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Durrington H.J.,University of Cambridge | Firth H.V.,Addenbrookes Hospital | Patient C.,Rosie Hospital | Belham M.,Addenbrookes Hospital | And 4 more authors.
American Journal of Medical Genetics, Part A | Year: 2013

Capillary malformation-arteriovenous malformation (CM-AVM) is a newly recognized clinical entity caused by mutation of the RASA1 gene, which encodes p120-RasGAP. Here we describe, for the first time, a patient with CM-AVM presenting during the late stages of pregnancy with pulmonary "capillary level" microvascular shunt, worsening cutaneous capillary malformations, and gross fluid overload. Sequencing revealed a novel mutation of the RASA1 gene involving a frameshift mutation in the RASGAP domain of RASA1. This report extends our current genetic and clinical understanding of CM-AVM. © 2013 Wiley Periodicals, Inc. Source


Dunselman G.A.J.,Maastricht University | Vermeulen N.,European Society of Human Reproduction and Embryology | Becker C.,University of Oxford | Calhaz-Jorge C.,University of Lisbon | And 10 more authors.
Human Reproduction | Year: 2014

STUDY QUESTIONWhat is the optimal management of women with endometriosis based on the best available evidence in the literature?SUMMARY ANSWERUsing the structured methodology of the Manual for ESHRE Guideline Development, 83 recommendations were formulated that answered the 22 key questions on optimal management of women with endometriosis.WHAT IS KNOWN ALREADYThe European Society of Human Reproduction and Embryology (ESHRE) guideline for the diagnosis and treatment of endometriosis (2005) has been a reference point for best clinical care in endometriosis for years, but this guideline was in need of updating.STUDY DESIGN, SIZE, DURATIONThis guideline was produced by a group of experts in the field using the methodology of the Manual for ESHRE Guideline Development, including a thorough systematic search of the literature, quality assessment of the included papers up to January 2012 and consensus within the guideline group on all recommendations. To ensure input from women with endometriosis, a patient representative was part of the guideline development group. In addition, patient and additional clinical input was collected during the scoping and review phase of the guideline.PARTICIPANTS/MATERIALS, SETTING, METHODSNA.MAIN RESULTS AND THE ROLE OF CHANCEThe guideline provides 83 recommendations on diagnosis of endometriosis and on the treatment of endometriosis-associated pain and infertility, on the management of women in whom the disease is found incidentally (without pain or infertility), on prevention of recurrence of disease and/or painful symptoms, on treatment of menopausal symptoms in patients with a history of endometriosis and on the possible association of endometriosis and malignancy.LIMITATIONS, REASONS FOR CAUTIONWe identified several areas in care of women with endometriosis for which robust evidence is lacking. These areas were addressed by formulating good practice points (GPP), based on the expert opinion of the guideline group members.WIDER IMPLICATIONS OF THE FINDINGSSince 32 out of the 83 recommendations for the management of women with endometriosis could not be based on high level evidence and therefore were GPP, the guideline group formulated research recommendations to guide future research with the aim of increasing the body of evidence. © 2014 The Author. Source


Everett T.R.,Rosie Hospital | Wilkinson I.B.,University of Cambridge | Lees C.C.,Rosie Hospital
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2012

Drug development in pregnancy and particularly in preeclampsia has been long neglected. Preeclampsia is a leading cause of maternal mortality, and early-onset preeclampsia can result in serious long-lasting consequences to the neonate. Many treatments have been trialed with varying success including vitamin supplementation, low-molecular-weight heparins, and aspirin. In this commentary, we particularly focus on the current status of drugs in development specifically aimed at preeclampsia. We outline the current understanding of the causes of the endothelial dysfunction seen in preeclampsia and, as such, potential therapeutic targets. With treatment of preeclampsia being largely unchanged in decades, there is an urgent need for novel therapies particularly those directed at the underlying causes that may allow for extremely preterm delivery, and its myriad consequences, to be avoided. © 2012 Informa UK, Ltd. Source


Lees C.,Rosie Hospital | Lees C.,Catholic University of Leuven | Marlow N.,University College London | Bilardo C.M.,University of Groningen | And 29 more authors.
Ultrasound in Obstetrics and Gynecology | Year: 2013

Objectives: Few data exist for counseling and perinatal management of women after an antenatal diagnosis of early-onset fetal growth restriction. Yet, the consequences of preterm delivery and its attendant morbidity for both mother and baby are far reaching. The objective of this study was to describe perinatal morbidity and mortality following early-onset fetal growth restriction based on time of antenatal diagnosis and delivery. Methods: We report cohort outcomes for a prospective multicenter randomized management study of fetal growth restriction (Trial of Randomized Umbilical and Fetal Flow in Europe (TRUFFLE)) performed in 20 European perinatal centers between 2005 and 2010. Women with a singleton fetus at 26-32 weeks of gestation, with abdominal circumference < 10th percentile and umbilical artery Doppler pulsatility index > 95th percentile, were recruited. The main outcome measure was a composite of fetal or neonatal death or severe morbidity: survival to discharge with severe brain injury, bronchopulmonary dysplasia, proven neonatal sepsis or necrotizing enterocolitis. Results: Five-hundred and three of 542 eligible women formed the study group. Mean ± SD gestational age at diagnosis was 29 ± 1.6 weeks and mean ± SD estimated fetal weight was 881 ± 217 g; 12 (2.4%) babies died in utero. Gestational age at delivery was 30.7 ± 2.3 weeks, and birth weight was 1013 ± 321 g. Overall, 81% of deliveries were indicated by fetal condition and 97% were by Cesarean section. Of 491 liveborn babies, outcomes were available for 490 amongst whom there were 27 (5.5%) deaths and 118 (24%) babies suffered severe morbidity. These babies were smaller at birth (867 ± 251 g) and born earlier (29.6 ± 2.0 weeks). Death and severe morbidity were significantly related to gestational age, both at study entry and delivery and also with the presence of maternal hypertensive morbidity. The median time to delivery was 13 days for women without hypertension, 8 days for those with gestational hypertension, 4 days for pre-eclampsia and 3 days for HELLP syndrome. Conclusions: Fetal outcome in this study was better than expected from contemporary reports: perinatal death was uncommon (8%) and 70% survived without severe neonatal morbidity. The intervals to delivery, death and severe morbidity were related to the presence and severity of maternal hypertensive conditions. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd. Source


Mahendru A.A.,Rosie Hospital | Everett T.R.,Rosie Hospital | Wilkinson I.B.,University of Cambridge | Lees C.C.,Rosie Hospital | And 3 more authors.
Journal of Hypertension | Year: 2014

OBJECTIVE:: Our objective was to investigate the extent of changes in maternal cardiovascular function, lipids and renal function during normal pregnancy from preconception to postpartum period. METHODS:: In this prospective study of 54 normal pregnancies, detailed hemodynamics were performed preconception, at 6, 23 and 33 weeks during pregnancy and 16 weeks postpartum. RESULTS:: Although the greatest reduction of blood pressures (BPs) and augmentation index occurred in early pregnancy (Δbrachial systolic: 4±7 mmHg, Δcentral systolic: 7±7 mmHg; P < 0.001), the peripheral vascular resistance reached a nadir (Δ: 222±215 dynes.s.cm; P < 0.001) by the second trimester. The greatest increase in cardiac output occurred by the second trimester (Δ: 0.6±1 l/min, P < 0.001), whereas the heart rate increased maximally by the third trimester (Δ: 13±11 bpm; P=0.001). The unadjusted aortic pulse wave velocity decreased in the second trimester (P < 0.001), however, when adjusted for mean arterial pressure this was not significant (P=0.06). BPs were lower (Δ brachial systolic: 5±8 mmHg; P < 0.001) and augmentation index higher (Δ: 2.5±7%; P=0.01) postpartum than preconception. The cholesterol:high-density lipoprotein ratio, serum low density lipoprotein and serum creatinine all fell (P < 0.001) in the first trimester. CONCLUSION:: We have shown that normal pregnancy, irrespective of parity, is associated with significant changes commencing very early in pregnancy, continuing throughout pregnancy, and some of these changes persisted postpartum. Therefore, first trimester or postpartum baselines will underestimate the true extent of pregnancy-related changes. Prospective studies of cardiovascular function from preconception to postpartum will provide more reliable estimates of the influence of cardiovascular maladaptation during pregnancy complications and their effect on longer term cardiovascular function. Copyright © Lippincott Williams & Wilkins. Source

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