Publications by authors named "Lars Hellmeyer"

19 Publications

  • Page 1 of 1

Peripartum Covid-19 Pneumonia with Severe ARDS - A Case Report.

Z Geburtshilfe Neonatol 2021 04 19;225(2):183-187. Epub 2021 Apr 19.

Department of Gynecology and Obstetrics, Vivantes Klinikum im Friedrichshain, Berlin, Germany.

Introduction: SARS-CoV-2 is a novel coronavirus that was first isolated in Wuhan, China, and resulted in a rapidly spreading pandemic worldwide. Currently there is only limited evidence on the effect of COVID-19 on pregnant women.

Case: Here we present one of the first serious COVID-19 cases in pregnancy at term with subsequent delivery. Postpartum the mother required antibiotic and symptomatic treatment. She experienced acute worsening of symptoms and developed acute respiratory failure requiring endotracheal intubation and subsequently extracorporeal membrane oxygenation.

Conclusion: COVID-19 affects all medical disciplines, requiring interdisciplinary approaches and development of patient care regimes. Obstetricians should be aware and be prepared for the special needs of pregnant women with potential prenatal and postnatal issues. Ideally pregnant COVID-19 patients should be cared for at a tertiary perinatal center with experienced perinatologists and neonatologists.
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April 2021

Patients' subjective assessment as a decisive predictor of malignancy in pelvic masses: results of a multicentric, prospective pelvic mass study.

J Psychosom Obstet Gynaecol 2020 Nov 30:1-6. Epub 2020 Nov 30.

Department of Gynecology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Objective: The prognosis for ovarian cancer patients remains poor. A key to maximizing survival rates is early detection and treatment. This requires an accurate prediction of malignancy. Our study seeks to improve the accuracy of prediction by focusing on early subjective assessment of malignancy. We therefore investigated the assessment of patients themselves in comparison to the assessment of physicians.

Methods: One thousand three hundred and thirty patients participated in a prospective and multicenter study in six hospitals in Berlin. Using univariate analysis and multivariate logistic regression models, we measured the accuracy of the early subjective assessment in comparison to the final histological outcome. Moreover, we investigated factors related to the assessment of patients and physicians.

Results: The patients' assessment of malignancy is remarkably accurate. With a positive predictive value of 58%, the majority of patients correctly assessed a pelvic mass as malignant. With more information available, physicians achieved only a slightly more accurate prediction of 63%.

Conclusions: For the first time, our study considered subjective factors in the diagnostic process of pelvic masses. This paper demonstrates that the patients' personal assessment should be taken seriously as it can provide a significant contribution to earlier diagnosis and thus improved therapy and overall prognosis.
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November 2020

Severe Lactational Mastitis With Complicated Wound Infection Caused by .

J Hum Lact 2021 Feb 17;37(1):200-206. Epub 2020 Nov 17.

27695 Department of Gynecology and Obstetrics, Baby-friendly Hospital Initiative certified, Tertiary Perinatal Center, Charité University hospital affiliate, Vivantes Klinikum im Friedrichshain, Berlin, Germany.

Introduction: Puerperal mastitis, a complication occurring during the breastfeeding period, is often caused by . Here we report on severe mastitis in a lactating breast, with subsequent invasive disease and wound healing problems.

Main Issue: The 41-year-old woman (G2, P2) presented at 2 weeks postpartum to our hospital with painful swelling and reddening of the left breast, in addition to fever and malaise, and complained about a nipple fissure on the left breast. Previously, her 4-year-old son was treated for an acute otitis media and her husband experienced flu-like symptoms.

Management: Due to the severity of the symptoms, Clindamycin antibiotic treatment was initiated intravenously. was isolated in the milk. This strain is commonly known to cause infections of the upper respiratory tract, skin, and soft tissue, but rarely mastitis. Furthermore, the participant developed invasive disease with abscess formation and skin erosion with a milk fistula. Special dressing was applied to promote wound healing. The participant continued breastfeeding well into the child's 2nd year of life.

Conclusion: This rare form of complicated mastitis with invasive disease caused by called for an interdisciplinary approach. We want to draw attention to other pathogens causing mastitis and to alert health care workers to promote hygiene in lactating women to prevent transmission.
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February 2021

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

J Perinat Med 2020 11;48(9):950-958

Department of Obstetrics and Gynaecology, Ospedale di San Leonardo, Castellammare di Stabia, Italy.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.
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November 2020

Do we need a 200 μg misoprostol vaginal insert? A retrospective cohort study comparing the misoprostol vaginal insert to oral misoprostol.

J Obstet Gynaecol Res 2020 Jun 3;46(6):851-857. Epub 2020 May 3.

Department of Obstetrics and Gynecology, Vivantes Klinikum im Friedrichshain, Berlin, Germany.

Aim: The misoprostol vaginal insert (MVI) was reported to be more effective than dinoprostone but discussed critically because of high rates of fetal heart rate changes due to uterine tachysystole. The aim of this study was to investigate the outcome of induced labor using the MVI compared to off-label orally-administered misoprostol (OM).

Methods: Retrospective study including a total of 401 patients with singleton pregnancies in whom labor was induced at ≥36 0/7 gestational weeks with MVI (203) or OM (198). Primary outcomes were the time from induction to delivery, vaginal delivery in 24 h and the mode of delivery and the neonatal outcome.

Results: Median time until any delivery was 833 min (645-1278) for MVI and 1076.5 min (698-1686.3) for OM group; 83.7% of the patients in the MVI group gave birth within 24 h versus 63.6% in the OM group. The MVI group needed significantly less pre-delivery oxytocin (29%). Tachysystole (6.4%) and pathological CTG (30.5%) occurred at a significantly higher frequency in the MVI group. The cesarean section rate was significantly higher in the MVI group amounting to 21.7% versus 14.6% in the OM group (P < 0.05). Neonatal outcome did not differ between the groups.

Conclusion: The MVI might be an option if you are in need for an approved and faster method to induce labor. Although we observed a significantly higher rate of fetal heart rate changes and cesarean sections in the MVI group this did not affect the neonatal outcome.
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June 2020

Synthetic osmotic dilators in the induction of labour-An international multicentre observational study.

Eur J Obstet Gynecol Reprod Biol 2018 Oct 3;229:70-75. Epub 2018 Aug 3.

Ex-Medicem International, Prague, Czech Republic. Electronic address:

Introduction: To evaluate the effects of synthetic osmotic dilators (Dilapan-S/ Dilasoft) in women who required induction of labour in a large prospective multicentre international observational study.

Materials And Methods: Primary outcomes were duration of Dilapan-S/Dilasoft insertion (hours), total induction - delivery interval (hours) and the rate of vaginal deliveries within 24 h (%). Secondary outcomes were the number of dilators inserted, Bishop score increase after extraction of Dilapan-S/Dilasoft, complications during induction (uterine contractions, uterine tachysystole and hyperstimulation, effect on the fetus) and post induction (infections and neonatal outcomes), agents / procedures used for subsequent induction of labour, immediate rate of spontaneous labours following cervical ripening period, rate of spontaneous vaginal deliveries, rate of instrumental vaginal deliveries and caesarean sections.

Results: Total of 543 women were recruited across 11 study sites, of which, 444 women were eligible for analysis. With Dilapan-S/Dilasoft use of <12 h (n = 188) the overall vaginal delivery rate was 76.6% with 45.7% of these births occurring within 24 h, 66% within 36 h and 75.5% within 48 h from insertion of Dilapan-S/Dilasoft. The mean insertion-delivery interval for this group was 24.3(±10.4) hours. With Dilapan-S/Dilasoft use of >12 h (n = 256), the overall vaginal delivery rate was 64.8%, with 16% of these births occurring within 24 h, 48.4% within 36 h and 54.7% within 48 h from insertion of Dilapan-S/Dilasoft. The mean insertion-delivery interval for this group was 39.1(±29.2) hours. The mean gain in the Bishops score was +3.6(±2.3). The mean number of Dilapan-S/Dilasoft dilators used was 3.8 (±1.1). The overall rate of caesarean section was 30.1%. The overall complication rate was low including infection risk. No adverse neonatal outcome was attributable to the use of Dilapan-S/Dilasoft.

Conclusion: Dilapan-S/Dilasoft are safe and effective methods for cervical ripening. Their use is associated with low maternal and neonatal complication rates. Future research should aim at level I clinical trials comparing Dilapan-S to other mechanical or pharmacological cervical ripening agents.

Clinical Trial Registration:
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October 2018

Perinatal Outcome in Women with a Vietnamese Migration Background - Retrospective Comparative Data Analysis of 3000 Deliveries.

Geburtshilfe Frauenheilkd 2018 Jul 25;78(7):697-706. Epub 2018 Jul 25.

Vivantes Klinikum im Friedrichshain, Klinik für Gynäkologie und Geburtsmedizin, Berlin, Germany.

Introduction: Perinatal data of women with a Vietnamese migration background have not been systematically studied in Germany to date. Numerous details of important maternal and child outcomes were compared and analysed. The study's primary parameters were the frequency of and indication for c-section.

Methodology: The perinatal data from a Berlin hospital were analysed retrospectively. The women (Vietnamese migration background vs. autochthonous) were grouped using name analysis. Datasets of 3002 women giving birth, including 999 women with a Vietnamese migration background, were included. The associations between primary or secondary cesarean delivery and different child outcomes depending on the migration background (exposure) were studied using logistical regression analysis.

Results: Women with a Vietnamese migration background have a lower c-section rate of 8.0% for primary and 12.6% for secondary c-section than women without a migration background (11.1% primary and 16.4% secondary c-section respectively). Regression analysis shows that the odds that women with a Vietnamese migration background will have a primary (OR 0.75; p = 0.0884) or secondary c-section (OR 0.82; p = 0.1137) are not significantly lower. A Vietnamese migration background was associated with higher odds for an episiotomy but not for a grade 3 - 4 perineal tear. A Vietnamese migration background does not have a significant influence on poor 5-min Apgar scores ≤ 7 and low umbilical cord arterial pH values ≤ 7.10. Newborns of mothers with a Vietnamese migration background have higher odds of a relatively higher birth weight (> 3110 g).

Summary: There was no evidence that women with a Vietnamese migration background are delivered more often by caesarean section. There were also no differences as regards important child outcome data from women in the comparator group. Overall, the results do not provide any evidence for poorer quality of care of women with a Vietnamese migration background in Berlin despite the cultural and communication barriers in the reality of care provision.
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July 2018

Induction of labor in patients with an unfavorable cervix after a cesarean using an osmotic dilator versus vaginal prostaglandin.

J Perinat Med 2018 Apr;46(3):299-307

Department of Obstetrics and Gynecology, Vivantes Klinikum im Friedrichshain, Affiliate of Charité University, Berlin, Germany.

Background: Trial of labor after cesarean (TOLAC) is a viable option for safe delivery. In some cases cervical ripening and subsequent labor induction is necessary. However, the commonly used prostaglandins are not licensed in this subgroup of patients and are associated with an increased risk of uterine rupture.

Methods: This cohort study compares maternal and neonatal outcomes of TOLAC in women (n=82) requiring cervical ripening agents (osmotic dilator vs. prostaglandins). The initial Bishop scores (BSs) were 2 (0-5) and 3 (0-5) (osmotic dilator and prostaglandin group, respectively). In this retrospective analysis, Fisher's exact test, the Kruskal-Wallis rank sum test and Pearson's chi-squared test were utilized.

Results: Vaginal birth rate (including operative delivery) was 55% (18/33) in the osmotic dilator group vs. 51% (25/49) in the dinoprostone group (P 0.886). Between 97% and 92% (32/33 and 45/49) (100%, 100%) of neonates had an Apgar score of >8 after 1 min (5, 10 min, respectively). The time between administration of the agent and onset of labor was 36 and 17.1 h (mean, Dilapan-S® group, dinoprostone group, respectively). Time from onset of labor to delivery was similar in both groups with 4.4 and 4.9 h (mean, Dilapan-S® group, dinoprostone group, respectively). Patients receiving cervical ripening with Dilapan-S® required oxytocin in 97% (32/33) of cases. Some patients presented with spontaneous onset of labor, mostly in the dinoprostone group (24/49, 49%). Amniotomy was performed in 64% and 49% (21/33 and 24/49) of cases (Dilapan-S® group and dinoprostone group, respectively).

Conclusions: This pilot study examines the application of an osmotic dilator for cervical ripening to promote vaginal delivery in women who previously delivered via cesarean section. In our experience, the osmotic dilator gives obstetricians a chance to perform induction of labor in these women.
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April 2018

Pregnancy-associated transient osteoporosis of the hip: results of a case-control study.

Arch Osteoporos 2017 Dec 21;12(1):11. Epub 2017 Jan 21.

Faculty of Medicine, Philipps-University of Marburg, Marburg, Germany.

The etiology and underlying mechanisms of transient of osteoporosis of the hip (TOH) during pregnancy are still unclear, since no systematic analyses exist. Our results support the hypothesis that TOH is a multifactorial disease, which is associated with immobility, dental problems, and lack of exercise in childhood.

Introduction: Pregnancy-associated transient osteoporosis of the hip (TOH) is a rare but severe form of osteoporosis, which may affect a subgroup of women in the last trimester of pregnancy or immediately postpartum. Common symptoms include acute pain of the hip(s) due to bone marrow edema or even hip fractures. The exact underlining mechanisms of this disorder are still unknown since no published systematic analyses exist.

Methods: Out of a total of 52 TOH patients, 33 TOH patients could be matched with 33 healthy controls according to age, region, and gravity. The aim of this retrospective case-control study was to evaluate the risk factors for TOH in a homogenous population of women.

Results: The baseline characteristics of the two study groups were similar. Overall, 12.1% of the TOH patients sustained a hip fracture. Expectedly, 90.9% of the TOH patients complained about pain of the hip (p ≤ 0.001). TOH patients suffered more frequently from severe dental problems during childhood (p = 0.023) and performed less often sports before and after puberty (p ≤ 0.001), whereas the frequency of immobilization during pregnancy was threefold higher compared to the control group (p = 0.007). We found a significant increase of the TOH risk in patients with dental problems in childhood (OR 3.7; CI 1.3-10.7) as well as in patients with lack of exercise during childhood (OR 4.2; CI 1.3-12.9).

Conclusions: Our results support the hypothesis that pregnancy-associated TOH is a multifactorial disease, to which several individual factors may contribute. Hereby, we found significant associations with immobility, dental problems, and lack of exercise in childhood.
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December 2017

Antenatal body mass index (BMI) and weight gain in pregnancy - its association with pregnancy and birthing complications.

J Perinat Med 2016 May;44(4):397-404

Background: Overweight and obesity is a serious health risk in both developed and developing nations. It is a common finding among women in their reproductive age. Half of patients entering their pregnancy in the US have a BMI >25.0 and therefore qualify as overweight or obese. Moreover, there is a tendency towards increased weight gain during pregnancy. Studies have shown that gestational overweight is associated with complications in pregnancy and birthing as well as short-term and long-term impacts on neonatal outcome in childhood and adulthood.

Methods: Five hundred and ninety-one women visiting our tertiary perinatal center in 2014 were analyzed for antenatal BMI, gestational weight gain, as well as pregnancy outcome and complication together with neonatal weight and outcome. Pregnancy weight gain was assessed based on the IOM guidelines (Institute of Medicine) issued in 2009.

Results: Twenty-nine percent of our population was overweight with a BMI of more than 25.0. The general weight gain was in every BMI group similar (median ranging from 12.0 to 14.0 kg). Approximately one third gained more than the appropriate amount (37%, P<0.001). Women with more gestational weight were at risk of labor induction (55.0% vs. 45.7% labor induction in total, P=0.007). Strikingly, those patients were found to have significantly higher rates of secondary cesarean section (22.4% vs. 15.4%) and decreased chances of spontaneous vaginal birth (57.5% vs. 61.4%) (P=0.008). Furthermore women with a pregnancy weight gain in excess of the guidelines gave birth to neonates with a higher birth weight (>75.centile, 28.3% vs. 21.3%, P<0.001).

Conclusions: Altogether, one third of the analyzed population is already overweight or obese when entering pregnancy. A higher gestational weight gain than the recommended amount was found in 37% of cases. We found an association with pregnancy and birthing complications as well as higher infant weight. This highlights the importance of preconceptive and prenatal advice, and if necessary, intervention on BMI and weight gain.
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May 2016

The underestimation of immaturity in late preterm infants.

Arch Gynecol Obstet 2012 Sep 5;286(3):619-26. Epub 2012 May 5.

Department of Prenatal and Perinatal Medicine, Asklepios Clinic, Hamburg-Barmbek, Germany.

Purpose: Late preterm infants with gestational ages between 34 0/7 and 36 6/7 weeks are known to be at higher risk of mortality and morbidity than term newborns. This study aims to investigate the nature and frequency of neonatological complications in the late preterm population resulting in neonatal intensive care unit admissions as well as to draw obstetrical conclusions from the results.

Methods: Neonatological outcomes of 893 consecutively born late preterm infants were evaluated and classified by the frequency of occurrence in relation to potential maternal or fetal risk factors.

Results: Out of 893 late preterm infants, 528 (59.1 %) required intensive neonatal care. The incidence of apnea and bradycardia, the occurrence of feeding difficulties and the requirement of continuous positive airway pressure (CPAP) were inversely proportional to gestational age (p < 0.001). Gestational diabetes of the mother was more frequently associated with hypoglycemia (p < 0.001), but showed a reduced risk of hypothermia (p < 0.001). Small for gestational age neonates had a significantly lower rate of respiratory disorders (p < 0.001), but were more often affected by feeding difficulties (p < 0.01). Normal vaginal delivery had a significant advantage with regard to the necessity of CPAP (p < 0.01) and the occurrence of feeding difficulties (p < 0.05). Infants born by cesarean section were at higher risk of hypoglycemia (p < 0.001), but at lower risk of hyperbilirubinemia (p < 0.001).

Conclusions: The high risk of a problematic neonatological outcome in late preterms requires fundamental reconsideration. All efforts to prolong a pregnancy should be made beyond the 34th week of gestation.
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September 2012

Treatment with teriparatide in a patient with pregnancy-associated osteoporosis.

Gynecol Endocrinol 2010 Oct;26(10):725-8

Department of Obstetrics and Perinatal Medicine, Philipps University Marburg, Marburg, Germany.

Introduction: The decrease of BMD during a physiological pregnancy can in rare cases be intensified and lead to dramatic microarchitectural changes, which causes an increase incidence of fractures, preferably at the spine. This dramatic clinical picture is called pregnancy-associated osteoporosis.

Case History: We present the case of a 40-year-old woman (gravida IV, para II) with acute back pain right after delivery due to four fractures of the spine. The diagnosis was confirmed by dual-energy X-ray absorptiometry measurement result (T-score -4.1 SD (0.598 g/cm(2)) at the lumbar spine (L1-L4), T-score -1.5 SD (0.759 g/cm(2)) at the total hip). Due to the severity of symptoms, a therapy with teriparatide (20 mg daily) was started for a period of 18 months.

Results: After end of therapy, the T-score had significantly increased at the lumbar spine as well as at the hip (T-score of -2.1 (0.813 g/cm(2)) and -0.6 (0.864 g/cm(2)), respectively. The relative increase of BMD at the spine and total hip was 36% and 13.8%, respectively.

Discussion: Our report demonstrates the successful use of teriparatide underlined by the increase of bone mineral density and the improvement of clinical symptoms in a case of severe pregnancy-associated osteoporosis for the first time.
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October 2010

Interleukin-4 and interleukin-13 stimulate the osteoclast inhibitor osteoprotegerin by human endothelial cells through the STAT6 pathway.

J Bone Miner Res 2008 May;23(5):750-8

Department of Medicine, Philipps-University, Marburg, Germany.

Introduction: Endothelial cells of the bone vasculature modulate development, remodeling, and repair of bone by secreting osteotropic cytokines and hormones, which can act on osteoblastic and osteoclastic lineage cells. RANKL is the essential factor for differentiation, activation, and survival of osteoclasts, whereas osteoprotegerin (OPG) is a soluble decoy receptor and inhibitor for RANKL.

Materials And Methods: In this study, we analyzed the regulation of OPG by T helper 2 (Th2) cytokines interleukin (IL)-4 and the closely related IL-13 in human umbilical vein endothelial cells (HUVECs), the underlying signaling pathway, and its functional relevance on osteoclastic resorption.

Results: IL-4 and IL-13 induced OPG mRNA levels and protein secretion in HUVEC by up to 4-fold in a dose- and time-dependent fashion (maximum effect after 48 h and at 10 ng/ml). Activation of the transcription factor STAT6 preceded IL-4-induced OPG expression, and blockade of IL-4-induced STAT6 activation by the phospholipase C-specific inhibitor D609 decreased OPG expression. Soluble IL-4 receptor (sIL-4R) dose-dependently abolished both IL-4-induced STAT6 phosphorylation and OPG expression. RANKL stimulated the activity of osteoclasts, which was antagonized by HUVEC-derived supernatant containing OPG. The inhibitory effect on osteoclastogenesis was completely and specifically abrogated by a neutralizing OPG antibody in unstimulated HUVEC supernatant and partially in IL-4-stimulated HUVEC supernatant.

Conclusions: In summary, IL-4 and IL-13 induced OPG expression through activation of STAT6 in endothelial cells, and HUVEC-derived OPG is an IL-4/IL-13-induced inhibitor of osteoclastic resorption. These data underline the impact of Th2 cytokines on bone resorption through modulation of endothelial cell-derived cytokines.
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May 2008

Impact of fetal blood sampling on vaginal delivery and neonatal outcome in deliveries complicated by pathologic fetal heart rate: a population based cohort study.

J Perinat Med 2006 ;34(6):479-83

Center of Gynecology and Obstetrics, University of Giessen and Marburg, Göttingen, Germany.

Objective: To compare the impact of electronic fetal monitoring (EFM) alone vs. EFM with additional fetal blood sampling (FBS) in vaginal deliveries complicated by pathologic fetal heart rate (FHR).

Methods: All deliveries in Hesse between 1990 and 2000 were evaluated for participation in this study. Inclusion criteria comprised (1) pathologic fetal heart rate, (2) singleton pregnancy, (3) cephalic presentation, (4) vaginal delivery, and (5) gestational age at delivery of more than 35 weeks' gestation. In order to analyze the meaning of additional risk factors at birth for the effectiveness of FBS two subgroups were selected depending on the presence of additional risk factors at birth. To examine the impact of FBS in deliveries with pathologic FHR on the mode of delivery and on neonatal outcome, univariate regression analysis was performed and odds ratios (OR) and their corresponding 95% confidence intervals (95% CI) were calculated.

Results: The study population comprised 49,560 deliveries, among deliveries complicated by pathologic FHR, 26% underwent FBS. Deliveries with pathologic FHR and controlled by FBS, with no additional antepartum risk factors, were associated with an increase in spontaneous births OR 1.41 (95% CI 1.27-1.58), and in the presence of additional risk factors OR 1.24 (1.19-1.30). Short-term neonatal outcome parameters were characterized by a lower frequency of severe fetal acidosis (umbilical artery pH <7.0) OR 0.55 (0.42-0.72), and Apgar score <5 after 5 min, OR 0.71 (0.55-0.90).

Conclusion: In vaginal deliveries with pathologic FHR the use of FBS as an additional means of intrapartum fetal surveillance is associated with less vaginal operative deliveries, and with an improved short-term neonatal outcome.
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March 2007

Twenty-four-hour CTG monitoring: comparison of normal pregnancies of 25-30 weeks of gestation versus 36-42 weeks of gestation.

Arch Gynecol Obstet 2007 Jun 21;275(6):451-60. Epub 2006 Nov 21.

Department of Obstetrics and Perinatology, Universitiy Hospital Marburg, Baldingerstrasse, 35033 Marburg, Germany.

Objective: Routinely antepartal cardiotocogram (CTG) is recorded for 30 min in order to obtain normal resting phases (<30 min) or a decrease of irregulatory due to hypoxia (>30 min) or to differentiate these from each other. In case of early onset of hypoxia first pathological findings might only be seen by chance in incidentally recorded CTG. The goal of this study was, if a continuous 24-h CTG allows an earlier detection of beginning hypoxia in case of normal pregnancies of 36-42 weeks compared to pregnancies of 25-30 weeks of gestation, and if there are any differences between both groups concerning the qualitative and quantitative description or the detection of a circadian rhythm.

Methods: 21 patients in each group had 24-h CTGs by means of telemetry (Hewlett-Packard type 78101A, 80110A). In both study groups, fetal heart-rate tracing included a full qualitative and quantitative description. Comparison of the results of both groups was done to look for early signs of pathological findings concerning reduced fetal well-being and a potential day and night rhythm.

Results: In comparison to 36-42 weeks of pregnancies 25-30 weeks had significantly more physiological undulatory oscillation and less narrowed undulatory oscillation (P < 0.001), as well as less resting phases (P < 0.001). Baseline tachycardia and bradycardia showed significantly increasing quantity (P < 0.001).

Conclusion: Twenty-four-hour CTG is a good screening method to detect early onset of hypoxia in case of second and third trimester pregnancies and a big help to detect a fetus at risk earlier. In future computerized CTG-systems should be proved in this connection and should be compared with our study.
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June 2007

Suppression of IL-2 and IFN-gamma production in women with spontaneous preterm labor.

J Perinat Med 2006 ;34(1):20-7

Department of Clinical Chemistry and Molecular Diagnostics, Central Laboratory, University Hospital Giessen and Marburg, Baldingerstrasse, 35033 Marburg, Germany.

Aims: To determine the TH-1/TH-2 cytokine pattern in peripheral blood leukocytes (PBL) in late second- and third trimester in normal pregnancies, in comparison to patients with spontaneous preterm delivery (PTD; < 37 completed weeks' gestation).

Methods: A cross-sectional retrospective study was performed in a tertiary care obstetric unit with healthy non-pregnant women (n=7); healthy pregnant women (n=25); patients (n=25) with preterm labor (defined as uterine contractions or changes in cervical length). The phenotypic analysis of TH-1/TH-2 immune deviation was examined in PBL.

Results: 26% PTD (n=13) were recorded. Patients delivering at term (n=37, 74%) were characterized by an upregulation of IL-2, IFN-gamma and IL-4 production during weeks 20-25, followed by a strong suppression in cytokine production, except for TGF-beta. Towards the end of pregnancy cytokine levels returned to normal as observed in non-pregnant women. In contrast, PTD showed an inverse pattern for IL-2 and IFN-gamma with marked suppression in IL-2 and IFN-gamma production between weeks 20-25, followed by a strong stimulation of these cytokines. No differences were observed in IL-4 and TGF-beta production.

Conclusion: An inverse pattern in IL-2 and IFN-gamma production in PBLs between weeks 20-30 is seen in PTD as compared to patients delivering at term.
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January 2007

Assessment of rapid fetal fibronectin in predicting preterm delivery.

Obstet Gynecol 2005 Feb;105(2):280-4

Department of Obstetrics and Perinatal Medicine, Philipps University of Marburg, Pilgrinstein 3, D-35037 Marburg, Germany.

Objective: The aim of this study was to estimate the effectiveness of cervical fetal fibronectin assayed by the rapid fetal fibronectin assay in predicting preterm delivery in patients with signs or symptoms of preterm labor.

Methods: Patients with preterm labor between 24 and 34 weeks of gestation were included. At the time of speculum examination, fetal fibronectin samples were collected from the cervix. The probe was analyzed for fetal fibronectin using the rapid fetal fibronectin assay. Managing obstetricians were blinded to fetal fibronectin results. Outcome data were collected after delivery.

Results: One hundred seventy patients had fetal fibronectin samples and outcome data. The mean (+/- standard deviation) gestational age at delivery was 38.63 +/- 2.5 weeks among those with negative fetal fibronectin results (n = 124) and 35.71 +/- 3 weeks for those with positive results (n = 46; P < .001). The admission-to-delivery interval was 27.3 days shorter in the group with positive fetal fibronectin results (36.1 +/- 29.9 compared with 63.4 +/- 29.2; P < .001). The rapid fetal fibronectin assays were useful in predicting risk of delivery within 7, 14, or 21 days (sensitivity 81.8%, 87.5%, and 77.3%; specificity 76.7%, 79.2%, and 80.4; positive predictive value 19.6% [9/46], 30.4% [14/46], 37% [17/46]; negative predictive value 98.4% [122/124], 98.4% [122/124], and 96% [119/124], respectively).

Conclusion: In a population of patients with signs and symptoms of preterm labor, the presence of cervical fetal fibronectin is effective in predicting risk of delivery within 7, 14, or 21 days. The negative predictive values of fetal fibronectin using the Tli systems compared well with data from previous reports using enzyme-linked immunosorbent assay-based assays.

Level Of Evidence: III.
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February 2005

Assessment of fetal lung development by quantitative ultrasonic tissue characterization: a methodical study.

Prenat Diagn 2004 Sep;24(9):671-6

Department of Obstetrics and Perinatal Medicine, Philipps University, Marburg, Germany.

Objectives: This study was performed to evaluate the quantitative ultrasonic tissue characterization of the normal fetal lung development by using acoustic raw data captured after preprocessing.

Methods: One hundred and sixty-two patients with completed gestational ages between 22 and 37 weeks were enrolled in this study. Longitudinal and transverse sections of the fetal thorax and upper abdomen were imaged. A region of interest of constant size was defined and the tissue-specific gray scale was determined by using an interactive software.

Results: A total of 162 patients met the inclusion criteria. The echogenicity of the fetal lung showed a particular changing pattern during pregnancy: the mean gray value of the fetal lung (MGV) is almost the same as the MGV of the fetal liver at 22 and 23 weeks, decreases between 22 and 31 weeks and increases between 31 and 37 weeks. The MGV of the fetal liver decreases significantly from 24 weeks to 31 weeks and increases significantly again toward 37 weeks. We stated that the MGV of the lung is smaller than the MGV of the liver during 31 weeks of gestation and the relation reverses in late gestation. At term, the MGV of the liver is greater than the MGV of the lung. The lung-to-liver ratio is <1 between 24 and 29 weeks and >1 between 30 and 35 weeks.

Conclusion: The echogenicity of the fetal lung showed a particular changing pattern during pregnancy, which corresponds to morphologic changes of the fetal lung development.
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September 2004

Evaluation of quantitative ultrasound tissue characterization of the cervix and cervical length in the prediction of premature delivery for patients with spontaneous preterm labor.

Am J Obstet Gynecol 2003 Aug;189(2):532-9

Department of Obstetrics and Perinatal Medicine, Philipps University Marburg, Marburg, Germany.

Objective: This study was to evaluate the predictive value of the uterine cervix tissue with the use of quantitative ultrasound gray level analysis for preterm delivery.

Study Design: Sixty-eight patients with preterm labor between 20 and 35 weeks of gestation were included. When two-dimensional transvaginal ultrasound measurement of cervical length was completed, a region of interest of constant size was defined in the midsection of the posterior wall, and the tissue-specific gray scale was determined. Preterm delivery of <37 weeks of gestation was sought.

Results: Twenty-eight patients (41.2%) were delivered preterm. The risk for preterm delivery was increased significantly in patients with cervical length of /=4 (odds ratio, 3.44; 95% CI, 1.21-9.75), and with decreased mean gray scale value (odds ratio, 12.13; 95% CI, 3.69-39.88). Parity and uterine contractions were not significant as predictors for preterm delivery, although the risk for preterm delivery increased with higher parity (odds ratio, 1.8; 95% CI, 0.68-4.79). The risk for preterm delivery remained nearly the same by uterine contractions (odds ratio, 0.92; 95% CI, 0.28-3.01). A mean scale value of
Conclusion: Quantitative ultrasound tissue characterization of the uterine cervix predicts premature delivery and provides additional information in the prediction of potential premature delivery.
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August 2003