Dilworth M.R.,Maternal and Fetal Health Research Group |
Kusinski L.C.,Maternal and Fetal Health Research Group |
Cowley E.,Maternal and Fetal Health Research Group |
Ward B.S.,University of Manchester |
And 5 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010
Evidence is emerging that the ability of the placenta to supply nutrients to the developing fetus adapts according to fetal demand. To examine this adaptation further, we tested the hypothesis that placental maternofetal transport of calcium adapts according to fetal calcium requirements.We used a mouse model of fetal growth restriction, the placental-specific Igf2 knockout (P0) mouse, shown previously to transiently adapt placental System-A aminoacid transporter activity relative to fetal growth. Fetal and placental weights in P0 mice were reduced when compared with WT at both embryonic day 17 (E17) and E19. Ionized calcium concentration [Ca 2+] was significantly lower in P0 fetal blood compared with both WT and maternal blood at E17 and E19, reflecting a reversal of the fetomaternal [Ca 2+] gradient. Fetal calcium content was reduced in P0 mice at E17 but not at E19. Unidirectional maternofetal calcium clearance ( CaK mf) was not different between WTand P0 at E17 but increased in P0 at E19. Expression of the intracellular calcium-binding protein calbindin-D9K, previously shown to be rate-limiting for calcium transport, was increased in P0 relative to WT placentas between E17 and E19. These data show an increased placental transport of calcium from E17 to E19 in P0 compared to WT.We suggest that this is an adaptation in response to the reduced fetal calcium accumulation earlier in gestation and speculate that the ability of the placenta to adapt its supply capacity according to fetal demand may stretch across other essential nutrients.
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.
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.
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.
Samanta S.,St Marys Hospital |
Farrer K.,Rosie Hospital |
Breathnach A.,St Georges Hospital |
Heath P.T.,St George's, University of London
Archives of Disease in Childhood: Fetal and Neonatal Edition | Year: 2011
Objectives: To determine the incidence, mortality and risk factors for neonatal late onset gram-negative sepsis and meningitis (LOGNS). Design: Retrospective case-control study. Setting: Tertiary neonatal unit in London. Patients: Consecutive inborn infants with late onset (>48 h of life) invasive gram-negative infections diagnosed between 1999 and 2005. Controls were healthy infants matched for gestation and time of admission to the neonatal unit. Main outcome measures: Clinical and risk factor data. Results: 73 cases of LOGNS were identified of which 48 were inborn and included in the study (incidence 1.85/1000 live births). Enterobacter spp. (28%), Escherichia coli (27%) and Klebsiella spp. (21%) were the most common pathogens. The majority of infants were of very low birthweight (VLBW; 79%), and cases and controls were well matched (median gestation 26 weeks). Overall case death was 27% in cases versus 13.5% in controls (p=0.08). There was no significant difference between cases and controls regarding maternal risk factors. Mechanical ventilation, total parenteral nutrition (TPN) and its duration, presence of a central venous line and its duration, use of specific antibiotics and the occurrence of necrotising enterocolitis at or before the first positive culture were all significantly associated with case status in univariate analysis. In multivariate logistic regression analysis, only duration of TPN at or before first positive blood culture remained independently associated with LOGNS (p<0.001). Conclusions: LOGNS occurs predominantly in VLBW infants. When the influence of gestational age is accounted for, the only independent risk factor found for late onset gram-negative neonatal infections is the duration of TPN.
Venkatesh V.,Rosie Hospital |
Ponnusamy V.,Norwich University |
Anandaraj J.,Luton and Dunstable Hospital NHS Foundation Trust |
Chaudhary R.,Norwich University |
And 4 more authors.
European Journal of Pediatrics | Year: 2011
Introduction: There has been a significant increase in premedication use for neonatal intubation in the UK over the past decade. We aimed to determine the adverse events during neonatal intubation using the most commonly used premedication regimen in the UK. Discussion: We prospectively studied all intubations performed using morphine, suxamethonium and atropine during a 3-month period in three UK tertiary neonatal units. Premedication was administered for 87/93 (94%) of intubations. Median time taken to prepare premedication was 16 min (IQR 10-35). Median time to successful intubation was 5 min (IQR 2-9) following premedication. Median lowest recorded oxygen saturation after administration of premedication was 65% (IQR 39-85). A bradycardia in the range 61-99/min accompanied the procedure in 24/93 (26%) intubations, with a median duration of bradycardia of 8 s (IQR 1-10). Conclusion: Despite the widespread move to premedication for neonatal intubation, many deficiencies in everyday practice remain. The rate of haemodynamic complications is high in this commonly used premedication regimen. This study shows that there are important factors to control at the local level in terms of timely preparation and administration of premedication drugs, training and supervision of staff carrying out this high-risk procedure. © 2010 Springer-Verlag.
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.
Mikaelsson M.A.,University of Cardiff |
Mikaelsson M.A.,Karolinska Institutet |
Constancia M.,Rosie Hospital |
Constancia M.,University of Cambridge |
And 4 more authors.
Nature Communications | Year: 2013
Imprinted, maternally silenced insulin-like growth factor-2 is expressed in both the foetus and placenta and has been shown to have roles in foetal and placental development in animal models. Here we compared mice engineered to be null for the placenta-specific P0 transcript (insulin-like growth factor-2-P0 KO) to mice with disruptions of all four insulin-like growth factor-2 transcripts, and therefore null for insulin-like growth factor-2 in both placenta and foetus (insulin-like growth factor-2-total KO). Both models lead to intrauterine growth restriction but dissociate between a situation where there is an imbalance between foetal demand and placental supply of nutrients (the insulin-like growth factor-2-P0 KO) and one where demand and supply is more balanced (the insulin-like growth factor-2-total KO). Increased reactivity to anxiety-provoking stimuli is manifested later in life only in those animals where there is a mismatch between placental supply and foetal demand for nutrients during gestation. Our findings further distinguish placental dysfunction from intrauterine growth restriction and reveal a role for the placenta in long-term programming of emotional behaviour. © 2013 Macmillan Publishers Limited.
PubMed | Rosie Hospital
Type: Journal Article | Journal: Nursing standard (Royal College of Nursing (Great Britain) : 1987) | Year: 2016
Nursing skills are an integral part of effective health care, yet the profession has had to work extremely hard to gain recognition for its contribution to patient care. Strong and Robinson ( 1988 ) described nursing as the Black Hole: Everyone knew it was there and that there was a lot of it but nobody knew much about it.
PubMed | Rosie Hospital
Type: Journal Article | Journal: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology | Year: 2013
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.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 < 10(th) percentile and umbilical artery Doppler pulsatility index > 95(th) 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.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.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.