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This guidance updates and replaces the previous guideline on the investigation and management of antiphospholipid syndrome (APS) published in 2000 (Greaves et al, 2000), though where there have not been changes we refer back to them when appropriate. The guidance is updated with reference to relevant publications since 2000. Publications known to the writing group were supplemented with additional papers identified by searching PubMed for publications in the last 11 years using the key words: lupus anticoagulant, anticardiolipin, antiphospholipid, β2–glycoprotein I, antiprothrombin and limits (clinical trial, randomized control trial, meta-analysis, humans, core clinical journals, English language). The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology. The guideline was then reviewed by a sounding board of approximately 50 UK haematologists, the Royal College of Obstetricians and Gynaecologists (RCOG), and the British Committee for Standards in Haematology (BCSH) Committee and comments incorporated where appropriate. The ‘GRADE’ system was used to quote levels and grades of evidence, details of which can be found at http://www.bcshguidelines.com/BCSH_PROCESS/EVIDENCE_LEVELS_AND_GRADES_OF_RECOMMENDATION/43_GRADE.html. The objective of this guideline is to provide healthcare professionals with clear guidance on the diagnosis and management of patients with antiphospholipid syndrome though individual patient circumstances may dictate an alternative approach. The antiphospholipid syndrome (APS) is an acquired autoimmune condition. The clinical features are thrombosis (venous, arterial and microvascular) and/or pregnancy complications and failure. It is important to recognize the syndrome in the context of these problems and to institute appropriate therapy to reduce the risk of recurrence. The reader is directed to reviews published since our previous guideline (Lim et al, 2006; Robertson & Greaves, 2006; Ruiz-Irastorza et al, 2007; Giannakopoulos & Krilis, 2009; Giannakopoulos et al, 2009). Antiphospholipid syndrome is diagnosed in a patient with thrombosis and/or defined pregnancy morbidity (see below) who has persistent antiphospholipid antibodies (aPL). Venous thrombosis in APS is most commonly lower limb deep vein thrombosis (DVT) and/or pulmonary embolism (PE) but any part of the venous system may be involved, including superficial, portal, renal, mesenteric and intracranial veins. The most frequent site of arterial thrombosis in APS is in the cerebral vasculature resulting in transient cerebral ischaemia/stroke. Myocardial infarction is less common, although subclinical myocardial ischaemia may be under-recognized (Sacre et al, 2010). Despite these clear associations between aPL and thrombosis, APS makes only a minor contribution to the overall burden of disease from VTE and stroke. Microvascular thrombosis in APS is least common but may manifest as the potentially lethal ‘catastrophic antiphospholipid syndrome’ (CAPS). In CAPS there is typically multiorgan failure involving, but not confined to, the lungs, brain and kidneys. Historically aPL have been detected as either a lupus anticoagulant (LA) or as anticardiolipin antibodies (aCL). LA is an in vitro phenomenon in which there is prolongation of a phospholipid-dependent coagulation test that is not due to an inhibitor specific to a coagulation factor (see Section ‘4.2’). It was originally thought that the LA phenomenon was due to autoantibodies against anionic phospholipids interfering with the assembly of the tenase and prothrombinase complexes, and the aCL assay (see Section ‘4.4’) was developed as an alternative way of detecting these hypothetical antibodies. However it became clear in the early 1990s that these tests were detecting antibodies not to anionic phospholipids but to phospholipid binding proteins. The aCL enzyme-linked immunosorbent assay (ELISA) typically detects antibodies to β2–glycoprotein I (β2GPI) (Galli et al, 1990; McNeil et al, 1990) and LA tests are sensitive to antibodies to β2GPI (anti-β2GPI) and also antibodies to prothrombin (Bevers et al, 1991). β2GPI is an apolipoprotein and a member of the complement control protein family; it binds to cell surface receptors and negatively charged surfaces. Among anti-β2GPI it has been demonstrated that it is those that bind specifically to a limited epitope on domain 1 of the protein (Gly40-Arg43) that are most strongly associated with thrombosis (de Laat et al, 2005). Antiprothrombin antibodies are weakly associated with thrombosis; they usually have a low affinity, but in some patients higher affinity antibodies are produced which cause the rare complication of hypoprothrombinaemia. APS has been described as secondary if there is an associated autoimmune disorder, such as systemic lupus erythematosus (SLE) or rheumatoid arthritis, and primary if not. In order to ensure consistency in research, consensus criteria for the diagnosis of APS have been agreed (Miyakis et al, 2006) (Table 1). Whilst these criteria are useful for encouraging uniformity in clinical studies their uncritical application to the individual case in the clinic should be avoided; rather, the diagnosis should depend upon a thorough assessment of the clinical history, consideration of alternative causes of thrombosis or pregnancy morbidity and review of the laboratory data in the light of knowledge of the limitations of the assays (see Section ‘4’). In addition to thrombosis and pregnancy morbidity there have been many claims of other clinical associations with aPL. Thrombocytopenia, heart valve disease (which is most commonly occult), chorea, livedo reticularis/racemosa and nephropathy are likely associations, although like the thrombotic and pregnancy manifestations, none is specific to APS (Miyakis et al, 2006). Transverse myelopathy occurs in SLE and may be more frequent in those with aPL (Cervera et al, 2002). A purported association with infertility has not been substantiated (Buckingham & Chamley, 2009) and an association with migraine is controversial with one recent study finding a relationship (Cavestro et al, 2011) but others not (Montalban et al, 1992; Tietjen et al, 1998). Another controversial concept is that APS may manifest as a disorder closely mimicking multiple sclerosis and responsive to anticoagulant therapy (Hughes, 2003). However, aPL may be present in some cases of otherwise typical multiple sclerosis (Heinzlef et al, 2002) perhaps representing an epiphenomenon in a disorder with an immune pathogenesis. Even more controversial is the suggestion that there may be a seronegative form of APS (Hughes & Khamashta, 2003). The principal manifestations of APS, thrombosis and pregnancy failure, are common and in most cases have no autoimmune basis; as such the diagnosis of ‘seronegative APS’ would be difficult to sustain. This guideline considers only thrombosis (primarily venous thromboembolism and arterial ischaemic stroke) and pregnancy morbidity, in APS. In relation to venous thrombosis Galli et al (2003a,b) published two papers, which looked at the evidence for an association with aPL. There was evidence of an association with LA, odds ratios (OR) across studies ranging from 4·1 to 16·2. Although some studies suggested an association with aCL (Ginsburg et al, 1992; Schulman et al, 1998), others did not (Stegnar et al, 1991; Bongard et al, 1992; Oger et al, 1997) and overall Galli et al. concluded that aCL were not independently associated with DVT. For anti-β2GPI the same authors found 7/14 studies showed a significant association with venous thrombosis but only in retrospective studies. In 2004 β2GPI dependent LA was shown to be associated with venous thrombosis (de Laat et al, 2004). The following year the presence of IgG anti-β2GPI was shown to predict thrombosis in patients with LA (Zoghlami-Rintelen et al, 2005). An analysis of the Leiden Thrombophilia Study demonstrated that the presence of LA, anti-β2GPI and anti -prothrombin antibodies are risk factors for DVT in a general population, the strongest association being for the combination of LA, aβ2GPI and anti-prothrombin antibodies (de Groot et al, 2005). In a prospective population-based nested cohort study, aCL did not predict a first episode of venous thrombosis (Naess et al, 2006). In the WAPS study (Galli et al, 2007) IgG anti-β2GPI were associated with thrombosis whereas IgM anti-β2GPI, IgG aCL and IgM aCL were not. The authors proposed that anti-β2GPI replace aCL measurement and that only the IgG isotype should be tested for. With regard to arterial thrombosis the aforementioned reviews found that both LA and IgG aCL were associated with arterial thrombosis but that IgM aCL were not (Galli et al, 2003a,b). For anti-β2GPI they found 3/10 studies showed a significant association with arterial thrombosis and concluded that the evidence did not support an association with arterial events. β2GPI-dependent LA has been shown to be associated with arterial thrombosis (de Laat et al, 2004). In the RATIO (Risk of Arterial Thrombosis in Relation to Oral. Contraceptives) study of 175 patients with ischaemic stroke and 203 patients with myocardial infarction (Urbanus et al, 2009) the OR of LA for myocardial infarction was 5·3 (95% confidence interval [CI] 1·4–20·8) and for ischaemic stroke 43·1 (12·2–152·0). In women who had anti-β2GPI antibodies the risk of ischaemic stroke was 2·3 (1·4–3·7), but the risk of myocardial infarction was not increased (0·9, 0·5–1·6). Neither aCL nor antiprothrombin antibodies affected the risk of myocardial infarction or ischaemic stroke. There are fewer data on antibodies of IgA isotype but inclusion of IgA aCL tests does not improve diagnostic efficiency (Bertolaccini et al, 2001; Samarkos et al, 2006). In general, among aPL, the specificity for thrombosis is higher for LA than aCL or anti-β2GPI and greater for higher than lower titre aCL. In one study, patients positive for a LA in both a dilute Russell viper venom time (DRVVT) and a sensitive activated partial thromboplastin time (APTT) were more likely to have thrombosis than patients with only one positive LA test (Swadzba et al, 2011). IgM and IgA antibodies are poorly specific. In addition, among patients with thrombosis, the highest risk of recurrence is the relatively small cohort positive for all of LA, aCL and anti-β2GPI (Pengo et al, 2010). There is substantial evidence linking aPL to an increased risk of recurrent and late pregnancy loss (Ginsberg et al, 1992; Rai et al, 1995; Laskin et al, 1997; Robertson et al, 2006). LA has a stronger association with pregnancy loss than the other anti-phospholipid antibodies, while the importance of anti-β2GPI and pregnancy loss is uncertain (Opatrny et al, 2006). In the meta-analysis by Opatrny et al (2006), both IgG and IgM aCL were associated with recurrent fetal loss but it was not possible to determine the significance of isolated IgM aCL as studies have not distinguished between women having isolated IgM aCL and women having additional aPL antibodies. With regard to pre-eclampsia, placental abruption and fetal growth restriction (FGR), there is an association between these complications and the presence of aPL but this is less strong than with recurrent pregnancy loss (Branch et al, 2001; Robertson et al, 2006). Whether the association of aPL with thrombosis is causal has been contentious though studies in experimental animals do suggest that aPL are directly prothrombotic (Blank et al, 1991). Many mechanisms for thrombosis in APS have been suggested, such as increased expression of tissue factor on monocytes and endothelial cells (Branch & Rodgers, 1993; Amengual et al, 1998), interference in the protein C anticoagulant pathway (Malia et al, 1990; Atsumi et al, 1998a), inhibition of fibrinolysis (Atsumi et al, 1998b) and inhibition of annexin V binding to phospholipids et al, 1998). has on anti-β2GPI (see Giannakopoulos et al for a β2GPI can in two in et al, a form and an The is by between the first and domain of in the a epitope in the first domain bind to a of receptors receptors and annexin and in the on cell including endothelial monocytes and (de Groot & 2011) and may and failure may be due to thrombosis in the placental although alternative mechanisms may and may the to early to aPL to have a on et al, & et al and there is evidence for of complement in pregnancy failure in experimental APS et al, & and in et al, 2007; et al, 2009). may the of in the of early fetal in APS as has been shown to potentially on in vitro et al and to complement in experimental APS et al, & 2004). The for LA and aPL assays was in in the previous guideline (Greaves et al, should be should be by at 2000 for at This should with a of is not as this may as the is not for the same et al, should not be and coagulation tests are in and anticoagulant for a LA test of should be to ensure that LA is detected and to improve though patients are as having a LA if one test is evidence on associations with thrombosis that the has and should be one of these The other test usually be an using a with LA a or a dilute prothrombin A test may be used to an inhibitor and a using a phospholipid or is to phospholipid the is of LA but the is a in the a of specificity test and is to the criteria for tests are a for LA and improve the However, they a factor and may LA In the of any other causes of such should be LA positive if the and tests on positive et al, 1993; et al, et al, & 2006). this should be by a that there are in and specificity between et al, 1995; et al, & for LA should be specific for the and of et al, et al, may be from the but is have used the for as a but the recent on Thrombosis and Haemostasis consensus (Pengo et al, 2009) has the 2·3 for which would improve specificity but reduce UK the either with a of is and which be may be useful in this The of the reference interval with small is and of and a of et al, have been or are they may be in of et al, A should be tested with of and the patient and should be as ratios against The for the of the that has been by the should be that this the This should either the of as described (Greaves et al, 2000), or a the the and an as or should be be with of using and should be in the same way as test For the positive from a patient with APS and LA may be should be with the and as in between and can to while of the should also in an LA is not in patients of a LA is the is in the it is thought to be in the of of therapy for diagnostic is not a risk in most LA is for patients the of the is 1990; et al, 2009) and tests on may be and on of patient and may be the on the is this may be as for that an inhibitor is present and the phospholipid to the in studies does not the presence of a The venom time is a useful secondary test to in patients with specificity for LA et al, et al, It can be used with a or time as LA tests should not be if the patient is of this may cause et al, 1993; et al, et al, 2002). and low have less on the and most a to should be in due to the for positive LA positive are from aCL or anti-β2GPI these are for the diagnosis of APS. assays may those for pathway factors on should be at as interference by the inhibitor and In this using higher of the test can but the also be a can be used for Another is to an assay system that is less dependent on phospholipid such as a assay or It should be that some patients with factor may also have a guidance for the of aCL assays has been published & features are the of or fetal as a and and & or et al, with in IgG or IgM antiphospholipid should be in using the but it should be that the of APS used for levels greater than the or assays have greater specificity than but are poorly The and of the and are to ensure that the relevant anti-β2GPI are antibodies, such as and have been as et al, et al, but are not have been developed that domain 1 of anti-β2GPI, and may and specificity for clinical although more evidence is A and should be in assay for both aCL and anti-β2GPI may be using or APS patient or or LA is the most test for thrombosis and the presence of IgG aCL or IgG anti-β2GPI in those who are the There is to suggest that IgM antibodies in patients with thrombosis useful should be an interval of to of aPL is common, in the Leiden study, a population-based case control study of LA was present in of of and anti-β2GPI in of of (de Groot et al, 2005). Even when antibodies have been thought to be associated with a low of thrombosis, of were found to have IgG aCL positive for but none had thrombosis the et al, In a study, of aPL were for and no episode of thrombosis was detected et al, 2004). However, a recent identified that were positive for LA, aCL and anti-β2GPI, and for a of years identified first et al, 2011). did not the of with a randomized in which with was in with aPL but no clinical manifestations randomized to or the thrombosis were for and for the et al, therapy a substantial risk of Although the risk is in the first it for the of is for at least the of an episode of VTE should be on an individual assessment of the The risk of recurrence is higher an et al, 2010). studies have shown a of thrombosis recurrence in patients with aPL & 1992; et al, 1995; et al, In these et al, & and et al, 1997) had venous In the prospective of study a aCL positive test the risk of a recurrence et al, 1998). In patients with venous thrombosis, a of is for patients with a transient risk factor but is in those with an et al, do not for aPL in patients with venous thrombosis due to a transient risk factor as we do not there is evidence to if the patient has aPL. it is to DVT or for aPL is as their presence the risk of recurrence a of retrospective and studies it was thought that stroke associated with aPL a risk of recurrence the of or and should be with & 1992; et al, 1995; et al, The Antiphospholipid and Study et al, was a prospective cohort study the Study a randomized with of stroke patients were aPL positive LA, and aPL did not predict OR and for the patients on and It should be that tests for aPL were only on a and that IgG aCL was as For patients with a positive aPL test and and for recurrent stroke. have no evidence for patients with stroke who have APS to the et al criteria (Table 1). The cohort studies to suggest that patients with ischaemic stroke and APS may be at risk of recurrence who are positive for LA, aCL and anti-β2GPI have the highest and that with should be but there is no strong evidence that it is more than A small retrospective study patients with APS with for a of years an ischaemic there were two in a of patient years on to a recurrence of to the general stroke et al, 2003). In a small study, ischaemic stroke patients with aPL were randomized to either or et al, 2010). The of stroke in patients with only was higher than that in patients the combination of and The authors suggested a study with more patients would be In the general stroke population, or are to CAPS is an cause of failure (Cervera et al, 2009). It is a rare that may APS or present There are no data from randomized to which is upon the thrombotic features and autoimmune of are typically used including with including and have been in all with thrombosis, should be to risk factors such as and Although there is and some of to anticoagulant to reduce thrombosis risk in APS, specifically et al, and et al, 1997; et al, et al, their experimental at A retrospective study of patients with venous suggested that a of was to a of et al, prospective randomized have et al randomized patients with aPL and thrombosis to a of or and them for a of were in the low group and in the For venous thrombosis the were and et al randomized patients with aPL and thrombosis venous arterial to a of or and them for a of were in the low group and in the The of patients with APS have a prothrombin time in the of other or anticoagulant the is it is due to but it has been suggested that the may be increased by interference of LA with the phospholipid of the where tissue factor is and phospholipids are used for such as and et al, to be more sensitive to the is should be should be used with for in APS et al, et al, 2010). APS as a specific to their In rare patients with prolongation of the study et al, found this in of cases using which causes in the of factor assays may be et al, 2001; et al, 2003). A of approximately to a in patients et al, 2010). The investigation and of women with recurrent pregnancy loss is in an guideline The may have some on tests for aPL, that investigation should be between where possible et al, are used to reduce the of pregnancy In APS this management is by clinical & Rai et al, 1997) and review et al, which that in combination with low the of pregnancy loss in women with a of recurrent Although data are the of with low does not to the risk of pregnancy loss & et al, 2005). therapy has not been shown to reduce pregnancy loss with or & 1997; et al, 1997; et al, et al, 2005). In to the combination of and low did not in a of pregnancy loss with et al, et al, Laskin et al, 2009). Although has in pregnancy of a more and & there are data and However, in two small studies the combination of and low to and low in recurrent pregnancy loss et al, et al, 2005). Although there is limited evidence of has in for of recurrent in APS of and of Despite inclusion of fetal placental and early in the consensus criteria for diagnosis of APS, the data the associations have been to and there is a of evidence to 2011). is for of and and is appropriate to in women with APS and a of these However there is a of evidence to that or additional for secondary of these late pregnancy complications in women with APS. while such therapy may be on an from recurrent pregnancy loss evidence, at present this is not by the limited evidence An guideline that women with previous thrombosis and APS should be both and of and that women with persistent aPL with no previous VTE and no other risk factors or fetal for may be with but should be for for the and in these is to be and at the time of to the the British for Haematology nor the any for the of these authors to the for papers, of and the and all the of the authors have a of Task at time of writing this guideline was A I I

<scp>WHO</scp> Statement on Caesarean Section Rates

BJOG An International Journal of Obstetrics & Gynaecology2015-07-22作者：Ana Pilar Betrán, MR Torloni, JJ Zhang

In 1985 when a group of experts convened by the World Health Organization in Fortaleza, Brazil, met to discuss the appropriate technology for birth, they echoed what at that moment was considered an unjustified and remarkable increase of caesarean section (CS) rates worldwide.1 Based on the evidence available at that time, the experts in Fortaleza concluded: ‘there is no justification for any region to have a caesarean section rate higher than 10–15%’.1 Over the years, this quote has become ubiquitous in scientific literature, being interpreted as the ideal CS rate. Although this reference range was intended for ‘populations’, which are defined by geopolitical boundaries, in many instances it has been mistakenly used as the measurement for healthcare facilities regardless of their complexity or other characteristics. In addition to the case mix of the obstetric population served, the use of CS at healthcare facilities is also affected by factors such as their capacity to handle cases, availability of resource and the clinical management protocols used locally. Since its publication and for the last 30 years, this reference rate for CS has received intense criticism and has led to controversy, concern, polarised opinions and heated debates, while in parallel, the use of CS as a mode of delivery has continued its worrying rise worldwide. The need to revisit the recommended CS rate has been considered more and more necessary in view of the significant improvements in clinical obstetric care and in the methodology to assess evidence and issue recommendations in the last three decades. The global concern around CS rates is understandable. When medically justified, a CS can prevent maternal and perinatal mortality and morbidity. There is no evidence, however, showing the benefits of the procedure for women or infants where it is not required. CS is associated with short- and long-term risk, which can extend beyond the current delivery and affect future pregnancies. In addition, the increase in CS rates seems uncontrollable, with no signs that it is slowing down. The situation is aggravated by the fact that the causes of the rise are not fully understood but emerge as a complex multifactorial labyrinth involving health systems, health care providers, women, societies, and even fashion and media.2-6 Lastly, non-clinical interventions to reduce unnecessary CS have shown limited effectiveness to date.7 In light of these issues, WHO convened a meeting in Geneva, Switzerland, on 8–9 October 2014 with the objective of (1) establishing the current WHO position on the CS rate or range for optimal maternal and perinatal outcomes at population level, and (2) agreeing on a proposal for a tool to monitor CS rates at facility level. The Statement on Caesarean Section Rates recently released by WHO summarises the results of the systematic reviews and analyses conducted for this purpose and conveys the thinking emerging from the discussions of the meeting.8 A systematic review and an ecological analysis were performed and concluded that at population level, CS rates higher than 10% were not associated with reductions in maternal and newborn mortality rates.9, 10 The Statement notes, however, that the association between CS rates and other relevant outcomes such as stillbirths, maternal and perinatal morbidity, paediatric outcomes and psychological or social well-being could not be determined due to the lack of data on these other outcomes at the population level. This lack of data represents a limitation of these analyses that needs to be borne in mind. Beyond numbers and rates, the Statement emphasises that the critical role played by the quality of care in this equation cannot be overstated. As with any surgery, CS is associated with short- and long-term risks, particularly in settings that lack the facilities or capacity to conduct safe surgery or treat surgical complications properly, or where access to labour care or repeat CS in subsequent pregnancies cannot be taken for granted. On the other hand, inadequate access to timely CS may result in perinatal asphyxia, stillbirth, uterine rupture or obstetric fistula, a marker for exceptionally prolonged, obstructed labour.11 Thus, CS should be undertaken when medically necessary, and rather than striving to achieve a specific rate, efforts should focus on providing caesarean section to all women in need. How to define the woman ‘in need’ can only be ascertained by the health care providers caring for the woman on a case-by-case basis. Most importantly, at the healthcare facility level, clinicians and administrators struggle to monitor CS rates in a meaningful, reliable and action-oriented manner. Historically, caesarean sections have often been categorised using its indications as the unit being classified. Using indications to classify CS has always been problematic due to the lack of uniform definitions for most common indications and has resulted in poor reproducibility and unsatisfactory comparisons.12 In 2001, Dr Michael Robson proposed a system of 10 groups that classifies all women admitted for delivery (and not indications) according to five obstetric characteristics that are generally routinely collected in most maternities.13 Two systematic reviews conducted at WHO identified this classification as the most appropriate system to fulfil current international and local needs.12, 14 The WHO Statement proposes the use of the Robson classification as the global standard for assessing, monitoring and comparing CS rates within healthcare facilities over time, and between facilities. In the last decade, this classification has witnessed an extraordinary expansion in its use worldwide, particularly in healthcare facilities, due to its intrinsic appealing characteristics: simplicity of design, validity of purpose, ease of implementation and directness of initial interpretation.14 WHO envisions that the information stemming from the classification can be a powerful tool to inform practice. The classification will allow not only for stratification of CS rates in more uniform groups of women but also the assessment of CS rates in relation to other perinatal outcomes and processes (e.g. rates of oxytocin usage, postpartum haemorrhage, newborn outcomes, length of labour). WHO will guide and support countries in the use, implementation and interpretation of the classification so that we can start comparing CS rates in a meaningful, targeted, transparent and useful manner. By endorsing the Robson classification, this Statement should become a catalyst for action. The time has come to put the debate about the preferable rate of CS on hold. Let's start to collect data uniformly so that in the near future we will be able to move our focus from CS rates at population level to monitoring and discussing CS rates and outcomes in each group of the Robson classification. Only then will we have the data and evidence that will lead us more clearly to actions to improve care.15 Ultimately, we hope the debate can recommence with more valuable, solid and informative data to support our discussions. None declared. Completed disclosure of interests form available to view online as supporting information. All authors contributed to the writing of the commentary. This commentary has been written without any external funding. No ethical approval was sought for the writing of this commentary. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions or policies of the World Health Organization or other organizations. WHO Working Group on Caesarean Section: HA Aleem (Department of Obstetrics and Gynecology, Women's Health Center, Assiut University Hospital, Assiut, Egypt), F Althabe (Institute for Clinical Effectiveness and Health Policy, Buenos Aires, Argentina), T Bergholt (Department of Obstetrics, University of Copenhagen, Copenhagen, Denmark), L de Bernis (United Nations Population Fund, Geneva, Switzerland), G Carroli (Centro Rosarino de Estudios Perinatales, Rosario, Argentina), C Deneux-Tharaux (INSERM U1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Center for Epidemiology and Statistics Sorbonne Paris Cité, Paris Descartes University, Paris, France), R Devlieger (UZLeuven, Campus Gasthuisberg, Department of Obstetrics and Gynecology, Leuven, Belgium), S Debonnet (International Confederation of Midwives, 2517 AN The Hague, the Netherlands), T Duan (Shanghai No.1 Maternal & Infant Health Hospital, Shanghai, China), C Hanson [International Federation of Gynecology & Obstetrics (FIGO), London, UK], J Hofmeyr (Department of Health, Effective Care Research Unit, University of Fort Hare, East London, Eastern Cape, South Africa), R Gonzalez Pérez (Department of Maternal and Gynaecological Health, Pontificia Universidad Catolica de Chile, Santiago de Chile, Chile), A de Jonge (Midwifery Science, AVAG and the EMGO Institute of Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands), K Khan (Women's Health Research Unit, Multi-disciplinary Evidence Synthesis Hub, The Blizard Institute, London, UK), S Lansky (Ministry of Health, Belo Horizonte Minas Gerais, Brazil), G Lazdane (WHO Regional Office for Europe, Copenhagen, Denmark), P Lumbiganon (Department of Obstetrics and Gynecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand), D Mackeen (Department of Obstetrics and Gynecology, Division of Maternal–Fetal Medicine, Geisimger Health System, Danville, PA, USA), R Mahaini (WHO Office for the Eastern Mediterranean Region, Cairo, Egypt), S Manyame (Department of Obstetrics & Gynaecology, Harare Hospital & University of Zimbabwe, Harare, Zimbabwe), M Mathai (Department of Maternal and Child Health, World Health Organization, Geneva, Switzerland), R Mikolajczyk (ESME – Epidemiological and Statistical Methods Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany), R Mori (Department of Health Policy, National Center for Child Health and Development, Tokyo, Japan), B De Mucio (Latin American Center for Perinatology, Women and Reproductive Health (CLAP/WR), WHO Regional Office for the Americas, Montevideo, Uruguay), OT Oladapo (UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO, Geneva, Switzerland), E Ortiz-Panozo (Center for Population Health Research, National Institute of Public Health, Cuernavaca, Mexico), L Ouedraogo (WHO Regional Office for Africa, Brazzaville, Congo), C Parker (Obstetrics and Gyneacology Department, Baragwanath Maternity Hospital, Johannesburg, South Africa), M Robson (National Maternity Hospital, Dublin, Ireland), S Serruya (Latin American Center for Perinatology, Women and Reproductive Health (CLAP/WR), WHO Regional Office for the Americas, Montevideo, Uruguay), JP Souza [Department of Social Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto (SP), Brazil], CY Spong (Deputy Director, Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda, MD, USA), C Stanton (Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA), ME Stanton (USAID, Washington DC, USA), EA Sullivan (Faculty of Health, University of Technology, Sydney, Australia), M Temmerman (UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO, Geneva, Switzerland), A Tita (Department of Obstetrics and Gynecology, Division of Maternal–Fetal Medicine, University of Alabama at Birmingham, Birmingham, AL, USA), Ӧ Tunçalp (UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO, Geneva, Switzerland), P Velebil (Perinatal Center of the Institute for the Care of Mother and Child, Prague, Czech Republic), JP Vogel (UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO, Geneva, Switzerland), M Weber (WHO Regional Office for Europe, Copenhagen, Denmark), D Wojdyla (Duke Clinical Research Institute, Durham, NC, USA), J Ye (Ministry of Education–Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China), K Yunis (Department of Pediatrics & Adolescent, Medicine and Department of Pediatrics, American University of Beirut, Beirut, Lebanon), J Zamora (Clinical Biostatistics Unit, Hospital Ramón y Cajal, Madrid, Spain), A Zongo (Research Institute for Development, Université Paris Descartes, Sorbonne Paris Cité, UMR 216, Paris, France and Direction de la santé de la famille, Ministère de la Santé, Ouagadougou, Burkina Faso) Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Obstetrics and Gynecology Pediatrics, Perinatology and Child Health Pediatrics, Perinatology and Child Health

The CROWN Initiative: journal editors invite researchers to develop core outcomes in women's health

Contraception2014-07-11作者：Khalid S. Khan

Clinical trials, systematic reviews and guidelines compare beneficial and nonbeneficial outcomes following interventions. Often, however, various studies on a particular topic do not address the same outcomes, making it difficult to draw clinically useful conclusions when a group of studies is looked at as a whole [[1]Williamson P.R. Altman D.G. Blazeby J.M. Clarke M. Devane D. Gargon E. et al.Developing core outcome sets for clinical trials: issues to consider.Trials. 2012; 13: 132-139Crossref PubMed Scopus (1077) Google Scholar]. This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention, which found that among 103 randomised trials, no fewer than 72 different outcomes were reported [[2]Meher S. Alfirevic Z. Choice of primary outcomes in randomised trials and systematic reviews evaluating interventions for preterm birth prevention: a systematic review.BJOG. 2014; https://doi.org/10.1111/1471-0528Crossref PubMed Google Scholar]. There is a growing recognition among clinical researchers that this variability undermines consistent synthesis of the evidence, and that what is needed is an agreed standardised collection of outcomes—a "core outcomes set"—for all trials in a specific clinical area [[1]Williamson P.R. Altman D.G. Blazeby J.M. Clarke M. Devane D. Gargon E. et al.Developing core outcome sets for clinical trials: issues to consider.Trials. 2012; 13: 132-139Crossref PubMed Scopus (1077) Google Scholar]. Recognising that the current inconsistency is a serious hindrance to progress in our specialty, the editors of over 50 journals related to women's health have come together to support The CoRe Outcomes in WomeN health (CROWN) Initiative (Box 1).Box 1Aims of the CROWN Initiative1.Form a consortium among all gynaecology–obstetrics and related journals to promote core outcome sets in all areas of our specialty.2.Encourage researchers to develop core outcome sets using robust consensus methodology involving multiple stakeholders, including patients.3.Strongly encourage the reporting of results for core outcome sets.4.Organise robust peer review and effective dissemination of manuscripts describing core outcome sets.5.Facilitate embedding of core outcome sets in research practice, working closely with researchers, reviewers, funders and guideline makers.www.crown-initiative.org 1.Form a consortium among all gynaecology–obstetrics and related journals to promote core outcome sets in all areas of our specialty.2.Encourage researchers to develop core outcome sets using robust consensus methodology involving multiple stakeholders, including patients.3.Strongly encourage the reporting of results for core outcome sets.4.Organise robust peer review and effective dissemination of manuscripts describing core outcome sets.5.Facilitate embedding of core outcome sets in research practice, working closely with researchers, reviewers, funders and guideline makers.www.crown-initiative.org Development of consensus is required around a set of well-defined, relevant and feasible outcomes for all trials concerning particular obstetric and gynaecologic health conditions, such as preterm birth, incontinence, infertility and menstrual problems. With so many subspecialties involved, this is no easy task. Duplication of effort can be avoided by working with the Core Outcome Measures in Effectiveness Trials (COMET) Initiative, which is working toward core data sets for all medical specialties [[3]Williamson P.R. Altman D.G. Blazeby J.M. Clarke M. Gargon E. The COMET (Core Outcome Measures in Effectiveness Trials) Initiative.Trials. 2011; 12: A70Crossref PubMed Google Scholar]. Production of trustworthy core outcome sets will require engagement with patients, healthcare professionals, researchers, industry and regulators and the employment of scientifically robust consensus methods [[1]Williamson P.R. Altman D.G. Blazeby J.M. Clarke M. Devane D. Gargon E. et al.Developing core outcome sets for clinical trials: issues to consider.Trials. 2012; 13: 132-139Crossref PubMed Scopus (1077) Google Scholar]. The data for these core outcome sets, once agreed upon, should be collected in trials and reported in publications as standard practice in the future. Journal editors now invite researchers to take the lead in beginning this work. What will we do as editors to support them and their colleagues? First, we are drawing wide attention to the CROWN Initiative by publishing this editorial in the journals listed below. We shall ensure that the global research community, which includes our many reviewers, is aware of the need for core outcome sets. Submissions which describe development of core outcome sets, if deemed acceptable after peer review, will be effectively disseminated. Our collaboration is not for enforcing harmony at the expense of innovation. To quote from the COMET home page (www.comet-initiative.org): "The existence or use of a core outcome set does not imply that outcomes in a particular trial should be restricted to those in the relevant core outcome set. Rather, there is an expectation that the core outcomes will be collected and reported, making it easier for the results of trials to be compared, contrasted and combined as appropriate; while researchers continue to explore other outcomes as well." We also expect that as new or superior ways of capturing outcomes emerge, core outcome sets themselves will need updating. Producing, disseminating and implementing core outcome sets will ensure that critical and important outcomes with good measurement properties are incorporated and reported. We believe that this is the next important step in advancing the usefulness of research, in informing readers, including guideline and policy developers, who are involved in decision-making, and in improving evidence-based practice. The CROWN Initiative includes the following journals, in alphabetical order (correct on May 13, 2014, up to date list available at www.crown-initiative.org):1.Acta Obstetricia et Gynecologica Scandinavica2.American Journal of Obstetrics & Gynecology3.American Journal of Perinatology4.Archives of Gynecology and Obstetrics5.Australian and New Zealand Journal of Obstetrics and Gynaecology6.Best Practice & Research: Clinical Obstetrics & Gynaecology7.Birth: Issues in Perinatal Care8.BJOG: An International Journal of Obstetrics and Gynaecology9.BMC Pregnancy and Childbirth10.BMC Women's Health11.Climacteric12.Clinical Obstetrics and Gynecology13.Clinics in Perinatology14.Cochrane Menstrual Disorders and Subfertility Group15.Cochrane Pregnancy and Childbirth Group16.Contraception17.Current Opinion in Obstetrics and Gynecology18.European Journal of Obstetrics & Gynecology and Reproductive Biology19.Fertility and Sterility20.Fetal Diagnosis and Therapy21.Ginekologia Polska22.Gynecological Surgery23.Gynecologic Oncology24.Gynecologic Oncology Reports25.Human Fertility26.Human Reproduction27.Human Reproduction Update28.Hypertension in Pregnancy29.International Journal of Fertility and Sterility30.International Breastfeeding Journal31.International Journal of Gynecology & Obstetrics32.International Urogynecology Journal33.Journal of Family Planning and Reproductive Health Care34.Journal of Gynecologic Oncology35.Journal of Lower Genital Tract Disease36.Journal of Midwifery & Women's Health37.Journal of Obstetrics & Gynaecology38.Journal of Obstetrics and Gynaecology Canada39.Journal of Obstetric, Gynecologic & Neonatal Nursing40.Journal of Perinatal & Neonatal Nursing41.Journal of Perinatal Medicine42.Maturitas43.MCN The American Journal of Maternal Child Nursing44.Menopause Review (Przegląd Menopauzalny)45.Menopause: The Journal of The North American Menopause Society46.Neurourology and Urodynamics47.Obstetrics & Gynecology48.Paediatric and Perinatal Epidemiology49.Placenta50.Prenatal Diagnosis51.Reproductive Health52.The Breast Journal53.The European Journal of Contraception and Reproductive Health Care54.The Obstetrician & Gynaecologist (TOG)55.Twin Research and Human Genetics56.Ultrasound in Obstetrics & Gynecology Reproduced from CROWN Initiative with permission from the Royal College of Obstetricians and Gynaecologists and John Wiley & Sons Ltd. The CROWN Initiative is grateful to James Duffy (Trainee Scientific Editor, BJOG) and Louisa Waite (Assistant Editor, BJOG) for the drafting, revision and coordination required for the preparation of this article.

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