Agata Szpera-Goździewicz

Prenatal diagnosis of vasa previa

Abstract Vasa previa is a rare condition in which unsupported by the placenta, umbilical cord blood vessels runs within the placental membranes between internal os of the cervix and presenting part of the fetus. We report an antenatal diagnostic procedure and management of a patient with low-lying placenta and velamentous cord insertion near to the internal os with two large fetal blood vessels coursing between the internal cervical os and fetal presenting part. An elective cesarean section was performed at 36 weeks gestation.

Detailed analysis of cortisol, cortisone and their tetrahydro- and allo-tetrahydrometabolites in human urine by LC–MS/MS

&NA; Cortisol (F) and cortisone (E) are metabolized to A‐ring reduced metabolites in the reactions catalyzed by 5&agr;‐ and 5&bgr;‐reductase. 5&agr;‐tetrahydrocortisol (alloTHF) and 5&bgr;‐tetrahydrocortisol (THF) are produced from F. The metabolism of E takes place in analogy to form alloTHE and THE. Up to now, the analysis of endogenous glucocorticoids did not consider alloTHE, limiting the metabolism of E to THE only. Nevertheless, such simplification can generate inaccuracy in the assessment of the function of enzymes crucial for glucocorticoids metabolism: 11&bgr;‐hydroxysteroid dehydrogenase type 1 and type 2 (11&bgr;‐HSD1 and 11&bgr;‐HSD2), as well as 5&agr;‐ and 5&bgr;‐reductase. The paper presents the new LC–MS/MS method for the simultaneous analysis of F and E with their tetrahydro‐ (THF and THE) and allo‐tetrahydrometabolites (alloTHF and alloTHE) in urine. The method was fully validated and allows determining both the unconjugated and total concentrations of urinary glucocorticoids. The method meets the EMAs recommendations and was proved to be useful in the analysis of clinical samples. The LLOQ of 1 ng/mL allows the determination of free urinary F, E, THF and THE, but not alloTHF and alloTHE, in samples obtained from pregnant women. The range of concentrations is wide enough for the analysis of total levels of F, E, THF, alloTHF, THE and alloTHE. The undisputed advantage of the method, distinguishing it among others, is the ability to determine F and E and their both 5&agr;‐ and 5&bgr;‐metabolites. Taking alloTHE into consideration enables the thorough analysis of the glucocorticoid equilibrium in human. HighlightsThorough analysis of glucocorticoid balance.Versatility: determination of free and total amounts of steroids.Metabolism of cortisone without simplification.Novelty: analysis of allo‐tetrahydrocortisone.Full validation and reliable analysis of clinical samples.

Circulating endothelial cells, circulating endothelial progenitor cells, and von Willebrand factor in pregnancies complicated by hypertensive disorders

We tested the hypothesis that the number of both CECs and CEPCs as well as the vWf blood plasma concentration are altered in pregnant women with hypertensive disorders.

Smith-Lemli-Opitz Syndrome- a challenging prenatal diagnosis

OBJECTIVES The aim of the study was to present a case of Smith-Lemli-Opitz syndrome (SLOS) in a fetus of a 33-year-old patient. At 31 weeks of gestation, the following fetal malformations were detected on an ultrasound: atrioventricular septal defect (AVSD), aortic coarctation, shortening of the lower limbs, narrow forehead, hyperthelorism, micrognathia, anteverted nares, ambiguous genitalia, and signs of intrauterine growth restriction. The baby died 11 days after birth. Further genetic screening of the parents revealed the 7-DHCR enzyme mutation in both of them. Although the prenatal diagnosis of SLOS presents a challenge due to the fact that little is known about its prenatal phenotype but it may be vital while attempting to treat the fetus in utero.

Conservative management of placenta previa complicated by abnormal placentation.

Abstract Objective: Abnormal implantation of placenta previa is life-threatening condition. The purpose of this study was to evaluate the impact of the conservative management of pregnancies with such complication on maternal morbidity rate and the chance for uterine preservation (fertility). Methods: Eleven patients with abnormal implantation of placenta previa were analyzed prospectively. This complication was diagnosed antenatally by two-dimensional ultrasound and color flow Doppler. The following outcomes were analyzed: need for blood transfusion, admission and duration of stay in intensive care unit, infections, coagulopathies, time between cesarean section and delivery of placenta, hysterectomy and preservation of uterus. Results: Among the 20 085 women who had a singleton gestation, 11 (0.054%) were identified with placenta previa with abnormal placentation. In five patients (group A), hysterectomy was performed because of hemorrhage or placenta ablation. In six patients (group B), conservative management succeeded and placenta were preserved. In group A, placenta were delivered earlier (2 d–8 weeks) in comparison with group B (6–15 weeks). Estimated blood loss during the delayed delivery of placenta was higher in the group with hysterectomy (respectively, 450–1600 and 300–500 ml). Conclusions: Conservative management of placenta previa with abnormal implantation decreases the risk of severe hemorrhage at the time of delivery and can preserve fertility.

Acquired uterine arteriovenous malformation — a diagnostic dilemma

Uterine arteriovenous malformations are uncommon but potentially life-threatening condition. They can be congenital or acquired and should be suspected in cases of severe or persistent uterine bleeding. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, caesarean delivery and curettage. This paper presents the case of unexplained vaginal bleeding with subsequent suspicion and diagnosis of uterine arteriovenous malformation. Unexplained uterine bleeding should be always an indication for colour Doppler ultrasonography and the presence of AVM should be always excluded.

Increased cortisol metabolism in women with pregnancy-related hypertension

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.

High-performance liquid chromatography methods for the analysis of endogenous cortisol and cortisone in human urine: comparison of mass spectrometry and fluorescence detection:

Background The analysis of steroids in biological matrices is challenging. One can apply immunoassay as well as gas and liquid chromatography with various types of detection, depending on the available equipment and the experience of the analyst. The question is how the methods are interchangeable between themselves. Doubts were reported having compared immunoassays and chromatography-mass spectrometry, but there are scarce data on chromatographic methods with detection types other than mass spectrometry. Methods Here, we present the detailed comparison of two liquid chromatographic methods for the determination of free urinary cortisol and cortisone: one with fluorescence detection (high-performance liquid chromatography [HPLC-FLD]) and the other with tandem mass spectrometry (HPLC-MS/MS). The comparison was made with 199 human urine samples. The data analysis included Passing–Bablok and Deming regression, Bland–Altman test, Wilcoxon test, mountain plot and Lin’s concordance correlation coefficient. Results The validation data indicated that both methods met the requirements of the European Medicines Agency. However, the statistical analysis revealed the systematic bias between the two assays. The Passing–Bablok and the Deming tests showed that the HPLC-FLD method overestimated results for cortisol and underestimated measurements for cortisone. The Bland–Altman analysis estimated the mean differences between the methods: 18.8 nmol/L for cortisol and −16.9 nmol/L for cortisone measurement. Conclusions Both methods’ results led to the same conclusion in observational studies, but the techniques are not interchangeable. The literature data, the observations from the clinical setting and our experience clearly indicate that the future of steroid measurements will belong to chromatography coupled with mass spectrometry.

Association between the presence of autoantibodies against adrenoreceptors and hypertensive disorders in pregnancy: a pilot study

Patients and methods The study was performed with approval from the Bioethics Committee of the Poznan University of Medical Sciences, Poznań, Poland (No. 563/13). Each woman re‐ ceived detailed information about the project and provided informed consent before partici‐ pating in the study. A case control study was conducted in the De‐ partment of Perinatology and Gynecology of the Poznan University of Medical Sciences be‐ tween November 2014 and March 2016. We an‐ alyzed the following groups of women—preg‐ nant patients with preeclampsia (n = 16), those with CH (n = 13), and those with GH (n = 17). The control group consisted of 17 healthy, normo‐ tensive pregnant women. The compared groups were matched for the mother’s age, parity, pre‐ pregnancy body mass index, and gestational age at the time of recruitment into the study and blood collection. Hypertensive disorders were defined in accor‐ dance with the National High Blood Pressure Ed‐ ucation Program Working Group on High Blood Pressure in Pregnancy classification.4 The exclu‐ sion criteria for the control and study groups were systemic diseases related to endothelial dysfunc‐ tion (eg, kidney diseases, diabetes mellitus, ath‐ erosclerotic diseases, inflammatory/infectious Introduction There are numerous factors consid‐ ered to cause pregnancy ‐related hypertension, in‐ cluding genetic, immunological, environmental, and behavioral ones, as well as those related to endothelial dysfunction. The immune system can identify foreign anti‐ gens and eliminate them from the human body. In the case of immune control mechanism fail‐ ure, the immune system may be directed at a self‐ ‐antigen. More recent data have shown character‐ istic molecular targets of autoantibodies common in patients with preeclampsia and essential hy‐ pertension, potentially explaining how elevated autoantibody titers might contribute to hyper‐ tension. Wallukat and Schimke1 demonstrated the presence of autoantibodies against α1‐, β1‐, and β2 ‐adrenoreceptors (anti –α1 ‐ARs, anti –β1‐ ‐ARs, and anti –β2 ‐ARs, respectively) that bind to the second extracellular loop of receptors and are highly prevalent in the serum of hyperten‐ sive patients. It is well known that neoangiogenesis is a mul‐ tistep process closely associated with endothelial cell migration and proliferation.2 Stimulation of α1 ‐ARs localized in endothelial cells leads to neg‐ ative regulation of angiogenesis, whereas β2 ‐ARs stimulate neoangiogenesis. Moreover, in hyperten‐ sion characterized by the impairment of angiogen‐ esis, the α1 ‐AR tone is higher than that of β2 ‐ARs. 3

Prenatal and postnatal detection of congenital heart diseases

Congenital heart defects are among the most common birth defects and represent a major challenge in prenatal diagnosis and therapy of a newborn.