[Clinical impact of fetal MRI in addition to ultrasonography in brain anomalies--three case reports]. / Klinische Bedeutung der MRT in Ergänzung zur Sonografie bei fetalen Hirnfehlbildungen--drei Fallberichte.

Fetal magnetic resonance imaging (MRI) is a reliable method to further evaluate brain anomalies detected on ultrasonography. MRI can reveal additional brain abnormalities which are consequential for counselling parents about the fetal prognosis and subsequently influence the decision about continuing the pregnancy. In case of fatal malformations, MRI can confirm a diagnosis established on ultrasonography, supplying more reliability.

Feto-amniotic shunting -- experience of six centres.

AIM: Foeto-amniotic shunting is an ultrasound-guided, therapeutic intervention for drainage of persistent intracavital fluid retention in severely affected foetuses with a high risk of mortality. In order to weigh up the comparatively high risk of intervention against the possible benefit, we evaluated the value of different indications, the complication rate and the time span of drains in situ. PATIENTS AND METHODS: We made a survey of all level III ultrasound centres of German-speaking countries from 1993 to 2001. Six level III centres returned the questionnaire: forty-seven foeto-amniotic shunting procedures were performed in 30 foetuses [megacystis in 18 foetuses (three of these with urinary ascites), hydrothorax in eight foetuses, hydronephrosis in two foetuses, cystic adenomatoid malformation of the lung in one foetus, ovarian cyst in one foetus]. RESULTS: The median gestational age at time of shunting was 23.5 (range 16 - 33) weeks, at time of delivery 35 (range 23 - 41) weeks. The median time span of drains in situ was 19 (range 0 - 170) days. Altogether 18 of 30 foetuses (60 %) had a benefit of foeto-amniotic shunting. CONCLUSION: The best possible selection of pregnancies which might profit from foeto-amniotic shunting is required. The decisive criteria are the underlying defect as well as the severity and progression of the disorder.

Ultrasound-guided large-core needle biopsies of breast lesions: analysis of 962 cases to determine the number of samples for reliable tumour classification.

The objective of this one-institutional study was to determine the number of large-core needle biopsies (LCNB), under three-dimensional ultrasound (3D-US) validation, that are sufficient to obtain a reliable histological diagnosis of a sonographically detectable breast lesion. Over an 28-month period, 962 sonographically guided LCNB were performed under 3D-US validation to assess 962 breast lesions. All biopsies were carried out with an automated core biopsy device fitted with 14-gauge (22 mm excursion) needles. Data of 962 biopsied breast lesions were gathered. Surgical follow-up was available for 659 lesions. Breast malignancies were diagnosed by ultrasound-guided LCNB with a sensitivity of 98.2% by performing three cores per lesion. In few cases, the open surgical specimen revealed the presence of invasive carcinomas in contrast to initial LNCB-based classification as ductal carcinomas in situ (DCIS, 11 lesions), lobular carcinoma in situ (one lesion), and atypical ductal hyperpasia (one lesion). Owing to disagreement between classification based on breast-imaging and histological findings, eight of these tumours were subsequently excised. Of the lesions that were removed at the patients' requests despite benign LCNB diagnosis, two were infiltrating carcinoma and one a DCIS. We demonstrate that three 3D-US-guided percutaneous core specimens are sufficient to achieve tissue for a reliable histological assessment of sonographically detectable breast lesions and allow the detection of malignancies with high sensitivity and low rate of false-negative diagnoses.

Three-dimensional ultrasound-validated large-core needle biopsy: is it a reliable method for the histological assessment of breast lesions?

OBJECTIVE: The use of three-dimensional (3D) ultrasound may help to determine the exact position of the needle during breast biopsy, thereby reducing the number of core samples that are needed to achieve a reliable histological diagnosis. The aim of this study was to demonstrate the efficacy of 3D ultrasound-validated large-core needle biopsy (LCNB) of the breast. METHODS: A total of 360 core needle biopsies was obtained from 169 breast lesions in 146 patients. Additional open breast biopsy was performed in 111 women (127/169 breast lesions); the remaining 42 lesions were followed up for at least 24 months. 3D ultrasound visualization of the needle in the postfiring position was used to classify the biopsy as central, marginal or outside the lesion. Based on this classification it was decided whether another sample had to be obtained. RESULTS: A median of two core samples per lesion provided for all the lesions a sensitivity for malignancy of 96.9%, specificity of 100%, false-positive rate of 0% and false-negative rate of 3.1%, and for the excised lesions a sensitivity of 96.5%, specificity of 100%, false-positive rate of 0%, false-negative rate of 3.5% and an underestimation rate of 3.4%. CONCLUSIONS: 3D ultrasound validation of the postfiring needle position is an efficient adjunct to ultrasound-guided LCNB. The advantages of 3D ultrasound validation are likely to include a reduction in the number of core samples needed to achieve a reliable histological diagnosis (and a possible reduction in the risk of tumor cell displacement), reduced procedure time and lower costs.

Multi-channel magnetocardiography for detecting beat morphology variations in fetal arrhythmias.

OBJECTIVE: Over the last few years, a number of studies have shown that fetal magnetocardiography (fMCG) is useful in describing fetal cardiac activity. A 55-channel MCG system in Ulm was used to record fetal cardiac activity in 12 pregnant women (with normal fetal heart activity in echocardiography) and in 5 pregnant women in whom the echocardiography showed fetal arrhythmias. METHOD: The recorded MCG data were treated in order to eliminate the maternal signal and three MCG channels with the best signals were used to emulate a standard electrocardiogram (ECG) recording so that standard MCG analysis could be performed. RESULTS: The results in assessing fetal electrophysiology, demonstrating its potential, are presented here for two fetuses with recorded supraventricular extrasystoles (SVES) and for one with ventricular extrasystoles (VES). Concerning the SVES, the analysis software OMEGA was able to separate three different beat morphologies. The VES could be detected exactly and have been confirmed by postnatal ECG. CONCLUSION: The beat morphology and the beat-to-beat variations allow new insights into the electrophysiology of the fetal heart.

Coping styles of pregnant women after prenatal ultrasound screening for fetal malformation.

OBJECTIVE: Ultrasound is a widespread noninvasive method of prenatal diagnosis. The detection of fetal abnormalities can provoke anxiety, which needs coping. The coping process of pregnant women with different risk conditions for fetal abnormality were studied in a longitudinal design and compared with a nonrisk control group of women with healthy uncomplicated pregnancies. METHODS: The coping strategies of women (n=664) during the second trimester were assessed with a questionnaire [Heim E, Augustiny KF, Blaser A, Schaffner L. Berner Bewältigungsformen (BEFO) Handbuch. Bern: Huber, 1991]. Data were collected at three points in time: immediately before the ultrasound scanning for fetal malformation, at 5-6 and 10-12 weeks after the prenatal ultrasound examination. Questionnaires were also used to collect information about sociodemographic data, anxiety, pregnancy data and personality. RESULTS: The analysis of the coping strategies of women with high-risk pregnancies (n=497) and as well of these with no-risk conditions in the control group (n=167) revealed three different factors of coping: Factor I: positive emotional attitude/distance, Factor II: negative emotional attitude/disapproval and Factor III: active coping. At all three points in time, Factor I correlated significantly with anxiety decrease, Factor II with increase and Factor III did not correlate with anxiety at all. CONCLUSIONS: Women with risk-pregnancies used coping strategies similar to those women in the control-group. Different spectrums of coping strategies corresponded significantly to increasing or decreasing anxiety. These women with high levels of anxiety, especially, should be offered sensitive care or psychotherapeutic counseling, as their coping processes did not lead to successful coping in the form of a reduction in anxiety.

Prediction of fetal anemia with Doppler measurement of the middle cerebral artery peak systolic velocity in pregnancies complicated by maternal blood group alloimmunization or parvovirus B19 infection.

OBJECTIVES: To confirm the relationship between the middle cerebral artery peak systolic velocity (MCA PSV) and hemoglobin values in fetuses at risk for anemia (due to maternal blood group alloimmunization or parvovirus B19 infection) and to investigate the clinical value of this method in the management of these pregnancies regardless of previous transfusions. SUBJECTS AND METHODS: Forty singleton pregnancies, 30 affected by alloimmunization and 10 by intrauterine parvovirus B19 infection, were referred to our tertiary center between 1998 and 2000. All cases underwent Doppler measurement of the MCA PSV immediately before fetal blood sampling and just before and after intrauterine transfusion. Hemoglobin determination was always performed after diagnostic cordocentesis, before starting and after terminating fetal transfusion. RESULTS: Overall, we performed 165 fetal blood samplings (hemoglobin values) and obtained 165 corresponding MCA PSV values, 140 in pregnancies complicated by red-cell alloimmunization and 25 by parvovirus B19 infection. In order to adjust for the effect of gestational age on the measurements, the data were expressed in multiples of the median (MoM). We found a good correlation between MCA PSV MoM and Hb MoM in both groups (alloimmunization, r2 = 0.6; y = 2.21 - 1.41 x + 0.24 x 2; parvovirus infection, r2 = 0.68; y = 2.09 - 0.58 x - 0.16 x 2). The reduction of post-transfusion MCA PSV values was statistically significant ( P < 0.0001). Using a threshold of 1.29 for MoM PSV, the sensitivity and the specificity of MCA pulsatility indices on pretransfusion values in predicting any degree of fetal anemia (Hb < or = 0.84 MoM) were 73.1% and 81.5% in the alloimmunization group and 100% and 100% in the parvovirus infection group, respectively. CONCLUSION: We can confirm the presence of an inverse correlation between MCA PSV measurements and hemoglobin values in fetuses at risk for anemia due to maternal blood group alloimmunization and fetal parvovirus B19 infection. The MCA PSV is a reliable method for the prediction of anemia not only in fetuses before the first intrauterine transfusion, but also in those which have undergone one or more transfusions, with good sensitivity and specificity in both groups of fetuses at risk.

Prenatal diagnosis of an aortico-left ventricular tunnel.

Aortico-left ventricular tunnel is a rare abnormal communication between the ascending aorta and the left ventricle. Early diagnosis and prompt surgical repair prevent congestive heart failure or consecutive valvular insufficiency. However, in utero diagnosis of this heart malformation has been rarely described and none of those children survived. We report on a case of aortico-left ventricular tunnel detected at 32 weeks' gestation with a favourable outcome after surgical repair at three months of age.

Effects of low-dose aspirin on uterine and fetal blood flow during pregnancy: results of a randomized, placebo-controlled, double-blind trial.

OBJECTIVE: This study was conducted to evaluate uteroplacental and fetal hemodynamics in fetuses exposed to low-dose aspirin (100 mg/d). DESIGN: Randomized, placebo-controlled, double-blind trial. SUBJECTS: The study protocol included singleton pregnancies of less than 20 gestational weeks at risk for pre-eclampsia or fetal growth restriction. Exclusion criteria were diabetes mellitus, pre-existing proteinuric hypertension or fetal malformations. Forty-three pregnant women were randomly allocated to daily treatment with 100 mg aspirin (n = 22) or placebo (n = 21). METHODS: Pulsed Doppler measurements of the uterine artery, fetal middle cerebral artery, fetal aorta, ductus arteriosus and atrioventricular valves were performed longitudinally at 14 day intervals starting from 18 gestational weeks until delivery. Results were expressed as group medians (aspirin vs. placebo) and were analyzed by Mann-Whitney U-test. RESULTS: There was no difference in uterine, umbilical, aortic, middle cerebral and ductus arteriosus blood flow between the aspirin group and controls. Median ductal peak flow velocities increased with gestational age in both groups, but differences between groups did not reach significance. In the third trimester of pregnancy, ductal peak velocities > 140 cm/s were occasionally observed in both groups. However, end diastolic velocities > 35 cm/s or atrioventricular valve regurgitation never occurred. CONCLUSIONS: Daily administration of low-dose aspirin during the second and third trimesters of pregnancy does not alter uteroplacental or fetoplacental hemodynamics and does not cause moderate or severe constriction of the ductus arteriosus.

[Laparoscopic intraoperative differential diagnosis of adnexal tumors. A pilot study of 20 premenopausal patients]. / Laparoskopische Sonographie zur intraoperativen Differenzialdiagnostik von Adnextumoren. Eine Pilotstudie an 20 prämenopausalen Patientinnen.

AIM: The purpose of the study was to determine the feasibility and potential clinical value of laparoscopic intraoperative sonography in the female genital tract. PATIENTS AND METHOD: Intraoperative ultrasound was performed in 20 consecutive premenopausal patients with adnexal masses during laparoscopy using a 7.5 MHz semiflexible transducer. RESULTS: Laparoscopic ultrasound of the female genital tract improves image resolution. Furthermore, this new method allows accurate localisation of early tubal pregnancy and may be helpful if laparoscopic evaluation of the inner genital tract is impaired by severe adhesions. In 7 out of 20 patients, the therapeutical procedure was clearly influenced by the laparoscopic ultrasound findings, resulting in a benefit for the patients in all seven cases. CONCLUSION: Intraoperative laparoscopic ultrasound may improve minimal invasive management of adnexal masses.

Cardiac changes in fetuses secondary to immune hemolytic anemia and their relation to hemoglobin and catecholamine concentrations in fetal blood.

OBJECTIVES: Immune hemolytic anemia in the fetus may cause cardiac decompensation and intrauterine death. Postnatally, norepinephrine (noradrenaline) is released in chronic heart failure, and may lead to myocardial hypertrophy. The aim of this study was to determine fetal cardiac changes associated with immune hemolytic anemia by means of echocardiography, and to relate them to fetal hemoglobin and norepinephrine levels. DESIGN: Thirty anemic fetuses underwent a total of 76 umbilical venous transfusions. Before the procedure, fetal echocardiography was performed, and end-diastolic myocardial wall thicknesses and ventricular dimensions together with Doppler flow patterns at the atrioventricular and semilunar valves were measured. Fetal hemoglobin, epinephrine and norepinephrine concentrations were determined before the transfusion. Statistical analysis of this prospective study comprised descriptive statistics including linear regression and correlation analyses. Two samples of measurements were compared by the Mann-Whitney U test. RESULTS: The mean hemoglobin concentration before the first transfusion was 6.9 g% at a mean gestational age of 26.8 weeks. Norepinephrine values were elevated in comparison to a reference range, and were higher than epinephrine values. The most striking echocardiographic finding was myocardial hypertrophy of all ventricular walls. Mean blood flow velocities were increased; at the left ventricle, they were negatively related to the hemoglobin concentrations, and positively to the norepinephrine values. CONCLUSIONS: Fetal myocardial hypertrophy in anemia may be the result of an augmented cardiac workload, indicated by the increased left ventricular mean velocities. This reaction reflects the redistribution of blood flow that may depend on hemoglobin and norepinephrine concentrations.

[Interobserver reproducibility of Doppler ultrasound measurements of the fetal ductus arteriosus]. / Interobserver-Reproduzierbarkeit von dopplersonographischen Messungen im fetalen Ductus arteriosus.

In a subgroup of 418 Doppler flow velocimetries of the fetal ductus arteriosus, which were performed to evaluate possible effects of low dose aspirin on fetal hemodynamics, an interobserver reproducibility study was carried out. 55 pulsed Doppler measurements of the fetal ductus arteriosus were performed within 24 hours by two different examinators. Pulsatility Index (PI), peak velocity (Vmax), mean velocity (Vmean) and enddiastolic velocity (Vmin) were obtained from the flow velocity profiles and correlation and variability coefficients were calculated. Peak velocity has been shown to be the most reproducible parameter with highest correlation and lowest variability.

[Utero- and fetoplacental hemodynamic measurements with low dose aspirin]. / Utero- und fetoplazentare hämodynamische Messungen unter low-dose Aspirin.

A prospective randomized double-blind study of low-dose aspirin treatment (100 mg/d) was conducted on a population of 43 pregnant women at risk of pregnancy-induced hypertension, preeclampsia, intrauterine growth retardation. Doppler ultrasound blood flow measurements of the uterine arteries and the umbilical cord, at the fetal and placental end, were obtained on a two-weekly interval in between 18 to 40 weeks of gestation. During the course of pregnancy Doppler indices of both vessels decreased, whereas the absolute velocity of the uterine arteries increased. Perfusion of both vessels did not show any relevant differences in between the aspirin- and placebo-group. Both groups showed a similar median duration of gestation at time of delivery (278 d aspirin vs. 270 d placebo). Comparison of median birthweight (3152.5 g aspirin vs. 2900 g placebo) did not show any significant difference. There were no haemodynamic effects of low-dose aspirin on the utero- and fetoplacental circulation to be demonstrated.

Treatment of fetal erythroblastosis by intravascular transfusions: outcome at 6 years.

OBJECTIVE: To assess 6 years' neurologic outcome of a complete cohort of survivors of intrauterine intravascular transfusions. METHODS: From January 1986 to December 1991, 136 intravascular transfusions were performed in 43 fetuses presenting with signs of severe erythroblastosis. Before the initial transfusion, 11 of 43 fetuses had some degree of hydrops fetalis, and hemoglobin values ranged between 1.5 and 10.7 g/dL. Neurologic outcome of a complete cohort of 35 long-time survivors was assessed for up to 6 years by reviewing the hospital charts and questionnaires sent to the family physicians or pediatricians. RESULTS: Long-time follow-up was available in all survivors with hydrops at initial transfusion (seven of seven) and in 23 of 28 survivors without hydrops. Only one of 35 survivors had mild psychomotoric disabilities up to 1 year of age, but was free of sensorineural problems on further examination. In a second case, delayed speech development was observed. Fetuses presenting with hydrops fetalis before initial transfusion tended to have a higher perinatal mortality and had a significantly higher rate of preterm delivery (P = .03). However, moderate or severe neurologic impairment was never observed, even when severe cases with hydrops fetalis or extremely low hemoglobin levels were included. CONCLUSION: Treatment of severe fetal erythroblastosis by intrauterine intravascular transfusions is associated with a favorable neurologic long-time outcome.

False-negative findings in chorionic villus sampling. An experimental approach and review of the literature.

61 fetuses/newborns who had an aberrant karyotype in amniocentesis (AC) or percutaneous umbilical blood sampling (PUBS) were followed-up by chorionic villus sampling (CVS) at birth or after interruption. The overall rate of discrepancies is surprisingly high. Among 46 cases with a non-mosaic numerical aberration an AC or PUBS three had a discrepant finding in placental tissue. This was also true in one of seven cases with non-mosaic structural aberrations and in three of five cases with mosaic structural aberrations. All three cases with a mosaic numerical aberration in AC or PUBS were not represented by CVS and/or lymphocytes or fibroblasts, demonstrating the general problem of the unpredictable prognostic value of mosaicism. Our data suggest, that in case of prenatal diagnosis by CVS, using a combined procedure of short-term (STC) and long-term culture (LTC), in our sample we would have missed one case of 45,X (1.6 per cent). When relying only on STC another two cases, one with 47, +21 and one with 46,XX,der(22) would not have been recognized (4.9 per cent, n = 3). All other chromosome aberrations would have been detected by STC alone. On the other hand, one case of 45,X was 'nearly missed' because of low-grade mosaicism in AC (45,X[1]/46,XX[19]), whereas in placental tissues and PUBS only 45,X was represented. This study mimics a false-negative rate of about 1:3000 (STC plus LTC) or about 1:1000 (STC alone) for an a priori risk group of two per cent (e.g., advanced maternal age).

In vitro studies on clonal growth of chondrocytes in thanatophoric dysplasia.

Thanatophoric dysplasia (TD) is characterized by a disorganized growth plate with markedly reduced proliferative and hypertrophic cartilage zones. Therefore, we studied in vitro the proliferation rates of articular chondrocytes from five TD patients and age-matched controls in response to bFGF, IGF-I, IGF-II, and TGF-beta 1. In human fetal controls bFGF was the most potent growth factor. Clonal growth the articular chondrocytes in response to bFGF was reduced in two of five TD patients and slightly below the range of controls in a third case. Stimulation of chondrocyte proliferation by IGF I and II was reduced in the patient whose response to bFGF was most markedly impaired. The effect of TGF-beta 1 ranged from normal to slightly elevated values in TD fetuses. These results indicate heterogeneity of the underlying defects in TD. Low proliferative responses of chondrocytes to bFGF and IGF-I/II are likely to play a key role in the pathogenesis of some cases. In two of five patients studied, the mechanisms of bFGF and IGF-signal transduction are candidates for the primary molecular defect.