Publications by authors named "Grzegorz Breborowicz"

112 Publications

Fetal growth trajectory in type 1 pregestational diabetes (PGDM) - an ultrasound study.

Ginekol Pol 2021 ;92(2):110-117

Department of Reproduction, Chair of Obstertics, Gynecology and Gynecological Oncology, Poznan University of Medical Sciences, Poland, Poland.

Objectives: Growth disorders are frequent in diabetic pregnancies. However, they are difficult to predict and capture early during pregnancy. These newborns are at risk of obesity, diabetes, and cardiovascular disease. While developing, fetal growth abnormalities are typically progressive. Therefore, capturing the earliest moment when they emerge is essential to guide subsequent obstetric management.

Material And Methods: We aimed to analyze fetal ultrasound growth trajectories in type 1 diabetics. Moreover, we aimed to establish time points when first ultrasound manifestations of fetal growth abnormalities appear and to identify factors that affect fetal growth in women with diabetes. We collected clinical and ultrasound data from 200 patients with PGDM managed in the third-referential centre for diabetes in pregnancy. During every visit, patients underwent an ultrasound examination according to a standard protocol giving 1072 ultrasound scan's records. Every ultrasound consisted of fetal weight estimation, according to the Hadlock 3 formula. Retrospectively patients were divided into three groups depending on neonatal weight. In the group of 200 patients, 60 (30%) delivered LGA and 9 (4.5%) SGA newborns.

Results: Fetal growth trajectories show different patterns among fetuses with growth abnormalities in women with type 1 diabetes. The moment, when fetal growth curves diverge, seems to take place in the second trimester, just after the 23rd week of gestation.

Conclusions: It suggests that fetal growth abnormalities in type 1 diabetes may have its roots much earlier than expected. In the first trimester, there were differences in LDL-cholesterol, total cholesterol, triglyceride levels and in insulin requirements between AGA, SGA and LGA subgroups.
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http://dx.doi.org/10.5603/GP.a2020.0136DOI Listing
January 2021

Outcome dependent twin growth curves based on birth weight percentiles for Polish population.

J Matern Fetal Neonatal Med 2020 Jul 7:1-6. Epub 2020 Jul 7.

Department of Medical Education, Poznan University of Medical Sciences, Poznan, Poland.

Objective: The objective of this study is to determine a healthy fetal growth pattern of twins from a Polish population based on an outcome-dependent growth curve.

Methods: The fetal growth data of live-born twin pregnancies between 25th and 40th week gestation in the period of 1 January 2005 to 31 March 2018 from the database of a tertiary care women's hospital in Western Poland was used to calculate birth weight percentiles. The growth curves of singletons from the same database were used as comparison. Because this study aimed for an outcome-dependent approach for the calculation of fetal growth curves, all babies born that may have high risk of unfavorable outcome were excluded. After application of all exclusion criteria, 1317 records referring to 2634 children were included in our analysis. Growth curves of singletons from the same database were used as reference for this study.

Results: A linear relationship between 10th, 50th, and 90th percentiles and gestational age were found for twins but not for singletons suggesting the different mechanisms of intrauterine growth between singleton and twin pregnancies. Week-to-week weight gain equal to or higher than 150 g in twins also predict a favorable outcome in absence of other pathologies.

Conclusion: The calculated outcome-dependent fetal growth curves for twins in this study may help in the accurate diagnosis of small or large twin fetuses for their gestational age in this Western Poland population.
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http://dx.doi.org/10.1080/14767058.2020.1786810DOI Listing
July 2020

Cortisol metabolism in pregnancies with small for gestational age neonates.

Sci Rep 2019 11 29;9(1):17890. Epub 2019 Nov 29.

Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 6 Święcickiego Street, 60-781, Poznań, Poland.

Small for gestational age (SGA) newborns are often born from hypertensive pregnancies. 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: 11β-hydroxysteroid dehydrogenase type 1 and 2 (11β-HSD1 and 11β-HSD2), 5α- and 5β-reductase. The enzymes' 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 5α- and 5β-reductase. The increased function of 11β-HSD2 was noted in all pre-eclamptic pregnancies. Increased function of 5α- and 5β-reductase was specific only for SGA-PE pregnancies, and the function of 5α-reductase was dependent on fetal sex. The SGA-NT pregnancies with male fetuses trended towards the higher function of renal 11β-HSD2 and 5β-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.
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http://dx.doi.org/10.1038/s41598-019-54362-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884581PMC
November 2019

Preeclampsia with Intrauterine Growth Restriction Generates Morphological Changes in Endothelial Cells Associated with Mitochondrial Swelling-An In Vitro Study.

J Clin Med 2019 Nov 15;8(11). Epub 2019 Nov 15.

Department of Pathophysiology, Poznan University of Medical Sciences, 60-806 Poznań, Poland.

Pregnancy complicated by preeclampsia (PE) and intrauterine growth restriction (IUGR) promotes endothelial cell (EC) dysfunction. Our in vitro study aimed to evaluate the endothelial cell morphology after acute and chronic exposition to medium supplemented with serum taken from healthy pregnant women and women with IUGR and IUGR with PE. In the same condition, ECs viability, proliferation, reactive oxygen species (ROS) production, and serum concentration of vascular endothelial growth factor (VEGF) were also measured. Pregnant women with IUGR and IUGR with PE-delivered babies with reduced body mass and were characterized in elevated blood pressure, urine protein loss, and reduced level of VEGF. The 24 hours of exposition did not exert any morphological changes in ECs, except the reduction in cell viability, but prolonged exposition resulted in significant morphological changes concerning mostly the swelling of mitochondria with accompanying ROS production, cell autophagy, reduced cell viability, and proliferation only in complicated pregnancies. In conclusion, the sera taken from women with IUGR and IUGR with PE show a detrimental effect on ECs, reducing their viability, proliferation, and generating oxidative stress due to dysfunctional mitochondria. This multidirectional effect might have an adverse impact on the cardiovascular system in women with IUGR and PE.
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http://dx.doi.org/10.3390/jcm8111994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912746PMC
November 2019

Nutritional behavior in pregnancy.

Ginekol Pol 2019 ;90(9):527-533

Department of Perinatology and Gynecology, Poznan University od Medical Sciences, Poland.

Objectives: The aim of the study was to characterize nutritional behavior in pregnancy.

Material And Methods: The survey study included 250 pregnant women. The survey concerned dietary behavior refferedto the type of diet, the number of meals per day, snacking between meals, consumption of meat, fish, dairy products,bread, fruits and vegetables.

Results: 88.8% of the respondents were not on a special diet. The most of the women ate more than three times a day.The women usually ate fruits and vegetables, yogurt and sweets as snacks between meals. The majority of respondentsconsumed meat and sliced meats twice or once a day with the preference of poultry. Only 17.6% of them ate fish with therecommended frequency and as much as 21.2% chose not-recommended species. Almost 29.6% of patients consumed3 to 4 servings of milk or milk products a day and 16.8% of them excluded milk. Half of the respondents declared eatingwheat bread and 24% of them chose wheat roll during pregnancy. Despite the large number of women who consumedwheat baking, a considerable amount of women chose wholemeal bread and wholemeal rolls. Nutritional behaviors werecorrelated with on education level and weight gain during pregnancy.

Conclusions: The frequency of meals was adequate for the most of pregnant women as well as recommended consumptionof meat with poultry preference. However, the inappropriate nutrition was also observed in a low consumption of fishand dairy products, a high consumption of wheat breadstuff and sweets, as well as in a small intake of milk. Education leveland weight gain during pregnancy were associated with nutritional behaviors.
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http://dx.doi.org/10.5603/GP.2019.0090DOI Listing
May 2020

Serum endocan concentration and its correlation with severity of hypertensive disorders in pregnancy.

J Matern Fetal Neonatal Med 2020 Jul 2;33(14):2313-2319. Epub 2018 Dec 2.

Department of Perinatology and Gynecology, Poznan University of Medical Sciences, Poznań, Poland.

Endocan plays a role in the development of vascular tissue in health and disease and is an indicator of endothelial cells activation and angiogenesis. The aim of this study was to investigate the relationship between endocan serum levels and various types of hypertensive disorders in pregnant women. We created three study groups (preeclampsia [ = 60], chronic hypertension [ = 39], gestational hypertension [ = 58]) and the control group consisting of 59 healthy pregnant women. The endocan serum concentration was assessed using commercially available ELISA kit. There were no statistically significant differences in endocan serum levels (pg/mL) in each study group compared to controls. The multiple regression did not reveal significant differences between endocan levels in each study group after adjustment for prepregnancy BMI. We did not find any significant correlations between the endocan serum level and patients' age, gestational age (GA) at sample collection, prepregnancy BMI, systolic blood pressure, diastolic blood pressure, and 24-hour urinary protein excretion in each analyzed group. Moreover, in the preeclamptic participants, we did not observe a significant relationship between the endocan concentration and the features indicating the severity of the disease other than elevated blood pressure. There were no differences in endocan serum level in preeclampsia subgroups: early-onset versus late-onset and mild versus severe preeclampsia. Endocan is not involved in the pathogenesis of hypertensive disorders in pregnant women and could not be regarded as a marker of endothelial dysfunction in these cases.
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http://dx.doi.org/10.1080/14767058.2018.1548597DOI Listing
July 2020

Uterine arteriovenous malformation - diagnosis and management.

Ginekol Pol 2018 ;89(5):276-279

Poznan University of Medical Sciences, Polna St. 33, 60-535 Poznan, Poland.

Uterine arteriovenous malformations are uncommon but potentially life-threatening conditions. 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 in-creasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, caesarean delivery and curettage. This paper presents the review of the literature considered epidemiology, pathophysiology, diagnostic methods and treatment options. Unexplained uterine bleeding should be always an indication for colour Doppler ultrasonography and the presence of arteriovenous malformation should be always excluded.
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http://dx.doi.org/10.5603/GP.a2018.0047DOI Listing
September 2018

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

Ann Clin Biochem 2019 01 25;56(1):82-89. Epub 2018 Jun 25.

1 Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poznań, Poland.

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.
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http://dx.doi.org/10.1177/0004563218783789DOI Listing
January 2019

Differences in the Expression of TLR-2, NOD2, and NF-κB in Placenta Between Twins.

Arch Immunol Ther Exp (Warsz) 2018 Dec 23;66(6):463-470. Epub 2018 May 23.

Chair and Department of Oncologic Pathology and Prophylactics, Greater Poland Cancer Center, Poznań University of Medical Sciences and Department of Oncologic Pathology, Poznan, Poland.

Dizygotic twins share the same type of genetic relationship as non-twin siblings. Whereas monozygotic (MZ) twins are considered to have identical genetic material, they still differ. There is a number of reasons for early MZ twin discordance, including differences in the in utero environment, stochasticity, genetic mosaicism, and epigenetic factors. During gestation, the efficient innate immune system is of utmost importance. Our study was based on immunohistochemical evaluation of the differences in innate immune protein expression (TLR-2, NOD2, and NF-κB) in the 95 placentas between twins. Our study revealed statistical significant differences between diamniotic-dichorionic and monoamniotic-dichorionic twins. Monoamniotic-monochorionic twins exhibited no significant differences in protein expressions. To identify epigenetic factors causing the differences between twins, we made a series of comparisons with clinical data. The study revealed more cases with infections, miscarriages, in vitro fertilization, and premature rupture of membranes within the group with higher differences level of NF-κB, NOD2 and TLR-2 between twins. In case of twin-to-twin transfusion syndrome, there were no significant differences in innate immune protein expressions between twins. These results show that dissimilar genetic material and separate in utero environment promote discordance in innate immune protein expressions between twins. Moreover, additional blood flow between twins may be favorable in life-threatening conditions ensuring similar microenvironment.
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http://dx.doi.org/10.1007/s00005-018-0514-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245244PMC
December 2018

Acquired uterine arteriovenous malformation - a diagnostic dilemma.

Ginekol Pol 2018 ;89(4):227-8

Poznan University of Medical Sciences, Polna St. 33, 60-535 Poznań, Poland.

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.
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http://dx.doi.org/10.5603/GP.a2018.0039DOI Listing
July 2018

Maternal Serum Endocan Concentration in Pregnancies Complicated by Intrauterine Growth Restriction.

Reprod Sci 2019 03 9;26(3):370-376. Epub 2018 May 9.

1 Department of Perinatology and Gynecology, Poznan University of Medical Sciences, Poznan, Poland.

Objectives: Endocan plays a role in the development of vascular tissue in health and disease and is an indicator of endothelial cells activation and angiogenesis. Therefore, this study aimed to investigate the relationship between maternal endocan serum level and intrauterine growth restriction (IUGR) as well as ultrasound Doppler flow measurements indicating placental insufficiency.

Methods: This study included a group of women with IUGR (n = 37) and a group of healthy pregnant women (controls, n = 37). The endocan serum concentrations were assessed using commercially available enzyme-linked immunosorbent assay kit. Every woman underwent an ultrasound examination with Doppler flow measurements of the uterine arteries, umbilical vessels, and fetal middle cerebral artery. We used the cerebroplacental ratio (CPR) to determine placental insufficiency.

Results: We found significant differences in median (interquartile) endocan serum level (pg/mL) between study and control groups (464 [374-532] vs 339 [189-496], respectively; P < .001). The endocan serum level correlated neither with umbilical cord blood gases nor with Apgar score. Ultrasound Doppler findings revealed significant differences in middle cerebral artery pulsatility index (PI), umbilical artery PI, CPR, as well as mean uterine arteries PI between IUGR group and controls. In the study group, we found significant correlations between the serum endocan and CPR ( R = 0.56, P < .001) as well as between serum endocan and mean uterine arteries PI ( R = 0.46, P = .006).

Conclusion: Endocan is likely involved in the pathogenesis of IUGR in pregnant women and possibly is a useful marker of endothelial dysfunction in these cases.
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http://dx.doi.org/10.1177/1933719118773480DOI Listing
March 2019

Relationship between the von Willebrand Factor Plasma Concentration and Ultrasonographic Doppler Findings in Pregnancies Complicated by Hypertensive Disorders: A Pilot Study.

Gynecol Obstet Invest 2018 5;83(3):252-258. Epub 2018 Apr 5.

Department and Division of Perinatology and Gynecology, Poznan University of Medical Sciences, Poznan, Poland.

Background/aims: Recent evidence suggests that impaired cytotrophoblast proliferation and migration are major factors responsible for the development of hypertension in pregnancy. Studies report that von Willebrand factor (vWf) is a specific endothelial damage plasma marker. The aim of this study was to evaluate the relationship between vWf maternal plasma concentration and maternal and fetal Doppler flow measurements in pregnancies complicated by hypertension. It may provide additional insight into the pathophysiology of pregnancy-related hypertension and show the potential method for disease prevention and therapy.

Methods: We created 3 study groups: pregnant women with chronic hypertension (n = 10), gestational hypertension (n = 18), preeclampsia (n = 21), and control (22 healthy pregnant women). Every woman underwent ultrasound Doppler flow measurements performed simultaneously with venous blood collection. The vWf plasma concentrations were assessed using the commercially available enzyme-linked immunosorbent assay kit.

Results: The preeclampsia group had significantly higher vWf plasma concentrations in those patients with ultrasonographic features of placental insufficiency than in those without these characteristics (638 ± 208 vs. 377 ± 74 ng/mL; p < 0.017).

Conclusion: Our results may confirm the arrangement and severity of endothelial damage in preeclamptic patients and may have identified those patients with a significantly higher risk of developing cardiovascular disease.
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http://dx.doi.org/10.1159/000488290DOI Listing
September 2018

Increased cortisol metabolism in women with pregnancy-related hypertension.

Endocrine 2018 07 2;61(1):125-133. Epub 2018 Apr 2.

Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 6 Święcickiego Street, Poznań, 60-781, Poland.

Purpose: The 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.

Methods: We 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).

Results: We 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.

Conclusions: The 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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http://dx.doi.org/10.1007/s12020-018-1586-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997110PMC
July 2018

The agonistic autoantibodies to the angiotensin II type 1 receptor in pregnancies complicated by hypertensive disorders.

J Matern Fetal Neonatal Med 2019 Apr 13;32(7):1219-1223. Epub 2017 Nov 13.

a Department of Perinatology and Gynecology, Division of Perinatology and Gynecology , Poznan University of Medical Sciences , Poznań , Poland.

The etiology and pathogenesis of pregnancy-related hypertensive disorders is complex and multifactorial. The aim of our study is the investigation of the differences in the autoantibodies against angiotensin II type 1 receptor (AT1-AA) titers among pregnant patients with chronic hypertension, gestational hypertension, and preeclampsia compared to the healthy pregnant women. We created three study groups (preeclampsia [ = 16], chronic hypertension [ = 13], gestational hypertension [ = 17]) and the control group consisting of 17 healthy pregnant women. Every compared group was matched for mother's age, parity, prepregnancy BMI, and gestational age at time of recruitment into study. The autoantibodies titer were assessed using commercially available ELISA kit. We found a statistically higher AT1-AA titer in the group of patients with gestational hypertension (GH) and preeclampsia (PE) compared to healthy normotensive pregnant women (median 9.6 versus 7.8 ng/ml,  = .01 and 10.9 ng/ml versus 7.8 ng/ml,  = .02, respectively). There was no correlation between blood pressure values and AT1-AA titer in any group. We found no correlation in group with preeclampsia between urinary protein excretion and AT1-AA titer ( = .23, R = 0.32). We assume that pregnancy-related hypertensive disorders might be autoimmune diseases and AT1-AA contribute to the pathophysiology of the disease. Our study may have some therapeutic implications and shows the necessity of new research into the mechanisms involved in the production of AT1-AA. Such investigations might enable to inhibit the formation of these autoantibodies or elaborate another method for AT1-AA removal.
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http://dx.doi.org/10.1080/14767058.2017.1400006DOI Listing
April 2019

Prenatal and postnatal detection of congenital heart diseases.

Ginekol Pol 2017 ;88(9):515-516

Department of Perinatology and Gynecology, Poznan University of Medical Sciences, Polna St. 33, 60-535, Poznań, Poland.

Congenital heart defects are among the most common birth defects and represent a major challenge in prenatal diagnosis and therapy of a newborn.
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http://dx.doi.org/10.5603/GP.a2017.0094DOI Listing
July 2018

Screening for trisomy 21 based on maternal age, nuchal translucency measurement, first trimester biochemistry and quantitative and qualitative assessment of the flow in the DV - the assessment of efficacy.

Ginekol Pol 2017 ;88(9):481-485

Department of Obstetrics and Perinatology, Medical University of Warsaw, Zwirki i Wigury Str 63a, 02-091, Warsaw, Poland.

Objectives: The aim of the study was to compare effects of addition of two methods of ductus venosus (DV) flow assessment: qualitative - the assessment of shape of the A-wave (positive or negative), and quantitative - based on the pulsatility index for veins (DVPI) to the basic screening for trisomy 21 at 11 to 13 + 6 weeks of pregnancy.

Material And Methods: The ultrasound examination was performed in 8230 fetuses in singleton pregnancies at 11- -13 + 6 wks, as a part of a routine screening for chromosomal defects. In DV A-wave was assessed and DVPI was calculated. After the scan blood sample was taken for first trimester biochemistry (BC). Risk for chromosomal defects was calculated and high-risk patients were offered an invasive test for karyotyping.

Results: Basic screening with following combination of markers: MA, NT and BC provided lowest detection rate (DR) 87.50% for FPR = 6.94%. After adding qualitative DV A-wave assessment DR increased to 88.75% for FPR = 5.65%. The best DR = 93.75% for FPR = 5.55% was achieved when quantitative DVPI was added. The application of the Receiver Operating Curves curve confirmed validity of the addition of DV flow assessment to the screening model. The highest diagnostic power of the test was achieved when DVPI was added, with the ROC AUC of 0.974.

Conclusions: The assessment of DV flow performed at 11-13 + 6 weeks increases DR for trisomy 21 and reduces FPR. The screening model based on the quantitative DV flow analysis (DVPI) gives better results compared to the qualitative flow assessment.
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http://dx.doi.org/10.5603/GP.a2017.0088DOI Listing
July 2018

HSD11B2, RUNX3, and LINE-1 Methylation in Placental DNA of Hypertensive Disorders of Pregnancy Patients.

Reprod Sci 2017 11 12;24(11):1520-1531. Epub 2017 Feb 12.

1 Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Poznań, Poland.

Hypertensive Disorders of Pregnancy (HDsP) remain leading causes of maternal and perinatal morbidity and mortality. Growing evidence suggests the involvement of epigenetic factors, such as gene-specific and global DNA methylation changes, both in the etiology and as an effect of HDsP. In this study, we investigated the potential association between placental DNA methylation status in selected CpGs of HSD11B2 cortisol level controlling gene, RUNX3 tumor suppressor gene, and long interspersed nucleotide element-1 (LINE-1) repetitive elements and HDsP-preeclampsia (PE), gestational hypertension (GH), and chronic hypertension (CH). Methylation-specific polymerase chain reaction (MSP) and pyrosequencing (PSQ) were used to analyze placental DNA methylation. Plasma and urine cortisol and cortisone levels were measured using high performance liquid chromatography with fluorescence detection (HPLC-FLD), whereas serum progesterone level was determined by electrochemiluminescence immunoassay. The mean percentage of HSD11B2, RUNX3, and LINE-1 methylation was not altered in the placentas of patients with HDsP, as compared to the controls. However, among patients from PE, GH, and CH groups, several significant correlations were observed between the methylation status of HSD11B2, RUNX3, or LINE-1 and children's birth weight, gestational age at delivery, mother's age, and body mass index as well as hormones levels. These results indicate lack of association between methylation status of HSD11B2, RUNX3, or LINE-1 repetitive elements and HDsP. However, association of these parameters with some clinical variables may suggest the role of placental DNA methylation in fetal development and should be further explored.
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http://dx.doi.org/10.1177/1933719117692043DOI Listing
November 2017

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

J Pharm Biomed Anal 2017 Jun 21;140:174-181. Epub 2017 Mar 21.

Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 6 Święcickiego Street, Poznań 60-781, Poland. Electronic address:

Cortisol (F) and cortisone (E) are metabolized to A-ring reduced metabolites in the reactions catalyzed by 5α- and 5β-reductase. 5α-tetrahydrocortisol (alloTHF) and 5β-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: 11β-hydroxysteroid dehydrogenase type 1 and type 2 (11β-HSD1 and 11β-HSD2), as well as 5α- and 5β-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 EMA's recommendations and was proved to be useful in the analysis of clinical samples. The LLOQ of 1ng/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 5α- and 5β-metabolites. Taking alloTHE into consideration enables the thorough analysis of the glucocorticoid equilibrium in human.
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http://dx.doi.org/10.1016/j.jpba.2017.03.039DOI Listing
June 2017

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

Am J Reprod Immunol 2017 Mar;77(3)

Department of Perinatology and Gynecology, Poznan University of Medical Sciences, Poznan, Poland.

Problem: 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.

Method Of Study: Seventy-five pregnant women were enrolled in our study. We used multicolor flow cytometry for CEC and CEPC analysis and the commercial human VWF ELISA kit to measure vWf blood plasma concentration.

Results: The highest number of CECs was found in the chronic hypertension group and the lowest number in the healthy pregnant control group. The highest number of CEPCs was found in the control group and the lowest number in the chronic hypertension group. The vWf blood plasma concentration was the highest in the pre-eclampsia group. The CEPC/CEC ratio reached its lowest value in the chronic hypertension group and its highest value in the control group.

Conclusion: The number of both CECs and CEPCs as well as the vWf blood plasma concentration depends on the type of hypertension complicating the pregnancy.
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http://dx.doi.org/10.1111/aji.12625DOI Listing
March 2017

Effect of morphological and functional changes in the secundines on biometric parameters of newborns from dichorionic twin pregnancies.

Ginekol Pol 2016 ;87(11):755-762

Department of Anatomy, University School of Physical Education in Poznan, Poland.

Objectives: The aim of the study was to determine if, and to what extent, structural and functional changes of the secundines influence biometric parameters of neonates from dichorionic twin pregnancies.

Material And Methods: The study included neonates from dichorionic, diamniotic twin pregnancies, along with their secundines. Based on histopathological examination of the secundines, the mass and dimensions of the placenta, length and condition of the umbilical cord, chorionicity, focal lesions, and microscopic placental abnormalities were determined for 445 pairs of twins. Morphological development of examined twins was characterized on the basis of their six somatic traits, while birth status of the newborns was assessed based on their Apgar scores. Statistical analysis included Student t-tests, Snedecor's F-tests, post-hoc tests, non-parametric chi-squared Pearson's tests, and determination of Spearman coefficients of rank correlation.

Results: The lowest values of analyzed somatic traits were observed in twins who had placentas with velamentous or marginal cord insertion. Inflammatory lesions in the placenta and placental abruption turned out to have the greatest impact of all analyzed abnormalities of the secundines. Inflammatory lesions in the placenta were associated with lower values of biometric parameters and a greater likelihood of preterm birth. Neonates with a history of placental abruption were characterized by significantly lower birth weight and smaller chest circumference.

Conclusions: Morphological changes in the secundines have a limited impact on biometric parameters of neonates from dichorionic twin pregnancies. In turn, functional changes exert a significant effect and more often contribute to impaired fetal development.
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http://dx.doi.org/10.5603/GP.2016.0083DOI Listing
July 2018

Effects of Intrauterine Environment on the Magnitude of Differences Within the Pairs of Monozygotic and Dizygotic Twins.

Twin Res Hum Genet 2017 02 1;20(1):72-83. Epub 2016 Dec 1.

Institute of Human Genetics,Polish Academy of Sciences,Poznan,Poland.

The aim of this study was to determine the effects of intrauterine environment on the magnitude of intrapair differences in six somatic traits of monozygotic (MZ) and dizygotic (DZ) twins (1,263 pairs; 424 MZ twins and 839 DZ twins). Differences in intrauterine environments of MZ twins enforced division of the research material into four groups: (1) MZ-MC-TTTS - MZ twins from monochorionic (MC) pregnancies with twin-to-twin transfusion syndrome (TTTS), (2) MZ-MC (without TTTS)-MZ twins from MC pregnancies without TTTS, (3) MZ-DC-MZ twins from dichorionic (DC) pregnancies, and (4) DZ-DZ twins. The intrapair differences in all analyzed somatic traits, especially body weight and circumference of the chest, were the largest in the case of MZ twins from MC pregnancies with TTTS. DZ twins were the group presenting with the second largest intrapair differences in the analyzed traits. At the end of pregnancy, that is, in lunar months 9 and 10, the magnitude of intrapair differences in all traits of twins from this group was significantly greater than in MZ twins from both MC and DC pregnancies. Irrespective of the analyzed period, the least evident, statistically insignificant intrapair differences in the studied traits were documented in the case of MZ twins from MC pregnancies without TTTS and twins from DC pregnancies. These findings imply that the differentiating effect of intrauterine environment is associated with the occurrence of TTTS, rather than with chorionicity, as postulated previously.
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http://dx.doi.org/10.1017/thg.2016.91DOI Listing
February 2017

Variants of HSD11B2 gene in hypertensive disorders of pregnancy.

J Matern Fetal Neonatal Med 2017 Jun 10;30(11):1360-1365. Epub 2016 Aug 10.

a Department of Physical Pharmacy and Pharmacokinetics , Poznan University of Medical Sciences , Poznań , Poland.

Introduction: One of the hypotheses concerning the etiology of gestational hypertension (GH) and pre-eclampsia (PE) assumes that they develop as a result of placenta malfunctioning at the early stage of pregnancy. Placental dysfunction is also associated with the decreased activity of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), which in normal pregnancy protects the fetus from the excess of maternal cortisol.

Objective: The aim of the study was to analyze the sequence of HSD11B2, a gene that encodes 11β-HSD2, searching for mutations and haplotypes associated with the increased risk of GH or PE. Those may serve as potential genetic markers of GH and PE.

Methods: The study was performed in case-control structure and included pregnant women (in third trimester) diagnosed with: GH, PE or being normotensive (control group). The research comprised DNA sequencing of HSD11B2, followed by restriction analysis (PCR-RFLP). The linkage disequilibrium analysis and haplotype-based case-control analysis were performed.

Results: Six sequence variations were observed. Four mutations were indicated in the coding region of HSD11B2 and the other two in 3'-UTR. Two SNPs: c.468C > A and c.534G > A were found to be in total disequilibrium.

Conclusions: High variability in HSD11B2 sequence was indicated in the study population, but the relevance of observed SNPs to GH or PE development was not confirmed.
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http://dx.doi.org/10.1080/14767058.2016.1214125DOI Listing
June 2017

Smith-Lemli-Opitz Syndrome- a challenging prenatal diagnosis.

Ginekol Pol 2016 ;87(1):76-8

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.
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http://dx.doi.org/10.17772/gp/61327DOI Listing
July 2018

STUMP - atypowy mięśniak macicy - mimikra guza złośliwego?

Ginekol Pol 2016 ;87(2):148-52

Katedra Perinatologii i Ginekologii, Uniwersytet Medyczny w Poznaniu, Polska.

This study describes the ultrasound diagnostic process and management in a patient with a unique, rare form of fibroids, i.e. the atypical variant. According to the WHO definition, an atypical uterine myoma cannot be histologically unambiguously diagnosed as benign or malignant. Atypical leiomyomas are characterized by moderate or high quantity of pleomorphic atypical tumor cells, with a small number of mitotic divisions and lack of coagulative necrosis in the tumor. They have a low rate of extrauterine, intraabdominal recurrence, with a negligible risk for distant metastases. Due to the fact the atypical variant of leiomyomas is very rare, it presents a significant diagnostic challenge for obstetricians. The most reliable diagnosis can be made only on the basis of the histopathological examination. In this paper, we present a case of a patient in whom an echo with the diameter of 92 mm and a heterogeneous echogenicity with visible anechoic fields were discovered in the uterine fundus. HD color Doppler demonstrated high vascularization within the tumor, peripherally as well as centrally. The peripheral and central vascularization was rated at 4/4 points on a scale by Exacoustos. The tumor in the uterus met the criteria of high probability of malignancy i.e. 8 points on the vascular scale (power Doppler scale ≥ 7 pts.), solid tumor and a size over 8 cm. Blood flow velocity and vascular resistance in the tumor vessels were evaluated (PSV - 5.76 cm/s, ED - 3.16 cm/s, RI - 0.45 S / D - 1.82). Blood flow in the tumor presented low resistance. Hysterectomy without oophorectomy, with an intraoperative histopathological examination, was performed, and a fibroid was confirmed. The tumor was soft, yellow, with small and medium level of dispersed atypia in microscopic examination. There was no necrosis or mitotic figures. The histopathological image confirmed the atypical leiomyoma of low risk of recurrence. Atypical fibroids are rare in gynecological oncology and they do not have the characteristic clinical course. Furthermore, they do not show the typical characteristics during imaging studies, including ultrasound screening, Sometimes, due to the sonographic image, they should be differentiated from sarcomas. Also, it is necessary to exclude malignancy because of their ambiguous histological characteristics.
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http://dx.doi.org/10.17772/gp/61712DOI Listing
July 2018

Perinatal outcome according to chorionicity in twins - a Polish multicenter study.

Ginekol Pol 2016 ;87(5):384-9

Objectives: The aim of the study was to analyze the perinatal outcome of twin gestations and estimate the influence of chorionicity on the outcome in a large cohort of twin pregnancies in Poland.

Material And Methods: A retrospective analysis of 465 twin deliveries in 6 Polish centers in 2012 was conducted. Baseline characteristics, the course of pregnancy and labor, as well as the neonatal outcome were analyzed in the study group and according to chorionicity.

Results: A total of 356 twin pregnancies were dichorionic (DC group) (76.6%), and 109 were monochorionic (MC group) (23.4%). There were no differences in the occurrence of pregnancy complications according to chorionicity, except for IUGR of at least one fetus (MC 43.1% vs. DC 34.6%; p = 0.003). 66.5% of the women delivered preterm, significantly more in the MC group (78% vs. 62.9%; p = 0.004). Cesarean delivery was performed in 432 patients (92.9%). Mean neonatal birthweight was statistically lower in the MC group (2074 g vs. 2370 g; p < 0.001). Perinatal mortality of at least one twin was 4.3% (2.8% in the DC group vs. 9.2% in the MC group; p = 0.004). Neonatal complications, including NICU admission, respiratory disorders, and infections requiring antibiotic therapy, were significantly more often observed among the MC twins.

Conclusions: The overall perinatal outcome in the presented subpopulation of Polish twins and its dependence on cho-rionicity is similar to the reports in the literature. Nevertheless, the rates of preterm and cesarean deliveries remain higher. It seems that proper counselling of pregnant women and education of obstetricians may result in reduction of these rates.
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http://dx.doi.org/10.5603/GP.2016.0009DOI Listing
July 2018

[Placenta percreta--a severe obstetric complication despite correct diagnosis--a case report].

Ginekol Pol 2015 Dec;86(12):951-6

This paper presents a case of a pregnant woman with a history of two cesarean sections. The patient was admitted to the hospital because of vaginal bleeding. The ultrasound revealed a placenta covering the internal os. The placenta was characterized by heterogeneous echogenicity with visible irregular hypoechogenic areas and blurred border between the placenta and the cervix. Rich vascularity was observed on the border of the placenta, urethra and the urinary bladder. Cystoscopy showed severe congestion around the urethra. On the back wall of the bladder a slightly increased vascularity was seen, which did not allow to confirm or exclude placental ingrowth in the urinary bladder. At 38 weeks, the patient was scheduled for an elective cesarean section. A classic perpendicular incision and leaving the placenta in the uterine cavity were proposed. After opening the abdomen, a strong vascularization in the region of lower part of the uterus and the urinary bladder was seen. Uterine incision in the fundus and the posterior wall was performed. A female fetus (weight: 2950g, Apgar: 10,10) was born. Then, the umbilical cord was ligated with non-absorbable suture and inserted back into the uterus. However, due to the presence of abundant and persistent vaginal bleeding during the next few minutes, conversion to obstetric hysterectomy was required. During relaparotomy fragments of the placenta appeared on the right side after sliding the urinary bladder. The bladder and the left ureter were damaged during surgery. The urinary bladder was sewn after removal of the uterus. Next, the urologist anastomosed end-to-end the left ureter on the pigtail catheter In the third hour of operation, cardiac arrest was caused by ventricular fibrillation. Immediate resuscitation with defibrillation allowed to restore normal function of the cardiovascular system. Total blood loss during the operation was 3000-4000 ml. During surgery 10 units of packed RBCs, 7 units of fresh frozen plasma, and 4 units of cryoprecipitate were transfused. The patient received antibiotics and anticoagulation therapy. Polyuria was diagnosed in the following days of puerperium, accompanied by electrolyte disturbances in serum and urine. The patient was treated with vasopressin and the electrolyte disturbances were corrected. On day 10 postpartum, the urinary catheter was removed, and clear significant improvement and stabilization of renal function and patient health were obtained. The patient was discharged from the hospital on day 19 of the puerperium. In summary it is clear that the steadily increasing rate of cesarean deliveries may result in the future in an increased number of abnormal placentation cases. Abnormal placentation is one of the most important risk factors of severe obstetric complications, including perinatal massive hemorrhage, which can lead to abnormal organ perfusion with cardiac arrest. Therefore, prenatal diagnosis and identification of abnormal placentation are vital in order to plan adequately the date, place, and mode of delivery as well as to ensure the availability of highly qualified specialists in the field of obstetrics and anesthesia, and organize sufficient amount of blood products and blood substitutes.
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http://dx.doi.org/10.17772/gp/60833DOI Listing
December 2015