Development of pre-eclampsia within 4 weeks of sFlt-1/PlGF ratio > 38: comparison of performance at 31-34 vs 35-37 weeks' gestation.

OBJECTIVE: To compare the performance of screening by soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) ratio > 38 for the prediction of delivery with pre-eclampsia (PE) at < 1 week and < 4 weeks from assessment when the test is carried out at 31-34 vs 35-37 weeks' gestation. METHODS: This was a prospective observational study in women attending a third-trimester ultrasound scan as part of routine pregnancy care; the visit was at 30-34 weeks' gestation in the first phase of the study and at 35-37 weeks in the second phase. Serum sFlt-1 and PlGF were measured and their ratio calculated. We estimated the detection rate (DR) and false-positive rate (FPR) of sFlt-1/PlGF ratio > 38 for predicting delivery with PE at < 1 week and < 4 weeks after assessment and compared the performance of screening when the test was carried out at 31 + 0 to 33 + 6 vs 35 + 0 to 36 + 6 weeks' gestation. RESULTS: The study population included 8063 singleton pregnancies that were examined at 31-34 weeks and 3703 at 35-37 weeks. Delivery with PE occurred at < 1, < 4 and ≥ 4 weeks from assessment in five (0.1%), 29 (0.4%) and 202 (2.5%) women assessed at 31-34 weeks, respectively, and in seven (0.2%), 39 (1.1%) and 21 (0.6%) of those assessed at 35-37 weeks. In women without PE, the median sFlt-1/PlGF ratio increased with gestational age at screening and a ratio of 38 was just below the 99th percentile at 32 weeks' gestation and just below the 90th percentile at 36 weeks. In the two gestational windows, the DR of PE delivering < 4 weeks from assessment was similar (75.9% (95% CI, 56.5-89.7%) vs 79.5% (95% CI, 63.5-90.7%)), but the FPR was substantially lower at 31-34 weeks than at 35-37 weeks (1.7% (95% CI, 1.4-2.0%) vs 9.6% (95% CI, 8.7-10.6%)). The number of cases with PE delivering < 1 week from assessment was small, but similarly, in the two gestational windows, the DR was comparable (80.0% (95% CI, 28.4-99.5%) vs 85.7% (95% CI, 42.1-99.6%)), and the FPR was substantially lower at 31-34 weeks than at 35-37 weeks (1.9% (95% CI, 1.6-2.2%) vs 10.2% (95% CI, 9.3-11.3%)). CONCLUSION: The performance of sFlt-1/PlGF ratio > 38 in the prediction of delivery with PE at < 1 and < 4 weeks from assessment is substantially different when the assessment is at 31-34 weeks' gestation compared to at 35-37 weeks. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

[Rate of prenatal detection of congenital right heart defects]. / Pränatale Detektionsrate angeborener Rechtsherzfehler.

Congenital right heart lesions (including tetralogy of Fallot, pulmonary valve stenosis, pulmonary atresia with intact ventricular septum, Ebstein's anomaly and dysplastic tricuspid valve) account for about 19% of congenital cardiac anomalies. We performed a retrospective study in order to assess the percentage of patients with significant right heart lesions (requiring therapy in the first year of life), which is detected prenatally and referred to a centre for perinatal treatment. From 1/1990 until 12/1997 congenital right heart lesions were diagnosed in 21 fetuses and 190 infants (211 patients. The majority of patients had tetralogy of Fallot (64%), less frequently we found critical pulmonary valve stenosis (9%), pulmonary atresia with intact ventricular septum (9%), tricuspid atresia (14%) and Ebstein's anomaly or dysplastic tricuspid valve (4%). Prenatally the cardiac anomaly was diagnosed in all 21 cases who were referred to our center (10%). The highest referral and detection rate was found among fetuses with Ebstein's anomaly or dysplastic tricuspid valve (5/8 patients = 63%) followed by fetuses with pulmonary atresia and intact ventricular septum (5/20 = 25%), critical pulmonary stenosis (4/18 = 22%) or tricuspid atresia (4/29 = 14%). The prenatal referral rate was disappointing in children with tetralogy of Fallot (3/136 = 2.2%). A higher prenatal detection rate of congenital right heart lesions can be achieved only by an improvement of prenatal screening including the 4-chamber view and the origin of the great arteries. A first step would be the inclusion of the fetal 4-chamber view into the routine examination during the 18th-20th week of pregnancy (stage 1 of a multistage concept of prenatal screening) and by assessment of the outflow tracts and the great arteries in pregnancies associated with risk factors or anomalies of the fetus (stage 2 and 3 of a multistage concept).

[Congenital Langerhans-cell histiocytosis presenting as a varicella infection]. / Kongenitale Langerhans-Zellen-Histiozytose unter dem klinischen Bild einer Varizelleninfektion.

UNLABELLED: We report on a preterm infant (33rd gestational week) with a varicella-like congenital rash, which initially appeared to respond to therapy with acyclovir. At the age of 3 weeks, lesions were in different stages of evolution and still resembled a varicella zoster virus (VZV) infection. However, since proof of VZV infection was lacking and new lesions erupted at the age of 4 weeks, a skin biopsy was performed which revealed a diagnosis of Langerhans cells histiocytosis. Therapy with prednisone resulted in prompt healing of the lesions. DISCUSSION: Congenital Langerhans cell histiocytosis is rare and symptoms may vary substantially from case to case. Like in our observation it may be confused with congenital varicella. In case of congenital skin lesions of uncertain etiology a skin biopsy should be performed.

[Incidence and treatment of reactive infundibular obstruction after balloon dilatation of critical pulmonary valve stenoses]. / Inzidenz und Behandlung der reaktiven infundibulären Obstruktion nach Ballondilatation von kritischen Pulmonalstenosen.

Seventeen consecutive newborn and premature babies with critical pulmonary stenosis underwent a technically successful balloon valvuloplasty at our institution from March 1991 to February 1998. The only major complication was a thrombosis of the femoral vein in one patient, causing no clinical problems. Four patients (24%) showed a reactive infundibular obstruction after balloon valvuloplasty. The outflow tract obstruction became evident immediately after successful dilatation of the pulmonary valve with persistently high pressures in the right ventricle. Pathognomonic was a typical notch in the ascending part of the right ventricular pressure curve. We were unable to predict this reaction based on echocardiography or angiography. To relieve the muscular subvalvar obstruction, we treated the first two patients with i.v. Propranolol (0.05 mg/kg over 2 min). The last 2 patients received Esmolol (0.5 mg/kg over 2 min followed by a continuous infusion with 100 micrograms/kg/min), a very short acting beta-blocker. In the medium-term follow-up, all 17 patients had a very good result with only mild pulmonary valve regurgitation. All 4 patients with a reactive infundibular obstruction required no repeat intervention. In the medium-term follow-up there were no differences between these 4 patients and the whole group.

Clinical relevance of monosomy 22q11.2 in children with pulmonary atresia and ventricular septal defect.

UNLABELLED: The purpose of our study was to describe the prevalence and the clinical spectrum of monosomy 22q11.2 in a population of patients with pulmonary atresia and ventricular septal defect. We examined all 44 patients with this conotruncal cardiac malformation who presented to our institution from January 1994 until December 1997. The type of collateral lung perfusion was recorded including anomalies of the pulmonary arteries as well as facial and immunological abnormalities. Molecular-cytogenetic testing for a 22q11.2 microdeletion was performed using the probes D22S75 and cHKAD26. Statistical differences were evaluated with the Fisher's Exact Test. Monosomy 22q11.2 was present in ten children (23%) with major aortopulmonary collateral arteries (group 1). The remaining 13 children (29%) with major aortopulmonary collateral arteries (group 2) and all 21 children (48%) with ductus arteriosus (group 3) were negative for this microdeletion. All children in group 1 had facial anomalies, six had mild immunological abnormalities including decreased CD 4 + or CD 8 + cells. Anomalies of the pulmonary vascular bed were significantly more frequent in children of group 1 (9/10) than in children of group 2 (4/13) or group 3 (0/21). Due to these pulmonary vascular anomalies, corrective surgery had been accomplished in fewer children with monosomy 22q11.2 (none in group 1) as compared to 7/13 children in group 2 and 14/21 children in group 3. CONCLUSION: In children with pulmonary atresia and ventricular septal defect, monosomy 22q11.2 is preferentially associated with major aortopulmonary collateral arteries. Due to the higher incidence of pulmonary arterial abnormalities, successful surgical repair will require a different therapeutic approach in most patients with this microdeletion.

Possible sources of right-to-left shunting in patients following a total cavopulmonary connection.

Despite a good haemodynamic result, many children have a mildly decreased arterial-oxygen saturation following a total cavopulmonary connection. Our study was performed to determine possible mechanisms of right-to-left shunting in these patients. We performed elective cardiac catheterization in 19 children at a mean interval of 3.6 years following a total cavopulmonary connection. The intrapulmonary right-to-left shunt, the intracardiac right-to-left shunt and the total right-to-left shunt were calculated under mechanical ventilation with 100% oxygen. The intrapulmonary right-to-left shunt was 10.8+/-3.5% of the pulmonary blood flow, and the total right-to-left shunt accounted for 18.9+/-5.2% of the systemic blood flow. The intracardiac right-to-left shunt in patients with no relevant venovenous collaterals or leaks in the atrial tunnel was calculated at 6.4+/-3.0% of the systemic blood flow, while the intracardiac right-to-left shunt in patients with relevant collaterals or leaks accounted for 13.0+/-5.9% of the systemic blood flow. Since intrapulmonary arteriovenous fistulas were not demonstrated angiographically in any of our patients, the intrapulmonary right-to-left shunt is probably due to low ratios of perfusion to ventilation in some pulmonary segments. The intracardiac right-to-left shunt was due to leaks across the interatrial baffle, collaterals between systemic and pulmonary veins, and to the coronary sinus draining to the pulmonary venous atrium.

Incidence and significance of 22q11.2 hemizygosity in patients with interrupted aortic arch.

Interruption of the aortic arch (IAA) is a severe malformation of the heart with known association to DiGeorge syndrome (DGS) and 22q11.2 hemizygosity. The aim of this study was to establish incidence and significance of 22q11.2 hemizygosity in an unbiased sample of patients with IAA. All 15 children with IAA who were referred to our hospital in a 3-year period were tested by chromosome and fluorescence in situ hybridization (FISH) analysis with the probes D22S75, Tuplel, and cHKAD26 and by a set of 10 simple tandem repeat polymorphic (STRP) markers. In nine of 11 children with IAA type B, 22q11.2 hemizygosity was demonstrated by FISH and STRP analysis, but in none of the four children with type A. In all but one child, deletion size was approximately 3 Mb. The girl with the smaller deletion of approximately 1.5 Mb differed because of an Ullrich-Turner syndrome-like phenotype and severe T-cell defect. Additionally, in one patient with phenotypic signs of DGS, a small deletion distal to the known DGS region containing the marker D22S308 was suspected by STRP analysis. One deletion was shown to be inherited from a healthy father and one IAA type A recurred in a sib. T-cell anomalies were evident in eight of the nine children with classical deletion, five of whom suffered also from hypoparathyroidism. With respect to cause and clinical course, IAA type A and B were shown to represent different entities. This study showed that variable symptoms of 22q11.2 hemizygosity may cluster.

Monosomy 22q11 in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries.

OBJECTIVE: To describe the morphology of the pulmonary arteries in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries with and without monosomy 22q11. DESIGN: A retrospective analysis of all patients with this congenital heart defect who are being followed at the University Children's Hospital Erlangen. SETTING: A tertiary referral centre for paediatric cardiology and paediatric cardiac surgery. PATIENTS: 21 patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries. Monosomy 22q11 was diagnosed by fluorescent in situ hybridisation using the D22S75 probe (Oncor). The morphology of the pulmonary arteries was assessed on the basis of selective angiograms. RESULTS: 10 patients (48%) were shown to have a microdeletion in 22q11 (group I). There was no difference with respect to the presence of confluent central pulmonary arteries between these patients (80%) and the remaining 11 patients (group II) without monosomy 22q11 (91%). Patients of group I, however, more often had arborisation anomalies of the pulmonary vascular bed (90% in group I v 27% in group II). Because of the more severe abnormalities of the pulmonary arteries, a biventricular repair had not been possible in any of the children with monosomy 22q11, though repair had been carried out in 64% of the children in group II. CONCLUSION: The developmental disturbance caused by the monosomy 22q11 seems to impair the connection of the peripheral pulmonary artery segments to the central pulmonary arteries in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries, resulting in a lower probability of biventricular repair.

Monozygotic twins concordant for Cayler syndrome.

Deletions within chromosome band 22q11.2 are associated with a variety of conditions, although a simple genotype-phenotype correlation has not been established so far. Environmental factors, chance events, or a second hit theory were supported by two observations of monozygotic twins with 22q11.2 deletions and discordant phenotypes [Goodship et al., J Med Genet 1995;32:746-748; Fryer, J Med Genet 1996;33:173]. We present monozygotic twins concordant for 22q11.2 deletion and Cayler syndrome, favoring the view that there exists a predominant genetic determination of the del 22q11.2 phenotype. As these twins are diamniotic and dichorionic, they may offer a more reliable insight in genetic phenotype determination than the other published, probably monochorionic, twins who may have a discordant malformation by twinning itself.

Increased spontaneous in vitro apoptosis in double negative T cells of humans with a fas/apo-1 mutation.

We describe a 17 year old patient suffering from Canale-Smith syndrome (CSS) including chronic lymphadenopathy, splenomegaly, hypergammaglobulinemia and recurrent Coombs positive hemolytic crises. The parents are not consanguine, all other family members including two brothers are healthy. Peripheral blood mononuclear cells of the patient showed an increased rate of CD3 positive, CD4/CD8 double negative T-lymphocytes. In vitro assays showed these cells to have an increased rate of spontaneous apoptosis. Though expression of Fas/Apo-1 (CD95) and Fas-ligand (FasL) was detected on RNA- and protein level we found Fas/Apo-1 mediated apoptosis being significantly reduced. Sequencing of the fas/apo-1 gene proved the patient RT and his father to carry a point mutation at position 804 located in exon 9 (death domain) leading to an amino acid substitution. For developing of CSS, a fas/apo-1 mutation seems to be necessary but not sufficient. An additional independent mechanism must be involved in the pathogenesis of human lpr<-phenotype.

Azathioprine-induced severe pancytopenia due to a homozygous two-point mutation of the thiopurine methyltransferase gene in a patient with juvenile HLA-B27-associated spondylarthritis.

Severe pancytopenia due to azathioprine (AZA) toxicity in patients with autoimmune diseases is not uncommon. We describe a 14-year-old girl with HLA-B27+ spondylarthritis who was treated with AZA 3 mg/kg/day and who suddenly developed severe pancytopenia in the seventh week of treatment. Analysis of the catabolic pathway of AZA revealed a homozygous deficiency of thiopurine methyltransferase (TPMT) on the basis of a combined 2-point mutation at nucleotide positions 460 and 719 in the gene for TPMT, causing a toxic level of the metabolic active 6-thioguanine nucleotides (6-TGN) (2,394 pmoles/8 x 10(8) red blood cells). The patient was transfusion dependent and finally recovered 8 weeks after the development of the pancytopenia. At that time, 6-TGN had already returned to normal therapeutic levels. Family studies revealed another homozygous deficiency in the mother, while the other family members were heterozygous.

[Rashkind PDA occluder and detachable metal spiral for interventional occlusion of the ductus arteriosus Botalli. Indications, outcome and complications]. / Rashkind-PDA-Occluder und ablösbare Metallspirale zum interventionellen Verschluss des Ductus arteriosus Botalli. Indikationen, Ergebnisse und Komplikationen.

The intention of this study was to determine the efficacy and complication rate of the interventional duct occlusion. Furthermore, we wanted to compare the meanwhile well-known Rashkind-PDA-Occluder system (ROS) with the results of the considerably cheaper detachable duct occlude coils (PDA-S). For this purpose, we analyzed the data of 53 consecutive patients who received a total of 28 ROS and 25 PDA-S. The ROS was implanted in the slightly larger ducts (O 3.1 +/- 0.6 mm), the PDA-S in the smaller ones (O 2.2 +/- 0.6 mm). The rate of residual shunting was 20% in the ROS-group (follow-up: 104 to 1099 days, mean 580 +/- 300 days) and 7.7% in the PDA-S-group (follow-up: 90 to 384 days, mean 161 +/- 101 days). One patient after ROS showed a significant residual shunting and received 2.5 years after the first procedure a PDA-S which eliminated the shunt. In a second patient the attempt of implanting two coils in a 4 mm duct resulted in the embolization of the first coil into the right pulmonary artery. The coil could not be retrieved and was left in the pulmonary artery without sequelae. All other patients received only one ROS or one PDA-S. There were no further complications. The complication rate for all interventional duct occlusions therefore was 1.9% (0% for the ROS-group; 4.0% for the PDA-S-group). In comparison with the Gianturco coils that have been introduced since 1975, the new detachable coils can be manipulated much more easily, because they remain fixed at the delivery wire until an ideal position is achieved. Then the coil is set free by unscrewing it from the delivery wire. For small ducts with a diameter up to 3 mm the detachable coil is an effective and cheap alternative which can be handled easily. Because of the smaller delivery systems in comparison to the ROS (4-5 F versus 8 F or 11 F) the PDA-S is also suitable for small children and infants. larger ducts should be closed with the ROS.

Changes in pulmonary artery size before and after total cavopulmonary connection.

OBJECTIVE: To assess changes in size of the central pulmonary arteries following a total cavopulmonary connection (TCPC). DESIGN: A retrospective analysis of the angiographic diameters of the central pulmonary arteries, expressed as z scores, in infancy before the TCPC and 3.5 (0.9) years (mean (SD)) later. Analysis of the relation between the pulmonary arteriolar resistance and the z scores at follow up. SETTING: Tertiary referral centre. PATIENTS: 32 patients who had TCPC from February 1990 to July 1993. RESULTS: The patients were divided into two groups (n = 16) depending on their preoperative flow ratio: group I, Qp/Qs < or = 1; group II, Qp/Qs > 1. At the initial study in infancy the mean z scores in group I were -6.0 for the right pulmonary artery (RPA) and -9.6 for the left pulmonary artery (LPA); in group II the respective values were -2.7 and -3.0. Before the TCPC the values increased to 0.5 (RPA) and -0.5 (LPA) in group I, and to 8.8 (RPA) and 8.2 (LPA) in group II. At follow up the z scores decreased to -2.4 (RPA) and -4.9 (LPA) in group I, and to 2.2 (RPA) and -0.7 (LPA) in group II. The changes in pulmonary artery diameters were significant for both groups (p < 0.02). Following the TCPC, no significant difference in pulmonary arteriolar resistance index was found between patients with relatively small pulmonary arteries (z score RPA + LPA < or = 0) and those with relatively large pulmonary arteries (z score RPA + LPA > 0). CONCLUSIONS: Creation of a TCPC results in a significant reduction in size of the central pulmonary arteries. At a mean interval of 3.5 years following the TCPC, however, there was no significant difference in pulmonary arteriolar resistance index between patients with smaller and larger central pulmonary arteries.

[Acute mesenteric vein thrombosis. A rare complication after splenectomy due to autoimmune hemolytic anemia in childhood]. / Akute Mesenterialvenenthrombose. Seltene Komplikation nach einer Splenektomie aufgrund einer autoimmunhämolytischen Anämie im Kindesalter.

Mesenteric vein thrombosis is a rare but severe complication in children requiring splenectomy. We report on a 5-year-old boy with an autoimmune hemolytic anemia who underwent splenectomy because of severe side effects from cortisone therapy. 10 months after splenectomy he presented with signs of a paralytic ileus. Laparotomy showed mesenteric vein thrombosis with hemorrhagic bowel infarction requiring resection of two thirds of the small intestine. An early recognition and thrombolytic or surgical treatment of mesenteric vein thrombosis may reduce the incidence of hemorrhagic infarction, peritonitis, and secondary complications in these patients.