin pohlavních hormonů a neuroaktivních steroidů. Je obecně známo, že tyto látky ovlivňují stabilitu těhotenství a psychickou kondici matky.

• MeSH
• indukovaný potrat MeSH
• intrahepatální cholestáza MeSH
• metabolom MeSH
• prediktivní hodnota testů MeSH
• steroidy MeSH
• žlučové kyseliny a soli MeSH

• Konspekt
• Gynekologie. Porodnictví
• NLK Obory
• gynekologie a porodnictví
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

Intrahepatic cholestasis of pregnancy (ICP) is a common liver disorder, mostly occurring in the third trimester. ICP is defined as an elevation of serum bile acids, typically accompanied by pruritus and elevated activities of liver aminotransferases. ICP is caused by impaired biliary lipid secretion, in which endogenous steroids may play a key role. Although ICP is benign for the pregnant woman, it may be harmful for the fetus. We evaluated the differences between maternal circulating steroids measured by RIA (17-hydroxypregnenolone and its sulfate, 17-hydroxyprogesterone, and cortisol) and GC-MS (additional steroids), hepatic aminotransferases and bilirubin in women with ICP (n = 15, total bile acids (TBA) >8 μM) and corresponding controls (n = 17). An age-adjusted linear model, receiver-operating characteristics (ROC), and multivariate regression (a method of orthogonal projections to latent structure, OPLS) were used for data evaluation. While aminotransferases, conjugates of pregnanediols, 17-hydroxypregnenolone and 5β-androstane-3α,17β-diol were higher in ICP patients, 20α-dihydropregnenolone, 16α-hydroxy-steroids, sulfated 17-oxo-C19-steroids, and 5β-reduced steroids were lower. The OPLS model including steroids measured by GC-MS and RIA showed 93.3% sensitivity and 100% specificity, while the model including steroids measured by GC-MS in a single sample aliquot showed 93.3% sensitivity and 94.1% specificity. A composite index including ratios of sulfated 3α/β-hydroxy-5α/β-androstane-17-ones to conjugated 5α/β-pregnane-3α/β, 20α-diols discriminated with 93.3% specificity and 81.3% sensitivity (ROC analysis). These new data demonstrating altered steroidogenesis in ICP patients offer more detailed pathophysiological insights into the role of steroids in the development of ICP.

• MeSH
• 17-alfa-hydroxypregnenolon chemie   krev   MeSH
• 17-alfa-hydroxyprogesteron chemie   krev   MeSH
• alanintransaminasa krev   MeSH
• aspartátaminotransferasy krev   MeSH
• dospělí MeSH
• gestační stáří MeSH
• hydrokortison chemie   krev   MeSH
• intrahepatální cholestáza * diagnóza   metabolismus   patologie   MeSH
• jaterní testy MeSH
• komplikace těhotenství * diagnóza   metabolismus   patologie   MeSH
• lidé MeSH
• nuclei raphe dorsalis MeSH
• plocha pod křivkou MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• radioimunoanalýza MeSH
• ROC křivka MeSH
• steroidy * chemie   krev   metabolismus   MeSH
• těhotenství MeSH
• žlučové kyseliny a soli analýza   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH

UNLABELLED: Background and aims. Patients with intrahepatic cholestasis of pregnancy (ICP) benefit from ursodeoxycholic acid (UDCA) treatment. Since there is still certain reluctance to use UDCA in pregnant women, mainly due to warnings in the official SPC information in respective drug leaflets, our objective was to assess the efficacy and safety of UDCA during pregnancy. MATERIAL AND METHODS: Our retrospective multicentric study was performed on 191 consecutive pregnant women with ICP treated with UDCA. Any maternal and/or fetal complications of the UDCA treatment were searched for; healthy pregnant women (n = 256) served as controls. RESULTS: The UDCA treatment improved liver disease status in the majority of the affected women (86.1%). This treatment was well tolerated, with only negligible skin reactions (0.5%) and mild diarrhea (4.7%). No complications attributable to UDCA treatment were detected during the fetal life, delivery, or the early neonatal period. CONCLUSION: We confirmed the good efficacy and safety of UDCA treatment in pregnancy for both mothers and fetuses/neonates.

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• MeSH
• cholagoga a choleretika škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• hodnocení rizik MeSH
• intrahepatální cholestáza * diagnóza   farmakoterapie   MeSH
• komplikace těhotenství diagnóza   farmakoterapie   MeSH
• kyselina ursodeoxycholová škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• těhotenství MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH

Intrahepatic cholestasis of pregnancy (ICP) is a disorder of liver function, commonly occurring in the third trimester but sometimes also as soon as the end of the second trimester of pregnancy. Symptoms of this disorder include pruritus, plus abnormal values of bile acids and hepatic transaminases. After birth, symptoms disappear and liver function returns to normal. Though ICP is relatively non-complicated and often symptomatically mild from the point-of-view of the mother, it presents a serious risk to the fetus, making this disease the subject of great interest. The etiology and pathogenesis of ICP is multifactorial and as yet not fully elucidated. Hormonal factors likely play a significant role, along with genetic as well as exogenous factors. Here we summarize the knowledge of changes in steroid hormones and their role in the development of intrahepatic cholestasis of pregnancy. In addition, we consider the role of exogenous factors as possible triggers of steroid hormone changes, the relationship between metabolic steroids and bile acids, as well as the combination of these factors in the development of ICP in predisposed pregnant women.

• MeSH
• intrahepatální cholestáza krev   etiologie   genetika   MeSH
• komplikace těhotenství krev   etiologie   genetika   MeSH
• lidé MeSH
• pohlavní steroidní hormony fyziologie   MeSH
• těhotenství MeSH
• žlučové kyseliny a soli krev   genetika   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder of pregnancy. Diagnosis is based on the clinical picture, particularly the presence of pruritus with a deterioration of liver function tests, and typically elevated serum levels of total bile acids. ICP manifests in the second half of pregnancy, predominantly during the third trimester. Symptoms of the disease resolve spontaneously after delivery. Etiology is still not fully understood. Genetic defects in specific transport proteins, elevated levels of sex hormones, and various environmental factors are thought to play a role in the development of this disorder. Although practically benign for the pregnant woman, ICP represents a serious threat to the fetus. It increases the risk of preterm delivery, meconium excretion into the amniotic fluid, respiratory distress syndrome, and sudden intrauterine fetal death. Identifying fetuses at risk of ICP complications remains challenging. The ideal obstetrical management of ICP needs to be definitively determined. The aim of this review is to summarize the current knowledge on fetal complications of ICP and describe management options for their prevention.

• MeSH
• intrahepatální cholestáza * MeSH
• komplikace těhotenství * MeSH
• lidé MeSH
• nemoci plodu * etiologie   MeSH
• předčasný porod * etiologie   MeSH
• syndrom respirační tísně novorozenců * etiologie   MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH

BACKGROUND: Remifentanil has been suggested for its short duration of action to replace standard opioids for induction of general anaesthesia in caesarean section. While the stabilizing effect of remifentanil on maternal circulation has been confirmed, its effect on postnatal adaptation remains unclear, as currently published studies are not powered sufficiently to detect any clinical effect of remifentanil on the newborn. METHODS: Using a double-blinded randomized design, a total of 151 parturients undergoing caesarean delivery under general anaesthesia were randomized into two groups--76 patients received a bolus of remifentanil prior to induction, while 75 patients were assigned to the control group. Remifentanil 1 μg/kg was administered 30 seconds before the standard induction of general anaesthesia. The primary outcome measure was an assessment of neonatal adaptation using the Apgar score, while secondary outcomes included the need for respiratory support after delivery and differences in umbilical blood gas analysis (Astrup). RESULTS: The incidence of lower Apgar scores between 0 and 7 was significantly higher in the remifentanil group at one minute (25% vs. 9.3% of newborns, p = 0.017); whilst at five minutes and later no Apgar score differences were observed. There was no difference in the need for moderate (nasal CPAP) or intensive (intubation) respiratory support, but significantly more neonates in the remifentanil group required tactile stimulation for breathing support (21% vs. 7% of newborns, p = 0.017). There was no difference in the parameters from umbilical cord blood gas analysis between the groups. CONCLUSION: At a dose of 1 μg/kg, remifentanil prior to induction of general anaesthesia increases the risk of neonatal respiratory depression during first minutes after caesarean delivery but duration of clinical symptoms is short. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01550640.

• MeSH
• anestetika celková škodlivé účinky   MeSH
• Apgar skóre MeSH
• celková anestezie škodlivé účinky   MeSH
• císařský řez * MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• fyziologická adaptace účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• opioidní analgetika škodlivé účinky   MeSH
• piperidiny škodlivé účinky   MeSH
• poruchy dýchání chemicky indukované   MeSH
• prospektivní studie MeSH
• těhotenství MeSH
• umělé dýchání MeSH
• výsledek těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Unfavorable post-partum changes to mental well-being affect more than half of all women, and are a risk to the health of both mother and baby. Their effects place strains on health and social systems. Currently, no generally accepted theory exists of the causes and mechanisms of post-partum mental disorders. METHODS: Literature search up to 2012, using PubMed and search words: neuroactive steroids, post-partum mental disorders, depression, corticotropin-releasing hormone and estrogens. RESULTS: There are several theories for post-partum depression. One is that autoimmune diseases are involved. Others revolve around genes responsible or that lead to increased disposition to the disorder. It is likely however that the process is associated with the separation of the placenta and the fetal zone of fetal adrenal gland, the main sources of corticotropin-releasing hormone and sexual and neuroactive steroids during pregnancy, and the ability of the receptor system to adapt to these changes. The central nervous system is able to produce neurosteroids, but the drop in levels of peripheral steroids likely leads to a sudden deficit in neuroinhibitory steroids modulating ionotropic receptors in the brain. CONCLUSIONS: Post-partum depression is a multifactorial disease with unknown etiology. It is probably associated with sudden changes in the production of hormones influencing the nervous system, and on the other hand the ability of the receptor system to adapt to these changes. When the relative changes in concentrations of hormones, rather than their absolute levels, is likely more important.

• MeSH
• dospělí MeSH
• lidé MeSH
• metabolomika metody   MeSH
• pohlavní steroidní hormony krev   MeSH
• poporodní deprese krev   MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The initiation of human parturition is not fully understood to date. The data from animal experiments demonstrate that the primary impulse for the initiation of physiological labor arises from the fetal hypothalamo-pituitary-adrenal axis (HPA). HPA is responsible for the stimulation of steroid synthesis and prostaglandin production and, in turn, the cervical dilation and the beginning of myometrial contractions. Animal experiments, however, are only partly suitable for understanding the mechanism of human labor due to substantial species-specificity. In human, the changing levels of placental CRH control the production of fetal and placental steroids. The fundamental pathogenic manifestation of spontaneous preterm labor is inflammation and similar processes also underlie the full term one. While in full term labor it is not yet precisely known what starts this process, in the preterm one, several factors have been discussed like infection, uteroplacental ischemia, and hormonal abnormalities (progesterone- or CRH-related). Inflammatory processes affect both the mother and the fetus. Fetal inflammatory response (FIRS), which can be expected for children born preterm, is frequently associated with long-term complications, in particular neurological and pulmonary. Research in this field is therefore aimed at predicting preterm labor, and on predicting the fetal inflammatory response. The role of progesterone and its receptors in the pathophysiology of preterm labor are likewise intensively studied. Clinical results on the use of additive doses of progesterone in secondary prevention of preterm labor and current experimental studies point to progesterone and its receptors playing a key role in the pathophysiology of preterm labor. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.

• MeSH
• lidé MeSH
• mediátory zánětu fyziologie   MeSH
• předčasná porodní činnost imunologie   metabolismus   MeSH
• progesteron fyziologie   MeSH
• těhotenství MeSH
• zánět metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Postpartum depression affects 10-15 % women after childbirth. There is no currently generally accepted theory about the causes and mechanisms of postpartum mental disorders. The principal hypothesis concerns the association with sudden changes in the production of hormones affecting the nervous system of the mother and, on the other hand, with the ability of receptor systems to adapt to these changes. We observed changes in steroidogenesis in the period around spontaneous delivery. We collected three samples of maternal blood. The first sampling was 4 weeks prior to term; the second sampling was after the onset of uterine contractions (the beginning of spontaneous labour); the third sampling was during the third stage of labour (immediately after childbirth). Additionally, we collected mixed umbilical cord blood. The almost complete steroid metabolome was analyzed by gas chromatography-mass spectrometry followed by RIA for some steroids. Mental changes in women in the peripartum period were observed using the Hamilton Depression Rating Scale. The local Ethics Committee approved the study. We found already the changes in androgens levels correlating with postpartum mood disorders four weeks prior to childbirth. The strongest correlations between steroid and postpartum mood change were found in venous blood samples collected from mothers after childbirth and from umbilical cord blood. The main role played testosterone, possibly of maternal origin, and estrogens originating from the fetal compartment. These results suggest that changes in both maternal and fetal steroidogenesis are involved in the development of mental changes in the postpartum period. Descriptions of changes in steroidogenesis in relation to postpartum depression could help clarify the causes of this disease, and changes in some steroid hormones are a promising marker of mental changes in the postpartum period.

• MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• dospělí MeSH
• lidé MeSH
• metabolomika metody   MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• pohlavní steroidní hormony krev   MeSH
• poporodní deprese krev   diagnóza   MeSH
• radioimunoanalýza MeSH
• stupeň závažnosti nemoci MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Steroids are important markers in pregnancy. Although estimating their levels separately in umbilical arterial (UA) and venous blood (UV) enable more precise insights into the functioning fetoplacental unit compared to using mixed umbilical blood (UM), selective aspiration of UA and UV is technically more demanding than collecting UM. We measured the levels of 67 unconjugated steroids and steroid polar conjugates in UA and UV using GC-MS in 80 women giving birth within weeks 28 to 42 of gestation. The samples were sorted into three groups: women entering labor within weeks 28-32 (group A, n=19), weeks 33-37 (group B, n=19), and weeks 38-42 (group C, n=42) of gestation, respectively. The preterm labors were due to pathologies unrelated to steroid status. Most unconjugated steroids exhibited pronounced arteriovenous differences (AVD). The AVD were less distinct in more stable steroid conjugates. Most steroids positively correlate with gestational age, but unconjugated 5beta-reduced pregnanes show negative correlations, as do testosterone and androstenediol, substrates for the placental synthesis of estrogens. Tight correlations between steroids in UA and UV indicate that steroid measurements in UA, UV and UM can be accurately derived from each other, which is important for the diagnostics of steroid related diseases in newborns.

• MeSH
• arteriae umbilicales metabolismus   MeSH
• dospělí MeSH
• fetální krev metabolismus   MeSH
• lidé MeSH
• metabolom fyziologie   MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• předčasný porod krev   MeSH
• pupečník metabolismus   MeSH
• steroidy krev   MeSH
• těhotenství MeSH
• venae umbilicales metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH