scispace - formally typeset
Search or ask a question

Showing papers in "Best Practice & Research in Clinical Obstetrics & Gynaecology in 2011"


Journal ArticleDOI
TL;DR: Determinants of pre-eclampsia rates include a bewildering array of risk and protective factors, including familial factors, sperm exposure, maternal smoking, pre-existing medical conditions (such as hypertension, diabetes mellitus and anti-phospholipid syndrome), and miscellaneous ones such as plurality, older maternal age and obesity.
Abstract: Hypertensive disorders of pregnancy include chronic hypertension, gestational hypertension, pre-eclampsia and chronic hypertension with superimposed pre-eclampsia. Pre-eclampsia complicates about 3% of pregnancies, and all hypertensive disorders affect about five to 10% of pregnancies. Secular increases in chronic hypertension, gestational hypertension and pre-eclampsia have occurred as a result of changes in maternal characteristics (such as maternal age and pre-pregnancy weight), whereas declines in eclampsia have followed widespread antenatal care and use of prophylactic treatments (such as magnesium sulphate). Determinants of pre-eclampsia rates include a bewildering array of risk and protective factors, including familial factors, sperm exposure, maternal smoking, pre-existing medical conditions (such as hypertension, diabetes mellitus and anti-phospholipid syndrome), and miscellaneous ones such as plurality, older maternal age and obesity. Hypertensive disorders are associated with higher rates of maternal, fetal and infant mortality, and severe morbidity, especially in cases of severe pre-eclampsia, eclampsia and haemolysis, elevated liver enzymes and low platelets syndrome.

807 citations


Journal ArticleDOI
TL;DR: The familial nature of pre-eclampsia has been known for many years and, as such, extensive genetic research has been carried out in this area using strategies that include candidate gene studies and linkage analysis.
Abstract: Hypertension is the most frequent medical complication occurring during pregnancy. In this chapter, we aim to address the genetic contribution to these disorders, with specific focus on pre-eclampsia. The pathogenic mechanisms underlying pre-eclampsia remain to be elucidated; however, immune maladaptation, inadequate placental development and trophoblast invasion, placental ischaemia, oxidative stress and thrombosis are all thought to represent key factors in the development of disease. Furthermore, all of these components have genetic factors that may be involved in the pathogenic changes occurring. The familial nature of pre-eclampsia has been known for many years and, as such, extensive genetic research has been carried out in this area using strategies that include candidate gene studies and linkage analysis. Interactions between fetal and maternal genotypes, the effect of environmental factors, and epistasis will also be considered.

203 citations


Journal ArticleDOI
TL;DR: It is proposed that changes in the population and function of immunocytes at the maternal-fetal interface can be part of the mechanism of disease of obstetrical disorders, and this requires further investigation.
Abstract: Failure of physiologic transformation of the spiral arteries has been studied using placental bed biopsies in several obstetrical syndromes. Contrary to what was originally believed, this lesion is not restricted to preeclampsia and/or intrauterine growth restriction. A review of published evidence indicates that failure of physiologic transformation can be observed in women with spontaneous second trimester abortions, preterm labor with intact membranes, preterm prelabor rupture of membranes and abruptio placentae. Therefore, disorders of deep placentation are present in a wide range of complications of pregnancy, emphasizing the importance of understanding the physiology and pathology of transformation of the spiral arteries. We propose that changes in the population and function of immunocytes at the maternal-fetal interface can be part of the mechanism of disease of obstetrical disorders, and this requires further investigation.

173 citations


Journal ArticleDOI
TL;DR: Pre-eclampsia is a disease of many risk factors and theoretical speculations and it is, for unknown reasons, more prevalent among primiparous women, while a change of sexual partner before the next pregnancy increases the risk.
Abstract: Pre-eclampsia is a disease of many risk factors and theoretical speculations. It is, for unknown reasons, more prevalent among primiparous women. Some observations show that a change of sexual partner before the next pregnancy increases the risk, but this association disappears when correction is made for time interval since the last birth. Risk factors may be pregnancy-specific, such as twinning or mole, whereas others are linked to the woman, such as obesity and diabetes. Genetic risk factors are being searched for, but as yet with relatively little success. A previous pregnancy complicated by pre-eclampsia is probably the strongest risk factor. For practical purposes, women at increased risk can be identified and should be followed closely. No effective primary preventative action is available. Prevention of the serious consequences of pre-eclampsia still relies on early detection of increases in blood pressure and proteinuria.

139 citations


Journal ArticleDOI
TL;DR: Evidence is emerging that the origin of defective deep placentation may not lie in primary defect of the trophoblast, but in abnormalities of the endometrium and inner myometrium before or during the early stages of placentations.
Abstract: Defective deep placentation is characterised by defective remodelling of the utero-placental arteries. Under certain conditions, it is also characterised by the presence of arterial lesions, such as acute atherosis and the persistence of endovascular trophoblast. The condition has been associated with a spectrum of complications during pregnancy, including pre-eclampsia, intrauterine growth restriction, pre-term birth, pre-term premature rupture of membranes, late sporadic miscarriage and abruptio placentae. Criteria are proposed for the classification of defective deep placentation into three types based on the degree of restriction of remodelling and the presence of obstructive lesions in the myometrial segment of the spiral arteries. Although the underlying mechanisms are not understood, evidence is emerging that the origin of defective deep placentation may not lie in primary defect of the trophoblast, but in abnormalities of the endometrium and inner myometrium before or during the early stages of placentation.

131 citations


Journal ArticleDOI
TL;DR: If gestational diabetes develops, there is good evidence that clinical management reduces the risk of adverse pregnancy outcomes, and Limiting gestational weight gain to 5-9 kg among pregnant obese women is likely to improve obstetric outcomes, but how to achieve this remains an active area of research.
Abstract: An epidemic of obesity is affecting growing numbers of women in their childbearing years increasing their risk of obstetric complications including diabetes, hypertension, pre-eclampsia, some malformations, macrosomia and the need for obstetric intervention. There is growing evidence that maternal obesity may increase the risk of obesity and diabetes in the offspring. Obesity and diabetes in pregnancy have independent and additive effects on obstetric complications, and both require management during pregnancy. Management of obesity including weight loss and physical activity prior to pregnancy is likely to be beneficial for mother and baby, although the benefits of bariatric surgery remain unclear at this time. Limiting gestational weight gain to 5-9 kg among pregnant obese women is likely to improve obstetric outcomes, but how to achieve this remains an active area of research. If gestational diabetes develops, there is good evidence that clinical management reduces the risk of adverse pregnancy outcomes.

123 citations


Journal ArticleDOI
TL;DR: There are a number of unique challenges facing LMIC but the principles of care for women with pre-eclampsia remain the same as in well resourced settings and the health care worker shortage is particularly significant.
Abstract: Pre-eclampsia and eclampsia are leading causes of maternal and perinatal morbidity and mortality worldwide. The exact prevalence, however, is unknown. The majority of pre-eclampsia related deaths in LMIC occur in the community and therefore, interventions must be focused at this level. There are a number of unique challenges facing LMIC but the principles of care for women with pre-eclampsia remain the same as in well resourced settings. Three primary delays lead to an increased incidence of maternal mortality from pre-eclampsia- delays in triage, transport and treatment. There are a number of other challenges facing LMIC and the health care worker shortage is particularly significant. Task shifting is a potential strategy to address this challenge. Community health care workers, specifically lady health care workers, are an integral part of the health care force in many LMIC and can be employed to provide timely care to women with pre-eclampsia. Prevention strategies should be applied to every pregnant woman since we cannot predict who will develop pre-eclampsia given the limitation in resources. Aspirin and calcium are the only two recommended therapies at this time. Measuring blood pressure and proteinuria is challenging in LMIC due to financial cost and lack of training. A detection tool that is affordable and can be easily applied is needed. Magnesium sulfate is the drug of choice for the prevention and treatment of eclampsia but it is underutilized due to barriers on multiple levels.

109 citations


Journal ArticleDOI
TL;DR: The need for alternative approaches and specific biomarkers to aid objective CIN lesion grading, and to identify true high-grade cervical disease, is highlighted.
Abstract: Accurate histological grading of cervical intraepithelial neoplasia (CIN) lesions is important for clinical management of patients, because CIN1 and CIN2 and 3 lesions are treated differently. In general, there tends to be poor inter and intra-observer reproducibility of CIN grade evaluation among pathologists. In particular, the differential diagnosis between immature squamous metaplasia and CIN1 and 2, or between low-grade (CIN1) and high-grade (CIN2 and 3) lesions, tend to be difficult. These difficulties mean that patients tend to be over-treated for CIN lesions, which will naturally regress. Collectively, this highlights the need for alternative approaches and specific biomarkers to aid objective CIN lesion grading, and to identify true high-grade cervical disease. In this review we focus on the aetiology, pathobiology, the natural history of CIN, current issues with diagnosis and classification of CIN and the diagnostic and prognostic utility of specific biomarkers in identifying true cancerous precursor lesions.

95 citations


Journal ArticleDOI
TL;DR: Decidual vascular changes during human implantation are assessed, and the involvement of angiogenesis in the pathogenesis of miscarriages, pre-eclampsia and intrauterine growth restriction is evaluated.
Abstract: The timing of decidualisation and vascular processes during the implantation period is of paramount importance for the development of a receptive endometrium suitable for implantation. The endometrium transforms during the secretory phase into a well-vascularised receptive tissue characterised by increased vascular permeability, oedema, proliferation and differentiation of stromal cells into decidual cells, invasion of leucocytes, vascular remodelling and angiogenesis. Decidualisation continues in the presence of conception and an influx of immune cells, trophoblasts and vascular adaptation will occur. Vascular changes include spiral artery remodelling, angiogenesis and the induction of angiogenic factors. Disturbances in uterine blood supply are associated with first-trimester miscarriages and third-trimester perinatal morbidity and mortality caused by pre-eclampsia and foetal growth restriction. This article assesses decidual vascular changes during human implantation, and evaluates the involvement of angiogenesis in the pathogenesis of miscarriages, pre-eclampsia and intrauterine growth restriction.

92 citations


Journal ArticleDOI
TL;DR: Evidence is accumulating, however, to support the incorporation of umbilical artery and venous Doppler velocimetry in the evaluation of such fetuses, especially in cases of associated placental insufficiency.
Abstract: Pre-eclampsia is associated with a number of short- and long-term perinatal and neonatal complications, including death. These are mostly related to birth weight and gestational age at delivery, and therefore are most relevant to severe or early onset pre-eclamptic toxaemia. Currently, little information is available on the optimal antenatal testing modality to be used for pre-eclampsia. Significant limitations are associated with fetal movement counts and the biophysical profile. Evidence is accumulating, however, to support the incorporation of umbilical artery and venous Doppler velocimetry in the evaluation of such fetuses, especially in cases of associated placental insufficiency. Pre-eclampsia might confer some survival advantage to small gestational age infants and prematurely born infants compared with infants born after spontaneous preterm labour. The degree of intrauterine growth restriction also has a negative effect on early morbidity. Longer term outcomes for prematurely born infants are dependent on gestational age, and it is unclear whether the survival advantage conferred by pre-eclampsia translates into better long-term neurodevelopmental outcomes. Abnormal umbilical artery flows might predict poorer cognitive outcomes, although evidence for this is not strong.

89 citations


Journal ArticleDOI
TL;DR: Advances in new technology are summarized, which might improve preoperative detection and enhance referral to gynaecologic oncologists for optimal staging surgery and treatment, and current progress in different imaging modalities.
Abstract: Uterine sarcomas are uncommon tumours from mesenchymal elements. They are thought to arise primarily from endometrial stroma and uterine muscle, respectively. When endometrial stroma undergoes malignant transformation, it might be accompanied by a malignant epithelial component. Thus, malignant mesenchymal uterine tumours comprise leiomyosarcoma, endometrial stromal sarcoma, undifferentiated uterine sarcoma and carcinosarcoma. In this chapter, we discusses preoperative presentation, diagnosis and current progress in different imaging modalities, including ultrasonography, computed tomography, magnetic resonance image and positron emission tomography scan. We summarise advances in new technology, which might improve preoperative detection and enhance referral to gynaecologic oncologists for optimal staging surgery and treatment.

Journal ArticleDOI
TL;DR: The occurrence of human-like deep invasion was confirmed in gorillas and chimpanzees, and such information may reveal the evolutionary roots of this disease of impaired maternal-fetal interaction.
Abstract: It is now possible to view human placentation in an evolutionary context because advances in molecular phylogenetics provide a reliable scenario for the evolution of mammals. Perhaps the most striking finding is the uniqueness of human placenta. The lower primates have non-invasive placentae and even tarsiers and New World monkeys show restricted trophoblast invasion. Moreover, a truly villous placenta occurs only in Old World monkeys and great apes. The two latter groups of haplorhine primates show varying degrees of trophoblast–uterine interaction, including differences in the extent of decidualization, formation and disintegration of a cytotrophoblastic shell, degree of interstitial trophoblast invasion and depth of trophoblast invasion into spiral arteries. Recently, the occurrence of human-like deep invasion was confirmed in gorillas and chimpanzees. As the still enigmatic disease of pre-eclampsia also occurs in these species, such information may reveal the evolutionary roots of this disease of impaired maternal–fetal interaction.

Journal ArticleDOI
TL;DR: There is a need for new strategies for improving glycaemic control to near-normal levels throughout pregnancy and for preventing and treating hypertensive disorders in pregnancy.
Abstract: Pregnancy in women with pregestational diabetes is associated with high perinatal morbidity and mortality. Stillbirth accounts for the majority of cases with perinatal death. Intrauterine growth restriction, pre-eclampsia, foetal hypoxia and congenital malformations may be contributing factors, but more than 50% of stillbirths are unexplained. Majority of stillbirths are characterised by suboptimal glycaemic control during pregnancy. Foetal hypoxia and cardiac dysfunction secondary to poor glycaemic control are probably the most important pathogenic factors in stillbirths among pregnant diabetic women. There is thus a need for new strategies for improving glycaemic control to near-normal levels throughout pregnancy and for preventing and treating hypertensive disorders in pregnancy. Antenatal surveillance tests including ultrasound examinations of the foetal growth rate, kick counting and non-stress testing of foetal cardiac function are widely used. However, future research should establish better antenatal surveillance tests to identify the infants susceptible to stillbirth before it happens.

Journal ArticleDOI
TL;DR: In studying the normal processes that occur during human placentation and early pregnancy, a greater understanding of what may go awry in pre-eclampsia is developed and will be crucial in discovering novel biomarkers for prediction of the disorder and, eventually, in finding targets for effective interventions.
Abstract: Pre-eclampsia is a multisystem disorder with profound implications for both mother and fetus. Its origins lie in the earliest stages of pregnancy. Abnormal interactions between fetal trophoblast and maternal decidua, including the cells of the maternal immune system, lead to inadequate placental invasion and maternal vascular remodelling. However, abnormal placentation is only one step in the cascade of events that ultimately result in maternal organ dysfunction. Pre-existing maternal conditions predisposing to inflammation and vascular pathology, fetal factors, including multiple gestations and macrosomia, and environmental exposures, including infection, may contribute to the release of placental substances, including anti-angiogenic molecules, into the maternal circulation. These may act directly or indirectly upon the endothelia of end organs, including the kidney, liver and brain. The liberation of reactive oxygen species, cytokines, and microthrombi from damaged endothelia contribute further to organ damage. In studying the normal processes that occur during human placentation and early pregnancy, we will develop a greater understanding of what may go awry in pre-eclampsia. Such research will be crucial in discovering novel biomarkers for prediction of the disorder and, eventually, in finding targets for effective interventions.

Journal ArticleDOI
TL;DR: The implications of a recent international consensus statement on new diagnostic criteria for GDM are discussed, as well as issues relating to the timing of diagnosis, and the potential place for a risk calculator for adverse outcomes in GDM pregnancy that takes into account glycaemic and non-glycaemic risk factors is considered.
Abstract: Gestational diabetes mellitus (GDM) and controversy are old friends. However, several major studies in the field have clarified some of the main issues. There is now no doubt that hyperglycaemia, at levels less than those that occur in overt diabetes, is associated with adverse pregnancy outcomes, such as large-for-gestational age infants, neonatal hyperinsulinism, neonatal hypoglycaemia and pre-eclampsia. We also have evidence now that a standard approach to GDM with diagnosis at 24-28 weeks, dietary advice, self-monitoring of blood glucose and insulin therapy as needed reduces these adverse perinatal outcomes. Unknown, however, is if this same approach is effective at reducing long-term risks of metabolic syndrome, type 2 diabetes and cardiovascular disease in both the mothers and babies. For example, could our management strategies miss critical time points of fuel-mediated injury to the foetus important for the baby's long-term metabolic health? The implications of a recent international consensus statement on new diagnostic criteria for GDM are discussed, as well as issues relating to the timing of diagnosis. The potential place for a risk calculator for adverse outcomes in GDM pregnancy that takes into account glycaemic and non-glycaemic risk factors is considered. Such a tool could help stratify GDM women to different levels of care. Ongoing issues relating to maternal glycaemic and foetal growth targets, and the use of oral hypoglycaemic agents in GDM are discussed. To resolve some of the remaining controversies, further carefully designed randomised controlled trials in GDM with long-term follow-up of both mothers and babies are necessary.

Journal ArticleDOI
TL;DR: The available evidence on the efficacy and safety of the use of oral diabetes agents during pregnancy for both maternal and neonatal outcomes as an alternative management option is summarized to summarise key points for the practicing clinician.
Abstract: With the increase in obesity and sedentary lifestyles, the incidence of diabetes among reproductive-aged women is rising globally. Providers are expected to care for a growing number of women with gestational diabetes (GDM) in the coming decades. Traditionally, insulin has been considered the standard for management of GDM, when diet and exercise fail to achieve tight maternal glucose control without the risk of transfer of insulin across the placenta. Understanding the effectiveness and safety of the use of oral diabetes agents during pregnancy for both maternal and neonatal outcomes as an alternative management option is essential to the care of women with GDM and their offspring. In this review, our objectives were to (1) summarise the available evidence on the efficacy these medications, (2) review available data on adverse effect, (3) discuss current gaps in research, outlining limitations in current study designs that deserve attention and (4) summarise key points for the practicing clinician.

Journal ArticleDOI
TL;DR: The ability to predict the most severe forms of pre-eclampsia would allow closer surveillance and earlier intervention to improve outcomes, and it is likely that prospective treatments would need to start early in pregnancy to alter pathogenesis.
Abstract: Pre-eclampsia remains an important cause of maternal and perinatal mortality. The ability to predict the most severe forms of pre-eclampsia would allow closer surveillance and earlier intervention to improve outcomes. Although no definitive preventative treatment has been found to date, it is likely that prospective treatments would need to start early in pregnancy to alter pathogenesis. Following recent advances in the understanding of the pathogenesis of this complex syndrome, new predictive tests are being evaluated. The most promising models incorporate biochemical and biophysical tests that combine assessments of placentation and maternal disease susceptibility.

Journal ArticleDOI
TL;DR: The pathology of leiomyosarcomas is discussed, including an update on smooth-muscle tumours of uncertain malignant potential, with emphasis on the controversy of labelling of atypical leiomers, and the problems with histologic diagnosis, immunohistochemical studies and molecular pathology are reviewed.
Abstract: Uterine leiomyosarcomas are the most common uterine sarcomas. For clinicians, they are difficult tumours to manage. Preoperative detection is difficult because of the similarity in clinical presentation to ordinary fibroids. They are highly aggressive tumours and the effectiveness of adjuvant therapy remains controversial with surgery remaining the mainstay of treatment. Despite treatment, disease frequently recurs. For pathologists, diagnosis of most leiomyosarcomas using current diagnostic criteria is usually straightforward, as most tumours often possess two or more diagnostic microscopic features, including diffuse atypia, high mitotic count and tumour cell necrosis. Diagnostic difficulties usually relate to tumours having only one of these worrisome features, with or without other additional unusual morphologic findings. These latter tumours have been labelled as uterine smooth-muscle tumours of uncertain malignant potential. Those that are followed by a recurrence are biologically low-grade leiomyosarcomas. Epithelioid and myxoid leiomyosarcomas are less common, and their diagnostic criteria are different to tumours of usual spindle cell differentiation. In this review, we discuss the pathology of leiomyosarcomas, including an update on smooth-muscle tumours of uncertain malignant potential, with emphasis on the controversy of labelling of atypical leiomyomas. The problems with histologic diagnosis, immunohistochemical studies and molecular pathology are reviewed.

Journal ArticleDOI
TL;DR: None of the tests used to predict the onset of pre-eclampsia are sufficiently accurate to recommend them for routine use in clinical practice.
Abstract: Pre-eclampsia is associated with increased maternal and perinatal mortality and morbidity. Early recognition of women at risk of pre-eclampsia will enable the identification of high-risk women who may benefit from enhanced surveillance and prophylaxis. In this chapter, we summarise the accuracy of various tests used to predict the onset of pre-eclampsia and the effectiveness of preventative treatment. The tests used to predict pre-eclampsia include clinical history, examination findings, laboratory and haemodynamic tests. In general, tests in early pregnancy for predicting later development of pre-eclampsia have better specificity than sensitivity, as Body Mass Index greater than 34, alpha-fetoprotein, fibronectin and uterine artery Doppler (bilateral notching) all have specificities above 90%. Only uterine artery Doppler resistance index and combinations of indices have a sensitivity of over 60%. Test such as kallikreinuria not used in clinical practice, has shown high sensitivity above 80%, without compromising specificity, and require further investigation. None of the tests are sufficiently accurate to recommend them for routine use in clinical practice. The various treatment options for preventing pre-eclampsia include pharmacological agents, dietary supplementation and lifestyle modification. Antiplatelet agents, primarily low-dose aspirin, reduce the risk of pre-eclampsia by 10% (RR 0.90, 95% CI 0.84 to 0.97). Calcium effectively prevents pre-eclampsia (RR 0.45, 95% CI 0.31 to 0.65); the beneficial effect being observed in the high-risk group (RR 0.22; 95% CI 0.12 to 0.42) and in the group with low nutritional calcium intake (RR 0.36, 95% CI 0.20 to 0.65). Pharmacological agents, such as low molecular weight heparin, progesterone, nitric oxide donors, anti-hypertensive medication and diuretics are not effective in preventing pre-eclampsia. Dietary supplements, such as magnesium, anti-oxidants, marine oils and folic acid, do not reduce the incidence of pre-eclampsia. Evidence is lacking to support lifestyle preventative interventions for pre-eclampsia, such as rest, exercise and reduced dietary salt intake.

Journal ArticleDOI
TL;DR: Despite improvements in services for people with diabetes and an increased focus on care of diabetes in pregnancy, there has been no significant reduction in neonatal complications after pregnancy complicated by maternal diabetes.
Abstract: Despite improvements in services for people with diabetes and an increased focus on care of diabetes in pregnancy, there has been no significant reduction in neonatal complications after pregnancy complicated by maternal diabetes. Some complications are severe and life threatening or lead to long-term difficulties, whilst others are transient and are unlikely to lead to long-term harm, if managed according to standard guidelines. Most neonatal complications are, in theory, avoidable by optimal diabetes care, those that arise directly as a result of poor control of diabetes in pregnancy or as a result of obstetric interventions related to maternal diabetes control. Of greater concern are iatrogenic complications that arise from decisions which have no clear rationale (e.g., 'routine' admission of a baby to a neonatal unit). Planning for neonatal management must take into account known risks and the likelihood of occurrence, start in advance of delivery, involve all relevant groups of professionals and be centred on the needs of the mother and baby and not upon historical organisational policies.

Journal ArticleDOI
TL;DR: The term 'mixed Müllerian tumour' applies to uterine tumours composed of epithelial and mesenchymal elements of Müllersian origin, which are currently thought to be metaplastic carcinomas rather than uterine sarcomas.
Abstract: The term 'mixed Mullerian tumour' applies to uterine tumours composed of epithelial and mesenchymal elements of Mullerian origin. These neoplasms are classified into adenomyomas, adenofibromas, adenosarcomas, and carcinosarcomas (malignant Mullerian mixed tumours) based on whether the epithelial and stromal elements are benign or malignant. The rare atypical polypoid adenomyoma usually involves the lower uterine segment and, on curettings, may be confused with invasive adenocarcinoma. Adenosarcomas are low-grade neoplasms classified halfway along the spectrum of mixed Mullerian tumours, with adenofibromas at one end and carcinosarcomas (malignant Mullerian mixed tumours) at the other. Some tumours currently classified as 'adenofibromas' on the basis of their low mitotic count and lack of nuclear atypia are, in fact, well differentiated adenosarcomas. Carcinosarcoma is composed of admixed but distinctive carcinomatous and sarcomatous elements. On the basis of the clonal origin of both tumour components, carcinosarcomas are currently thought to be metaplastic carcinomas rather than uterine sarcomas.

Journal ArticleDOI
TL;DR: Continuous glucose monitoring can offer better insights into the glycaemic profile than self-monitoring of blood glucose levels by the patients but the place of these new monitoring techniques has yet to be established more clearly.
Abstract: Optimal glycaemic control is of the utmost importance to achieve the best possible outcome of a pregnancy complicated by diabetes. This holds for pregnancies in women with preconceptional type 1 or type 2 diabetes as well as for pregnancies complicated by gestational diabetes. Glycaemic control is conventionally expressed in the HbA1c value but the HbA1c value does not completely capture the complexity of glycaemic control. The daily glucose profile measured by the patients themselves through measurements performed in capillary blood obtained by finger stick provides valuable information needed to adjust insulin therapy. Hypoglycaemia is the major threat to the pregnant woman or the woman with tight glycaemic control in the run-up to pregnancy. Repetitive hypoglycaemia can lead to hypoglycaemia unawareness, which is reversible with prevention of hypoglycaemia. A delicate balance should be struck between preventing hyperglycaemia and hypoglycaemia. Insulin requirements are not uniform across the day: it is low during the night with a more or less pronounced rise at dawn, followed by a gradual decrease during the remainder of the day. A basal amount of insulin is needed to regulate the endogenous glucose production, short-acting insulin shots are needed to handle exogenous glucose loads. Insulin therapy means two choices: the type of insulin used and the method of insulin administration. Regarding the type of insulin, the choice is between human and analogue insulins. The analogue short-acting insulin aspart has been shown to be safe during pregnancy in a randomised trial and has received registration for this indication; the short-acting analogue insulin lispro has been shown to be safe in observational studies. No such information is available on the long-acting insulin analogues detemir and glargine and both are prescribed off-label with human long-acting insulin as obvious alternatives. Randomised trials have not been able to show superiority of continuous subcutaneous insulin administration (CSII (insulin pump)) over intensive insulin injection therapy (multiple-dose insulin (MDI)) on any maternal or foeto-neonatal end point. However, group sizes were far too small to allow assessment of superiority and issues such as manageability of the disease and quality of life were never assessed. These two issues are of major importance to patients. The first trimester is often the period of most hypoglycaemic events, and insulin therapy should be especially closely monitored and adjusted in this period. After midterm, insulin requirements increase. Continuous glucose monitoring can offer better insights into the glycaemic profile than self-monitoring of blood glucose levels by the patients but the place of these new monitoring techniques has yet to be established more clearly. Insulin therapy during labour means short-acting insulin adjusted to achieve glucose levels between 4 and 8 mmol l(-1) to prevent neonatal hypoglycaemia as much as possible. After delivery, glycaemic control must be relaxed to prevent hypoglycaemia, especially in women who breastfeed.

Journal ArticleDOI
TL;DR: The key issues that will be discussed include the prognostic relevance of pathological and biological variables other than tumour stage in the different histological subtypes of uterine sarcoma.
Abstract: Uterine sarcomas usually have an aggressive clinical behaviour, with great tendency to local and distant spread, with unfavourable clinical outcome, excluding endometrial stromal sarcomas and adenosarcoma. Tumour stage is the strongest prognostic factor for all uterine sarcomas, with 5-year survival of about 50–55% for stage I and 8–12% for more advanced stages. Multivariate analysis of some studies have shown that women with leiomyosarcoma have a poorer survival than those with carcinosarcoma. The key issues that will be discussed include the prognostic relevance of pathological and biological variables other than tumour stage in the different histological subtypes of uterine sarcoma. Immunomarkers for cell proliferation and apoptosis have been tested for the identification of tumours with different clinical behaviour, but they are still subject to research and are not currently used in clinical practice.

Journal ArticleDOI
TL;DR: Clinicians should consider the whole clinical picture when assessing women with pre-eclampsia and making decisions around expectant management compared with stabilisation and delivery.
Abstract: The hypertensive disorders of pregnancy (HDP) remain one of the major causes of maternal mortality and morbidity worldwide. Many international guidelines exist for the classification and assessment of women with hypertension in pregnancy, but definitions and recommendations within these documents are variable. Many recommended investigations do not actually correlate with increased risk of adverse outcomes, making it difficult to determine true prognosis. Although standardised assessment and surveillance has been shown to improve outcomes, the application of these monitoring strategies in many areas of the world is not possible owing to the cost associated with them. Not all of the tests recommended for surveillance of women with pre-eclampsia are independently predictive of adverse outcomes, and many unnecessary tests could be avoided if those tests that are most informative where identified. The Pre-eclampsia Integrated Estimate of RiSk study has identified a group of tests that can be used to predict risk of outcomes accurately up to 7 days after admission to a tertiary hospital with pre-eclampsia. This model needs to be validated in new populations and in different clinical settings before it can be implemented into clinical practice. Until this happens, clinicians should consider the whole clinical picture when assessing women with pre-eclampsia and making decisions around expectant management compared with stabilisation and delivery. Future research in the area of prognosis should focus on women with variable definitions of pre-eclampsia and the other HDP. All studies reviewed were limited to cases of severe pre-eclampsia, and results may not be generalisable across the spectrum of the disorder.

Journal ArticleDOI
TL;DR: Pregnant women with diabetes have to manage both the effect of pregnancy on glucose control and its effect on pre-existing diabetic complications, which impacts on daily living.
Abstract: Pregnant women with diabetes have to manage both the effect of pregnancy on glucose control and its effect on pre-existing diabetic complications. Most women experience hypoglycaemia as a consequence of tightened glycaemic control and this impacts on daily living. Less commonly, diabetic ketoacidosis, a serious metabolic decompensation of diabetic control and a medical emergency, can cause foetal and maternal mortality. Microvascular complications of diabetes include retinopathy and nephropathy. Retinopathy can deteriorate during pregnancy; hence, regular routine examination is required and, if indicated, ophthalmological input. Diabetic nephropathy significantly increases the risk of obstetric complications and impacts on foetal outcomes. Pregnancy outcome is closely related to pre-pregnancy renal function. Diabetic pregnancy is contraindicated if the maternal complications of ischaemic heart disease or diabetic gastropathy are known to be present before pregnancy as there is a significant maternal mortality associated with both of these conditions.

Journal ArticleDOI
Joo-Hyun Nam1
TL;DR: Recent changes in, and updates of, the surgical treatment of the three most common types of malignant uterine sarcomas are described.
Abstract: Uterine sarcomas are rare, heterogeneous malignant tumours of several histologic types originating from mesenchymal tissues of the uterus. The most common histologic types are carcinosarcoma, leiomyosarcoma, and endometrial stromal sarcoma, accounting for 90% of uterine sarcomas. To date, no effective treatment has been found to achieve a high rate of cure or prolong survival. Although complete surgical excision of the tumour is the only curative treatment modality, the rarity of these tumours and their diversity of histologic types have precluded the development of standard surgical strategies. Surgery may also be optimal for recurrent uterine sarcomas, but indications for secondary surgical treatment have not been established. Here, we describe recent changes in, and updates of, the surgical treatment of the three most common types of malignant uterine sarcomas.

Journal ArticleDOI
TL;DR: It seems to be necessary to evaluate the best management of CIN2 in young and in vaccinated women and to focus more on how the quality of colposcopy and the overall management concept determines the clinical outcome.
Abstract: Management of cervical intraepithelial neoplasia (CIN) needs to protect women at risk from developing cervical cancer and to avoid over-treatment as well as obstetrical complications in women undergoing invasive treatment. Strong evidence shows that CIN3 is a true precursor and must be treated, whereas CIN1 lesions do not benefit from immediate surgery and should be followed conservatively. Although the clinical course of CIN2 differs from CIN3, it should be treated the same way for legal reasons. Colposcopy plays a central role in selection of patients and treatments. Treatment of CIN2 and 3 should be excisional. Large loop excision of the transformation zone, high-frequency-needle or laser conisation are equally good, whereas cold-knife conisation is associated with an excess risk for subsequent obstetrical complications. Human papillomavirus testing and cytology at 6 months seems to be the best post-treatment monitoring, although this needs to be confirmed by randomised-controlled trials. Future research needs to focus more on how the quality of colposcopy and the overall management concept determines the clinical outcome instead of exploring the role of single technical methods. Furthermore, it seems to be necessary to evaluate the best management of CIN2 in young and in vaccinated women.

Journal ArticleDOI
TL;DR: The limited number of studies about women's perceptions of diabetes and pregnancy, based on interviews conducted during or shortly after pregnancy, are reviewed and information about how health professionals may manage these perceptions and expectations is presented.
Abstract: Given the increasing incidence of type 1 diabetes, the recent emergence of type 2 diabetes as a condition that can begin during childhood, and the increasing prevalence of gestational diabetes mellitus, the number of women who have some form of diabetes during their pregnancies is increasing. The perceptions and expectations of women with diabetes during pregnancy may affect their psychological response to pregnancy as well as their behaviour during and after pregnancy. This article provides an overview of the epidemiology of diabetes in pregnancy, including diabetes diagnosed before pregnancy and gestational diabetes mellitus. Then, the limited number of studies about women's perceptions of diabetes and pregnancy, based on interviews conducted during or shortly after pregnancy, are reviewed. We present information about how health professionals may manage these perceptions and expectations, based on the findings of these studies, as well as areas for future research.

Journal ArticleDOI
TL;DR: Newer evidence shows that routine lymphadenectomy and bilateral salpingo-oophorectomy may not be necessary, unless in the presence of extra-uterine spread, suspicious ovaries or lymph nodes, and certain poor histological types, such as undifferentiated endometrial sarcoma and adenosarcoma with sarcomatous overgrowth.
Abstract: Uterine sarcomas comprise leiomyosarcoma, endometrial stromal sarcoma, adenosarcoma, undifferentiated endometrial sarcoma, and their variants. Carcinosarcoma is historically classified as sarcoma, but it is now regarded as a metaplastic carcinoma. Uterine sarcomas are rare, and are traditionally staged in the same way as endometrial carcinoma. Because of their different clinical and biological behaviours, the International Federation of Gynecology and Obstetrics introduced a new staging system in 2009 for leiomyosarcoma, endometrial stromal sarcoma and adenosarcoma, and carcinosarcoma, respectively. Following an extensive literature review no good evidence was found to support the modification of the staging system. This is mainly because of the rarity of the sarcomas and the heterogeneity of the reports, the different diagnostic criteria and treatments changing over the decades the retrospective nature and small sample size in most studies, and the lack of uniform pathological review even in large studies. Currently, evidence is still lacking about the use of preoperative imaging for staging purpose, and uterine sarcomas remain to be surgically staged. Total hysterectomy is the cornerstone for both staging and treatment. Newer evidence shows that routine lymphadenectomy and bilateral salpingo-oophorectomy may not be necessary, unless in the presence of extra-uterine spread, suspicious ovaries or lymph nodes, and certain poor histological types, such as undifferentiated endometrial sarcoma and adenosarcoma with sarcomatous overgrowth. More research and data collection are definitely needed in order to verify and further revise the current staging systems.

Journal ArticleDOI
TL;DR: Advances in ultrasound technology have improved the ability to observe the pathophysiologic changes that occur with pre-eclampsia and intrauterine growth restriction early in pregnancy, bringing us closer to a reproducible screening model.
Abstract: Pre-eclampsia and intrauterine growth restriction are responsible for significant maternal and fetal morbidity and mortality worldwide. Identifying pregnancies at highest risk for their development would allow increased surveillance in individual pregnancies and also allow therapeutic trials to decrease their incidences in the future. To date, multiple attempts to develop a screening test for these disorders have met with limited success. Proposed screening methods have included maternal serum biochemical parameters as well as ultrasonographic markers. Uterine artery Doppler, direct evaluation of the spiral arteries using colour and spectral Doppler, three-dimensional placental volume analysis and, most recently, three-dimensional power Doppler angiography have all been suggested. Although an adequate screening method remains elusive, advances in ultrasound technology have improved our ability to observe the pathophysiologic changes that occur with these conditions early in pregnancy, bringing us closer to a reproducible screening model.