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1.
Geburtshilfe Frauenheilkd ; 83(10): 1221-1234, 2023 Oct.
Article En | MEDLINE | ID: mdl-37808257

Purpose The aim was to develop evidence-based recommendations where possible. The guideline presents the medical principles and scientific evidence for indications, counselling of affected persons, performing terminations, the choice of method, and the care and monitoring of a terminated pregnancy up until week 12 + 0 of gestation p. c. Methods In accordance with the requirements for an S2k-guideline, the contents of the guideline were drafted following a systematic search of the literature by a representative interdisciplinary group of experts. Guideline authors held several formal meetings under the auspices of the German Society for Gynaecology and Obstetrics (DGGG) during which the contents of the guideline were finalised and agreed upon. Recommendations The guideline provides recommendations on the surgical termination of pregnancy and follow-up care after termination of pregnancy.

2.
Geburtshilfe Frauenheilkd ; 83(10): 1205-1220, 2023 Oct.
Article En | MEDLINE | ID: mdl-37808261

Purpose The aim was to develop evidence-based recommendations where possible. The guideline presents the medical principles and scientific evidence for indications, the counselling of affected women, performing terminations, the choice of method, and the care and monitoring of a terminated pregnancy up until week 12 + 0 of gestation p. c. Methods In accordance with the requirements for S2k-guidelines, the contents of the guideline were drafted following a systematic search of the literature by a representative interdisciplinary group of experts. Guideline authors held several formal meetings under the auspices of the German Society for Gynaecology and Obstetrics (DGGG) during which the contents of the guideline were finalised and agreed upon. Recommendations A total of 61 recommendations are provided, covering care structures, provision of information and counselling to support decision-making, the measures to be taken before terminating the pregnancy, and medical termination of the pregnancy.

3.
Best Pract Res Clin Obstet Gynaecol ; 84: 143-154, 2022 Nov.
Article En | MEDLINE | ID: mdl-35589537

In twin-to-twin transfusion syndrome (TTTS) communicating placental vessels on the chorionic plate between the donor and recipient twins are responsible for the chronic imbalance of blood flow. Evidence demonstrates that fetoscopic laser ablation is superior to serial amnioreductions in terms of survival and neurological outcome for stages II-IV TTTS. However, the optimal management of stage I TTTS remains poorly understood. It is well established that all chorionic plate anastomoses should be closed by laser ablation. Compared to the selective laser method, the Solomon technique yields a significant reduction of recurrent TTTS and post-laser twin anemia polycythemia sequence (TAPS). Over the past 25 years, survival rates after fetoscopic laser surgery have significantly increased. High volume centers report up to 70% double survival and at least one survivor in >90% cases. In this review, we discuss the controversies in the diagnosis and management of TTTS, especially, the optimal management in stage I cases, very early or late diagnosis, and the optimal laser technique. Furthermore, we will discuss a stage-related outcome after laser surgery and examine whether it is necessary at all to distinguish between stages I and II. Finally, the optimal timing as well as mode of delivery after TTTS laser treatment will be discussed.


Fetofetal Transfusion , Polycythemia , Female , Pregnancy , Humans , Fetofetal Transfusion/diagnosis , Fetofetal Transfusion/surgery , Placenta , Pregnancy, Twin , Fetoscopy/methods , Polycythemia/diagnosis , Polycythemia/etiology , Polycythemia/therapy
4.
Article En | MEDLINE | ID: mdl-30850326

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.


Fetofetal Transfusion/surgery , Fetoscopy/methods , Laser Coagulation/methods , Placenta/physiopathology , Female , Fetofetal Transfusion/diagnosis , Fetoscopy/adverse effects , Gestational Age , Humans , Laser Coagulation/adverse effects , Placenta/surgery , Pregnancy , Pregnancy, Twin , Ultrasonography, Doppler , Ultrasonography, Prenatal
5.
Placenta ; 76: 19-22, 2019 01 15.
Article En | MEDLINE | ID: mdl-30803710

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 ±â€¯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.


Fetofetal Transfusion/diagnostic imaging , Umbilical Cord/diagnostic imaging , Adult , Female , Fetofetal Transfusion/physiopathology , Humans , Imaging, Three-Dimensional , Pregnancy , Ultrasonography, Doppler, Color , Ultrasonography, Prenatal , Umbilical Cord/physiopathology
6.
Arch Gynecol Obstet ; 299(2): 421-430, 2019 02.
Article En | MEDLINE | ID: mdl-30511192

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.


Delivery, Obstetric/adverse effects , Factor XIII/adverse effects , Postpartum Hemorrhage/etiology , Adult , Female , Humans , Pregnancy , Prospective Studies , Young Adult
8.
Ultraschall Med ; 39(3): 343-351, 2018 Jun.
Article En | MEDLINE | ID: mdl-27626240

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.


Cesarean Section , Cicatrix , Hysterotomy , Female , Humans , Hysterotomy/methods , Pregnancy , Prospective Studies , Uterus/diagnostic imaging , Uterus/pathology
9.
Acta Obstet Gynecol Scand ; 96(12): 1484-1489, 2017 Dec.
Article En | MEDLINE | ID: mdl-28832909

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.


Cesarean Section , Cicatrix/diagnostic imaging , Myometrium/diagnostic imaging , Myometrium/surgery , Suture Techniques , Ultrasonography/methods , Adult , Female , Humans , Pregnancy , Treatment Outcome , Wound Healing/physiology
11.
Am J Obstet Gynecol ; 217(2): 194.e1-194.e8, 2017 08.
Article En | MEDLINE | ID: mdl-28412085

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.


Magnetic Resonance Imaging , Parturition/physiology , Pelvic Floor/diagnostic imaging , Pelvic Floor/physiology , Delivery, Obstetric , Female , Humans , Imaging, Three-Dimensional , Pregnancy , Young Adult
12.
J Perinat Med ; 45(3): 305-308, 2017 Apr 01.
Article En | MEDLINE | ID: mdl-27219097

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.


Fetus/diagnostic imaging , Head/diagnostic imaging , Labor Stage, Second/physiology , Magnetic Resonance Imaging/methods , Biomechanical Phenomena , Computer Systems , Female , Fetus/physiology , Head/physiology , Humans , Infant, Newborn , Labor Presentation , Male , Pregnancy , Young Adult
13.
J Perinat Med ; 45(4): 427-435, 2017 May 24.
Article En | MEDLINE | ID: mdl-27442353

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.


Postpartum Hemorrhage/blood , Thrombelastography , Adult , Female , Fibrinogen/metabolism , Humans , Pilot Projects , Predictive Value of Tests , Pregnancy , Prospective Studies , Young Adult
14.
Arch Gynecol Obstet ; 294(4): 745-51, 2016 10.
Article En | MEDLINE | ID: mdl-26899183

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).


Delivery, Obstetric , Fibrinogen/metabolism , Postpartum Hemorrhage/epidemiology , Adult , Female , Humans , Incidence , Labor, Obstetric , Parity , Pregnancy , Prospective Studies , Risk Factors , Young Adult
15.
J Perinat Med ; 44(2): 179-85, 2016 Mar.
Article En | MEDLINE | ID: mdl-26378487

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.


Birth Weight , Cerebral Ventricles/diagnostic imaging , Hydrocephalus/diagnostic imaging , Hydrocephalus/etiology , Intracranial Hemorrhages/complications , Intracranial Hemorrhages/diagnostic imaging , Cerebral Ventricles/pathology , Female , Gestational Age , Humans , Infant, Newborn , Infant, Premature , Male , Pregnancy , Prognosis , Prospective Studies , Reference Values , Ultrasonography
16.
J Perinat Med ; 44(4): 433-9, 2016 May 01.
Article En | MEDLINE | ID: mdl-26353161

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.


Blood Specimen Collection/instrumentation , Postpartum Hemorrhage/diagnosis , Adult , Blood Volume , Female , Germany/epidemiology , Hemoglobins/metabolism , Humans , Incidence , Postpartum Hemorrhage/blood , Postpartum Hemorrhage/epidemiology , Pregnancy , Prospective Studies , Surgical Drapes , Young Adult
17.
J Perinat Med ; 44(6): 705-9, 2016 Aug 01.
Article En | MEDLINE | ID: mdl-26677883

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.


Gene Expression Regulation, Developmental , Hypertension/embryology , Nephrons/embryology , Organogenesis/physiology , Renin-Angiotensin System/genetics , Animals , Biomarkers/metabolism , Hypertension/genetics , Hypertension/metabolism , Nephrons/metabolism , Rats , Rats, Wistar , Renin-Angiotensin System/physiology
18.
Eur J Hum Genet ; 23(12): 1735-8, 2015 Dec.
Article En | MEDLINE | ID: mdl-25873012

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.


DNA, Mitochondrial/genetics , Muscular Diseases/genetics , Mutation , RNA, Transfer, Ala/genetics , Adult , Aged , Base Sequence , Electron Transport Complex IV/genetics , Female , Humans , Molecular Sequence Data , Muscular Diseases/diagnosis
19.
J Perinat Med ; 41(2): 165-70, 2013 Mar.
Article En | MEDLINE | ID: mdl-23096449

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.


Ultrasonography, Prenatal , Umbilical Arteries/diagnostic imaging , Uterine Artery/diagnostic imaging , Adult , Birth Weight , Blood Flow Velocity , Female , Humans , Infant, Newborn , Laser-Doppler Flowmetry , Male , Predictive Value of Tests , Pregnancy , Pregnancy Outcome , Pregnancy Trimester, Third , Prospective Studies , Pulsatile Flow , Risk Factors , Ultrasonography, Doppler , Umbilical Arteries/physiology , Uterine Artery/physiology , Vascular Resistance
20.
Fetal Diagn Ther ; 33(3): 143-8, 2013.
Article En | MEDLINE | ID: mdl-23221275

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.


Fetal Macrosomia/diagnostic imaging , Ultrasonography, Prenatal , Birth Weight , Female , Fetal Macrosomia/complications , Humans , Imaging, Three-Dimensional , Pregnancy , Risk Factors
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