In an ultrasound screening study at 10 to 14 weeks of gestation for measurement of fetal nuchal translucency thickness there were 102 monochorionic and 365 dichorionic twin pregnancies. In the monochorionic compared with the dichorionic pregnancies there was a higher rate of fetal loss before 24 weeks of gestation (12.2%versus 1.8%), perinatal mortality (2.8%versus 1.6%), prevalence of delivery before 32 weeks (9.2%versus 5.5%), and prevalence of birthweight below the 5th centile in both twins (7.5%versus 1.7%). However, the proportion of pregnancies with a birthweight discordancy of more than 25% was similar in the two groups (11.3%versus 12.1%).

Objective To assess the clinical effectiveness of endoscopic laser coagulation of placental vessels in the Design Prospective study.Setting Three referral centres for the management of twin-to-twin transfusion syndrome.Population One hundred and thirty-two pregnancies complicated by severe twin-to-twin transfusion syndrome, reflected by polyhydramnios and enlarged bladder of one twin and oligoanhydramnios and collapsed bladder of the other twin, presenting before 28 weeks of gestation.Methods Prospective collection of data on pre-procedure assessment, the procedure and the follow up were collected prospectively. Laser coagulation of placental vessels crossing the intertwin membrane on the chorionic surface under sono-endoscopic guidance, followed by amniodrainage. Main outcome measuresMaternal and pregnancy complications, perinatal death and morbidity were assessed over the last five years with follow up of survivors.Results Endoscopic laser was carried out at a median gestation of 21 weeks. The total number of surviving infants was 144 (55%) and there was at least one survivor in 97 cases (73%). At a minimum age of one year neurological handicap was suspected in six survivors (4.2%). ConclusionsThe results of this multicentre study are similar to those in our original report on the first 45 cases. In comparison with serial amniodrainage, the survival rate may be similar, but the handicap rate in survivors appears much lower. This study stresses the need for a prospective study comparing treatment of severe transfusion syndrome.threse two techniques. INTRODUCTIONMonochorionic twin pregnancies presenting during the second trimester with severe twin-to-twin transfusion syndrome is associated with a high risk of miscarriage, perinatal death and subsequent handicap in Although survival can be improved by serial amniodrainage, there remains a risk of serious handicap in 15% to 50% of survivors"8. A more recent development in the management of this condition is fetoscopy and laser coagulation to interrupt the placental vascular communications between the twins which may constitute the underlying mechanism of the syndrome9J O. Preliminary data have suggested that survival of at least one twin can be achieved in about 70% of pregnancies, and this improved survival may be associated with a substantially reduced risk of handicap (about 5%)". We report the results of a multicentre study on endoscopic laser coagulation reports in the management of 132 pregnancies with severe twin-to-twin transfusion syndrome including at least one year follow up. METHODSSono-endoscopic laser coagulation was carried out in 132 pregnancies complicated by severe twin-to-twin transfusion syndrome with severe polyhydramnios during the second trimester of pregnancy, between 1992 and 1996. The women were managed in one of three centres by members of the original team who developed this technique". The subsequent obstetric care was undertaken in the referring hospital. In all cases, ultrasound examination demonstrated the characteristic features of...

Objective To assess the clinical effectiveness of endoscopic laser coagulation of placental vessels in the Design Prospective study. Setting Three referral centres for the management of twin-to-twin transfusion syndrome. Population One hundred and thirty-two pregnancies complicated by severe twin-to-twin transfusion syndrome, reflected by polyhydramnios and enlarged bladder of one twin and oligoanhydramnios and collapsed bladder of the other twin, presenting before 28 weeks of gestation. Methods Prospective collection of data on pre-procedure assessment, the procedure and the follow up were collected prospectively. Laser coagulation of placental vessels crossing the intertwin membrane on the chorionic surface under sono-endoscopic guidance, followed by amniodrainage. Main outcome measures Maternal and pregnancy complications, perinatal death and morbidity were assessed over the last five years with follow up of survivors. Results Endoscopic laser was carried out at a median gestation of 21 weeks. The total number of surviving infants was 144 (55%) and there was at least one survivor in 97 cases (73%). At a minimum age of one year neurological handicap was suspected in six survivors (4.2%). Conclusions The results of this multicentre study are similar to those in our original report on the first 45 cases. In comparison with serial amniodrainage, the survival rate may be similar, but the handicap rate in survivors appears much lower. This study stresses the need for a prospective study comparing treatment of severe transfusion syndrome. threse two techniques. Ultrasound probe Fig. 1. Diagram of the spatial organisation for endoscopic laser coagulation. 0 RCOG 1998 Br J Obstet Gynaecol 105, 446-453

Objective To examine options of management and outcome of twin pregnancies discordant for Design Retrospective study.Setting Research Centre for Fetal Medicine. Population Twenty-four twin pregnancies discordant for anencephaly.Methods A computer search was made of our database for twin pregnancies discordant for anencephaly.The data were reviewed for gestation at presentation, chorionicity, management and pregnancy outcome.anencephaly.Main outcome measures Pregnancy outcome in relation to chorionicity and management. Results There were 13 dichorionic and 11 monochorionic twin pregnancies discordant for anencephaly.In the dichorionic group five pregnancies had selective fetocide at 17 to 2 1 weeks; one pregnancy resulted in spontaneous abortion but in the others a healthy infant was born at a median gestation of 37 weeks. The other eight dichorionic pregnancies were managed expectantly, but three developed polyhydramios at 26 to 30 weeks; in one case amniodrainage was performed and in another selective fetocide was carried out. In this group the median gestation at delivery was 35 weeks. All 11 monochorionic pregnancies were managed expectantly and in three there was intrauterine death of both fetuses. In the other eight cases the normal twin was livebom at a median gestation of 34 weeks; in four of these pregnancies polyhydramnios developed and two were managed by amniodrainage.Conclusions In monochorionic pregnancies, expectant management is associated with a high rate of intrauterine lethality of the normal twin. In dichorionic pregnancies selective fetocide in the second trimester prevents the development of polyhydramnios and is associated with a lower risk of preterm delivery but can cause miscarriage.~

AbstractNeuroblastoma is an embryonal childhood cancer that arises from aberrant development of the neural crest, mostly within the fetal adrenal medulla. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer (n=16,591) with fetal adrenal single cell transcriptomes (n=57,972). Our principal finding was that the neuroblastoma cancer cell resembled fetal sympathoblasts, but no other fetal adrenal cell type. The sympathoblastic state was a universal feature of neuroblastoma cells, transcending cell cluster diversity, individual patients and clinical phenotypes. We substantiated our findings in 652 neuroblastoma bulk transcriptomes and by integrating canonical features of the neuroblastoma genome with transcriptional signals. Overall, our observations indicate that there exists a pan-neuroblastoma cancer cell state which may be an attractive target for novel therapeutic avenues.One Sentence SummaryComparisons of neuroblastoma cells and relevant normal cells reveal a uniform cell state that characterizes neuroblastoma across patients and disease phenotypes.

Background: Hypertrophic cardiomyopathy (HCM) is characterized by a complex phenotype that is only partly explained by the biological effects of individual genetic variants. The aim of this study was to use proteomic analysis of myocardial tissue to explore the postgenomic phenotype. Methods: Label-free proteomic analysis was used initially to compare protein profiles in myocardial samples from 11 patients with HCM undergoing surgical myectomy with control samples from 6 healthy unused donor hearts. Differentially expressed proteins of interest were validated in myocardial samples from 65 unrelated individuals (HCM [n=51], controls [n=7], and aortic stenosis [n=7]) by the development and use of targeted multiple reaction monitoring-based triple quadrupole mass spectrometry. Results: In this exploratory study, 1586 proteins were identified with 151 proteins differentially expressed in HCM samples compared with controls ( P <0.05). Protein expression profiling showed that many proteins identified in the initial discovery study were associated with metabolism, muscle contraction, calcium regulation, and oxidative stress. Proteins downregulated in HCM versus controls included creatine kinase M-type, fructose-bisphosphate aldolase A, and phosphoglycerate mutase ( P <0.001). Proteins upregulated in HCM included lumican, carbonic anhydrase 3, desmin, α-actin skeletal, and FHL1 (four and a half LIM domain protein 1; P <0.01). Myocardial lumican concentration correlated with the left atrial area (ρ=0.34, P =0.015), late gadolinium enhancement on cardiac magnetic resonance imaging ( P =0.03) and the presence of a pathogenic sarcomere mutation ( P =0.04). Conclusions: The myocardial proteome of HCM provides supporting evidence for dysregulation of metabolic and structural proteins. The finding that lumican is raised in HCM hearts provides insight into the myocardial fibrosis that characterizes this disease.

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All cases of first histologically confirmed complete and partial moles registered between 1985 and 1999 were identified from the database of a Trophoblastic Disease Registration Centre. The maternal age distribution at diagnosis was calculated for the 7916 molar pregnancies and compared with the maternal age distribution of an unselected population of women from a routine obstetric database. Likelihood ratios were calculated for complete and partial molar pregnancies by maternal age. A positive relationship was found between the risk of molar pregnancy and both upper and lower extremes of maternal age ( 45 years and 15 years, respectively). This association, although present for both complete and partial moles, is much greater for complete mole at all maternal ages, and the degree of risk is much greater with older ( 45 years) rather than younger ( 15 years) maternal age. This study provides, for the first time, data regarding specific risk of partial versus complete hydatidiform mole with maternal age.