Prospective detection of open spina bifida at 11-13 weeks by assessing intracranial translucency and posterior brain.

We describe a case series of six fetuses with open spina bifida (OSB) from four different prenatal units, where the anomaly was detected at the routine 11-13-week ultrasound examination. Crown-rump length ranged from 49 to 78 mm. All cases were first suspected during nuchal translucency thickness measurement in the mid-sagittal plane of the face. OSB was lumbosacral in five fetuses and cervical in one. The intracranial translucency (IT) was obliterated in two cases, but some fluid was found in the other four cases. However, in all cases the typical landmarks of a normal posterior brain and normal IT were absent. In all six cases the ratio of brainstem diameter to brainstem-occipital bone distance was increased (≥ 1). This detection of an abnormal posterior brain led to a targeted examination and detection of the spinal lesion during the same examination in five cases, whereas in one suspicious case the patient was recalled at 17 weeks, when the abnormality was detected. Two fetuses had both multiple anomalies and trisomy 18. These prospective cases demonstrate the feasibility of using the standard mid-sagittal plane commonly used for NT measurement to assess the IT and the posterior brain and to determine the presence of OSB during NT screening.

Intraobserver and interobserver reliability of transvaginal cervical length measurements and quantitative ultrasound tissue characterization of the cervix in the second and third trimester of pregnancy.

PURPOSE: To determine the intraobserver and interobserver reliability of transvaginal ultrasound measurements of cervical length and quantitative ultrasonic tissue characterization (QUTC). MATERIALS AND METHODS: 20 healthy women in the second and third trimester of pregnancy underwent transvaginal ultrasound examination of the cervix by two sonographers. 3 replicate vaginal measurements of cervical length and QUTC were taken by each observer for each woman. The repeatability coefficient and intraclass correlation coefficient as well as the interclass correlation coefficient and limits of agreement were calculated. RESULTS: The reliability coefficient for transvaginal cervical length measurements was 0.95 for sonographer 1 and 0.99 for sonographer 2. The corresponding intraclass correlation coefficients for cervical length measurements were 0.872 and 0.973. The interclass correlation coefficient for transvaginal cervical length measurements was 0.986, the mean interobserver difference was -2 mm, and the limits of agreement were -5.4 mm to 1.5 mm. The reliability coefficients for QUTC were 0.90 (sonographer 1) and 0.97 (sonographer 2) and the corresponding intraclass correlation coefficients for cervical length measurements were 0.74 and 0.9. The interclass correlation coefficient was 0.56, the mean interobserver difference was 0.14, and the limits of agreement were -22.46 to 22.74. CONCLUSION: Transvaginal cervical length measurements showed a high intraobserver and interobserver reliability, while quantitative ultrasonic tissue characterization had poor interobserver reliability and should currently not be applied in clinical practice.

[Prenatal diagnosis of an inguino-scrotal hernia in a fetus with trisomy 18]. / Pränatale Diagnose einer Skrotalhernie bei einem Feten mit Trisomie 18.

In spite of its prevalence in neonates, an inguino-scrotal hernia is a rarely detected condition in prenatal life. The sonographic findings, i. e., a scrotal mass with intestinal peristalsis, the differential diagnosis, and possible associations between a scrotal hernia and chromosomal aberrations are described by presenting the case of a fetus with trisomy 18 and major structural anomalies.

Prenatal diagnosis and management of a fetal intra-abdominal teratoma: a case report and review of the literature.

We report on a case of a large intra-abdominal teratoma diagnosed antenatally and managed successfully after birth. Intra-abdominal teratomas are rare in prenatal life. Ultrasound examination shows a heterogenic tumor with cystic and solid components. After postpartum surgical removal, the prognosis is generally good.

Specific transcriptional changes in human fetuses with autosomal trisomies.

Among full autosomal trisomies, only trisomies of chromosome 21 (Down syndrome), 18 (Edwards syndrome) and 13 (Patau syndrome) are compatible with postnatal survival. But the mechanisms, how a supernumerary chromosome disrupts the normal development and causes specific phenotypes, are still not fully explained. As an alternative to gene dosage effect due to the trisomic chromosome a genome-wide transcriptional dysregulation has been postulated. The aim of this study was to define the transcriptional changes in trisomy 13, 18, and 21 during early fetal development in order to obtain more insights into the molecular etiopathology of aneuploidy. Using oligonucleotide microarrays, we analyzed whole genome expression profiles in cultured amniocytes (AC) and chorionic villus cells (CV) from pregnancies with a normal karyotype and with trisomies of human chromosomes 13, 18 and 21. We observed a low to moderate up-regulation for a subset of genes of the trisomic chromosomes. Transcriptional levels of most of the genes on the supernumerary chromosome appeared similar to the respective chromosomal pair in normal karyotypes. A subset of chromosome 21 genes including the DSCR1 gene involved in fetal heart development was consistently up-regulated in different prenatal tissues (AC, CV) of trisomy 21 fetuses whereas only minor changes were found for genes of all other chromosomes. In contrast, in trisomy 18 vigorous downstream transcriptional changes were found. Global transcriptome analysis for autosomal trisomies 13, 18, and 21 supported a combination of the two major hypotheses.

Quantitative ultrasonometry of the phalanges during pregnancy: a longitudinal study.

OBJECTIVE: The aim of this study was to determine prospectively the change in results of bone ultrasonometry measurement during pregnancy in healthy German women. Study design Quantitative ultrasonometry (QUS) of the phalanges was performed in 60 healthy, pregnant women. Measurements of amplitude-dependent bone propagation velocity (speed of sound; AdSOS) and the bone transmission time (BTT) were performed during the three trimesters of pregnancy in 60 patients. RESULTS: During pregnancy, a significant increase in body weight and body mass index (p < or = 0.001) were observed. In accordance with bone ultrasonometry, a significant reduction in AdSOS was found in each trimester; AdSOS was significantly lower in the second and third trimesters compared with the first (p < or = 0.001). The BTT values also decreased significantly in the second and third trimesters compared with the first (p < or = 0.001). No significant influence was found of possible risk factors such as family risk of osteoporosis, previous pregnancies, age at menarche and prior use of oral contraceptives on QUS measurement results. CONCLUSIONS: During normal pregnancy, we found a significant reduction of quantitative ultrasonometry variables AdSOS and BTT in healthy pregnant women. This decrease had a large influence on the t score and Z score of QUS in our study and demonstrates therefore a possible clinical relevance. The decrease was independent of osteoporosis-related risk factors and the increase in body weight. More large-scale, prospective studies are needed to increase our knowledge about the mechanism of bone turnover during pregnancy and lactation.

[Combination therapy for fetal supraventricular tachycardia with flecainide and digoxin]. / Kombinationstherapie einer fetalen supraventrikulären Tachykardie mit Flecainid und Digoxin.

Persistent fetal supraventricular tachycardia (SVT) with more than 210 bpm frequently leads to congestive heart failure. We report on a case with SVT and congestive heart failure that converted into sinus rhythm within 19 days of therapy with flecainide and beta-acetyldigoxin. A 32-year-old II gravida I para (25 + 1 weeks of gestation) presented with fetal SVT of 267 bpm. A non-immunologic hydrops fetalis was diagnosed by ultrasound showing ascites, pleural and pericardial effusion and tricuspid regurgitation. Within 19 days of combination therapy with flecainide and digoxin, cardioversion was achieved. After 36 days of therapy no more signs of cardiac failure could be detected. A healthy boy was born at 38 + 6 weeks of gestation. Although cardioversion is expected after 72 h of therapy according to the literature, this fetus converted into sinus rhythm on day 19 of therapy. This indicates that patients should not be considered resistant to treatment within the first 3 - 4 days.

Evaluation and validation of a new risk score (CLEOPATRA score) to predict the probability of premature delivery for patients with threatened preterm labor.

OBJECTIVE: To develop a clinically useful tool to predict the probability of preterm delivery in patients with threatened preterm labor. METHODS: One hundred and seventy patients with preterm labor between 24 and 34 weeks of gestation were included. Preterm delivery < 37 weeks of gestation was the main endpoint of the study. The data were randomized and split into an evaluation set (n = 85) and a validation set (n = 85). The evaluation set was subjected to stepwise backward logistic regression analysis to quantify the relative impact of four potential risk factors, including individual patient factors, results of a rapid fetal fibronectin assay, and sonographic measurement of cervical length. Using the constant of the logistic regression analysis and the beta-coefficients for the identified risk factors the individual probability of preterm delivery for each woman of the validation dataset was calculated. The area under a receiver-operating characteristics curve (AUC) was used to evaluate the discriminating power of the score. RESULTS: The overall rate of preterm delivery was 27.1%. The logistic regression analysis was performed for the potential predictors of spontaneous preterm delivery, identified by univariate analysis. These were positive fetal fibronectin, cervical length, previous preterm delivery and maternal age. Two risk factors were independent predictors of preterm delivery and were included in the CLEOPATRA I (clinical evaluation of preterm delivery and theoretical risk assessment) score: cervical length measurement and previous preterm delivery were associated with a higher risk of preterm delivery (odds ratio, 7.65 and 6.74, respectively). Since fetal fibronectin assay is not available at all institutions worldwide, it was excluded from the initial model. In the CLEOPATRA II model the risk factors fetal fibronectin and previous preterm delivery were associated with higher risk of preterm delivery, with odds ratios of 17.9 and 4.56, respectively. The discrimination power (AUC) obtained from the models were: CLEOPATRA I, 0.69 (95% CI, 0.56-0.82); CLEOPATRA II, 0.81 (95% CI, 0.69-0.93). CONCLUSION: In symptomatic women the risk for preterm delivery can be predicted best with the CLEOPATRA II score based on fetal fibronectin and previous preterm delivery.

Fetal lung development in pregnancies of diabetic women assessed by quantitative ultrasonic tissue characterization.

OBJECTIVES: This study was performed to compare quantitative ultrasonic tissue characterization of the fetal lung at different gestational ages in uncontrolled diabetic patients with that in normal uncomplicated pregnancies. METHODS: A total of 44 women at 24-37 weeks' gestation with the diagnosis of diabetes in pregnancy were enrolled. Data were compared to those of the control group, which consisted of 140 women with uncomplicated pregnancies of the same gestational age. Longitudinal and transverse sections of the fetal thorax and upper abdomen were examined. A region of interest of constant size was defined and the tissue-specific gray scale was determined by using interactive software. RESULTS: Compared with normal pregnancies, fetal lungs of diabetic pregnancies have a higher echogenicity between 28 and 37 weeks of gestation. The lung mean gray values (MGV) only differed significantly between 30 and 31 weeks of gestation in the group with diabetes (P = 0.033) compared to the control group. The MGV of the liver in diabetic and normal pregnancies is similar during pregnancy, significant differences being found only at 30-31 weeks of gestation (P = 0.038). The lung-to-liver ratio in the control group showed a significant increase from 24 to 31 weeks and a slight non-significant decrease after 31 weeks. The ratio in the group with diabetes increased slightly up to week 33 and decreased slightly afterwards. CONCLUSION: Fetal lung MGV in uncontrolled diabetic pregnancies compared to that in uncomplicated pregnancies differs significantly only between 30 and 31 weeks of gestation.

Evaluation of the development of lung hypoplasia in the premature lamb.

BACKGROUND: The death rate from human diaphragmatic hernia (CDH) ranges from 50 to 80%, mainly due to the associated lung hypoplasia. To prevent these irreversible pathological and physical defects, the question of intrauterine surgical intervention arises. The histological changes of the lung tissue after inducement of a diaphragmatic hernia were examined. Of special interest was the time elapsing until the development of lung hypoplasia. METHODS: A model of intrauterine inducement of diaphragmatic hernia was established using five fetal lambs to study consecutive pulmonary hypoplasia. Inducement of a diaphragmatic hernia was undertaken between 105 and 108 days' gestation. Lung tissue was examined histologically on postoperative days 8, 17, 21, 22, and 25 after inducement of the defect. RESULTS: On postoperative days 8, 17, and 21, no signs of pulmonary hypoplasia were found on histological examination. A pulmonary hypoplasia was found in two fetuses (on the 22nd and 25th postoperative day). The pathological and anatomical examination of a unilateral pulmonary hypoplasia after a short period of time shows that the artificially created diaphragmatic defect is a good model for producing a congenital diaphragmatic hernia. DISCUSSION: The severity of the pulmonary hypoplasia is related to the duration of lung compression by the herniated organs. The time elapsing until the development of lung hypoplasia is shorter than expected. Tracheal occlusion seems to be an effective strategy for treatment of the defect CDH, but the best technique for achieving occlusion, and particularly the ideal point in time to carry out "Fetendo," are unknown. Further research into this congenital illness is required in order to treat it.

[Quantitative ultrasonic tissue characterization of the cervix - A new predictor for prematurity?]. / Quantitative sonographische Gewebetypisierung der Zervix uteri - ein neuer Prädiktor der Frühgeburtlichkeit?

BACKGROUND: Since the incidence of premature delivery has remained constant for the last decade despite intensive safeguarding methods, the texture features of the uterine cervix were evaluated using quantitative sonographic gray level analysis at different gestational ages. MATERIALS AND METHODS: For this purpose, quantitative ultrasonic tissue densitometry of the uterine cervix was obtained from 30 asymptomatic female patients (group A, mean: 30,3 GA) and compared with values obtained from 16 symptomatic female patients (group B, mean: 29,5 GA) with uterine contractions and shortening of the cervix at similiar gestational ages. Once the two-dimensional transvaginal sonographic measurement of cervical length was completed, a region of interest of constant size was defined in the mid-section of the posterior wall, and the tissue-specific gray scale distribution was determined. RESULTS: Quantitative ultrasonic tissue characterization of uterine cervix was feasible in all 46 patients at all gestational ages. In patients with premature contractions and shortening of cervix the average gray scale values were found to be significantly reduced in comparison with those obtained from asymptomatic patients. These results showed good reproducibility and low intraobserver variability and were found to be independent of the measured cervical length. CONCLUSION: Our results prove that quantitative ultrasonic tissue characterization of the uterine cervix might serve as a new parameter for predicting premature delivery.

[Dynamics of thrombin-antithrombin-III complex (TAT-III) and prothrombin fragments F1 + 2 during labour with and without aprotinin administration]. / Die Dynamik des Thrombin-Antithrombin-III-Komplexes und der Prothrombinfragmente F1 + 2 sub partu mit und ohne Aprotiningabe.

OBJECTIVE: The aim of this study was to determine if aprotinin could affect postpartal fibrinolysis when given at the latest 15 min before delivery and if there is a difference between normal delivery and caesarean section. Furthermore we wanted to examine if the thrombin-antithrombin-III-complex (TAT-III) and prothrombin fragments F1 + 2 changed in the peripartal period and if prethrombotic stages could be recognized. PATIENTS AND METHODS: 84 patients (15 - 44 years of age) have been examined (41 normal deliveries, 43 cesarean sections). After giving informed consent and randomization, 30 of these patients were administered 1 Mio KIE aprotinin (Trasylol(R)) at the latest 15 min before delivery (15 normal deliveries, 15 cesarean sections). The results of TAT-III, prothrombin fragments F1 + 2, factor VIII and partial thromboplastin-time (PTT) were collected shortly before and after delivery and 30 and 120 min after detachment of the placenta. RESULTS: Normal deliveries without aprotinin showed a significant increase of TAT-III and an evident increase of prothrombin fragments F1 + 2. After administration of aprotinin this increase was significantly lower. The increase of TAT-III and prothrombin fragments F1 + 2 in patients with caesarean sections was evidently lower than in normal deliveries and was not influenced significantly by aprotinin. Factor VIII and partial thromboplastin time (PTT) showed no relevant changes in all study groups. DISCUSSION AND CONCLUSION: The consumption of coagulation and fibrinolysis factors induced by delivery of the child and detachment of the placenta can be reduced after administration of aprotinin given at the latest 10 - 18 min before partus. This could be used in therapy and prophylactic treatment in high-risk patients (e. g., pre-eclampsia, HELLP syndrome, etc.).

[Evaluation of the reproducibility of Doppler ultrasonographic measurements in obstetrics]. / Evaluierung der Reproduzierbarkeit dopplersonographischer Messungen in der Geburtshilfe.

BACKGROUND: Are obstetric doppler ultrasonographic measurements of the fetal and maternal flow parameters reproducible? PATIENTS AND METHODS: For internal quality management, doppler ultrasonographic measurements were performed on 81 patients (random screening sample) with an Acuson Sequoia Ultrasound at the Universitätsfrauenklinik Marburg. Successively two experienced investigators measured the umbilical artery, medial cerebral artery, and the uterine arteries. The correlation between the measurements of the two investigators was presented in a spread chart. In order to exclude systematic differences between the measurements, linear regression was analyzed and the distance to the abscissa was calculated. A relative divergence of more than 20% was determined as a non corresponding measurement. RESULTS: The distance of the linear regression to the abscissa was calculated for the four vessels: umbilical artery 0.4 (95% CI; 0.124 - 0.486), medial cerebral artery 0.9 (95% CI; 0.534 - 1.264), right uterine artery 0.2 (95% CI; 0.124 - 0.305), and left uterine artery 0.2 (95% CI; 0.121 - 0.317). Concerning the four arteries, a divergence of more than 20% between the two investigators was found: umbilical artery 16%, medial cerebral artery 42%, right uterine artery 28%, and left uterine artery 37%. CONCLUSIONS: Because the interobserver variability was surprisingly high and acceptable correlation could be stated only for the umbilical artery, internal quality standards are essential. Routine use of different devices should be made after careful consideration only, especially if clinical decisions are to be based on them.

[Changes of fibrinolysis during labour with and without aprotinin application]. / Veränderungen der Fibrinolyse während der Geburt mit und ohne Gabe von Aprotinin.

OBJECTIVE: The aim of this study was to determine (a) if alpha-2-antiplasmin, plasminogen and plasminogen-activator-inhibitors (PAI 1 - 4) change in the peripartal period, (b) if these changes are explainable by the detachment of the placenta and the release of coagulation factors, and (c) if aprotinin could affect postpartal fibrinolysis when given shortly before delivery. PATIENTS AND METHODS: 84 patients have been examined (41 normal deliveries, 43 cesarean sections). After informed consent and randomization, 30 of these patients were administered 1 million KIU aprotinin (Trasylol(R)) at the latest 15 minutes before delivery (15 normal deliveries, 15 cesarean sections). The results of PAI (1 - 4), alpha-2-antiplasmin and plasminogen were collected shortly before and after delivery and 30 and 120 min after detachment of the placenta. RESULTS: Normal deliveries and cesarean sections without aprotinin showed an evident decrease of PAI (1 - 4) after delivery while alpha-2-antiplasmin and plasminogen values did not change. After administration of aprotinin the activity of PAI (1 - 4) increased slightly after labour in normal deliveries and cesarean sections and then slowly decreased later. alpha-2-Antiplasmin levels increased post partum and then decreased to the original values. Plasminogen did not change. There were no significant differences between normal deliveries and cesarean sections with regard to the three parameters studied in this work. DISCUSSION AND CONCLUSION: Changes in PAI (1 - 4) and alpha-2-antiplasmin after administration of aprotinin could be the result of a minimal demand on the fibrinolytic system. Finally, aprotinin can reduce the consumption of coagulation and fibrinolysis factors induced by detachment of the placenta. This could be used in therapy and prophylactic treatment in high-risk patients (e.g., pre-eclampsia, HELLP syndrome, etc.).

Effects of combined renovascular hypertension and diabetes mellitus on myocardial cells, non-vascular interstitium and capillaries: a stereological study on rat hearts.

The effects of combined renovascular hypertension and diabetes mellitus on the rat heart were investigated in order to detect possible synergistic effects of the two conditions. Hypertensive diabetic and hypertensive non-diabetic animals were compared to diabetic and non-diabetic controls. Hypertension was established for 12 weeks by a surgical stenosis of the left renal artery; diabetes mellitus was maintained for 8 weeks by a single intraperitoneal injection of 60 mg/kg streptozotocin. Light microscopic stereology did not reveal significant divergences between diabetic hypertensives and non-diabetic hypertensives. Hypertension induced a focal perivascular and interstitial fibrosis with increased volume densities of non-vascular interstitium and fibrosis (P less than 0.001). Capillary density (QA) was decreased in transverse sections (P less than 0.01) and increased in longitudinal sections (P less than 0.01). This indicates a three-dimensional remodelling of the capillary bed with an increased number of obliquely running capillaries. At least the length density (LV) of capillaries (mm/mm3) tends to be normalized in long-term renovascular hypertension. At the ultrastructural level, a synergism of hypertension and diabetes mellitus was observed: the volume ratio of mitochondria to myofibrils was significantly decreased in hypertensive diabetics, but not in non-diabetic hypertensives or in diabetics. This may enhance the risk of cardiac deterioration. We conclude that the primary target of the synergistic damage in hypertensive diabetic heart muscle disease is the myocardial cell and not the cardiac interstitium.

[Differential diagnosis of a polyhydramnion in hyperprostaglandin E syndrome: a case report]. / Differenzialdiagnose des Polyhydramnions beim Hyperprostaglandin-E-Syndrom: Case-Report.

INTRODUCTION: A polyhydramnion is diagnosed in 0.4 to 3.3 % of all pregnancies. The most common causes of increased amniotic fluid include maternal diabetes mellitus, fetal malformations and chromosomal aberrations, twin-to-twin transfusion syndrome, rhesus incompatibility syndrome, and congenital infections. After exclusion of other etiologies for polyhydramnion, the very rare, autosomal-recessive transferred hyperprostaglandin E syndrome (HPS) has to be considered. PATIENTS AND METHODS: We report on a 31-year-old women who visited our obstetrical outpatient clinics at 22 + 4 weeks of gestation for prenatal ultrasound scanning and amniocentesis. This, the patient's third pregnancy had been without complications so far. She had delivered two children before, one of them bearing the HPS. The women herself suffered from epilepsy. At 26 + 0 weeks of gestation the pregnancy was complicated by a polyhydramnion requiring serial amniocentesis for reducing amniotic fluid load. Among others, her amniotic fluid was analyzed for chloride concentration and for genetic aberrations regarding HPS. Serological investigations and an oral glucose tolerance test (oGTT) were performed. RESULTS: Amniocentesis revealed a normal chromosomal pattern. The oGTT demonstrated values in the normal range. Serological investigations regarding TORCH infections were without pathological findings. The chloride concentration was highly increased in the amniotic fluid, which is suspicious for HPS. Finally, molecular analysis proved an NKCC2-mutation responsible for HPS. A cesarean section was performed at 33 + 3 weeks of gestation. CONCLUSION: If HPS is suspected to be the cause of polyhydramnions, the chloride concentrations in the amniotic fluid and molecular analysis for HPS should be performed. Interdisciplinary care, diagnostics and therapy in an experienced perinatal center are essential for an optimal outcome of the pregnancy and the newborn infant.