Visualization of the Third Ventricle, the Future Cavum Septi Pellucidi, and the Cavum Veli Interpositi at 11+3 to 13+6 Gestational Weeks on 3D Transvaginal Ultrasound Including Normative Data.

OBJECTIVES: To show the development of the third ventricle, commissural plate, future cavum septi pellucidi, and cavum veli interpositi in weeks 12-14 by transvaginal 3D ultrasound. METHODS: This is a prospective transvaginal 3D study carried out to define the third ventricle and the diencephalic midline structures surrounding it. 93 of 387 fetuses in which the commissural plate with the future cavum septi pellucidi, cavum veli interpositi, and the roof of the third ventricle could be well visualized, were selected with the choroid plexus of the third ventricle and the pituitary gland serving as leading structures. In a small number of fetuses, the optic chiasm could also be displayed. In addition, the following measurements were performed: third ventricle craniocaudal and anteroposterior, roof of the third ventricle/cavum veli interpositi, and fcsp. RESULTS: The sonomorphologic characteristics of the commissural plate, the future cavum septi pellucidi, and the cavum veli interpositi are described IN 9% OF THE FETUSES examined. Measurements of the third ventricle, cavum veli interpositi, and the roof of the third ventricle show the following results: 3rd V cc = 3.895 + 0.091*CRL mm; 3rd V ap = 4.175 + 0.036*CRL mm; CVI ap = 2.223 + 0.029*CRL mm; CVI cc = 0.139 + 0.02*CRL mm. CONCLUSION: Transvaginal neurosonography enables visualization and measurement of the normal fetal third ventricle at 12-14 weeks of gestation including visualization of the future cavum septi pellucidi and the cavum veli interpositi. BEFORE USE IN PATIENTS CAN BE CONSIDERED, FURTHER SCIENTIFIC WORK IS REQUIRED.

Prenatal aortic valvuloplasty as a definite treatment in fetuses with critical aortic stenosis, severe mitral regurgitation and giant left atrium: a report of two cases with medium-term follow-up.

Fetuses with critical aortic stenosis, severe mitral regurgitation and left atrial enlargement are at risk to develop heart failure and intrauterine death. We present two cases with this physiology who underwent fetal aortic balloon valvuloplasty at 25 + 5 and 28 + 2 weeks as their only intervention without requiring postnatal treatment during short- to medium-term follow-up of 1.4 and 4.9 years.

Complications Associated with Fetal Cardiac Interventions: Prevalence and Management - Experience from 213 Procedures.

INTRODUCTION: Fetal cardiac interventions (FCIs) were introduced to change the natural history of some congenital heart defects. The aim of this study was to analyze the complications and management strategies associated with FCI at our institution. METHODS: The local FCI database was retrospectively reviewed for all fetuses who underwent FCI in our center since 2000 regarding complications and fetal outcome. RESULTS: 213 FCIs have been performed in 165 fetuses since October 2000: 60 with fetal pulmonary valvuloplasty, 4 with atrial septostomy, 7 with atrial septal stents, and 142 with fetal aortic valvuloplasty (FAV). The median gestational age at intervention was 27+1/7 weeks (21+4/7-38+3/7) for all interventions. The most common complications needing treatment were bradycardia (37%) and pericardial effusions (12%). FAV procedure-related mortality was significantly lower in the recent period since 2014 (14% early vs. 4% recent era, p = 0.03) due to a learning curve and improved management strategies. There were no relevant maternal complications. Premature deliveries occurred in 22.8% percent of all patients. CONCLUSIONS: Complications during FCI were frequent and must be expected. Strategies to reduce their prevalence as well as timely and correct treatment are mandatory to keep mortality rates low.

Atrial septum stenting in a foetus with hypoplastic left heart syndrome and restrictive foramen ovale: an alternative to emergency atrioseptectomy in the newborn-a case report.

BACKGROUND: In patients with hypoplastic left heart syndrome (HLHS) premature closure or restriction of the interatrial communication causes severe cyanosis directly after birth with rapid deterioration in clinical state. An ex-utero intrapartum treatment (EXIT) procedure, extracorporal membrane oxygenation (ECMO), and emergency interventional cardiac catheterization or cardiac surgery has to be anticipated and prepared. We report the first case performing foetal atrial septum stenting in such a patient directly before birth to enable uncomplicated interatrial shunting postnatally. CASE SUMMARY: A 31-year-old pregnant woman was referred to our centre for further evaluation of the foetus due to HLHS. In the follow-up study before birth severe restriction of the foramen ovale with increased retrograde flow in the pulmonary veins [0.33 ratio antegrade/retrograde time velocity integral (TVI)] was detected. After careful consideration foetal atrial septum stenting was performed at 38 + 3 weeks of gestation. At 39 + 2 weeks of gestation the baby was born by caesarean section followed by an uncomplicated postnatal adaption. On the 7th day of life a Norwood procedure was performed and the baby was discharged on the 63rd postoperative day. DISCUSSION: Evaluation of the interatrial communication in foetuses with HLHS should be done carefully just before birth. In the case of severe restriction or closure of the foramen ovale atrial septum stenting just before birth can be considered as an alternative treatment to an EXIT procedure, ECMO, or emergency atrioseptectomy on bypass. However, a very experienced team of paediatric cardiologists and perinatologists with expertise in foetal cardiac interventions is needed to perform this technical difficult procedure.

Retrospective evaluation of established cut-off values for the sFlt-1/PlGF ratio for predicting imminent delivery in preeclampsia patients.

OBJECTIVE: The outcome of preeclampsia is difficult to predict. Laboratory markers such as soluble fms-like tyrosine kinase (sFlt-1) and placental growth factor (PlGF) are thought to be predictive factors. A 2012 study by Verlohren et al. evaluated cut-off values for assessing time to delivery in patients with elevated sFlt-1/PlGF ratios. The present study aimed to evaluate findings in patients with elevated sFlt-1/PlGF ratios who gave birth at Kepler University Hospital in Linz, Austria. The hypothesis was tested, that our patients show longer pregnancy duration despite elevated sFlt-1/PlGF ratios. STUDY DESIGN: This retrospective data analysis included all patients with sFlt-1/PlGF ratios above the established cut-off values between January 2014 and October 2017. Two groups were analyzed relative to gestational age and were matched with healthy controls: 24 + 0 to 33 + 6 gestational weeks, sFlt-1/PlGF ratio >655.2; and 34 + 0 to 36 + 6 gestational weeks, sFlt-1/PlGF ratio >201. MAIN OUTCOME MEASURES: sFlt-1/PlGF ratio and time to delivery correlation. RESULTS: In the <34-week group, 43.2% of the patients delivered beyond 48 h, with a mean sFlt-1/PlGF ratio of 885.06, showing a significantly lower sFlt-1/PlGF ratio than patients who delivered within 2 days (P = 0.04). In the >34-week group, 66.7% were still pregnant after 48 h, with a mean sFlt-1/PlGF ratio of 273.7. CONCLUSION: The sFlt-1/PlGF ratio appears to be a powerful tool for diagnosing and predicting preeclampsia. However, the data do not confirm the cut-off values described earlier, with longer pregnancy durations in this group of patients.

Diagnosis of Fetal Posterior Fossa Malformations in High-Risk Pregnancies at 12-14 Gestational Weeks by Transvaginal Ultrasound Examination.

OBJECTIVE: To demonstrate sonographic detectable abnormalities of the posterior fossa in fetuses with a crown-rump length of 45-84 mm in high-risk pregnancies. METHODS: This was a prospective, observational study including 47 fetuses with known outcome, whose mothers attended our centers for first trimester tests and showed an abnormal first trimester ultrasound scan. In these fetuses, we examined transvaginal acquired three-dimensional volume blocks for abnormalities of the fetal posterior fossa. In these fetuses, the measurements of the cerebellar vermis (VE) and of the anterior membranous area (AMA) were compared with published reference ranges. RESULTS: There were 8 fetuses with a ver-mian length below the 5th centile. In 5 of these fetuses, the AMA was also elongated and in 4 of these fetuses, pathology was confirmed. One case with a normal vermian length and normal AMA had a hypoplastic VE later on in the confirmatory test. CONCLUSION: Pathology of the posterior fossa can be directly diagnosed by assessing the VE and the AMA at the first trimester scan by examining transvaginal acquired volume blocks.

Reference Ranges for Transvaginal Examined Fossa Posterior Structures in Fetuses from 45 to 84 mm Crown-Rump Length.

OBJECTIVE: The study aimed to describe reference values for structures of the posterior fossa in fetuses with a crown-rump length (CRL) between 45 and 84 mm. MATERIALS AND METHODS: This was a prospective, cross-sectional study including 216 normal appearing fetuses. In transvaginal acquired 3-dimensional volume blocks, the longest diameter of the vermis (VE), posterior membranous area (PMA), medulla-oblongata-pons angle (MOPA), diameters of the medulla oblongata (MO) and pons (PO), and the area of Blake's pouch (BP) were measured. Polynomial or linear regression analysis were performed to calculate the mean, 5th and 95th centile according to CRL. In 20 fetuses, intra- and interobserver repeatability were calculated. RESULTS: There is a curvilinear correlation between CRL and PO (PO [mean] = 1.3893 + 0.004356 × CRL + 0.000002610 × CRL3; SD = 1.6818 - 0.03765 × CRL + 0.000003831 × CRL3; R2 = 0.489); CRL and MO (MO [mean] = 1.5959-0.001905 × CRL + 0.000003362*CRL3; SD = -0.1417 + 0.005404 × CRL + 0.0000004988 × CRL3; R2 = 0.525); CRL and VE (VE [mean] = -0.3640 + 0.04302 × CRL+ 0.000001486 × CRL3; SD = 0.5854 - 0.004812 × CRL + 0.0000005896 × CRL3; R2 = 0.643); CRL and PMA (PMA [mean] = 0.6901 + 0.04307 × CRL - 0.0000008459 × CRL3; SD = -0.4232 + 0.02026 × CRL - 0.000001320 × CRL3; R2 = 0.272); CRL and BP (mm2; BP [mean] -12.2067 + 0.3334 × CRL - 0.00001262 × CRL3; SD = -1.6431 + 0.06380 × CRL+ 0.0000003257 × CRL3; R2 = 0.289). The relation between CRL and MOPA (°) is best described by a linear regression (MOPA [mean] = 79.6332 + 0.6122 × CRL; SD = 4.8453 + 0.07333 × CRL; R2 = 0.318). CONCLUSION: We provide reference values for anatomical structures of the posterior fossa of fetuses between 45 and 84 mm CRL. The established reference values might ease the diagnosis of fetal malformations in early pregnancy.

Sonoembryology of the fetal posterior fossa at 11 + 3 to 13 + 6 gestational weeks on three-dimensional transvaginal ultrasound.

OBJECTIVE: To describe the sonographic appearance and temporal changes of the structures of the posterior cranial fossa in fetuses at a crown-rump length (CRL) between 45 and 84 mm in transvaginal acquired three-dimensional volume blocks. METHODS: This was a prospective, cross-sectional, observational study including 80 fetuses, whose mothers attended Kepler University Hospital Linz or the Ambulatorium für Fetalmedizin Feldkirch for first-trimester sonography. Three-dimensional volume blocks were acquired in a standardized way and after processing the sonographic characteristics of the brainstem, cerebellar vermis, choroid plexus, anterior membranous area (AMA) and Blake's metapore were described. Measurements of the length of the cerebellar vermis, the length of the AMA and the medulla-oblongata-pons angle (MOPA) were performed. In 20 fetuses the intra- and interobserver repeatability was calculated. RESULTS: The sonomorphologic characteristics of posterior fossa structures as cerebellar vermis, AMA, Blake's metapore, choroid plexus, pons and medulla oblongata were described. There is a significant correlation between CRL and vermis length, CRL and MOPA and CRL and AMA. CONCLUSIONS: Transvaginal three-dimensional sonography allows a detailed depiction of the structures of the posterior fossa and their temporal course in early pregnancy. © 2016 John Wiley & Sons, Ltd.

Lung cancer in pregnancy.

In the 26th week of gestation, a 29-year-old pregnant office employee was referred to the pulmonary department of Linz General Hospital (AKH) under the suspicion of tuberculosis. She complained of a cough with intermittent hemoptysis and pain in the thoracic spine from which she had been suffering the past 9 weeks. A plain chest X-ray showed a dense infiltrate on the right side and multiple smaller shadows in both lungs. Laboratory testing revealed anemia, leukocytosis, and an increase of C-reactive protein. All tests for tuberculosis were negative.A bronchoscopy was performed and biopsies were taken from the right upper and middle lobe. The histopathological examination found cells of an adenocarcinoma. A magnetic resonance imaging (MRI) revealed a large tumor and surrounding atelectasis were seen in the right upper and middle lobe, as well as multiple intrapulmonary metastases in both lungs. In addition, not only metastases in the thoracic spine (level Th2/3) but also at other osseous locations and multiple cerebral metastases were detected. The patient received one cycle of chemotherapy consisting of docetaxel and carboplatin (AUC5) in the 27th week of gestation. Additional radiotherapy was applied to the involved thoracic spine. Due to positive epidermal growth factor receptor mutation, therapy with gefitinib 250 mg/day was started 2 days after a Caesarean section (preceded by treatment for fetal lung maturation). A healthy girl was delivered in the 30th week of pregnancy. Staging with computed tomography (CT) after delivery revealed an unstable fracture of Th2 with compression of the spinal cord. Neurosurgery was performed, consisting of a ventral corporectomy of Th1-2 followed by an anterior and posterior osteosynthesis for stabilization. The patient was discharged without neurological deficits within 1 week. Subsequent treatment with gefitinib improved the performance status of the patient, and CT scans of the chest and an MRI of the brain showed the size of the tumor to be shrinking. Meanwhile, the infant developed appropriately for her age.After 14 months of the first diagnosis, the patient experienced neurological symptoms (aphasia, confusion) due to neoplastic meningeosis and cerebral venous sinus thrombosis together with local tumor progression in the lung. One course of chemotherapy, combining carboplatin/pemetrexed/bevacizumab, was given without clinical response. Despite best supportive care, the patient died 17 months after diagnosis in October 2013.

[In-utero treatment of hypoplastic left heart syndrome]. / Intrauterin behandling af hypoplastisk venstre ventrikel-syndrom.

In-utero treatment of fetal aortic stenosis (AS) may prevent hypoplastic left heart syndrome. A girl was diagnosed prenatally with severe AS and was referred to the Women's and Children's Hospital in Linz, Austria, where she underwent an intrauterine valvuloplasty of the aortic valve. Postnatally, the girl was given prostaglandin and operated a.m. Ross-Konno. An echocardiography at the age of four months showed a neoaorta without stenosis and insufficiency and a normal systolic function of the left ventricle. This treatment must be carefully considered when dealing with fetuses with AS.

Fetal cardiac interventions: rationale, risk and benefit.

Fetal congenital heart disease may progress during pregnancy and may lead to irreversible myocardial or pulmonary damage. The rationale of fetal intracardiac interventions is to change fetal hemodynamics, prevent secondary damage and improve long-term outcome at an acceptable risk for mother and fetus. This review focuses on the current experience about patient selection, risks and benefits of this technique.

Tocolysis with the ß-2-sympathomimetic hexoprenaline increases occurrence of infantile haemangioma in preterm infants.

BACKGROUND: Infantile haemangioma (IH) is the most commonly observed tumour in children. Off-label pharmacological treatment of IH with the beta-blocker propranolol induces regression of IH. Based on the fact that IH are more frequently observed in premature babies than in mature babies and the evidence that beta-blocker therapy leads to regression of IH, the authors generated the hypothesis that the use of ß-2-sympathomimetics during pregnancy for inhibiting premature labour might increase occurrence of IH in preterm infants. METHODS: For group comparison t test, Mann-Whitney U test and Fisher's exact test were used. Logistic regression was carried out by the forward stepwise method with Wald statistics. RESULTS: Data of 328 preterm infants (<32 gestational weeks) or with a birth weight of less than 1500 g (<36 gestational weeks) born between January 2006 and December 2008 were analysed. A total of 15 were excluded due do death within the 1st month of life, 38 because of lost to follow-up and six due to incomplete data. Complete data of 269 preterm infants were retrospectively analysed. During the follow-up period of median 1.6 years, 50 infants developed one or more IH within their first 6 months of life. IH occurred in 40/181 patients with intrauterine exposure to the ß-2-sympathomimetic hexoprenaline and in 10/88 without exposure (OR=4.3; 95% CI 1.4 to 13.8). Furthermore, the influence of antenatal exposure to glucocorticosteroids for induction of lung development was analysed. Prenatally exposed subjects showed reduced occurrence of IH (OR=0.2; 95% CI 0.05 to 0.8). CONCLUSION: Intrauterine exposure to the ß-2-sympathomimetic hexoprenaline might increase the occurrence of IH in preterm infants.

Pharmacological stimulation of sperm motility in frozen and thawed testicular sperm using the dimethylxanthine theophylline.

OBJECTIVE: To evaluate whether the use of theophylline improves sperm motility and treatment outcome in frozen-thawed testicular sperm extraction (TESE). DESIGN: Artificial sperm activation was offered to azoospermic patients between January and October 2010 in two different centers (identical lab conditions). SETTING: IVF units of public hospitals. PATIENT(S): Sixty-five patients participated and gave informed consent. INTERVENTION(S): Sibling oocytes were split into a study (intracytoplasmic sperm injection [ICSI] with thawed testicular sperm treated with theophylline) and a control group (ICSI with thawed untreated sperm). MAIN OUTCOME MEASURE(S): Sperm motility, time for sperm selection, rates of fertilization, implantation, clinical pregnancy, and live birth. RESULT(S): All patients but one (98.5%) showed a significant improvement in testicular sperm motility when theophylline was used. In addition, sperm selection took significantly less time in the study as compared with in the untreated control group. Corresponding rates of fertilization (79.9% vs. 63.3%) and blastulation (63.9% vs. 46.8%) were significantly increased. Significantly more patients achieved clinical pregnancy if embryos/blastocysts derived from oocytes that had been injected with pharmacologically stimulated testicular spermatozoa were transferred (53.9% vs. 23.8%). This also holds true for the implantation rate. CONCLUSION(S): Theophylline turned out to be a reliable tool in stimulating testicular spermatozoa after thawing. Its immediate effect allows for faster and more accurate selection of viable sperm, which in turn improved fertilization and pregnancy outcome in this prospective study.

Fetal surgery for cardiac lesions.

Intrauterine dilation of critical fetal aortic stenosis (AS) and pulmonary stenosis or atresia has the potential to change the natural course of these congenital heart defects preventing progression to a single ventricle circulation. This article reviews the world experience in fetal cardiac interventions. In carefully selected cases, fetal cardiac surgery can reverse end-stage heart failure and can provide biventricular outcome postnatally in about two thirds of the cases with successful interventions.

Amino terminal pro B-type natriuretic peptide levels are elevated in the cord blood of neonates with congenital heart defect.

This prospective study investigates whether amino terminal proB-type natriuretic peptide (NT-proBNP) levels are elevated in neonates with congenital heart defect (CHD). NT-proBNP levels in the umbilical cord blood of 60 neonates with prenatally diagnosed CHD, in the cord blood of 200 control subjects, and in the plasma of the respective mothers were analyzed using an automated enzyme immunoassay. NT-proBNP concentrations in the cord blood of the CHD group were significantly elevated compared with controls [median (range): 158 pg/mL (378-3631 pg/mL) and 626 pg/mL (153-2518 pg/mL); p value <0.001]. The NT-proBNP concentrations of the newborns and their mothers did correlate neither in the CHD nor in the control group. In 54 patients with CHD, NT-proBNP levels were measured on the median 5th day of life. They showed a significant increase (median 1665 pg/mL and 19222 pg/mL; p < 0.001). NT-proBNP levels in the cord blood of neonates with CHD are significantly elevated and show a marked increase in the first week of life. Furthermore, this study confirms previously published reference intervals of NT-proBNP in the cord blood of healthy neonates as well as the finding that there is no exchange of NT-proBNP across the placenta.

Assisted vaginal delivery versus caesarean section in breech presentation.

BACKGROUND: The Term Breech Trial (TBT), a well-known study conducted by Hannah and published in the Lancet, revealed a better outcome for neonates after primary caesarean section compared with attempted vaginal delivery. The aim of the present study was to determine whether the results of TBT have to be taken into account when counseling pregnant women in central Europe. METHODS: We investigated 882 women who had delivered infants in breech presentation over a period of 11 years. The neonates had a birthweight of >2500 g and no malformations. We compared mortality and serious neonatal morbidity after attempted vaginal delivery and after primary caesarean section. RESULTS: No infant or maternal mortality was registered in either group. Serious neonatal morbidity was higher (0.5%; n = 2) for attempted vaginal delivery than for primary caesarean section; in the latter group, no child fulfilled the criteria for serious neonatal morbidity. However, the difference was not statistically significant. As expected, after attempted vaginal delivery, the base excess, and 5-min APGAR scores were indicative of more markedly depressed children. CONCLUSION: After careful exclusion of risk factors and informing the patient in detail about the risks and possible complications, vaginal delivery from breech presentation is still warrantable.

Fetal pulmonary valvuloplasty for critical pulmonary stenosis or atresia with intact septum.

Progressive stenosis of the semilunar valves in utero can be life threatening. We treated two fetuses with complete or almost complete pulmonary atresia and imminent hydrops (increased cardiothoracic ratio, pericardial effusion, holosystolic tricuspid regurgitation extending into diastole, and abnormal venous Dopplers). We dilated the pulmonary valve of two fetuses in utero at 28 and 30 weeks' gestation, through the mothers' abdomens. After the procedure, the fetuses had decreased signs of circulatory failure and gestation continued until near term. In the neonatal period, we did a repeat valvuloplasty with systemic-to-pulmonary arterial shunt. Both children (now aged 18 months and 12 months) now have biventricular circulation. Surgery on selected fetuses with semilunar valve stenosis or atresia, or both, can extend pregnancy and favourably change the postnatal surgical options.