Publications by authors named "Christian Bamberg"

40 Publications

Update on twin-to-twin transfusion syndrome.

Best Pract Res Clin Obstet Gynaecol 2019 Jul 5;58:55-65. Epub 2019 Jan 5.

University Medical Center Hamburg-Eppendorf, Department of Obstetrics and Fetal Medicine, Hamburg, Germany.

Twin-to-twin transfusion syndrome (TTTS) is a serious complication that affects 10-15% of monochorionic multiple pregnancies. Communicating placental vessels on the chorionic plate between the donor and recipient twin are responsible for the imbalance of blood flow. There is evidence for the superiority of fetoscopic laser ablation over serial amnioreductions regarding survival and neurological outcome for stages II-IV TTTS. However, the optimal management of stage I is still debated. The "Solomon" technique showed a significant reduction in recurrent TTTS and post laser twin anemia-polycythemia sequence (TAPS) in comparison to the selective laser method without improvement in perinatal mortality or neonatal morbidity. Survival rates after fetoscopic laser surgery have significantly increased over the last 25 years. High volume centers report up to 70% double survival and at least one survivor in >90%. Long-term neurodevelopmental impairment occurs in about 10% of children after laser surgery. In this review we discuss the optimal management, innovations in laser technique, long-term neurodevelopmental outcome, and future aspects of TTTS treatment.
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http://dx.doi.org/10.1016/j.bpobgyn.2018.12.011DOI Listing
July 2019

Discordance of umbilical coiling index between recipients and donors in twin-twin transfusion syndrome.

Placenta 2019 01 18;76:19-22. Epub 2019 Jan 18.

Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Introduction: To compare the intertwin umbilical cord coiling in twin-twin transfusion syndrome (TTTS) before fetoscopic laser treatment and to correlate these with Doppler findings in both twins.

Methods: We performed a prospective study using three-dimensional (3D) ultrasound with color Doppler imaging of the umbilical cord in TTTS. Coiling index was measured as a reciprocal value of one complete vascular coil. Ultrasound hypocoiling was thus defined as < 0.2 coils/cm and hypercoiling as > 0.6 coils/cm, respectively. Umbilical artery pulsatility index (PI) and peak systolic velocity, middle cerebral artery peak systolic velocity and ductus venosus PI of flow-velocity waveformes of both twins were measured.

Results: We included 65 women in the study. The average gestational age was 21.1 ± 2.7 weeks. In 65 recipients and 56 donors coiling index could be quantified. The median (interquartile range) coiling index of recipient twins was significantly higher than of donors, 0.55 (0.41-0.68) vs. 0.26 (0.2-0.5); P < 0.0001. The proportions of abnormal intertwin coiling were significantly (P = 0.0015) different. Out of 65 recipient with coiling indices evaluation, 1 (1.5%) showed hypocoiled and 27 (41.5%) hypercoiled cords. In contrast, 27 donor twins (48.2%) showed hypocoiled and 5 (8.9%) hypercoiled umbilical cords. There were no significant correlations between the fetal Doppler values and coiling indices.

Discussion: Evaluation of umbilical cord coiling index using 3D color Doppler in both twins complicated by TTTS is feasible in both, donors and recipients. Coiling indices differ significantly between recipient and donor twins and do not correlate with Doppler findings.
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http://dx.doi.org/10.1016/j.placenta.2019.01.013DOI Listing
January 2019

The impact of antenatal factor XIII levels on postpartum haemorrhage: a prospective observational study.

Arch Gynecol Obstet 2019 02 3;299(2):421-430. Epub 2018 Dec 3.

Department of Obstetrics, Charité-University Medical Center, Augustenburger Platz 1, 13353, Berlin, Germany.

Purpose: Postpartum haemorrhage (PPH) is a leading cause of maternal mortality and morbidity. Our aim was to investigate the relationships between antenatal factor XIII (FXIII), fibrinogen levels, and blood loss at childbirth.

Methods: This prospective observational study evaluated an unselected cohort of pregnant women admitted for intended vaginal deliveries of singletons at term. To determine clotting factor levels, we obtained blood samples at a maximum of three days prior to vaginal delivery. A calibrated collecting drape was used to quantify blood loss in the third stage of labour. Moderate and severe PPH were diagnosed as blood losses ≥ 500 mL and ≥ 1000 mL, respectively. In a multiple logistic regression analysis, we determined whether coagulation factors and their interactions could independently predict (severe) PPH.

Results: We analysed 548 vaginal deliveries that occurred during the study period. Of those, 78 (14.2%) lost ≥ 500 mL and 18 (3.3%) lost ≥ 1000 mL of blood. The mean pre-delivery FXIII activity in women with PPH (79.33% ± 15.5) was significantly (p < 0.001) lower than in women without PPH (86.45% ± 14.6). A receiver operating characteristic curve analysis detected antenatal FXIII cutoff levels of 83.5% and 75.5% for PPH and severe PPH, respectively. The multiple logistic regression analysis showed that FXIII alone (p < 0.001) and its interaction with fibrinogen (p = 0.03) significantly predicted PPH. FXIII was not significantly correlated with blood loss among patients with severe PPH.

Conclusion: Our results suggested that antenatal FXIII levels may have a significant influence on PPH. The interaction between FXIII and fibrinogen might also provide slight advantages in forecasting PPH.
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http://dx.doi.org/10.1007/s00404-018-4980-5DOI Listing
February 2019

Cesarean scar niche and uterotomy closure technique.

Acta Obstet Gynecol Scand 2018 05 7;97(5):630. Epub 2018 Feb 7.

Department of Obstetrics, Charité-University Medical Center, Berlin, Germany.

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http://dx.doi.org/10.1111/aogs.13292DOI Listing
May 2018

Longitudinal transvaginal ultrasound evaluation of cesarean scar niche incidence and depth in the first two years after single- or double-layer uterotomy closure: a randomized controlled trial.

Acta Obstet Gynecol Scand 2017 Dec 21;96(12):1484-1489. Epub 2017 Sep 21.

Department of Obstetrics, Charité-University Medical Center, Berlin, Germany.

Introduction: Cesarean deliveries are the most common abdominal surgery procedure globally, and the optimal way to suture the hysterotomy remains a matter of debate. The aim of this study was to assess the incidence of cesarean scar niches and the depth after single- or double-layer uterine closure.

Material And Methods: We performed a randomized controlled trial in which women were allocated to three uterotomy suture techniques: continuous single-layer unlocked, continuous locked single-layer, or double-layer sutures. Transvaginal ultrasound was performed six weeks and 6-24 months after cesarean delivery [Clinicaltrials.gov (NCT02338388)].

Results: The study included 435 women. Six weeks after delivery, the incidence of niche was not significantly different between the groups (p = 0.52): 40% for single-layer unlocked, 32% for single-layer locked and 43% for double-layer sutures. The mean ± SD niche depths were 3.0 ± 1.4 mm for single-layer unlocked, 3.6 ± 1.7 mm for single-layer locked and 3.3 ± 1.3 mm for double-layer sutures (p = 1.0). There were no significant differences (p = 0.58) in niche incidence between the three groups at the second ultrasound follow up: 30% for single-layer unlocked, 23% for single-layer locked and 29% for double-layer sutures. The mean ± SD niche depth was 3.1 ± 1.5 mm after single-layer unlocked, 2.8 ± 1.5 mm after single-layer locked and 2.5 ± 1.2 mm after double-layer sutures (p = 0.61). There was a trend (p = 0.06) for the residual myometrium thickness to be thicker after double-layer repair at the long-term follow up.

Conclusions: The incidence of cesarean scar niche formation and the niche depth was independent of the hysterotomy closure technique.
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http://dx.doi.org/10.1111/aogs.13213DOI Listing
December 2017

Authors' Response to the Letter to the Editor: Single- vs. Double-Layer Closure of Hysterotomy at the Time of Cesarean Delivery.

Ultraschall Med 2017 08 14;38(4):449. Epub 2017 Jun 14.

Department of Obstetrics, Charité-University Medical Center, Berlin, Germany.

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http://dx.doi.org/10.1055/s-0043-113080DOI Listing
August 2017

In vivo evidence of significant levator ani muscle stretch on MR images of a live childbirth.

Am J Obstet Gynecol 2017 08 13;217(2):194.e1-194.e8. Epub 2017 Apr 13.

Department of Development and Regeneration, Cluster Organ Systems, Faculty of Medicine, KU Leuven, Leuven, Belgium. Electronic address:

Objective: Vaginal childbirth is believed to be a significant risk factor for the development of pelvic floor dysfunction later in life. Previous studies have explored the use of medical imaging and simulations of childbirth to determine the stretch in the levator ani muscle. A report in 2012 has recorded magnetic resonance images of a live childbirth of a 24 year old woman giving birth vaginally for the second time, using a 1.0 Tesla open, high-field scanner. Our objective was to determine the stretch ratios in the levator muscle using these magnetic resonance images of live childbirth.

Study Design: Three-dimensional magnetic resonance image sequences were obtained to visualize coronal and axial planes before and after the childbirth. These images were obtained before the expulsion phase without pushing and were used to reconstruct the levator muscle and the fetal head in 3 dimensions. The fetal head was approximated to be an ellipsoid, and it is assumed that its middle section is visible in dynamic magnetic resonance images. Assuming incompressibility, the full deformation field of the fetal head is then calculated. Real-time cine magnetic resonance images were acquired for the during the expulsion phase, occurring over 2 contractions in the midsagittal plane. The levator muscle stretch is estimated using a custom program. The program calculates points of contact between the fetal head ellipsoid and the levator ani muscle model as the head descends down the birth canal and moves them orthogonal to its surface. Circumferential stretch was calculated to represent the extension needed to allow the passage of the fetal head.

Results: Starting from a position in the preexpulsion phase, the levator muscle experiences a maximum circumferential stretch of 248% on the posterior-medial portion of the levator ani muscle, as shown in previously published finite element simulations. However, the maximal stretch was notably less than that predicted by finite element models. This is because our baseline 3-dimensional model of the levator muscle is created from images taken shortly before expulsion and thus is already in a stretched state. Furthermore, the finite element models are created from images of a healthy nulliparous woman, while this study uses images from a para 2 woman.

Conclusion: This study is the first attempt to estimate the stretch in levator ani muscle using magnetic resonance images of a live childbirth. The stretch was significant and the locations corroborate with previous findings of finite element models.
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http://dx.doi.org/10.1016/j.ajog.2017.04.014DOI Listing
August 2017

A Prospective Randomized Clinical Trial of Single vs. Double Layer Closure of Hysterotomy at the Time of Cesarean Delivery: The Effect on Uterine Scar Thickness.

Ultraschall Med 2018 Jun 14;39(3):343-351. Epub 2016 Sep 14.

Department of Obstetrics, Charité-University Medical Center, Berlin, Germany.

Purpose:  We undertook a randomized clinical trial to examine the outcome of a single vs. a double layer uterine closure using ultrasound to assess uterine scar thickness.

Materials And Methods:  Participating women were allocated to one of three uterotomy suture techniques: continuous single layer unlocked suturing, continuous locked single layer suturing, or double layer suturing. Transvaginal ultrasound of uterine scar thickness was performed 6 weeks and 6 - 24 months after Cesarean delivery. Sonographers were blinded to the closure technique.

Results:  An "intent-to-treat" and "as treated" ANOVA analysis included 435 patients (n = 149 single layer unlocked suturing, n = 157 single layer locked suturing, and n = 129 double layer suturing). 6 weeks postpartum, the median scar thickness did not differ among the three groups: 10.0 (8.5 - 12.3 mm) single layer unlocked vs. 10.1 (8.2 - 12.7 mm) single layer locked vs. 10.8 (8.1 - 12.8 mm) double layer; (p = 0.84). At the time of the second follow-up, the uterine scar was not significantly (p = 0.06) thicker if the uterus had been closed with a double layer closure 7.3 (5.7 - 9.1 mm), compared to single layer unlocked 6.4 (5.0 - 8.8 mm) or locked suturing techniques 6.8 (5.2 - 8.7 mm). Women who underwent primary or elective Cesarean delivery showed a significantly (p = 0.03, p = 0.02, "as treated") increased median scar thickness after double layer closure vs. single layer unlocked suture.

Conclusion:  A double layer closure of the hysterotomy is associated with a thicker myometrium scar only in primary or elective Cesarean delivery patients.
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http://dx.doi.org/10.1055/s-0042-112223DOI Listing
June 2018

Can prepartum thromboelastometry-derived parameters and fibrinogen levels really predict postpartum hemorrhage?

J Perinat Med 2017 May;45(4):427-435

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Background: Decreased postpartum rotational thromboelastometric parameters of coagulation (ROTEM®) and fibrinogen levels have been associated with postpartum hemorrhage (PPH). However, the predictive power of prepartum ROTEM® parameters and fibrinogen levels (Fbgpre) for PPH remains unknown.

Methods: This prospective observational pilot study included 217 healthy pregnant women. Maximum clot firmness (FIBTEM-MCF), fibrinogen levels and standard coagulation parameters were measured upon admission to the delivery room for labor and within 1 h after vaginal delivery. Blood loss was measured with a calibrated collecting drape during the third stage of labor. PPH was defined as blood loss ≥500 mL. Predictors for bleeding were identified via receiver operating characteristic analyses and bivariate and multivariate regression analyses.

Results: Women with and without PPH did not differ in median FIBTEM-MCF [23 mm (25th percentile 20 mm, 75th percentile 26 mm) vs. 23 mm (19 mm, 26 mm), respectively; P=0.710] or mean Fbgpre (4.57±0.77 g/L vs. 4.45±0.86 g/L, respectively; P=0.431). Blood loss and prepartum coagulation parameters were not correlated (FIBTEM-MCF, rs=-0.055, P=0.431; Fbgpre, rs=-0.017, P=0.810). The areas under the curves (predictive power for PPH) for FIBTEM-MCF and Fbgpre and were 0.52 (0.41-0.64, P=0.699) and 0.53 [95% confidence interval (95% CI) 0.40-0.65, P=0.644], respectively. Neither FIBTEM-MCF nor Fbgpre was associated with PPH. However, primiparity [odds ratio (OR) 4.27, 95% CI 1.32-13.80, P=0.015) and urgent cesarean section (2.77, 1.00-7.67, P=0.050) were independent predictors of PPH.

Conclusions: ROTEM® parameters, Fbgpre and postpartum blood loss were not associated, nor did these factors predict PPH. Sufficiently powered prospective studies are needed to confirm these results.
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http://dx.doi.org/10.1515/jpm-2016-0009DOI Listing
May 2017

Evaluating fetal head dimension changes during labor using open magnetic resonance imaging.

J Perinat Med 2017 Apr;45(3):305-308

Department of Obstetrics, Charité-University Medical Center, Berlin.

Aim: Fetal skull molding is important for the adaptation of the head to the birth canal during vaginal delivery. Importantly, the fetal head must rotate around the maternal symphysis pubis. The goals of this analysis were to observe a human birth in real-time using an open magnetic resonance imaging (MRI) scanner and describe the fetal head configuration during expulsion.

Methods: Real-time cinematic MRI series (TSE single-shot sequence, TR 1600 ms, TE 150 ms) were acquired from the midsagittal plane of the maternal pelvis during the active second stage of labor at 37 weeks of gestation. Frame-by-frame analyses were performed to measure the frontooccipital diameter (FOD) and distance from the vertex to the base of the fetal skull.

Results: During vaginal delivery in an occiput anterior position, the initial FOD was 10.3 cm. When expulsion began, the fetal skull was deformed and elongated, with the FOD increasing to 10.8 cm and 11.2 cm at crowning. In contrast, the distance from the vertex to the base of the skull was reduced from 6.4 cm to 5.6 cm at expulsion.

Conclusions: Fetal head molding is the change in the fetal head due to the forces of labor. The biomechanics of this process are poorly understood. Our visualization of the normal mechanism of late second-stage labor shows that MRI technology can for the first time help define the changes in the diameters of the fetal head during active labor.
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http://dx.doi.org/10.1515/jpm-2016-0005DOI Listing
April 2017

Predelivery maternal fibrinogen as a predictor of blood loss after vaginal delivery.

Arch Gynecol Obstet 2016 10 22;294(4):745-51. Epub 2016 Feb 22.

Department of Obstetrics, Charité-University Medical Center, Berlin, Germany.

Purpose: The present study investigated whether fibrinogen level during the first stage of labor is associated with bleeding severity in the third stage of labor.

Methods: We prospectively enrolled 1019 pregnant women with planned vaginal delivery. Upon admission to delivery, maternal fibrinogen levels, hemoglobin content, and coagulation parameters were evaluated. Blood loss in the third stage of labor was systematically measured using a calibrated collecting drape. Univariate and multivariate analyses were performed to identify predictors of PPH (blood loss ≥500 mL) and S-PPH (blood loss ≥1000 mL).

Results: Among 809 vaginal deliveries, mean maternal predelivery fibrinogen was 4.65 ± 0.77 g/L, PPH incidence was 12 %, S-PPH incidence was 3.5 %, and median blood loss was 250 mL. Fibrinogen levels were significantly lower in women with S-PPH (4.22 ± 0.82 g/L) than without S-PPH (4.67 ± 0.75 g/L; p = 0.004), but did not significantly differ between women with PPH (4.67 ± 0.84 g/L) and those without PPH (4.67 ± 0.75 g/L; p = 0.985). Instrumental delivery and predelivery fibrinogen levels were independent predictors of S-PPH. Primiparous status, birth weight >4000 g, genital tract laceration, episiotomy and instrumental delivery were independent predictors of PPH.

Conclusion: For each 1 g/L increase of predelivery fibrinogen level, the risk of S-PPH after vaginal delivery decreases by a factor of 0.405 (95 % CI 0.219-0.750; p = 0.004).
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http://dx.doi.org/10.1007/s00404-016-4031-zDOI Listing
October 2016

Genetic low nephron number hypertension is associated with altered expression of key components of the renin-angiotensin system during nephrogenesis.

J Perinat Med 2016 Aug;44(6):705-9

Aim: This study investigates key components of the renin-angiotensin system (RAS) which play a central role in nephrogenesis and possibly in fetal programming of arterial hypertension in adult life.

Methods: We compared a genetic rat model with inborn nephron deficit, the Munich Wistar Fromter rat (MWF), to normotensive Wistar rats during nephrogenesis at day 19 of fetal development (E19) and at postnatal day 7 (D7).

Results: At E19 renal mRNA of angiotensin II type 1a (AT1a) (-50%, P<0.05) and type 1b (AT1b) (-55%, P<0.05) receptors were significantly decreased and renal mRNA expression of angiotensin II type 2 (AT2) receptor was fivefold increased in MWF (n=8) as compared to Wistar rats (n=8). At D7 renal mRNA expression of AT1a (-42%, P<0.05) remained lower in MWF (n=8) as compared to Wistar (n=7). Renal mRNA expression of AT2 (-30%, P>0.05) decreased in MWF (n=8) to about the level of the Wistar control (n=6).

Conclusions: Altered fetal expression of key molecules of the renin-angiotensin system in MWF indicates a possible role in genetic low nephron number hypertension.
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http://dx.doi.org/10.1515/jpm-2015-0159DOI Listing
August 2016

Birth weight-related percentiles of brain ventricular system as a tool for assessment of posthemorrhagic hydrocephalus and ventricular enlargement.

J Perinat Med 2016 Mar;44(2):179-85

Besides remarkable improvements of neonatal medical therapy, neurological morbidity remains a major concern in preterm infants. In particular, intracranial hemorrhage is a severe complication strongly correlated to poor neurological outcome. For early clinical assessment of intracranial hemorrhage and its impact on the ventricular system, cranial sonography is an important bedside diagnostic tool. Reference values of ventricular sizes are available in relation to gestational age (GA). So far, it has not been demonstrated that ventricular size values are also reliable in relation to birth weight (BW). In this study, we performed cranial ultrasonography in 250 preterm and term newborn infants. Measurements of the intracranial ventricular system by cranial ultrasound examination were performed within 72 h after birth. We determined ventricular index, anterior horn width, width of the third ventricle, width and length of the fourth ventricle for statistical analysis in relation to BW and GA. GA ranged from 23 weeks, 3 days to 42 weeks, 1 day (mean: 33 weeks), BW ranged from 345 to 5620 g (mean: 2146 g). Ventricular index and fourth ventricle width revealed a significant correlation to birth weight with r=0.75, each. A significant correlation to birth weight was also obtained for width and length of the third ventricle (r=0.55 and 0.47, respectively). Correlations obtained for ventricular measures in relation to GA were similar to those referring to BW. In preterm and term infants, ventricular sizes in relation to BW seem reliable for assessment and monitoring of ventricular pathologies, i.e. after intracranial hemorrhage.
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http://dx.doi.org/10.1515/jpm-2015-0085DOI Listing
March 2016

Evaluation of measured postpartum blood loss after vaginal delivery using a collector bag in relation to postpartum hemorrhage management strategies: a prospective observational study.

J Perinat Med 2016 May;44(4):433-9

Aim: To evaluate the incidence of postpartum hemorrhage (PPH) and severe PPH via routine use of a pelvic drape to objectively measure blood loss after vaginal delivery in connection with PPH management.

Methods: This prospective observational study was undertaken at the obstetrical department of the Charité University Hospital from December 2011 to May 2013 and evaluated an unselected cohort of planned vaginal deliveries (n=1019 live singletons at term). A calibrated collecting drape was used to meassure blood loss in the third stage of labor. PPH and severe PPH were defined as blood loss ≥500 mL and ≥1000 mL, respectively. Maternal hemoglobin content was evaluated at admission to delivery and at the first day after childbirth.

Results: During the study period, 809 vaginal deliveries were analysed. Direct measurement revealed a median blood loss of 250 mL. The incidences of PPH and severe PPH were 15% and 3%, respectively. Mean maternal hemoglobin content at admission was 11.9±1.1 g/dL, with a mean decrease of 1.0±1.1 g/dL. Blood loss measured after vaginal delivery correlated significantly with maternal hemoglobin decrease.

Conclusions: This study suggests that PPH incidence may be higher than indicated by population-based data. Underbuttocks drapes are simple, objective bedside tools to diagnose PPH. Blood loss should be quantified systematically if PPH is suspected.
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http://dx.doi.org/10.1515/jpm-2015-0200DOI Listing
May 2016

Pathogenic mitochondrial mt-tRNA(Ala) variants are uniquely associated with isolated myopathy.

Eur J Hum Genet 2015 Dec 15;23(12):1735-8. Epub 2015 Apr 15.

Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, UK.

Pathogenic mitochondrial DNA (mtDNA) point mutations are associated with a wide range of clinical phenotypes, often involving multiple organ systems. We report two patients with isolated myopathy owing to novel mt-tRNA(Ala) variants. Muscle biopsy revealed extensive histopathological findings including cytochrome c oxidase (COX)-deficient fibres. Pyrosequencing confirmed mtDNA heteroplasmy for both mutations (m.5631G>A and m.5610G>A) whilst single-muscle fibre segregation studies (revealing statistically significant higher mutation loads in COX-deficient fibres than in COX-positive fibres), hierarchical mutation segregation within patient tissues and decreased steady-state mt-tRNA(Ala) levels all provide compelling evidence of pathogenicity. Interestingly, both patients showed very high-mutation levels in all tissues, inferring that the threshold for impairment of oxidative phosphorylation, as evidenced by COX deficiency, appears to be extremely high for these mt-tRNA(Ala) variants. Previously described mt-tRNA(Ala) mutations are also associated with a pure myopathic phenotype and demonstrate very high mtDNA heteroplasmy thresholds, inferring at least some genotype:phenotype correlation for mutations within this particular mt-tRNA gene.
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http://dx.doi.org/10.1038/ejhg.2015.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519577PMC
December 2015

Genetic low nephron number hypertension is associated with altered expression of osteopontin and CD44 during nephrogenesis.

J Perinat Med 2013 May;41(3):295-9

Aims: The study set out to investigate whether the osteopontin (OPN)-CD44-integrin-receptor-system is differently regulated during nephrogenesis in inborn nephron deficit, a major determinant of human primary hypertension and cardiovascular disease in adult life.

Methods: We compared a genetic rat model with an inherited nephron deficit, the Munich-Wistar-Froemter rat (MWF), to normotensive Wistar rats during nephrogenesis at day 19 of fetal development (E19) and at postpartal day 7 (D7).

Results: Renal OPN mRNA (-75%, P<0.05) and protein expression (-38%, P<0.05) were strongly decreased at E19 in MWF compared to Wistar. Renal mRNA-expression of CD44 was increased at E19 in MWF (+271%, P<0.05). At D7, renal OPN protein expression was increased (+115%, P<0.05) and renal mRNA-expression of CD44 remained elevated compared to Wistar control (+127%, P<0.05).

Conclusions: Altered fetal expression of the OPN-CD44-integrin-receptor-system in the MWF model points to a possible role in low nephron number hypertension and cardiovascular disease.
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http://dx.doi.org/10.1515/jpm-2012-0178DOI Listing
May 2013

Prenatal detection and consequences of fetal macrosomia.

Fetal Diagn Ther 2013 5;33(3):143-8. Epub 2012 Dec 5.

Department of Obstetrics, Charité University Medical Center, Berlin, Germany.

Macrosomia is diagnosed when excessive intrauterine fetal growth occurs and the birth weight surpasses an established limit. The causes and risk factors for fetal macrosomia are diverse. Pregnancies with fetal macrosomia are considered high risk and require intensive antenatal care. Prenatal ultrasound appears to be the best method for performing weight estimates before birth, as the correct birth weight is often underestimated when using biometric formulae to determine the fetal weight. Three-dimensional volume sonography has been shown to improve estimates of fetal weight by including limbs volumes. The recent Hart formula has been specifically developed for fetal macrosomia estimation and appears to improve accuracy. Delivery of a macrosomic baby is also high risk and should be performed in tertiary centres with experienced obstetricians.
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http://dx.doi.org/10.1159/000341813DOI Listing
December 2013

Value of Doppler sonography near term: can umbilical and uterine artery indices in low-risk pregnancies predict perinatal outcome?

J Perinat Med 2013 Mar;41(2):165-70

Department of Obstetrics, Charité University Medical Center, Berlin, Germany.

Aim: The goal of this study was to evaluate the umbilical and uterine Doppler velocimetry waveforms for predicting the perinatal outcome of low-risk pregnancies at term.

Methods: We prospectively recruited 514 women with low risk pregnancies and performed umbilical and uterine artery Doppler assessments between 37 and 41 weeks of gestation. Ultrasound measurements (completed in 365 patients) were correlated with the perinatal outcome.

Results: The velocimetry waveforms of the umbilical artery were significantly associated with birthweight, placental weight, and postpartal umbilical artery pH. Low pH, placental weight, and birthweight were correlated with increasing pulsatility index (PI) and resistance index (RI). An umbilical artery PI > 1.2 and a uterine artery RI > 0.5 were associated with statistically higher rates of infants that were small for gestational age (SGA). Also, high cesarean delivery rates were correlated with an umbilical artery PI > 1.2.

Conclusions: In our low-risk pregnancies population, the elevated umbilical artery indices at term appeared to be associated with the higher rates of infants that were SGA and cesarean deliveries. The Doppler waveforms at term had low prognostic value for predicting neonatal acidosis or decreased Apgar scores.
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http://dx.doi.org/10.1515/jpm-2012-0042DOI Listing
March 2013

Proteomic analysis of midtrimester amniotic fluid to identify novel biomarkers for preterm delivery.

J Matern Fetal Neonatal Med 2012 Dec 24;25(12):2488-93. Epub 2012 Aug 24.

Department of Gynecology, Berlin Centrum for Regenerative Therapies, Charité-University Hospital, Berlin, Germany.

Objective: The aim of this study was to identify possible biomarkers for preterm delivery by analyzing midtrimester amniotic fluid.

Methods: Thirty-two amniotic fluid samples were studied; 16 patients had a spontaneous preterm delivery and 16 patients delivered at term. The proteomic technique consisted of surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) using different types of solid chromatographic chips (Q10, CM10 and IMAC30).

Results: Mass spectrometry tracings were obtained from the amniotic fluids of both patients who delivered preterm and patients who delivered at term. Seven potential markers were identified to be differentially expressed in patients who delivered preterm.

Conclusions: Proteomic analysis of amniotic fluid obtained in the midtrimester reveals the presence of a set of proteins in patients at risk for preterm delivery.
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http://dx.doi.org/10.3109/14767058.2012.712565DOI Listing
December 2012

Maternal characteristics and twin gestation outcomes over 10 years: impact of conception methods.

Fertil Steril 2012 Jul 17;98(1):95-101. Epub 2012 May 17.

Department of Obstetrics, Charité University Medical Center, Berlin, Germany.

Objective: To compare maternal characteristics and obstetric outcomes of spontaneously conceived (SC) and after-fertility treatment (FT) twins.

Design: Retrospective study.

Setting: Single tertiary center (university hospital).

Patient(s): All twin pregnancies (n = 1,239) delivered ≥ 24 weeks of gestation and classified by the mode of conception.

Intervention(s): None.

Main Outcome Measure(s): Maternal age, prematurity, preterm rupture of membranes (PROM), delivery mode, cervical insufficiency, preeclampsia/HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome, gestational diabetes, and postpartum hemorrhage.

Result(s): Of 1,239 mothers evaluated, 34.4% received FT. We observed a continuous 3.2-year mean increase in maternal age over time in the FT population. The FT group had statistically significantly higher rates of women ≥ 35 years of age versus the SC group (37.6% vs. 22.9%). Mean maternal age (32.5 vs. 30.1 years) and the rates of cesarean delivery (72.3% vs. 63.9%), dichorionic twin prematurity (67.7% vs. 59.6%), postpartum hemorrhage (9.9% vs. 6%), PROM (2.3% vs. 0.6%), and cervical insufficiency (17.6% vs. 10%) were statistically significantly higher in the FT group. Preeclampsia/HELLP syndrome and gestational diabetes showed no significantly significant difference.

Conclusion(s): Mothers of twins after FT were statistically significantly older and had higher rates of prematurity, cesarean delivery, and obstetric morbidity.
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http://dx.doi.org/10.1016/j.fertnstert.2012.04.009DOI Listing
July 2012

Human birth observed in real-time open magnetic resonance imaging.

Am J Obstet Gynecol 2012 Jun 13;206(6):505.e1-6. Epub 2012 Jan 13.

Department of Obstetrics, Charité University Hospital Berlin, Berlin, Germany.

Objective: Knowledge about the mechanism of labor is based on assumptions and radiographic studies performed decades ago. The goal of this study was to describe the relationship between the fetus and the pelvis as the fetus travels through the birth canal, using an open magnetic resonance imaging (MRI) scanner.

Study Design: The design of the study used a real-time MRI series during delivery of the fetal head.

Results: Delivery occurred by progressive head extension. However, extension was a very late movement that was observed when the occiput was in close contact with the inferior margin of the symphysis pubis, occurring simultaneously with gliding downward of the fetal head.

Conclusion: This observational study shows, for the first time, that birth can be analyzed with real-time MRI. MRI technology allows assessment of maternal and fetal anatomy during labor and delivery.
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http://dx.doi.org/10.1016/j.ajog.2012.01.011DOI Listing
June 2012

Angle of progression measurements of fetal head at term: a systematic comparison between open magnetic resonance imaging and transperineal ultrasound.

Am J Obstet Gynecol 2012 Feb 25;206(2):161.e1-5. Epub 2011 Oct 25.

Department of Obstetrics, Charité University Hospital, Berlin, Germany.

Objective: During labor, transperineal sonography is increasingly used to evaluate fetal head descent. The aim of this study was to compare the angle of progression assessed by open magnetic resonance imaging (MRI) vs transperineal ultrasound.

Study Design: A total of 31 pregnant women at term (>37 weeks), who were not in labor, underwent MRI in an open 1.0-T system. A midsagittal plane of the maternal pelvis was stored. Immediately after, without changing the supine position, a transperineal ultrasound was performed. The angle of progression was measured offline by transperineal ultrasound and MRI.

Results: The angles of progression measured by transperineal ultrasound (mean, 79.05 degrees; SD 11.44) and MRI (mean, 80.48 degrees; SD 11.06) correlated significantly (P < .001). The intraclass correlation coefficient between the 2 methods was 0.89 (95% confidence interval, 0.78-0.94).

Conclusion: The angle of progression measurements obtained by transperineal ultrasound and open MRI showed very good agreement.
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http://dx.doi.org/10.1016/j.ajog.2011.10.867DOI Listing
February 2012

Correlation of midtrimester amniotic fluid cytokine concentrations with adverse pregnancy outcome in terms of spontaneous abortion, preterm birth, and preeclampsia.

J Matern Fetal Neonatal Med 2012 Jun 5;25(6):812-7. Epub 2011 Jul 5.

Department of Obstetrics, Charité-University Hospital, Berlin, Germany.

Objective: To assess midtrimester amniotic fluid concentrations of three major proinflammatory cytokines (IL-6, IL-8, and TNF-α) in asymptomatic pregnancies with adverse outcomes.

Methods: A prospective follow up study at the Charité University Hospital, Berlin, Germany of women with uncomplicated singleton pregnancies at second trimester and amniocentesis. Concentrations of IL-6, IL-8, and TNF-α were measured by enzyme-linked immunosorbent assay following amniotic fluid assessment by midtrimester amniocentesis performed from gestation days 15 weeks 0 days up to 20 weeks 6 days. Values from normal pregnancies were compared to those from pregnancies having adverse outcomes of spontaneous abortion, preterm delivery, preeclampsia, or eclampsia. Main outcome measure IL-6, IL-8 and TNF-α in relation to adverse pregnancy outcome.

Results: A total of 298 consecutive patients were evaluated. Median patient age was 35 years (range 19-43). Controls consisted of 273 women who delivered without further complications after 37 weeks gestation. The range values of IL-6, IL-8, and TNF-α in the control group were 4.9-2620 pg/mL, 36.2-5843 pg/mL, and 8.0-28.2 pg/mL, respectively. Patients with adverse pregnancy outcome (n = 25) were classified into three groups: spontaneous abortion group (n = 4), preterm delivery group (n = 17), and preeclampsia/eclampsia group (n = 4). There were no significant differences in IL-6, IL-8, and TNF-α between controls and study groups, regardless of the type of complication (p > 0.05).

Conclusion: Midtrimester amniotic fluid concentrations of the proinflammatory cytokines IL-6, IL-8, and TNF-α are not predictive of adverse pregnancy outcome in terms of spontaneous abortion, preterm delivery or preeclampsia/eclampsia in our study population.
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http://dx.doi.org/10.3109/14767058.2011.587918DOI Listing
June 2012

Mid-trimester amniotic fluid concentrations of the proinflammatory cytokines IL-6, IL-8, TNF-α, and lipopolysaccharide binding protein in normal pregnancies: a prospective evaluation according to parity, gestational age, and fetal gender.

J Perinat Med 2011 07 24;39(4):403-9. Epub 2011 Jun 24.

Department of Obstetrics, Charité-University Hospital, Berlin, Germany.

Objective: To assess mid-trimester amniotic fluid concentrations of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and lipopolysaccharide binding protein (LBP) in pregnancies with normal outcome and correlate them with gestational week (GW), parity, and fetal gender.

Methods: Cytokine concentrations were measured within a week of amniocentesis during GW 15+0 to 20+6 and correlated with GW at birth, parity, and fetal gender.

Results: After exclusion of women with an adverse pregnancy outcome or those lost to follow-up, 273 consecutive patients were evaluated (median parity: 1; range: 0-5). Ranges for IL-6, IL-8, TNF-α, and LBP were 4.9-2620 pg/mL, 36.2-5843 pg/mL, 8.0-28.2 pg/mL, and 0.06-1.9 μg/mL, respectively. IL-6, IL-8, and LBP values did not respectively differ among time points, but TNF-α values did between the 15(th) and 16(th) and the 15(th) and 18(th) weeks of gestation (P<0.05). No significant correlations between cytokine levels and parity or fetal gender were identified.

Conclusions: Cytokine concentrations in amniotic fluid during the mid-trimester did not differ with parity or fetal gender. IL-6, IL-8, and LBP levels appeared stable with GW, whereas GW significantly influenced TNF-α concentrations. Further analyses are warranted to establish the role of cytokines in predicting adverse pregnancy outcomes.
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http://dx.doi.org/10.1515/jpm.2011.041DOI Listing
July 2011

Prenatal two- and three-dimensional imaging in two cases of severe penoscrotal hypospadias.

J Clin Ultrasound 2011 Nov-Dec;39(9):539-43. Epub 2011 May 2.

Department of Obstetrics, Charité University Hospital, Berlin, Germany.

We present the prenatal two- and three-dimensional (3D) ultrasound (US) findings in two cases of severe penoscrotal hypospadias. 3D sonography was used for better definition of ambiguous genitalia. The images were compared with postnatal clinical features. Despite hypospadias being the most common urogenital anomaly of male neonates, the diagnosis is often missed before birth. Performing prenatal ultrasound should include the study of genitals, not only determining the sex.
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http://dx.doi.org/10.1002/jcu.20832DOI Listing
February 2012

Offspring sex determines the impact of the maternal ACE I/D polymorphism on maternal glycaemic control during the last weeks of pregnancy.

J Renin Angiotensin Aldosterone Syst 2011 Sep 10;12(3):254-61. Epub 2011 Mar 10.

Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.

Unlabelled: HYPOTHESIS/ INTRODUCTION: : We recently demonstrated that fetal sex may affect maternal glycaemic control in genetically prone mothers. We tested the hypothesis that fetal sex/fetal Y/X chromosomes might affect maternal glycaemic control during pregnancy depending on the maternal angiotensin converting enzyme (ACE) I/D polymorphism.

Material And Methods: : One thousand, three hundred and thirty-two Caucasian women without pre-existing diabetes and pre-existing hypertension with singleton pregnancies delivering consecutively at the Charité obstetrics department were genotyped. Glycaemic control was analysed by measuring total glycated haemoglobin at birth. Correction for confounding factors and multiple testing was done.

Results: : Maternal ACE I/D polymorphism showed significant interaction with fetal sex concerning maternal total glycated haemoglobin. Total glycated haemoglobin in DD mothers delivering boys was 6.42 ± 0.70% vs. 6.21 ± 0.66% in DD mother delivering girls (p < 0.005), whereas the II carrying mothers showed the opposite effect. II mothers delivering a girl had a higher (p = 0.044) total glycated haemoglobin at birth (6.40 ± 0.80%) compared to II mothers delivering boys (6.21 ± 0.81%). There was no interaction of the ACE I/D polymorphism and fetal sex with respect to new onset proteinuria, new onset edema and pregnancy-induced hypertension.

Conclusions: : Maternal glycaemic control during the last weeks of pregnancy seems to be influenced by an interaction of the ACE I/D genotyp and fetal sex.
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http://dx.doi.org/10.1177/1470320310387843DOI Listing
September 2011

Quality monitoring of acute stroke care in Rhineland-Palatinate, Germany, 2001-2006.

Stroke 2010 Jul 3;41(7):1495-500. Epub 2010 Jun 3.

Department of Neurology, Klinikum Ludwigshafen, Ludwigshafen am Rhein, Germany.

Background And Purpose: Quality monitoring projects are useful tools to improve the quality and to assess temporal trends of stroke care in larger populations.

Methods: In Rhineland-Palatinate, Germany, a statewide, hospital-based, acute stroke care quality monitoring project was started in 2001. Initially, participation was mandatory for all hospitals with dedicated stroke units and from 2006 onward was mandatory for all hospitals. Quality monitoring included a structured data assessment and quality indicators for procedural measures.

Results: Between 2001 and 2006, the numbers of patients registered annually (N=6389 vs N=10 610), admission <3 hours after stroke onset (28.2% vs 34.6%), admission via emergency medical systems (38.1% vs 50.3%), and treatment in stroke units (44.3% vs 59.5%) increased significantly (P<0.0001, respectively). In ischemic stroke, use of thrombolytic therapy increased (for patients admitted <3 hours after onset, 6.5% vs 14.1%), whereas therapy with high-dose heparin declined (24.5% vs 6.0%, P<0.0001). Several quality indicators (performance of neuroimaging and Doppler/duplex sonography, neuroimaging <3 hours after admission) showed stable results at a high level; more patients received echocardiography (62.2% vs 74.0%), but fewer patients were rapidly examined by extracranial Doppler/duplex sonography (68.7% vs 62.8%, P<0.0001). Diagnosis and treatment of hypertension and hyperlipidemia, use of aspirin and combined aspirin/dipyridamole, and diagnosis of atrial fibrillation increased (P<0.0001, respectively). Use of oral anticoagulation remained stable at approximately 38% of patients with cardioembolism.

Conclusions: Although these results reflect high standards of acute stroke care and improvements regarding early admission, thrombolytic therapy, and several secondary preventive measures, there is still the potential for further improvement regarding thrombolysis, use of oral anticoagulation and statins, and admission to stroke units, for example.
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http://dx.doi.org/10.1161/STROKEAHA.110.582239DOI Listing
July 2010

Pregnancy outcome in patients with complex pulmonary atresia: case report and review of the literature.

Eur J Heart Fail 2010 Feb 2;12(2):202-7. Epub 2010 Jan 2.

Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie, Charité-Universitätsmedizin Berlin, CCM, Charitéplatz 1, D-10117 Berlin, Germany.

Pulmonary atresia, a rare and complex congenital heart disease, is characterized by the absence of the central pulmonary artery and by the presence of a ventricular septal defect and aortopulmonary collaterals. Pregnancy reports concerning maternal and offspring outcome after palliative operation or repaired pulmonary atresia are sparse. We report here on the outcome of pregnancy in a woman, aged 36, with complex pulmonary atresia in whom palliative operation had been performed at the age of 23. We review the medical literature on pregnancy course as well as maternal and foetal outcome in cases involving this maternal congenital heart disease.
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http://dx.doi.org/10.1093/eurjhf/hfp192DOI Listing
February 2010

Interaction of maternal peroxisome proliferator-activated receptor gamma2 Pro12Ala polymorphism with fetal sex affects maternal glycemic control during pregnancy.

Pharmacogenet Genomics 2010 Feb;20(2):139-42

Department of Pediatrics, Institute of Pharmacology, Charité, Berlin, Germany.

It was suggested that fetal sex may substantially affect maternal glycemic control during pregnancy in genetically susceptible mothers. The peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism is known to affect glycemic control and may act in a sex-specific manner. This polymorphism is thus an attractive candidate to test this hypothesis using a second independent functionally relevant polymorphism. We analyzed the impact of fetal sex on maternal glycemic control during pregnancy in relation to the maternal PPARgamma2 Pro12Ala polymorphism. Two-thousand fourteen Caucasian women without preexisting diabetes and preexisting hypertension with singleton pregnancies delivering consecutively at the Charité obstetrics department were genotyped. Glycemic control was analyzed by measuring total glycated hemoglobin at birth. Correction for confounding factors and multiple testing was considered in the analysis. The maternal PPARgamma2 Pro12Ala polymorphism without consideration of fetal sex had no effect on blood pressure, new onset of proteinuria and total glycated hemoglobin at delivery. Mothers carrying both G alleles (GG genotype) delivering a girl had a higher (P = 0.015) total glycated hemoglobin (6.81 or - 0.50%) versus mothers carrying the same alleles but delivering boys (5.85 + or - 0.58%). Comparing mothers with the GG genotype delivering girls with mothers with CC or CG genotypes also delivering girls (6.32 + or - 0.72%) revealed a significantly higher maternal total glycated hemoglobin at delivery in the former group (P < 0.009). Fetal sex/sex chromosomes may substantially affect maternal glycemic control in mothers who are carriers of the GG alleles of the PPARgamma2 Pro12Ala polymorphism.
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http://dx.doi.org/10.1097/FPC.0b013e3283357337DOI Listing
February 2010

Impaired somatic growth and delayed lung development in infants with congenital diaphragmatic hernia--evidence from a 10-year, single center prospective follow-up study.

J Pediatr Surg 2009 Jul;44(7):1309-14

Department of Neonatology, Charité Campus Mitte, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.

Purpose: In infants with congenital diaphragmatic hernia (CDH), somatic growth and pulmonary development are key issues beyond the time of intensive care treatment. The aim of the study was to investigate the somatic growth and pulmonary function after discharge and to compare CDH patients with a group of matched controls.

Methods: Anthropometric measurements and lung function tests were performed in 26 infants after surgical repair of CDH and 26 non-CDH intensive care patients, matched for gestational age and birth weight. Spontaneously breathing infants were tested at a mean of 44 weeks postconceptional age (range, 36-58 weeks). Body weight, body length, respiratory rate (RR), tidal volume (V(T)), functional residual capacity by body plethysmography (FRC(pleth)), respiratory compliance (C(rs)), and respiratory resistance (R(rs)) were measured.

Results: The mean (SD) weight gain per week in the CDH infants was significantly lower compared to non-CDH infants (89 [39] g vs 141 [49] g; P = .002). The breathing pattern between both groups differed considerably. In CDH infants, V(T) was significantly lower (P < .001) and RR significantly higher (P = .005). The respiratory compliance was also significantly (P < .001) reduced, whereas R(rs) did not differ significantly. No statistically significant differences were seen in FRC(pleth) related to the body weight between CDH and non-CDH infants (20.3 [4.4] mL/kg vs 21.5 [4.9] mL/kg).

Conclusion: Despite apparently well-inflated lungs after surgery, evidence of early and significantly reduced weight gain and impaired lung function in CHD patients should prompt careful dietary monitoring and regular lung function testing.
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http://dx.doi.org/10.1016/j.jpedsurg.2008.10.047DOI Listing
July 2009