[Prognostic factors of perinatal short-term outcome in severe placental insufficiency using Doppler sonography to assess end-diastolic absent and reverse blood flow in umbilical arteries]. / Prognosefaktoren des perinatalen Kurzzeitergebnisses bei schwerer Plazentainsuffizienz mit dopplersonografisch enddiastolischem Null- und Rückfluss in der Art. umbilicalis.

Significant placental insufficiency, indicated by Doppler ultrasound findings of absent or reverse end-diastolic flow velocities (AREDV), is associated with increased morbidity and mortality. Analysis of blood flow in the ductus venosus should assist in early intrauterine recognition of threatened foetuses. 58 high-risk pregnancies with umbilical AREDV were repeatedly examined (n=364). Doppler findings were correlated with neonatal signs of deterioration (ratio of normoblasts to leukocytes, pH, base excess, Apgar score), as well as short-term morbidity [need for intubation, duration of assisted respiration, evidence of respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), necrotising enterocolitis (NEC), intraventricular haemorrhage (IVH grade III+IV)] against the analysis of the blood flow findings (normal or increased pulsitility, absence or reverse end-diastolic flow) in the umbilical arteries (AU), the middle cerebral arteries (ACM) and ductus venosus (DV) relating these to birth weight and the duration of the pregnancy. The median period of observation was 12.8 days, 48% of the foetuses showed an abnormal ductus venosus flow and 26% an absent venous or reverse end-diastolic flow. The median date of delivery was 30 weeks, with a mean birth weight of 816 g. 93% were live births with 12% dying postnatally. Although the criteria for postnatal morbidity (BPD, NEC, IVH III+IV) and mortality did not correlate with changes in arterial and venous Doppler parameters in our group, there was a significant relationship between the normoblast count, known to be a marker of chronic hypoxia. The Apgar 10 minte score, umbilical arterial pH and base excess were correlated with changes in the DV flow curves. Healthy survival started, irrespective of arterial or venous blood flow criteria, from 27+0 weeks of pregnancy. If born between 27.0 and 30+6 weeks, the infants were more likely to be healthy the less the blood flow had been compromised. A birth weight of 590 g (sensitivity 62.5%; specificity 93.5%) and gestational age of 28+5 weeks (sensitivity 87.5%; specificity 90.3%) were shown to be cut-off points between healthy survival and survival with serious neonatal complications.

Lethal junctional epidermolysis bullosa with pyloric atresia due to compound heterozygosity for two novel mutations in the integrin ß4 gene.

BACKGROUND: Junctional epidermolysis bullosa with pyloric atresia (JEB-PA) is a rare autosomal recessive disease with blister formation within the lamina lucida due to mutations in the integrin ß4 (ITGB4) and α6 (ITGA6) genes. CASE REPORT: A female preterm infant, first child of healthy non-consanguineous parents, was born at 26 + 4 weeks of gestation by caesarean section, following polyhydramnion and abruption of placenta. She presented with extensive areas of denuded skin on both lateral sides of the head, neck and extremities. Auricles were hypoplastic. Abdominal ultrasound and X-ray were suggestive of pyloric atresia which was revised surgically on the 4th day of life. Further course was complicated by progressive skin detachment, sepsis, and renal insufficiency with fatal outcome at 18 days of age. Immunofluorescence mapping of cryopreserved skin showed junctional cleft formation with negative staining for integrin α6 and integrin ß4. Mutational analysis disclosed compound heterozygosity for two novel nonsense mutations in the ITGB4 gene: c.600dupC/p.F201fsX14 and c.2533C>T/p.Q845X. 2 subsequent pregnancies were terminated following prenatal diagnosis disclosing the same ITGB4 mutations, a 4th pregnancy was unaffected. CONCLUSION: We describe a case of lethal JEB-PA with negative immunoreactivity to integrin α6 and integrin ß4 predicting a poor outcome. Identification of compound heterozygosity for two novel ITGB4 mutations in the affected preterm infant permitted prenatal diagnosis and finally birth of a healthy sibling.

[Sonographic abnormalities of the fetal CNS in the second trimester screening--clarifications according to the new maternity directives]. / Sonografische Auffälligkeiten des fetalen ZNS im Zweittrimesterscreening--Abklärung nach neuen Mutterschaftsrichtlinien.

Malformations of the central nervous system are among the most frequent congenital anomalies. At best, a qualified and standardised screening of the foetal brain is possible between the 18th and the 22nd week. The newly decided modification of the maternity directives envisages an extended screening upon request. This extended screening refers to the central nervous system and the representation of the ventricles, the evaluation of the head shape and the cerebellum and the back. The examination of the foetal brain should be carried out in a structured way. Three axial planes, the transventricular, the transthalamic and the transcerebellar planes, suffice to represent and measure all structures which are of importance for the screening. In case of ventricular anomalies, anomalies of the head shape, anomalies of the cerebellum and irregularities of the dorsal skin outlined in the second screening a further diagnostic procedure should be initiated. This diagnostic work-up should include a detailed neurosonography, a diagnostic evaluation of the organs and eventually further examination in the form of a caryotyping, determination of the infectology or a foetal MRI. The present article offers an overview of possible CNS abnormalities which could be recognised during the second screening according to the extended maternity directives and describes which differential diagnostics should be considered. In detail, anomalies of the head size (microcephaly, macrocephaly), of the head size (brachycephaly, dolichocephaly, cavities of the cranium, banana sign, etc.,), ventricular abnormalities, anomalies of the cerebellum (cerebellum hypoplasia, abnormal cerebellum shape) and abnormalities of the intermediate line and the intracerebral space requirements are discussed.

[Obstetric management of fetal growth retardation]. / Geburtshilfliches Management bei fetaler Retardierung.

Intrauterine growth restriction (IGUR) can have different etiologies, but placental insufficiency is the clinically most relevant. Fetuses with IUGR have a significantly higher morbidity and mortality than normally grown fetuses of the same gestational age. It is important to distinguish a growth restricted fetus from a normal, small fetus and from a fetus being small because of a disease, e.g., an aneuploidy. This differentiation requires the knowledge of the gestational age and the use of multiple imaging modalities. Serial assessments of fetal growth by ultrasound are necessary to recognize declining growth. Doppler sonography can detect changes in the uteroplacentar and the fetal perfusion. Blood vessels of clinical relevance are the uterine arteries, the umbilical artery, the middle cerebral artery and the ductus venosus. When no fetal anomalies can be detected, fetal growth is parallel to the percentiles and Doppler sonography measurements are normal, IUGR is unlikely. In most IUGR fetuses, a typical sequence of circulatory changes and ultrasound findings can be observed. As there is no evidence-based treatment option for IUGR until now, obstetric management consists in defining the optimal time of delivery. This means weighing the risks of prematurity against the risks of a potentially hostile intrauterine environment.

[Hypophosphatasia]. / Hypophosphatasie.

Hypophosphatasia (HP) is an inborn error of bone metabolism transmitted predominantly as an autosomal-recessive trait. It is characterized by a reduced activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSAP) and elevated concentrations of its substrates, including pyrophosphates. Clinical symptoms include defective bone mineralisation with bone deformities, fractures and as recently defined chronic non-bacterial osteomyelitis. Renal damage due to calcification, craniosynostosis and dental abnormalities with premature loss of dentition are further symptoms, which have been described as characteristic in the ESPED inquiry of 2004. Knowledge about the mechanisms underlying cell activation leading to inflammation and tissue destruction is still limited in HP. Recent investigations have provided evidence that calcium pyrophosphate crystals are essentially involved in activating inflammatory signal transduction pathways via different receptors of the innate immune system. Laboratory assays, genetic counselling and testing, and radiologic imaging can confirm the diagnosis. Because symptoms are highly variable in their clinical expression, patients should be followed by a HP-experienced multidisciplinary team (paediatrician, radiologist, orthopedist, neurosurgeon, dentist). At the moment symptomatic support and treatment is most important because a causative therapy, e. g. enzyme replacement therapy, is not yet available.

Specific weight formula for fetuses with abdominal wall defects.

OBJECTIVES: To develop and to evaluate a specific sonographic weight formula for fetuses with abdominal wall defects. METHODS: For formula finding, 380 preterm singleton pregnancies without fetal anomalies were included. Ultrasound examinations with complete biometric parameters were performed within 7 days before delivery. Stepwise regression analysis was carried out with birth weight as the dependent variable and sonographic parameters (abdominal measurements not included) as independent variables to obtain the best-fit formula. The new equation was evaluated in a group of 97 fetuses with either gastroschisis or omphalocele. RESULTS: In the evaluation group, the mean (SD) percentage error of the new equation was -0.84 (12.03), showing no systematic bias. The mean absolute percentage error was 9.29. The new specific method provided significantly greater accuracy than commonly used formulae. CONCLUSIONS: This specific weight formula for fetuses with abdominal wall defects is an accurate method of estimating fetal weight.

[Neonatal results of prgenancies in overweight and obese mothers at the University of Würzburg Gynaecology Clinic--a comparison of the years 1980 and 2005]. / Neonatales Ergebnis von Schwangerschaften übergewichtiger und adipöser Mütter an der Universitäts-Frauenklinik Würzburg - ein Vergleich zwischen 1980 und 2005.

BACKGROUND: The prevalence of overweight and obesity in pregnant women has increased during the last decades (in our examination period from 10.9 to 29.8 %). Maternal obesity is a risk factor for pregnancy, delivery and the newborn. Does the neonatal outcome of pregnancies with maternal overweight and obesity in 2005 differ from that in 1980? METHODS: All patients with a body mass index (BMI) > 25 kg / m (2) who delivered in 1980 (n = 130) and in 2005 (n = 392) at the University Hospital Würzburg were evaluated retrospectively. The neonatal result of singletons born at term was studied (1980: n = 125; 2005: n = 315). RESULTS: The rates of macrosomia > 4500 g (5.6 vs. 1.3 %) and shoulder dystocia (4.8 vs. 0.3 %) declined significantly. No significant differences were found regarding the mean newborn weight (3560 vs. 3508 g), weight percentile (55.5 vs. 56.4 %), length (51 cm), head size (35 cm), fetal distress (3.2 vs. 3.8 %), respiratory insufficiency (3.2 vs. 2.2 %), 5-min-Apgar (9.77 vs. 9.69) and arterial umbilical cord pH (7.27 vs. 7.26). Birth weight was not associated with the degree of obesity in 2005 compared to 1980. CONCLUSION: Despite the increasing prevalence and severity of obesity in pregnant women most parameters of neonatal outcome did not change. The observed relative rate of macrosomia and shoulder dystocia declined, but the case number of these complications is still relevant. Obviously obstetricians have responded appropriately to the changing risk profile.

[Prune belly syndrome and congenital kidney tumors]. / Prune-Belly-Syndrom und kongenitale Nierentumoren.

BACKGROUND: High end sonography allows the prenatal localization of the kidneys and the corresponding urine drainage system as early as 10-13 weeks of gestation. In mid second trimester, the voiding and filling of the urinary bladder can be demonstrated by ultrasound. Obstructions are the most common abnormalities of the urogenital tract. Though less frequent in incidence, more complex sequences of anomalies such as Prune Belly Syndrome or Megacystis-Microcolon-Intestinal-Hypoperistalsis-Syndrome (MMIHS) can also be detected in early gestational age. MATERIALS AND METHODS: Pathogenesis, prenatal diagnosis, pre- and postnatal treatment options and prognosis are discussed. RESULTS AND DISCUSSION: The same risk-adapted procedures aimed to protect the fetal urinary excretory function known in the therapeutic regimen of obstructive uropathy are available as treatment options. These range from non-invasive ultrasound for diagnosis and surveillance to needle procedures or even endoscopic interventions. Another rare entity of renal abnormalities are congenital neoplasm's--megaloblastic nephroma, nephroblastoma and neuroblastoma. CONCLUSION: Prognosis and obstetrical management are to be determined individually for each patient.

Normalisation of a severely abnormal ductus venosus Doppler flow velocity waveform in a growth-retarded fetus with absent end-diastolic flow in the umbilical artery and congenital anomalies.

Doppler recordings of fetal venous blood flow seem to be superior to arterial velocimetry and CTG concerning the prediction of fetal outcome and optimal time of delivery in pregnancies with fetal growth retardation and AREDV. An improvement of arterial Doppler flow velocities has been described. We report the reappearance of a normal end-diastolic flow velocity in a ductus venosus temporarily showing reversed end-diastolic flow in a growth-retarded fetus with congenital anomalies. This normalization was accompanied by an improvement of the CTG, a loss of umbilical vein pulsations, a reappearance of umbilical diastolic flow and a progressive return of cerebral and venous blood flow into the 'normal' range. Improvement of fetal condition may be the explanation for our observation.

[Placenta praevia percreta--a serious complication after previous cesarean section]. / Plazenta praevia percreta--eine schwere Komplikation nach vorausgegangener Sectio caesarea.

A 36-year-old G4P1 presented at 20 weeks gestation with vaginal bleeding. Her obstetrical history was significant for two first-trimester spontaneous abortions requiring curettage and a cesarean section. On admission placenta praevia was suspected by ultrasound. A placenta percreta was suspected by ultrasound follow-up at 30 weeks. At 33 weeks she underwent cesarean section because of serious vaginal bleeding. The profound blood loss with consecutive coagulopathy required an emergency hysterectomy and multiple blood transfusions. Placenta percreta is a rare but dramatic complication after previous cesarean section. This should be kept in mind as the rate of elective cesarean sections is rising continuously.