Publications by authors named "Ulrich Pecks"

50 Publications

Management of Intrahepatic Cholestasis of Pregnancy: Recommendations of the Working Group on Obstetrics and Prenatal Medicine - Section on Maternal Disorders.

Geburtshilfe Frauenheilkd 2021 Aug 9;81(8):922-939. Epub 2021 Aug 9.

Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Gynäkologie und Geburtshilfe, Kiel, Germany.

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease specific to pregnancy. The cardinal symptom of pruritus and a concomitant elevated level of bile acids in the serum and/or alanine aminotransferase (ALT) are suggestive for the diagnosis. Overall, the maternal prognosis is good. The fetal outcome depends on the bile acid level. ICP is associated with increased risks for adverse perinatal outcomes, including preterm delivery, meconium-stained amniotic fluid, and stillbirth. Acute fetal asphyxia and not chronic uteroplacental dysfunction leads to stillbirth. Therefore, predictive fetal monitoring is not possible. While medication with ursodeoxycholic acid (UDCA) improves pruritus, it has not been shown to affect fetal outcome. The indication for induction of labour depends on bile acid levels and gestational age. There is a high risk of recurrence in subsequent pregnancies.
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http://dx.doi.org/10.1055/a-1386-3912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354365PMC
August 2021

Induction of Labour. Guideline of the DGGG, OEGGG and SGGG (S2k, AWMF Registry No. 015-088, December 2020).

Geburtshilfe Frauenheilkd 2021 Aug 9;81(8):870-895. Epub 2021 Aug 9.

Klinik für Gynäkologie, St. Joseph Krankenhaus, Berlin Tempelhof, Berlin, Germany.

The aim of this official guideline published and coordinated by the German Society of Gynaecology and Obstetrics (DGGG) in cooperation with the Austrian Society of Gynaecology and Obstetrics (OEGGG) and the Swiss Society of Gynaecology and Obstetrics (SGGG) is to provide a consensus-based overview of the indications, methods and general management of induction of labour by evaluating the relevant literature. This S2k guideline was developed using a structured consensus process which included representative members from various professions; the guideline was commissioned by the guidelines commission of the DGGG, OEGGG and SGGG. The guideline provides recommendations on the indications, management, methods, monitoring and special situations occurring in the context of inducing labour.
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http://dx.doi.org/10.1055/a-1519-7713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354342PMC
August 2021

Babu and Magon uterine closure technique during cesarean section: A randomized double-blind trial.

J Obstet Gynaecol Res 2021 Sep 15;47(9):3186-3195. Epub 2021 Jun 15.

Department of Obstetrics and Gynecology, University Hospitals Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Aim: We compared the effectiveness of the Babu and Magon uterine closure technique and unlocked double-layer uterine closure on the integrity and thickness of the uterine scar.

Methods: A randomized double-blind trial was performed at Hazrat-e Rasoul -e-Akram Hospital, Tehran, Iran, from March 2018 to December 2019, in 72 pregnant women who were candidates for cesarean section for the first time. Women were randomly assigned to the Babu and Magon uterine closure technique (intervention group, n = 34) or double-layer closure of the uterine incision (control group, n = 38). The primary outcome of the study was the frequency of myometrial defects at the site of the scar (niche), and a large niche. Secondary outcomes, including the time taken for uterine closure and postpartum hemorrhage (early and late), were compared between groups.

Results: Adjacent myometrium thickness (AMT) between the two groups was not statistically significant. A niche was reported in 23.5% (8/34) and 50% (19/38) of women in the intervention and controls, respectively (p = 0.02). A large niche was reported in 2.9% (1/34) and 23.7% (9/38) of women in the intervention and controls, respectively (p < 0.01). The duration of uterine closure was not statistically significant between the two groups. Hemoglobin levels did not differ significantly between groups during the first 24 h post-surgery.

Conclusion: The results of the study showed that the technique of uterine closure is one of the main potential determinants of myometrial healing. The Babu and Magon uterine closure technique seems to lead to tissue alignment during suturing and consequently cause better myometrial healing, although this issue calls for well-founded longer studies of appropriate design.
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http://dx.doi.org/10.1111/jog.14889DOI Listing
September 2021

Mucinous Cystic Neoplasm of Pancreas in a Pregnant Woman Presenting with Severe Anemia and Gastric Bleeding: Case Report and Review of the Literature.

Healthcare (Basel) 2021 May 6;9(5). Epub 2021 May 6.

Department of Gynecology and Obstetrics, Campus Kiel, University Medical Center UKSH, Arnold-Heller-Straße 3, Haus C, 24105 Kiel, Germany.

Mucinous cystic neoplasms of the pancreas are uncommon and especially their occurrence during pregnancy is an extremely rare event which necessitates an individualized and interdisciplinary management. A 33-year old woman was referred to our department during her third trimester of pregnancy (34th week of gestation) with severe anemia and tarry stools. Based on gastroscopic findings, our interdisciplinary team suspected a gastrointestinal stromal tumor and therefore indicated a prompt delivery via cesarean section completed with an oncological resection of the neoplasm. Histological examination subsequently showed a mucinous cystic neoplasm of the pancreas with no evidence of malignancy. To review the prevalence of mucinous cystic neoplasms and to discuss diagnosis and treatment during pregnancy. Moreover, we critically value the indication of preterm delivery and the oncological procedure in the perspective of outcome for mother and infant. A bleeding gastrointestinal tumor during pregnancy represents a life-threatening risk for mother and infant and requires an immediate interdisciplinary treatment. The urgency and radicality of the therapy should be adapted according to individual findings. As our patient's tumor was suspected of having a malignant progression, an extensive surgical intervention was necessary.
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http://dx.doi.org/10.3390/healthcare9050540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148137PMC
May 2021

Profiling of intact blood proteins by matrix-assisted laser desorption/ionization mass spectrometry without the need for freezing - Dried serum spots as future clinical tools for patient screening.

Rapid Commun Mass Spectrom 2021 Jul;35(14):e9121

Proteome Center Rostock, Medical Faculty and Natural Science Faculty, University of Rostock, Schillingallee 69, Rostock, 18057, Germany.

Rationale: To open up new ways for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)-based patient screening, blood serum is the most preferred specimen because of its richness in patho-physiological information and due to ease of collection. To overcome deleterious freeze/thaw cycles and to reduce high costs for shipping and storage, we sought to develop a procedure which enables MALDI-MS protein profiling of blood serum proteins without the need for serum freezing.

Methods: Blood sera from patients/donors were divided into portions which after pre-incubation were fast frozen. Thawed aliquots were deposited on filter paper discs and air-dried at room temperature. Intact serum proteins were eluted with acid-labile detergent-containing solutions and were desalted by employing a reversed-phase bead system. Purified protein solutions were screened by MALDI-MS using standardized instrument settings.

Results: MALDI mass spectra from protein solutions which were eluted from filter paper discs and desalted showed on average 25 strong ion signals (mass range m/z 6000 to 10,000) from intact serum proteins (apolipoproteins, complement proteins, transthyretin and hemoglobin) and from proteolytic processing products. Semi-quantitative analysis of three ion pairs: m/z 6433 and 6631, m/z 8205 and 8916, as well as m/z 9275 and 9422, indicated that the mass spectra from either pre-incubated fast-frozen serum or pre-incubated dried serum spot eluted serum contained the same information on protein composition.

Conclusions: A workflow that avoids the conventional cold-chain and yet enables the investigation of intact serum proteins and/or serum proteolysis products by MALDI-MS profiling was developed. The presented protocol tremendously broadens the clinical application of MALDI-MS and simultaneously allows a reduction in the costs for storage and shipping of serum samples. This will pave the way for clinical screening of patients also in areas with limited access to health care systems, and/or specialized laboratories.
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http://dx.doi.org/10.1002/rcm.9121DOI Listing
July 2021

[Intrahepatic cholestasis of pregnancy].

Gynakologe 2021 Apr 20:1-16. Epub 2021 Apr 20.

Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universität Düsseldorf, Düsseldorf, Deutschland.

Intrahepatic cholestasis of pregnancy (ICP) is the most frequent pregnancy-specific liver disease. It is characterized by pruritus and an accompanying elevation of serum bile acid concentrations and/or alanine aminotransferase (ALT), which are the key parameters in the diagnosis. Despite good maternal prognosis, elevated bile acid concentration in maternal blood is an influencing factor to advers fetal outcome. The ICP is associated with increased rates of preterm birth, neonatal unit admission and stillbirth. This is the result of acute fetal asphyxia as opposed to a chronic uteroplacental insufficiency. Reliable monitoring or predictive tools (e.g. cardiotocography (CTG) or ultrasound) that help to prevent advers events are yet to be explored. Medicinal treatment with ursodeoxycholic acid (UDCA) does not demonstrably reduce adverse perinatal outcomes but does improve pruritus and liver function test results. Bile acid concentrations and gestational age should be used as indications to determine delivery. There is a high risk of recurrence in subsequent pregnancies.
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http://dx.doi.org/10.1007/s00129-021-04787-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056200PMC
April 2021

Recommendations of the AGG (Task Force for Obstetrics, Section Maternal Diseases) on the Management of Maternal Hepatitis B, C and D Infection in Pregnancy.

Geburtshilfe Frauenheilkd 2021 Apr 14;81(4):390-397. Epub 2021 Apr 14.

Gynäkologie und Geburtshilfe, Universitätsklinikum des Saarlandes, Homburg, Germany.

These statements and recommendations should provide appropriate information about maternal and fetal routes of infection, screening, detection of risk factors, diagnostic procedures, treatment, birth planning and peripartum and postpartum management of maternal hepatitis infection and offer pointers for prenatal counselling and routine clinical care on delivery wards.
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http://dx.doi.org/10.1055/a-1330-7514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046515PMC
April 2021

[COVID-19 and pregnancy].

Gynakologe 2021 Mar 18:1-7. Epub 2021 Mar 18.

Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Deutschland.

From March 3 to October 13, 2020, 27 cases with diabetes comorbidity have been recorded in the CRONOS registry (Covid-19 Related Obstetric and Neonatal Outcome Study in Germany) among 262 registered women with SARS-CoV‑2 infection during their pregnancy. Of those, 21 presented with gestational diabetes, 5 with type 2 diabetes and 1 with type 1 diabetes. About half of the women were asymptomatic and were diagnosed via general screening at hospital admission. The most common symptoms were nasal congestion, cough, tiredness, malaise and changes in smell and taste. The majority of pregnant women showed a mild to moderate course, three women were admitted to the intensive care unit and none required invasive ventilation. In the type 2 diabetes group, there were two cases with late fetal death (37 and 40 weeks of gestation) and one with a malformation, an association with diabetes being most likely. Pregnant women with diabetes mellitus represent a special subgroup; 1 in 10 women in this small cohort required intensive care monitoring due to COVID-19. In addition, this case series underscores the need for unrestricted access to pregnancy care, especially in times of pandemic, for optimal perinatal outcome.
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http://dx.doi.org/10.1007/s00129-021-04784-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972008PMC
March 2021

[Update on Recommendations for SARS-CoV-2/COVID-19 During Pregnancy, Birth and Childbed].

Z Geburtshilfe Neonatol 2020 08 24;224(4):217-222. Epub 2020 Aug 24.

Klinik für Geburtsmedizin, Universitätsklinikum Jena.

With begin of the SARS-CoV-2 pandemic the german obstetric, peri-/neonatological and pediatric professional societies published recommendations for care of pregnant and newborn, as well as for necessary staff protection in March 2020 [1-3]. Because of the rapid emerging increase of knowledge an update is required. This work therefore perceives as prosecution of the existing recommendations [1-3].Worldwide national recommendations were recently compared and published in a consensual review [4]. In methodological dependence this update of recommendations comments on key questions of pre-, peri- and postnatal care at SARS-CoV-2 and COVID-19, based on publications up to 30.05.2020. Statements represent a carefully concerned expert consensus and can change contemporary as new knowledge appears.The responsibility for concrete management remains at the local medical team, decisions should be supported by these recommendations.
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http://dx.doi.org/10.1055/a-1199-6404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516367PMC
August 2020

[SARS-CoV-2 and Perinatal Aspects].

Z Geburtshilfe Neonatol 2020 08 24;224(4):181-186. Epub 2020 Aug 24.

Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel.

The novel coronavirus SARS-CoV-2 has developed into a pandemic, yet still has many unknowns. The modalities of transmission, different symptoms and manifestations as well as concomitant circumstances of the disease are insufficiently characterized. Especially patient groups in special situations like pregnant women and newborns have to be considered separately. The current knowledge about pregnancy, labor and the first days of life is characterized by particular uncertainty due to the scarce data available. However, there is currently no evidence of significant unfavorable maternal and perinatal outcome. Many pregnant women with SARS-CoV-2 infection remain asymptomatic. The possibility of vertical transmission to the child cannot be excluded with certainty. However, indications of vertical transmission were detected only in individual cases. Newborn infections are also rather rare, unspecific and usually mild, with respiratory symptoms dominating. In this article, the data available to date are examined in order to provide better information, advice and treatment for pregnant women and newborns with SARS-CoV-2 and to provide suggestions for future research.
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http://dx.doi.org/10.1055/a-1192-7437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516365PMC
August 2020

Precision Diagnostics by Affinity-Mass Spectrometry: A Novel Approach for Fetal Growth Restriction Screening During Pregnancy.

J Clin Med 2020 05 7;9(5). Epub 2020 May 7.

Department of Obstetrics and Gynecology, Medical Faculty, University of Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.

Fetal growth restriction (FGR) affects about 3% to 8% of pregnancies, leading to higher perinatal mortality and morbidity. Current strategies for detecting fetal growth impairment are based on ultrasound inspections. However, antenatal detection rates are insufficient and critical in countries with substandard care. To overcome difficulties with detection and to better discriminate between high risk FGR and low risk small for gestational age (SGA) fetuses, we investigated the suitability of risk assessment based on the analysis of a recently developed proteome profile derived from maternal serum in different study groups. Maternal serum, collected at around 31 weeks of gestation, was analyzed in 30 FGR, 15 SGA, and 30 control (CTRL) pregnant women who delivered between 31 and 40 weeks of gestation. From the 75 pregnant women of this study, 2 were excluded because of deficient raw data and 2 patients could not be grouped due to indeterminate results. Consistency between proteome profile and sonography results was obtained for 59 patients (26 true positive and 33 true negative). Of the proteome profiling 12 contrarious grouped individuals, 3 were false negative and 9 were false positive cases with respect to ultrasound data. Both true positive and false positive grouping transfer the respective patients to closer surveillance and thorough pregnancy management. Accuracy of the test is considered high with an area-under-curve value of 0.88 in receiver-operator-characteristics analysis. Proteome profiling by affinity-mass spectrometry during pregnancy provides a reliable method for risk assessment of impaired development in fetuses and consumes just minute volumes of maternal peripheral blood. In addition to clinical testing proteome profiling by affinitymass spectrometry may improve risk assessment, referring pregnant women to specialists early, thereby improving perinatal outcomes.
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http://dx.doi.org/10.3390/jcm9051374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290972PMC
May 2020

[Does Apolipoprotein B Level in Early Pregnancy Predict Excessive Gestational Weight Gain and Adverse Pregnancy Outcome?]

Z Geburtshilfe Neonatol 2020 Dec 11;224(6):348-354. Epub 2020 Mar 11.

Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-Holstein Campus Kiel, Kiel.

Introduction: Excessive maternal gestational weight gain (GWG) is a risk factor for maternal and fetal complications. The lipid profile changes physiologically during pregnancy. Weight gain can affect lipid metabolism. The hypothesis of the study was that apoB levels early in pregnancy are associated with excessive GWG and predictive for adverse outcomes.

Methods: Out of 547 patients there were 95 women with inadequate GWG, 171 with adequate GWG, and 281 with excessive GWG. Out of 581 patients there were 14 patients with pregnancy-induced hypertonus/pre-eclampsia, 67 with small-for-gestational-age (SGA) infants, and 7 with fetal growth restriction (FGR). ApoB levels were measured by ELISA.

Results: There was no significant difference in apoB levels between the different GWG groups. We found significantly higher levels of apoB in overweight and obese patients compared to those with normal BMI. Smoking was correlated with higher apoB levels. There were no differences either between women with PIH/PE and normotensive women or between SGA/IUGR and pregnancies without. Women with pre-existing hypertension showed significantly higher apoB levels than the control group.

Conclusions: ApoB cannot be used as a marker for identifying the risk of excessive GWG or adverse pregnancy outcomes early in pregnancy. However, it may be involved in the pathophysiology of adverse pregnancy outcomes in high-risk patients.
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http://dx.doi.org/10.1055/a-1118-4084DOI Listing
December 2020

Apheresis as emerging treatment option in severe early onset preeclampsia.

Atheroscler Suppl 2019 Dec 17;40:61-67. Epub 2019 Aug 17.

Institute of Clinical Chemistry and Laboratory Medicine, Medical Center - University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Germany.

Based on an early suggestion by Winkler et al. 2003 and a subsequent successful study by Wang et al. 2006 using lipid apheresis (LA) in 9 patients with preeclampsia to prolong pregnancies, the use of apheresis as therapeutic option in severe early onset preeclampsia has received increasing attention. Further studies using different LA systems also prolonged pregnancy and have been published in the last few years. Albeit using different LA systems and relying on different working hypothesis, all studies demonstrated a promising stabilisation against the disease's progression. Overall time from hospitalisation to the need for mandatory delivery was longer for those patients receiving apheresis compared to historical or matched control patients not receiving apheresis. These data will be reviewed and different hypotheses about the beneficial mechanism of action of apheresis will be discussed. Since up to now there is no curative treatment for preeclampsia other than observation and delivery, future work shall be encouraged.
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http://dx.doi.org/10.1016/j.atherosclerosissup.2019.08.028DOI Listing
December 2019

Estimating fetal cholesterol synthesis rates by cord blood analysis in intrauterine growth restriction and normally grown fetuses.

Lipids Health Dis 2019 Oct 25;18(1):185. Epub 2019 Oct 25.

Institute for Clinical Chemistry and Clinical Pharmacology, University Clinics of Bonn, Bonn, Germany.

Background: Cholesterol is an essential component in human development. In fetuses affected by intrauterine growth restriction (IUGR), fetal blood cholesterol levels are low. Whether this is the result of a reduced materno-fetal cholesterol transport, or due to low fetal de novo synthesis rates, remains a matter of debate. By analyzing cholesterol interbolites and plant sterols we aimed at deeper insights into transplacental cholesterol transport and fetal cholesterol handling in IUGR with potential targets for future therapy. We hypothesized that placental insufficiency results in a diminished cholesterol supply to the fetus.

Methods: Venous umbilical cord sera were sampled post-partum from fetuses delivered between 24 weeks of gestation and at full term. IUGR fetuses were matched to 49 adequate-for-age delivered preterm and term neonates (CTRL) according to gestational age at delivery. Cholesterol was measured by gas chromatography-flame ionization detection using 5a-cholestane as internal standard. Cholesterol precursors and synthesis markers, such as lanosterol, lathosterol, and desmosterol, the absorption markers, 5α-cholestanol and plant sterols, such as campesterol and sitosterol, as well as enzymatically oxidized cholesterol metabolites (oxysterols), such as 24S- or 27-hydroxycholesterol, were analyzed by gas chromatography-mass spectrometry, using epicoprostanol as internal standard for the non-cholesterol sterols and deuterium labeled oxysterols for 24S- and 27-hydroxycholesterol.

Results: Mean cholesterol levels were 25% lower in IUGR compared with CTRL (p < 0.0001). Lanosterol and lathosterol to cholesterol ratios were similar in IUGR and CTRL. In relation to cholesterol mean, desmosterol, 24S-hydroxycholesterol, and 27-hydroxycholesterol levels were higher by 30.0, 39.1 and 60.7%, respectively, in IUGR compared to CTRL (p < 0.0001). Equally, 5α-cholestanol, campesterol, and β-sitosterol to cholesterol ratios were higher in IUGR than in CTRL (17.2%, p < 0.004; 33.5%, p < 0.002; 29.3%, p < 0.021).

Conclusions: Cholesterol deficiency in IUGR is the result of diminished fetal de novo synthesis rates rather than diminished maternal supply. However, increased oxysterol- and phytosterol to cholesterol ratios suggest a lower sterol elimination rate. This is likely caused by a restricted hepatobiliary function. Understanding the fetal cholesterol metabolism is important, not only for neonatal nutrition, but also for the development of strategies to reduce the known risk of future cardiovascular diseases in the IUGR fetus.
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http://dx.doi.org/10.1186/s12944-019-1117-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815065PMC
October 2019

Concomitant intrauterine growth restriction alters the lipoprotein profile in preeclampsia.

Pregnancy Hypertens 2019 Jan 31;15:154-160. Epub 2018 Dec 31.

Department of Obstetrics and Gynecology, University Hospital of the RWTH, Pauwelsstraße 30, 52074 Aachen, Germany; Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Arnold-Heller-Straße 3, 24105 Kiel, Germany. Electronic address:

Objective: Preeclampsia and intrauterine growth restriction (IUGR) are related conditions. We aimed to characterise common lipid changes.

Methods: Triglyceride and cholesterol levels of patients 24-42 weeks of gestation with IUGR (n = 52), hypertensive IUGR (HIUGR, n = 28), and preeclampsia without IUGR (PE, n = 56) were compared to a control group (CTRL, n = 167). In addition, 60 sera (n = 10 of each pathology IUGR, HIUGR, PE (without IUGR) compared to n = 30 matched CTRL) of severe early onset cases <34 weeks of gestation were chosen and further analysed by ultracentrifugation lipid subfractionation including VLDL, IDL, LDL, and HDL composition.

Results: In the full cohort we found low cholesterol in IUGR (p = 0.0405), while triglyceride levels were high in PE (p < 0.0001). Lipid concentrations in HIUGR did not differ significantly from CTRL. In the 60 patients analysed by lipid subfractionation, triglyceride levels were increased in the VLDL subfraction in PE (p < 0.01), however, LDL-bound ApoB and cholesterol levels were lower in IUGR and HIUGR (p < 0.0001 for total cholesterol and p < 0.001 for ApoB in both groups), but not in PE when compared to CTRL.

Conclusion: Low cholesterol, especially LDL cholesterol levels are a feature of IUGR while high triglyceride levels are a feature of preeclampsia. Increased VLDL-triglycerides suggest a disturbed conversion to LDL in preeclampsia. Of note, the presence of IUGR in hypertensive disorders further alters lipid profiles, which may explain heterogeneous data on lipid values for preeclampsia in the literature. Study groups have to be selected carefully to avoid misinterpretation.
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http://dx.doi.org/10.1016/j.preghy.2018.12.006DOI Listing
January 2019

Comparison of blood serum protein analysis by MALDI-MS from either conventional frozen samples or storage disc-deposited samples: A study with human serum from pregnant donors and from patients with intrauterine growth restriction.

Eur J Mass Spectrom (Chichester) 2019 Aug 26;25(4):381-390. Epub 2018 Dec 26.

1 Proteome Center Rostock, Medical Faculty and Natural Science Faculty, University of Rostock, Rostock, Germany.

Mass spectrometric profiling of intact serum proteins, i.e. determination of relative protein abundance differences, was performed using two different serum sample preparation methods: one with frozen and thawed serum, the other with at room temperature deposited and dried serum. Since in a typical clinical setting freezing of serum is difficult to achieve, sampling at room temperature is preferred and can be met when using the Noviplex™ card system. Once deposited and dried, serum proteins can be stored and shipped at room temperature. After resolubilization of serum proteins from "dried serum spots", mass spectra of high quality have been recorded comparable to those that were obtained using fresh-frozen and subsequently thawed serum samples. Differentiation between patients with intrauterine growth restriction and control individuals was achievable, independent from the sample work-up procedure. Having at hand a reliable and robust method for serum storage and shipment which works at room temperature bridges the gap between the clinics and the protein analysis laboratory. Our novel serum handling protocol reduces costs for both, storage and shipping, and ultimately enables clinical risk assessment based on mass spectrometric determination of intact protein abundance profiles.
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http://dx.doi.org/10.1177/1469066718820991DOI Listing
August 2019

Video analysis for the evaluation of vaginal births: a comment.

Swiss Med Wkly 2018 08 22;148:w14654. Epub 2018 Aug 22.

Department of Obstetrics and Gynaecology, University Hospital of Schleswig-Holstein, Kiel, Germany.

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http://dx.doi.org/10.4414/smw.2018.14654DOI Listing
August 2018

Maternal Apolipoprotein B100 Serum Levels are Diminished in Pregnancies with Intrauterine Growth Restriction and Differentiate from Controls.

Proteomics Clin Appl 2018 11 23;12(6):e1800017. Epub 2018 Jul 23.

Proteome Center Rostock, Medical Faculty and Natural Science Faculty, University of Rostock, Schillingallee 69, 18057, Rostock, Germany.

Purpose: Intrauterine growth restriction, a major cause of fetal morbidity and mortality, is defined as a condition in which the fetus does not reach its genetically given growth potential. Screening for intrauterine growth restriction biomarkers in the mother's blood would be of great help for optimal pregnancy management and timing of delivery as well as for identifying fetuses requiring further surveillance during their infancies.

Experimental Design: A multiplexing serological assay based on liquid chromatography-multiple-reaction-monitoring mass spectrometry is applied for distinguishing serum samples of pregnant women.

Results: Assessment of concentrations of apolipoproteins and of proteins that belong to the lipid transport system is performed with maternal serum samples, consuming only 10 μL of serum per multiplex assay from each patient. Of all investigated proteins the serum concentrations of apolipoprotein B100 shows the greatest power for discriminating intrauterine growth restriction from control samples, reaching areas under curves above 0.85 in receiver-operator-characteristics analyses.

Conclusions: These results indicate the potential of liquid chromatography-multiple-reaction-monitoring mass spectrometry to become of clinical importance in the future for intrauterine growth restriction risk assessment based on maternal apolipoprotein B100 serum levels.
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http://dx.doi.org/10.1002/prca.201800017DOI Listing
November 2018

ADAM17 inhibition enhances platinum efficiency in ovarian cancer.

Oncotarget 2018 Mar 23;9(22):16043-16058. Epub 2018 Mar 23.

Department of Gynecology and Obstetrics, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein Campus Kiel, Kiel, Germany.

Chemotherapeutic resistance evolves in about 70 % of ovarian cancer patients and is a major cause of death in this tumor entity. Novel approaches to overcome these therapeutic limitations are therefore highly warranted. A disintegrin and metalloprotease 17 (ADAM17) is highly expressed in ovarian cancer and required for releasing epidermal growth factor receptor (EGFR) ligands like amphiregulin (AREG). This factor has recently been detected in ascites of advanced stage ovarian cancer patients. However, it is not well understood, whether and how ADAM17 might contribute to chemo resistance of ovarian cancer. In this study, we identified ADAM17 as an essential upstream regulator of AREG release under chemotherapeutic treatment in ovarian cancer cell lines and patient derived cells. In the majority of ovarian cancer cells cisplatin treatment resulted in enhanced ADAM17 activity, as shown by an increased shedding of AREG. Moreover, both mRNA and the protein content of AREG were dose-dependently increased by cisplatin exposure. Consequently, cisplatin strongly induced phosphorylation of ADAM17-downstream mediators, the EGFR and extracellular signal-regulated kinases (ERK). Phorbol 12-myristate 13-acetate (PMA), similarly to cisplatin, mediated AREG shedding and membrane fading of surface ADAM17. Inhibition of ADAM17 with either GW280264X or the anti-ADAM17 antibody D1 (A12) as well as silencing of ADAM17 by siRNA selectively reduced AREG release. Thus, ADAM17 inhibition sensitized cancer cells to cisplatin-induced apoptosis, and significantly reduced cell viability. Based on these findings, we propose that targeting of ADAM17 in parallel to chemotherapeutic treatment suppresses survival pathways and potentially diminish evolving secondary chemo resistance mechanisms.
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http://dx.doi.org/10.18632/oncotarget.24682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882316PMC
March 2018

Lipoprotein turnover and possible remnant accumulation in preeclampsia: insights from the Freiburg Preeclampsia H.E.L.P.-apheresis study.

Lipids Health Dis 2018 Mar 14;17(1):49. Epub 2018 Mar 14.

Institute of Clinical Chemistry and Laboratory Medicine, Medical Center - University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany.

Background: Preeclampsia is a life-threatening disease in pregnancy, and its complex pathomechanisms are poorly understood. In preeclampsia, lipid metabolism is substantially altered. In late onset preeclampsia, remnant removal disease like lipoprotein profiles have been observed. Lipid apheresis is currently being explored as a possible therapeutic approach to prolong preeclamptic pregnancies. Here, apheresis-induced changes in serum lipid parameters are analyzed in detail and their implications for preeclamptic lipid metabolism are discussed.

Methods: In the Freiburg H.E.L.P.-Apheresis Study, 6 early onset preeclamptic patients underwent repeated apheresis treatments. Serum lipids pre- and post-apheresis and during lipid rebound were analyzed in depth via ultracentrifugation to yield lipoprotein subclasses.

Results: The net elimination of Apolipoprotein B and plasma lipids was lower than theoretically expected. Lipids returned to previous pre-apheresis levels before the next apheresis even though apheresis was repeated within 2.9 ± 1.2 days. Apparent fractional catabolic rates and synthetic rates were substantially elevated, with fractional catabolic rates for Apolipoprotein B / LDL-cholesterol being 0.7 ± 0.3 / 0.4 ± 0.2 [day] and synthetic rates being 26 ± 8 / 17 ± 8 [mg*kg*day]. The distribution of LDL-subclasses after apheresis shifted to larger buoyant LDL, while intermediate-density lipoprotein-levels remained unaffected, supporting the notion of an underlying remnant removal disorder in preeclampsia.

Conclusion: Lipid metabolism seems to be highly accelerated in preeclampsia, likely outbalancing remnant removal mechanisms. Since cholesterol-rich lipoprotein remnants are able to accumulate in the vessel wall, remnant lipoproteins may contribute to the severe endothelial dysfunction observed in preeclampsia.

Trial Registration: ClinicalTrails.gov, NCT01967355 .
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http://dx.doi.org/10.1186/s12944-018-0698-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853053PMC
March 2018

Measurement and evaluation of fetal fat layer in the prediction of fetal macrosomia in pregnancies complicated by gestational diabetes.

Arch Gynecol Obstet 2017 09 19;296(3):445-453. Epub 2017 Jun 19.

Department of Gynecology and Obstetrics, University Hospitals Schleswig-Holstein, Campus Kiel, Arnold-Heller Strasse 3, Haus 24, 24105, Kiel, Germany.

Objectives: To explore the predictive power of measuring the abdominal fetal fat layer (FFL) as a soft tissue marker at 31, 34, and 37 weeks' gestation to improve the detection of fetal macrosomia in pregnant women with GDM, in addition to the biometric values with close monitoring of maternal blood sugar level and BMI changes.

Methods: We conducted a prospective observational study at the Department of Obstetrics, University Hospitals, Campus Kiel, Germany, in collaboration with diabetic clinic staff. Participants underwent a third-trimester scan and extra FFL measurements were performed at 31, 34, and 37 weeks of gestation. The clinical outcomes of pregnancy and birth weight were collected from the obstetric record. All of the enrolled women had an early pregnancy ultrasound scan to confirm gestational age.

Results: The FFL at 34 and 37 weeks, with respective cutoff values of >0.48 cm and >0.59 cm, showed a very good sensitivity of 60% for both gestational points, and specificity of 89.3 and 90.6%, respectively. The probability of fetal macrosomia could be more than doubled if the FFL at 34 weeks was more than 0.48 cm. However, the probability of macrosomia dropped to 16% if the FFL was ≤0.48 cm. The median FFLs of macrosomic fetuses at 34 and 37 weeks were 0.50 (IQR 0.10) and 0.60 (IQR 0.25) cm, respectively. The mean age of the study population (n = 80) was 32.26 (SD = 5.06) years. In our study population, ten newborns were born with birth weight >4000 g. The body mass index (BMI) for the mothers of later-onset macrosomic newborns showed higher median values of 30 (IQR 8), 32 (IQR 5), and 33 (IQR 9) at 31, 34, and 37 weeks, respectively, in comparison to mothers of non-macrosomic newborn. However, the BMI did not show any statistically significant difference from those with normal-weight newborn and did not show any specific sensitivity for predicting macrosomia.

Conclusion: Measuring the FFL at 34 and 37 weeks of gestation, in addition to the standard measurement, might be useful for predicting macrosomia and is worth further evaluation.
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http://dx.doi.org/10.1007/s00404-017-4433-6DOI Listing
September 2017

Apolipoprotein E Genotype in Very Preterm Neonates with Intrauterine Growth Restriction: An Analysis of the German Neonatal Network Cohort.

Biomed Res Int 2017 5;2017:2837027. Epub 2017 Apr 5.

Department of Obstetrics and Gynecology, University Hospital of the RWTH Aachen, Aachen, Germany.

Cord blood of intrauterine growth restricted (IUGR) neonates displays lipid changes towards atherosclerotic profiles. Apolipoprotein E (ApoE) and its isoforms (e2, e3, and e4) are involved in the regulation of lipid metabolism. Specifically, ApoE e4 has been associated with atherosclerotic diseases, while e2 has a favorable effect. We therefore hypothesized that ApoE e4 haplotype is frequently observed in IUGR neonates and contributes to impaired fetal growth and the association of IUGR with cardiovascular and metabolic diseases later in life. A cohort of 4885 preterm infants (≥22+0 and <32+0 weeks of gestation and birth weight below 1500 g) from the GNN study cohort was analyzed. Neonates were categorized into subgroups of <3rd, 3rd-10th, and >10th birth weight percentile. Analysis of the single nucleotides rs429358 and rs7412, identifying the ApoE genotype, was carried out using TaqMan® SNP genotyping assays. The proportional odds model was used to assess data. No association was found between genotype and birth weight percentiles in each of the subgroups. ApoE genotype and low birth weight depict two distinct risk factors for cardiovascular disease without being directly associated.
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http://dx.doi.org/10.1155/2017/2837027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5396432PMC
February 2018

Maternal 27-hydroxycholesterol concentrations during the course of pregnancy and in pregnancy pathologies.

BMC Pregnancy Childbirth 2017 04 4;17(1):106. Epub 2017 Apr 4.

Department of Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Department of Clinical Research, University of Bern, Freiburgstrasse, 3010, Berne, Switzerland.

Background: The oxysterol 27-hydroxycholesterol (27-OHC) plays an important role in the regulation of cholesterol homeostasis. Pregnancy pathologies like preeclampsia (PE), HELLP-syndrome (HELLP), intrauterine growth restriction (IUGR) and intrahepatic cholestasis in pregnancy (ICP) are linked to disturbances in lipid metabolism. In the present study, we hypothesized a specific gestational regulation of 27-OHC and compromised 27-OHC levels due to placental and hepatic diseases in pregnancy resulting in a dysregulation of lipid metabolism.

Methods: The 27-OHC was measured by gas-chromatography-mass spectrometry (GC-MS) and related to cholesterol concentrations. In the longitudinal cohort, a complete set of samples of healthy patients (n = 33) obtained at three different time points throughout gestation and once post-partum was analyzed. In the cross sectional cohort, patients with pregnancy pathologies (IUGR n = 14, PE n = 14, HELLP n = 7, ICP n = 7) were matched to a control group (CTRL) of equal gestational ages.

Results: The 27-OHC levels already increased in the first trimester despite lower TC concentrations (p < 0.05). During the course of pregnancy, a subtle rise in 27-OHC concentrations results in an overall decrease of 27-OHC/TC ratio in between the first (p < 0.05) and second trimester. The ratio remains stable thereafter including the post-partum period. No significant differences have been observed in pregnancy pathologies as compared to the CTRL group.

Conclusion: In conclusion, 27-OHC may have a compensatory role in cholesterol metabolism early in pregnancy. The conserved 27-OHC/TC ratio in pregnancy pathologies suggest that neither the placenta nor the liver is majorly involved in the regulation of 27-OHC metabolism.
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http://dx.doi.org/10.1186/s12884-017-1287-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381014PMC
April 2017

2D Versus 3D in Laparoscopic Surgery by Beginners and Experts: A Randomized Controlled Trial on a Pelvitrainer in Objectively Graded Surgical Steps.

J Surg Educ 2017 Sep - Oct;74(5):867-877. Epub 2017 Feb 16.

Department of Gynecology and Obstetrics, University Hospitals Schleswig-Holstein Campus Kiel, Kiel, Germany. Electronic address:

Background And Objective: Progress in endoscopic surgery in the past few decades has led to the application of 3-dimensional (3D) procedures in operating rooms. This permits patient- and surgeon-friendly operations and also maximizes the superiority of laparoscopy over laparotomy. In this study, we compare 2-dimensional (2D) and 3D endoscopy techniques with regard to time, efficiency, optics, and handling by users with different degrees of experience at 4 difficulty levels.

Design: A randomized controlled trial on a pelvitrainer in objectively graded surgical steps for students and postgraduates.

Setting: The trials took place at the Kiel School of Gynaecological Endoscopy, a training unit of the Kiel University Department of Obstetrics and Gynecology, a tertiary academic medical center.

Participants: The 277 study participants, divided into students, residents, and specialists, worked on pelvitrainers with 2 different optical systems, the 2D full HD and the 3D mode. The following 4 exercises were performed with each optical system: (1) grasping and transferring of pins, (2) cutting predetermined marks, (3) vaginal closure with prevention of prolapse, and (4) sacrocolpopexy. The duration and success of the tasks were measured and compared. A self-assessment questionnaire was completed by the participants.

Results: Overall, the 3D-system permitted a greater improvement in working speed, superior optical visualization, and better endoscopic handling in all groups, independent of surgical experience. All students improved in speed (exercises: 1-3) and made significantly fewer mistakes (exercise 2) on 3D compared with 2D. Residents made progress in time (exercises: 1-4) and task performance (exercise 3). Specialists improved significantly in the more challenging tasks 3 and 4. Subjectively, 68.8% of participants preferred 3D for performing laparoscopy.

Conclusion: Systematic training programs on pelvitrainers can improve endoscopic skills not only in beginners but also in experienced surgeons. The 3D system offered distinct advantages over 2D imaging and was well accepted by surgeons.
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http://dx.doi.org/10.1016/j.jsurg.2017.01.011DOI Listing
June 2018

Serum cholesterol acceptor capacity in intrauterine growth restricted fetuses.

J Perinat Med 2017 Oct;45(7):829-835

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Aim: Intrauterine growth restriction (IUGR) is an independent risk factor for the development of cardiovascular diseases later in life. The mechanisms whereby slowed intrauterine growth confers vascular risk are not clearly established. In general, a disturbed cholesterol efflux has been linked to atherosclerosis. The capacity of serum to accept cholesterol has been repeatedly evaluated in clinical studies by the use of macrophage-based cholesterol efflux assays and, if disturbed, precedes atherosclerotic diseases years before the clinical diagnosis. We now hypothesized that circulating cholesterol acceptors in IUGR sera specifically interfere with cholesterol transport mechanisms leading to diminished cholesterol efflux.

Methods: RAW264.7 cells were used to determine efflux of [3H]-cholesterol in response to [umbilical cord serum (IUGR), n=20; controls (CTRL), n=20].

Results: Cholesterol efflux was lower in IUGR as compared to controls [controls: mean 7.7% fractional [3H]-cholesterol efflux, standard deviation (SD)=0.98; IUGR: mean 6.3%, SD=0.79; P<0.0001]. Values strongly correlated to HDL (ρ=0.655, P<0.0001) and apoE (ρ=0.510, P=0.0008), and mildly to apoA1 (ρ=0.3926, P=0.0122) concentrations.

Conclusions: Reduced cholesterol efflux in IUGR could account for the enhanced risk of developing cardiovascular diseases later in life.
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http://dx.doi.org/10.1515/jpm-2016-0270DOI Listing
October 2017

Size Does Not Make the Difference: 3D/4D Transperineal Sonographic Measurements of the Female Urethra in the Assessment of Urinary Incontinence Subtypes.

Biomed Res Int 2016 21;2016:1810352. Epub 2016 Nov 21.

Clinic for Gynaecology and Obstetrics, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.

The objective was to evaluate the usefulness of transperineal ultrasound in the assessment of the urethral length and urethral lumen by 3D/4D transperineal sonography to discriminate between female patients with subtypes of urinary incontinence. A total of 150 female patients underwent an examination because of urinary incontinence. 41 patients were diagnosed with urgency urinary incontinence (OAB), 67 patients were diagnosed with stress urinary incontinence (SUI), and 42 patients were in the control group (CTRL). Three diameters of the urethral lumen (proximal (U1), medial (U2), and distal (U3)) and the urethral length were measured. By the assessment of the urethral lumen, the presence of the urethral funneling was evaluated. We found a significant difference in the urethral length and urethral lumen U2 of OAB and SUI versus CTRL. The urethral length was significantly greater ( < 0.05) and the urethral lumen was significantly wider ( < 0.05) in the patients with urinary incontinence. The incidence of the urethral funneling was significantly higher ( < 0.05) in the study groups with urinary incontinence than in the control group. Our results have shown the urethral changes obtained by ultrasound in patients with urinary incontinence, but they are still insufficient to distinguish between subtypes of urinary incontinence.
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http://dx.doi.org/10.1155/2016/1810352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136624PMC
February 2017

Fetal gender and gestational age differentially affect PCSK9 levels in intrauterine growth restriction.

Lipids Health Dis 2016 Nov 14;15(1):193. Epub 2016 Nov 14.

Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Kiel, Germany.

Background: Maternal and fetal Low Density Lipoprotein-Cholesterol (LDL-C) concentrations are compromised in intrauterine growth restriction (IUGR). Generally, LDL-C catabolism is under control of PCSK9 by binding to the LDL-receptor leading to its degradation. Hence, we hypothesized a role for PCSK9 in the modulation of lipid metabolism and placental transport in IUGR.

Methods: 172 women, 70 IUGR and 102 controls were included in the study. Maternal and fetal serum PCSK9 levels and lipid profiles including LDL-C were measured. Placental LDL-receptor and PCSK9 expressions were estimated by tissue microarray immunohistochemistry, and analyzed by two blinded observers using an immunoreactivity score. Non-parametric tests and multivariate regression analyses were used for statistical estimations.

Results: PCSK9 levels in the maternal and fetal compartment independently predicted LDL-C levels (maternal compartment: adjusted R  = 0.2526; coefficient b  = 0.0938, standard error s =0.0217, r = 0.4420, t-value = 4.323, p < 0.0001; fetal compartment: adjusted R  = 0.2929; b  = 0.1156, s =0.020, r = 0.5494, t-value = 5.81, p < 0.0001). We did not find significant differences in maternal PCSK9 concentrations between IUGR and controls. However, we found lower fetal serum PCSK9 concentrations in IUGR than in controls (IUGR median 137.1 ng/mL (95% CI 94.8-160.0) vs. controls 176.8 (154.6-202.5), p = 0.0005). When subgrouping according to early onset, late onset IUGR, and fetal gender differences remained consistent only for male neonates born before 34 weeks of gestation. In the placenta we found no correlation between PCSK9 and LDL-receptor expression patterns. However, the LDL-receptor was significantly upregulated in IUGR when compared to controls (p = 0.0063).

Conclusions: Our results suggest that PCSK9 play a role in impaired fetal growth by controlling fetal LDL-C metabolism, which seems to be dependent on gestational age and fetal gender. This underlines the need to identify subgroups of IUGR that may benefit from individualized and gender-specific pharmacotherapy in future studies.
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http://dx.doi.org/10.1186/s12944-016-0365-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109703PMC
November 2016
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