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Mistry H.D.,Womens Health Academic Center | Kurlak L.O.,University of Nottingham | Broughton Pipkin F.,University of Nottingham

There is an inverse correlation between human birthweight and umbilical venous angiotensin II (AngII) concentrations. Oxidative stress and increased pro-renin receptor (PRR) both enhance the cleavage of angiotensin I from angiotensinogen (AGT). Pre-eclampsia, a hypertensive disorder of pregnancy, manifests as high blood pressure and proteinuria, and is a state of increased oxidative stress. Objectives, study design and main outcome measures: Hypothesis: Pre-eclampsia will be associated with increased placental expression of components of the renin-angiotensin system, which could result in reduced infant birthweight. Biopsies were taken 1 cm from the placental edge from 27 normotensive controls and 23 pre-eclamptic White European women. Immunohistochemistry was performed for AGT, PRR, glutathione peroxidase 3 (GPx3) and the AT1R and AT2R AngII receptors. Protein expression was semi-quantitatively assessed (H-score). Results: AT1R expression was significantly increased in pre-eclamptic placentae, and negatively correlated with birthweight (r = -0.529, P = 0.009). AT1R expression was also negatively correlated with GPx3 expression overall (r = -0.647; P = 0.005). AT2R expression positively correlated with AGT (r = 0.615, P = 0.002) in the pre-eclamptic placentae only. Conclusions: The raised AT1R expression in pre-eclampsia, together with inadequate antioxidant protection, possibly through lower GPx activity, might enhance the vasoconstrictor effect of locally-generated AngII, contributing to the restricted fetal growth characteristic of pre-eclampsia. Conversely, the AT2R:AGT association within the pre-eclamptic placenta may provide a compensatory mechanism. © 2012 Elsevier Ltd. All rights reserved. Source

Williamson C.,Womens Health Academic Center | Geenes V.,University College London
Obstetrics and Gynecology

Intrahepatic cholestasis of pregnancy is the most common pregnancy-specific liver disease that typically presents in the third trimester. The clinical features are maternal pruritus in the absence of a rash and deranged liver function tests, including raised serum bile acids. Intrahepatic cholestasis of pregnancy is associated with an increased risk of adverse perinatal outcomes, including spontaneous preterm delivery, meconium staining of the amniotic fluid, and stillbirth. It is commonly treated with ursodeoxycholic acid. There is accumulating evidence to suggest that intrahepatic cholestasis of pregnancy has a lasting influence on both maternal and fetal health. We review the etiology, diagnosis, and management of this intriguing condition. © 2014 by The American College of Obstetricians and Gynecologists. Source

Foo L.,Queen Charlottes and Chelsea Hospital | Bewley S.,Womens Health Academic Center | Rudd A.,Stroke Medicine
European Journal of Obstetrics Gynecology and Reproductive Biology

Objective In the United Kingdom (UK), the maternal mortality rate from stroke is reported at 0.3/100,000 deliveries, but only antenatal data have previously been reviewed. We hypothesise that the true rate is much higher due to a propensity for stroke occurring in the post-partum period, and that the rate will rise in parallel with trends of increasing maternal age and medical co-morbidities. Our objectives are to investigate the UK stroke mortality rate in pregnancy and the puerperium, and to examine temporal changes in fatal maternal strokes over a 30 year period. Study design Retrospective review of stroke-related maternal deaths reported to the UK confidential enquiries into maternal death between 1979 and 2008, encompassing 21,514,457 maternities. In accordance with the ICD.10 classification, cases were divided into direct or indirect deaths. Late and coincidental deaths were not included in analyses. Lessons from sub-standard care associated with maternal death from stroke were collated. Results In 1979-2008 there were 347 maternal deaths from stroke: 139 cases were direct deaths, i.e. the fatal stroke was a direct result of pregnancy. The incidence of fatal stroke is relatively constant at 1.61/100,000 maternities, with a 13.9% (95% CI 12.6-15.3) proportional mortality rate. Intracranial haemorrhage was the single greatest cause of maternal death from stroke. Conclusion This is the largest UK study examining the incidence of fatal maternal stroke in pregnancy and the puerperium. Our results highlight the high proportion of women who die from stroke in the puerperium. Sub-standard care featured especially in regard to management of dangerously high systolic blood pressure levels. These deaths highlight the importance of education in managing rapid-onset hypertension and superimposed coagulopathies. © 2013 Elsevier Ireland Ltd © 2013 Published by Elsevier Ireland Ltd. All rights reserved. Source

English F.A.,University College Cork | Kenny L.C.,University College Cork | McCarthy F.P.,University College Cork | McCarthy F.P.,Womens Health Academic Center
Integrated Blood Pressure Control

Preeclampsia, a hypertensive disorder of pregnancy is estimated to complicate 2%–8% of pregnancies and remains a principal cause of maternal and fetal morbidity and mortality. Preeclampsia may present at any gestation but is more commonly encountered in the third trimester. Multiple risk factors have been documented, including: family history, nulliparity, egg donation, diabetes, and obesity. Significant progress has been made in developing tests to predict risk of preeclampsia in pregnancy, but these remain confined to clinical trial settings and center around measuring angiogenic profiles, including placental growth factor or newer tests involving metabolomics. Less progress has been made in developing new treatments and therapeutic targets, and aspirin remains one of the few agents shown to consistently reduce the risk of developing preeclampsia. This review serves to discuss recent advances in risk factor identification, prediction techniques, and management of preeclampsia in antenatal, intrapartum, and postnatal patients. © 2015 English et al. Source

Ni Bhuinneain G.M.,Mayo Medical Academy | McCarthy F.P.,Womens Health Academic Center | McCarthy F.P.,University College Cork
BJOG: An International Journal of Obstetrics and Gynaecology

Background Progress in maternal survival in sub-Saharan Africa has been poor since the Millennium Declaration.Objectives This systematic review aims to investigate the presence and rigour of evidence for effective capacity building for Essential Obstetric and Newborn Care (EONC) to reduce maternal mortality in rural, sub-Saharan Africa, where maternal mortality ratios are highest globally.Search strategy MEDLINE (1990-January 2014), EMBASE (1990-January 2014), and the Cochrane Library were included in our search. Key developing world issues of The Lancet and the British Journal of Obstetrics and Gynaecology, African Ministry of Health websites, and the WHO reproductive health library were searched by hand.Selection criteria Studies investigating essential obstetric and newborn care packages in basic and comprehensive care facilities, at community and institutional level, in rural sub-Saharan Africa were included. Studies were included if they reported on healthcare worker performance, access to care, community behavioural change, and emergency obstetric and newborn care.Data collection and analysis Data were extracted and all relevant studies independently appraised using structured abstraction and appraisal tools.Main results There is moderate evidence to support the training of healthcare workers of differing cadres in the provision of emergency obstetric and newborn services to reduce institutional maternal mortality and case-fatality rates in rural sub-Saharan Africa. Community schemes that sensitise and enable access to maternal health services result in a modest rise in facility birth and skilled birth attendance in this rural setting.Authors' conclusion Essential Obstetric and Newborn Care has merit as an intervention package to reduce maternal mortality in rural sub-Saharan Africa. © 2014 Royal College of Obstetricians and Gynaecologists. Source

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