Dutch Consortium Research Articles

P-746 Recruitment in randomised controlled trials: a conundrum

Abstract Study question What factors are associated with recruitment failure within the pre-planned study period? Summary answer Trials with a no-treatment arm, over four inclusion criteria, without a previous pilot and with low funding, are more likely to experience recruitment failure. What is known already Randomised controlled trials are considered to be the best strategy in evaluating the effectiveness of medical interventions, but they are often hampered by failure to recruit enough patients with the pre-planned study period. This represents a form of research waste. Little is known on variables related to recruitment failure within the pre-planned study period. Study design, size, duration This study was designed as a nationwide cohort study and included 71 randomized controlled trials supported by the Dutch Consortium for Women’s Health Research. We included trials initiated between March 1st 2003 and March 1st 2022. We extracted study data and information on predefined barriers and facilitators. Participants/materials, setting, methods Primary outcome was recruitment target not achieved within 6 months after the pre-planned recruitment period. Secondary outcomes included recruitment target not achieved within an extension of at least 12 months and premature termination of the trial. We used logistic regression to evaluate the association between potential indicators of recruitment failure and expressed these as odds ratios (OR) with corresponding 95% confidence intervals (CI). Main results and the role of chance Of the 71 trials included in our cohort, recruitment was not achieved within the pre-planned study period with a maximal extension period of 6 months or 12 months in 38 (54%) and 33 trials (46%), respectively. Indicators associated with higher chances on recruitment failure were a no treatment arm (OR 8.53 (95% CI 1.01 to 72.36)), a compensation fee of less than 200 euros per included patient (OR 3.16 (95% CI 1.18 to 8.45)) and a funding of less than 350.000 euros (OR 4.30 (95% CI 1.56 to 11.64)). Indicators associated with lower chances on recruitment failure were less than 4 inclusion criteria (OR 0.31 (95% CI 0.10 to 0.97)) and a preceding pilot study (OR 0.53 (95% CI 0.15 to 1.85)). Limitations, reasons for caution If we could have accessed an even larger cohort of studies we might have been able to identify more potential indicators for recruitment failure. Wider implications of the findings Investigators and grantproviders should consider our findings before the start of their studies, to optimize recruitmentcircumstances. If a trial is destined to have a suspected long recruitment, it seems wise to consider the relevance and urgency of the research question, and then accept a longer recruitment period with its consequences. Trial registration number not applicable

Rationale and design of the ABOARD project (A Personalized Medicine Approach for Alzheimer's Disease).

ABOARD (A Personalized Medicine Approach for Alzheimer's Disease) is a public-private research project executed by 32 partners that functions as a network organization.Together, the project partners build toward a future with personalized medicine for Alzheimer's disease.Although ABOARD is a Dutch consortium, it has international relevance.ABOARD improves diagnosis, prediction, prevention, and patient-orchestrated care.

Notes on Contributors

Notes on Contributors

Internalizing problems before and during the COVID-19 pandemic in independent samples of Dutch children and adolescents with and without pre-existing mental health problems

The aim of the study was to assess internalizing problems before and during the pandemic with data from Dutch consortium Child and adolescent mental health and wellbeing in times of the COVID-19 pandemic, consisting of two Dutch general population samples (GS) and two clinical samples (CS) referred to youth/psychiatric care. Measures of internalizing problems were obtained from ongoing data collections pre-pandemic (NGS = 35,357; NCS = 4487) and twice during the pandemic, in Apr–May 2020 (NGS = 3938; clinical: NCS = 1008) and in Nov–Dec 2020 (NGS = 1489; NCS = 1536), in children and adolescents (8–18 years) with parent (Brief Problem Monitor) and/or child reports (Patient-Reported Outcomes Measurement Information System®). Results show that, in the general population, internalizing problems were higher during the first peak of the pandemic compared to pre-pandemic based on both child and parent reports. Yet, over the course of the pandemic, on both child and parent reports, similar or lower levels of internalizing problems were observed. Children in the clinical population reported more internalizing symptoms over the course of the pandemic while parents did not report differences in internalizing symptoms from pre-pandemic to the first peak of the pandemic nor over the course of the pandemic. Overall, the findings indicate that children and adolescents of both the general and clinical population were affected negatively by the pandemic in terms of their internalizing problems. Attention is therefore warranted to investigate long-term effects and to monitor if internalizing problems return to pre-pandemic levels or if they remain elevated post-pandemic.

Expanding the utility of the watch‐and‐wait approach to stage IV patients: Results from the Dutch consortium

-

Integrating Cognitive Developmental Neuroscience in Society: Lessons Learned From a Multidisciplinary Research Project on Education and Social Safety of Youth.

Integrating fundamental science in society, with the goal to translate research findings to daily practice, comes with certain challenges. Successfully integrating research projects into society requires (1) good collaboration between scientists and societal stakeholders, (2) collaboration partners with common expectations and goals, and (3) investment in clear communication. Here we describe an integrative research project conducted by a large Dutch consortium that consisted of neuroscientists, psychologists, sociologists, ethicists, teachers, health care professionals and policy makers, focusing on applying cognitive developmental neuroscience for the benefit of youth in education and social safety. We argue that to effectively integrate cognitive developmental neuroscience in society, (1) it is necessary to invest in a well-functioning, diverse and multidisciplinary team involving societal stakeholders and youth themselves from the start of the project. This aids to build a so-called productive interactive network that increases the chances to realize societal impact in the long-term. Additionally, we propose that to integrate knowledge, (2) a different than standard research approach should be taken. When focusing on integration, the ultimate goal of research is not solely to understand the world better, but also to intervene with real-life situations, such as education or (forensic) youth care. To accomplish this goal, we propose an approach in which integration is not only started after the research has been conducted, but taken into account throughout the entire project. This approach helps to create common expectations and goals between different stakeholders. Finally, we argue that (3) dedicating sufficient resources to effective communication, both within the consortium and between scientists and society, greatly benefits the integration of cognitive developmental neuroscience in society.

P–753 A randomised controlled trial comparing expectant management versus intrauterine insemination in couples with unexplained subfertility and a poor prognosis for natural conception

Abstract Study question Does 6 months expectant management reduces ongoing pregnancy rates compared to intrauterine insemination with ovarian stimulation (IUI-OS) in couples with unexplained subfertility? Summary answer In couples with unexplained subfertility and a poor prognosis for natural conception, 6 months of expectant management decreases ongoing pregnancy rates as compared to IUI-OS. What is known already In couples with unexplained subfertility and a poor prognosis, IUI-OS is a first line treatment. We have previously shown that in couples with unexplained subfertility and a good prognosis for natural conception (>30% in 12 months), 6 months expectant management does not reduce pregnancy changes. However, in couples with a poor prognosis for natural conception, effectiveness of IUI-OS is uncertain. Study design, size, duration We performed a non-inferiority multicentre randomised controlled trial (RCT) within the infrastructure of the Dutch Consortium for Healthcare Evaluation and Research in Obstetrics and Gynaecology. We studied couples with unexplained subfertility and a poor prognosis for natural conception. The couples were allocated in a 1:1 ratio to six months expectant management or six months IUI-OS with either clomiphene citrate or gonadotrophins. Participants/materials, setting, methods We intended to include 1091 couples. The trial was halted pre-maturely due to slow inclusion after randomisation of 178 couples. The primary outcome was ongoing pregnancy leading to a live birth with multiple pregnancy and miscarriage rate as important secondary outcomes. We calculated relative risks with 95% CI and a corresponding hazard-rate for ongoing-pregnancy-over-time based on intention-to-treat. Main results and the role of chance Between October 2016 and September 2020 92 couples were allocated to expectant management and 86 to IUI-OS. Baseline characteristics were equally distributed. Mean female age was 34 years, median duration of subfertility was 21 months. Within 6 months after randomisation, women allocated to expectant management had a lower ongoing pregnancy rate than women allocated to IUI-OS (12/92 [13.0%] vs 29/86 women [33.7%], risk ratio 0.39 (95%CI 0.21 to 0.71)). There were two ongoing twin pregnancies in the expectant management group versus none in the IUI-OS group. Of 15 clinical pregnancies in the expectant management group three miscarried (20%), of 36 clinical pregnancies in the IUI-OS group seven miscarried (19.4%) (RR 1.03 (95% CI 0.31 to 3.45)). For the outcome ongoing pregnancy, the hazard ratio for expectant management versus IUI-OS was 0.34 (95%CI 0.18 to 0.67). Limitations, reasons for caution Our trial did not reach the planned sample size and therefore the results are limited by the number of participants. As 8 women are still pregnant, in this abstract we report ongoing pregnancy rates. Live birth rates will be presented at the conference. Wider implications of the findings: In couples with unexplained subfertility and a poor prognosis for natural conception, expectant management is inferior to IUI-OS. We advise the basic work-up for subfertility to contain a prognostic assessment, and when subfertility is unexplained and natural fertility prospects are poor IUI-OS should be the preferred treatment. Trial registration number NTR5599

TOWARDS AN ENTREPRENEURIAL INNOVATION SYSTEM FOR SMALL-HOLDER FARMERS IN SUB-SAHARAN AFRIC

Growing population pressure, climate change and urbanization necessitate the increase of agricultural production and innovation. Horticulture by means of protected cultivation primarily for vegetables production seems promising by creating a controlled environment for light, temperature and moisture and against diseases. But there is a gap between the high-tech precision horticulture as practiced for instance in the Netherlands and the context and capacities of African smallholder farmers. On the one side high-tech large-scale greenhouse cultivation is introduced by foreign companies, management and capital, while on the other side many smallholders grapple with lack of quality inputs, lack of funding, lack of frugal small-scale technical solutions (greenhouses, irrigation systems, water provision, disease and residue treatment, monitoring soil fertility etc.), lack of infrastructure and lack of capacity. Over and above an analysis of the situation the paper proposes a way forward consisting of three elements: entrepreneurship and capacity training (1), a strategy of gradual growth (2), and finally a comprehensive business innovation system (3). The research is based on long-term student involvement by internships and master thesis studies from the Delft University of Technology and includes the experiences of a Dutch consortium of entrepreneurs and researchers (greenhouse constructors, seed companies, pest control, financial institutions and entrepreneurship). This consortium tries to raise the capacities of smallholder farmers and take them to a higher level. Findings show that in principle there is a business case for introducing existing smallholder farmers and young entrepreneurs to protected cultivation under the leadership of more experienced farmers, supported by a network of stakeholders (retailers, banks, Dutch and African companies, academic partners, NGOs, government agencies). Cooperation of many stakeholders, the creation of an enabling environment and training of capacity appear to be crucial conditions for success. 

Integrative medicine in Dutch curative and long-term healthcare centres: Mapping the field

IntroductionLittle is known about integration of Complementary and Alternative Medicine (CAM) in the Dutch healthcare system. The aim of the present study was to investigate how Integrative Medicine (IM) is practiced and how CAM is integrated with conventional medicine in curative and long-term healthcare centres in the Netherlands. MethodsA mixed methodology was applied, including a systematic internet search, an online survey and focus groups among healthcare professionals. ResultsMost hospitals (92%) offered some form of CAM to treat anxiety (72%), restlessness (68%), pain (65%), sleeping problems (50%), stress (48%) and fatigue (36%). Mostly offered modalities were relaxation exercises (88%), art therapy (44%) and mindfulness (42%). Similar percentages of CAM use were found in other healthcare centres. Most CAM modalities were implemented without organizational vision, guidelines or protocols. Only 5% of implemented CAM was labelled as IM. Focus groups with health care professionals revealed the need to increase knowledge and to develop a vision for integration of CAM with conventional medicine, as well as to support effectiveness research in this area. ConclusionsThis study is the first in the Netherlands to quantitatively map the extent of CAM integration in conventional health care. The number of CAM interventions offered at conventional health care settings was surprisingly high. However, integration was fragmented. Guidelines, education and research programs are needed to further integration of CAM, preferably organised in a Dutch Consortium for IM.

Unsolicited findings of next-generation sequencing for tumor analysis within a Dutch consortium: clinical daily practice reconsidered.

Cancer patients participating in studies involving experimental or diagnostic next-generation sequencing (NGS) procedures are confronted with the possibility of unsolicited findings. The Center for Personalized Cancer Treatment (CPCT), a Dutch consortium of cancer centers, is offering centralized large-scale NGS for the discovery of somatic tumor mutations with their germline DNA as reference. The CPCT aims to give all cancer patients with advanced disease stages access to tumor DNA analysis in order to improve selection for experimental therapy. In this article, our experiences at the CPCT will serve as an example to discuss the ethical and practical aspects regarding the management of unsolicited findings in personalized cancer research and treatment. Generic issues, relevant for all researchers in this field are discussed and illustrated by description of three patients faced with an unsolicited DNA finding, while they intended to be candidate for future anticancer treatment by participating in a trial that included NGS of both somatic and germline DNA. As options for DNA analysis expand and costs decrease rapidly, more and more patients are offered large-scale NGS testing. After reviewing current recommendations in literature, we conclude that classical informed consent procedures need to be adapted to become more explicit in asking patients if they want to be informed about unsolicited findings and if so, what level of detail of genetic risk information exactly they want to be returned after the analysis.

Dutch consortium plans to establish research centre to meet chemical supply chain challenges

Dutch consortium plans to establish research centre to meet chemical supply chain challenges

Quinine, Malaria, and the Cinchona Bureau: Marketing Practices and Knowledge Circulation in a Dutch Transoceanic Cinchona-Quinine Enterprise (1920s-30s).

In this study, we will show how a Dutch pharmaceutical consortium of cinchona producers and quinine manufacturers was able to capitalize on one of the first international public health campaigns to fight malaria, thereby promoting the sale of quinine, an antimalarial medicine. During the 1920s and 1930s, the international markets for quinine were controlled by this Dutch consortium, which was a transoceanic cinchona-quinine enterprise centered in the Cinchona Bureau in the Netherlands. We will argue that during the interwar period, the Cinchona Bureau became the decision-making center of this Dutch cinchona-quinine pharmaceutical enterprise and monopolized the production and trade of an essential medicine. In addition, we will argue that capitalizing on the international public health campaign in the fight against malaria by the Dutch cinchona-quinine enterprise via the Cinchona Bureau can be regarded as an early example of corporate colonization of public health by a private pharmaceutical consortium. Furthermore, we will show how commercial interests prevailed over scientific interests within the Dutch cinchona-quinine consortium, thus interfering with and ultimately curtailing the transoceanic circulation of knowledge in the Dutch empire.

ALIFE2 study: low-molecular-weight heparin for women with recurrent miscarriage and inherited thrombophilia--study protocol for a randomized controlled trial.

BackgroundA large number of studies have shown an association between inherited thrombophilia and recurrent miscarriage. It has been hypothesized that anticoagulant therapy might reduce the number of miscarriages and stillbirth in these women. In the absence of randomized controlled trials evaluating the efficacy of anticoagulant therapy in women with inherited thrombophilia and recurrent miscarriage, a randomized trial with adequate power that addresses this question is needed. The objective of the ALIFE2 study is therefore to evaluate the efficacy of low-molecular-weight heparin (LMWH) in women with inherited thrombophilia and recurrent miscarriage, with live birth as the primary outcome.Methods/DesignRandomized study of LMWH plus standard pregnancy surveillance versus standard pregnancy surveillance alone.Study population: pregnant women of less than 7 weeks’ gestation, and confirmed inherited thrombophilia with a history of 2 or more miscarriages or intra-uterine fetal deaths, or both.Setting: multi-center study in centers from the Dutch Consortium of Fertility studies; centers outside the Netherlands are currently preparing to participate.Intervention: LMWH enoxaparin 40 mg subcutaneously once daily started prior to 7 weeks gestational age plus standard pregnancy surveillance or standard pregnancy surveillance alone.Main study parameters/endpoints: the primary efficacy outcome is live birth. Secondary efficacy outcomes include adverse pregnancy outcomes, such as miscarriage, pre-eclampsia, syndrome of hemolysis, elevated liver enzymes and low platelets (HELLP syndrome), fetal growth restriction, placental abruption, premature delivery and congenital malformations.Safety outcomes include bleeding episodes, thrombocytopenia and skin reactions.DiscussionAfter an initial period of slow recruitment, the recruitment rate for the study has increased. Improved awareness of the study and acknowledgement of the need for evidence are thought to be contributing to the improved recruitment rates. We aim to increase the number of recruiting centers in order to increase enrollment into the ALIFE2 study.The study website can be accessed via www.ALIFE2study.org.Trial registrationThe ALIFE2 study was registered on 19 March 2012 under registration number NTR3361Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0719-9) contains supplementary material, which is available to authorized users.

Heart failure with preserved ejection fraction in women: the Dutch Queen of Hearts program.

Heart failure (HF) poses a heavy burden on patients, their families and society. The syndrome of HF comes in two types: with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). The latter is on the increase and predominantly present in women, especially the older ones. There is an urgent need for mortality-reducing drugs in HFpEF, a disease affecting around 5 % of those aged 65 years and over. HFpEF develops in patients with risk factors and comorbidities such as obesity, hypertension, diabetes, COPD, but also preeclampsia. These conditions are likely to drive microvascular disease with involvement of the coronary microvasculature, which may eventually evolve into HFpEF. Currently, the diagnosis of HFPEF relies mainly on echocardiography. There are no biomarkers that can help diagnose female microvascular disease or facilitate the diagnosis of (early stages of) HFpEF. Recently a Dutch consortium was initiated, Queen of Hearts, with support from the Netherlands Heart Foundation, with the aim to discover and validate biomarkers for diastolic dysfunction and HFpEF in women. These biomarkers come from innovative blood-derived sources such as extracellular vesicles and circulating cells. Within the Queen of Hearts consortium, we will pursue female biomarkers that have the potential for further evolution in assays with point of care capabilities. As a spin-off, the consortium will gain knowledge on gender-specific pathology of HFpEF, possibly opening up novel treatment options.

Resistance to Antibiotics and Antifungal Medicinal Products: Can Complementary and Alternative Medicine Help Solve the Problem in Common Infection Diseases? The Introduction of a Dutch Research Consortium

The increase of antibiotic resistance worldwide, rising numbers of deaths and costs associated with this, and the fact that hardly any new antimicrobial drugs have been developed during the last decade have increased the interest in Complementary and Alternative Medicine (CAM) therapeutic interventions, if proven safe and effective. Observational studies on clinical CAM practices demonstrate positive effects of treatment of infections with CAM therapies (clinical effects, patient satisfaction) in combination with small percentages of antibiotics prescription. However, Cochrane reviews and other studies demonstrate that in most instances the quality of clinical trials on CAM treatment of infections is currently too low to provide sufficient evidence. Therefore a Dutch consortium on (in vitro and clinical) scientific research on CAM and antibiotic resistance has been formed. The aim and objective of the consortium is to establish an enduring partnership and to develop expertise to further develop and investigate safe and effective CAM treatments for infectious diseases of humans (and animals). A first ongoing project on the development of safe and effective biobased CAM antimycotics in women with (recurrent) vaginal candidiasis infection is introduced.

A systemic framework for the progress test: Strengths, constraints and issues: AMEE Guide No. 71

There has been increasing use and significance of progress testing in medical education. It is used in many ways and with several formats to reflect the variety of curricula and assessment purposes. These developments have occurred alongside a recognised sensitivity for error variance inherent in multiple choice tests from which challenges to its validity and reliability have arisen. This Guide presents a generic, systemic framework to help identify and explore improvements in the quality and defensibility of progress test data. The framework draws on the combined experience of the Dutch consortium, an individual medical school in the United Kingdom, and the bulk of the progress test literature to date. It embeds progress testing as a quality-controlled assessment tool for improving learning, teaching and the demonstration of educational standards. The paper describes strengths, highlights constraints and explores issues for improvement. These may assist in the establishment of potential or new progress testing in medical education programmes. They can also guide the evaluation and improvement of existing programmes.

Annotation as a new paradigm in research archiving: Two case studies: Republic of letters ‐ hebrew text database

AbstractWe outline a paradigm to preserve results of digital scholarship, whether they are query results, feature values, or topic assignments. This paradigm is characterized by using annotations as multifunctional carriers and making them portable. The testing grounds we have chosen are two significant enterprises, one in the history of science, and one in Hebrew scholarship.The first one (CKCC) focuses on the results of a project where a Dutch consortium of universities, research institutes, and cultural heritage institutions experimented for 4 years with language techniques and topic modeling methods with the aim to analyze the emergence of scholarly debates. The data: a complex set of about 20.000 letters.The second one (DTHB) is a multi‐year effort to express the linguistic features of the Hebrew bible in a text database, which is still growing in detail and sophistication. Versions of this database are packaged in commercial bible study software.We state that the results of these forms of scholarship require new knowledge management and archive practices. Only when researchers can build efficiently on each other's (intermediate) results, they can achieve the aggregations of quality data by which new questions can be answered, and hidden patterns visualized. Archives are required to find a balance between preserving authoritative versions of sources and supporting collaborative efforts in digital scholarship. Annotations are promising vehicles for preserving and reusing research results.

507: Intraamniotic inflammatory response to bacteria in preterm prelabor rupture of membranes pregnancies: analysis of multiple amniotic fluid proteins

507 Intraamniotic inflammatory response to bacteria in preterm prelabor rupture of membranes pregnancies: analysis of multiple amniotic fluid proteins Marian Kacerovsky, Kristin Skogstrand, David Hougaard, Ali Khatibi, Bo Jacobsson University Hospital Hradec Kralove, Department of Obstetrics and Gynecology, Hradec Kralove, Czech Republic, Statens Serum Institut, 3Department of Clinical Biochemistry and Immunology, Copenhagen, Denmark, Statens Serum Institut, Department of Clinical Biochemistry and Immunology, Copenhagen, Denmark, Sahlgrenska University Hospital, Department of Obstetrics and Gynecology, Goteborg, Sweden, Sahlgrenska University Hospital, Department of Obstetrics and Gynecology, Gothenburg, Sweden OBJECTIVE: To analyze whether intraamniotic inflammatory response to bacteria is dependent on gestational age in preterm prelabor rupture membrane (PPROM) pregnancies with using a panel specific proteins. To determine whether is the difference in intraamniotic inflammatory response to genital mycoplasmas and other bacteria. STUDY DESIGN: A prospective follow-up study was performed and 115 women with singleton pregnancies complicated by preterm prelabor rupture of membranes at gestational age between 24 0 and 36 6 weeks were recruited. Amniotic fluid retrieved by transabdominal amniocentesis was analyzed with polymerase chain reaction for genital mycoplasmas, and cultured for aerobic and anaerobic bacteria. The concentrations of 26 proteins in the amniotic fluid were determined simultaneously using multiplex technology. RESULTS: The presence of bacteria in amniotic fluid was found in 43% (49/115) women. The women were stratified into three subgroups according to gestational age. The differences of amniotic fluid proteins between cohorts with and without bacteria were found in the groups with gestational age 24 0 32 0 weeks and 32 1 34 0 for six specific proteins (interleukin 6, 8, 10, granulocyte macrophage colony stimulating factor, monocyte chemotactic protein-1, and macrophage inflammatory protein-1 ) and two proteins (adiponectin, leptin), respectively. No differences were found between women with the presence of genital mycoplasmas and other bacteria in amniotic fluid. CONCLUSION: The intraamniotic inflammatory response to bacteria in amniotic fluid is dependent on gestational age. There is no difference in the intensity of intraamniotic inflammatory response to genital mycoplasmas and the other bacteria. 508 Working conditions and preterm birth in multiple pregnancies Marjo van Melick Dutch Consortium for Studies in Women’s Health and Reproductivity, Department of Obstetrics & Gynaecology, Maastricht, Netherlands OBJECTIVE: Multiple pregnancies are at high risk for preterm birth. Unfortunately, strategies for preventing preterm birth have been largely unsuccessful. Specific physical activities or working conditions are suspected for having an increased effect on preterm birth. The aim of this study was to perform an explorative analysis of the effect of specific work strain in the first 20 weeks of pregnancy on the occurrence of preterm birth in multiple pregnancies before 34 weeks of gestation. STUDY DESIGN: A prospective cohort study was conducted in the Netherlands alongside the multicentre randomized controlled trial ‘Pessaries in multiple pregnancies as a prevention of preterm birth (ProTWIN trial)’. Participants in the ProTWIN trial received questionnaires concerning their working conditions and physical work strain. From these questionnaires specific working conditions of women in the first 20 weeks of pregnancy could be assessed. We assessed whether these conditions were associated with preterm birth before 34 weeks of gestation. RESULTS: Of the 81 participants, 70 (86%) had a paid employment with a mean of 31 working hours per week (range 8-48 hours). The average gestational age at birth in women with and without paid employment was 34 weeks (p 0.79). There were 21 women that delivered before 34 weeks, 17 (81%) of them had a paid employment. Work containing repetitive movements was associated with preterm birth (OR 3.0, 95% CI 1.3 to 6.6). Walking, standing, sitting down, bending over and reaching as well as strenuous work, the need for physical power and an uncomfortable posture were not associated with preterm birth. CONCLUSION: Women with multiple pregnancies and paid employment with heavy physical work strain appear not to be more at risk for preterm birth before 34 weeks of gestation. However, work containing repetitive movements is associated with preterm birth in multiple pregnancies.

505: Prediction of preterm birth in triplet pregnancy

Lidewij van de Mheen, Anita Ravelli, Maria van Pampus, Christianne de Groot, Eva Pajkrt, Ben Willem Mol Onze Lieve Vrouwe Gasthuis Amsterdam, Obestetrics and Gynaecology, Amterdam, Netherlands, Academic Medical Center, Medical Informatics, Amsterdam, Netherlands, Onze Lieve Vrouwe Gasthuis, Obestetrics and Gynaecology, Amsterdam, Netherlands, VU Medical Centre, Obstetrics and Gynaecology, Amsterdam, Netherlands, Academic Medical Center, Department of Obstetrics and Gynaecology, Amsterdam, Netherlands, Dutch consortium AMPHIA trial, ., ., Netherlands OBJECTIVE: Some clinicians advise prophylactic administration of antenatal steroids for fetal lung ripening in women with a triplet pregnancy, irrespective of the development of signs and symptoms that announce preterm delivery. The aim of this study was to assess the natural course of triplet pregnancies by calculating the risk of delivery in a particular time frame during gestation. STUDY DESIGN: We collected data on all triplet pregnancies in the Netherlands from 1999-2007 from the Dutch Perinatal Registration (PRN). From these data, we constructed a Kaplan Meier curve for time to delivery, and calculated the risk of delivery within two weeks for different gestational ages. RESULTS: Between 1999 and 2007, there were 575 triplet pregnancies in the Netherlands, of which 367 after artificial reproductive techniques and 208 after spontaneous conception. The mean gestational age at delivery was 32.8 weeks (SD 3.8 weeks) (figure 1), Artificially conceived triplets were on average 0.4 weeks longer pregnant (data not shown). There were 22 pregnancies (4%) that ended before 24 weeks. At a gestational age of 24 weeks, the change to deliver within the next two weeks was 2%. For 26, 28, 30 and 32 weeks these risks were 5%, 6%,13% and 31%, respectively (table 1). The probability to continue the pregnancy until a gestational age of 37 weeks was approximately 7%. CONCLUSION: Mean gestational age for triplet pregnancies in The Netherlands was 32.8 weeks. Before 32 weeks of gestation, prophylactic administration of steroids is not indicated. At a gestational age of 32 weeks, prophylactic antenatal corticosteroids could be considered in a triplet pregnancy. 506 Midtrimester Vitamin D status is not associated with spontaneous preterm birth prior to 35 weeks Luisa Wetta, Joseph Biggio, Suzanne Cliver, Adi Abramovici, Stephen Barnes, Alan Tita University of Alabama at Birmingham, Obstetrics & Gynecology, Birmingham, AL, University of Alabama at Birmingham, Department of Pharmacology and Toxicology, Birmingham, AL OBJECTIVE: Preterm birth (PTB) has been associated with deficient maternal vitamin D status in some studies. Measurement methodologies, patient populations, and seasonal variation may all affect results. We evaluated whether midtrimester serum vitamin D levels are associated with spontaneous(S) PTB prior to 35 weeks gestation. STUDY DESIGN: We conducted a nested case-control study of 100 women with SPTB prior to 35 weeks gestation (cases) and 200 healthy women who delivered at 39-40 weeks (controls). Stored remnant serum specimens from a midtrimester sample drawn between 15-21 weeks gestation for multiple marker screening were tested for total 25-hydroxy vitamin D levels (25-OH D) using a validated liquid chromatography-tandem mass spectrometry method considered the gold standard for 25-OH D quantitation. We compared mean 25-OH D levels as well as prevalence of vitamin D insufficiency (25-OH D level 30 ng/mL) and vitamin D deficiency (25-OH D 15 ng/mL). Logistic regression was used for multivariable adjustments. RESULTS: A total of 90 SPTB cases and 177 controls had remnant specimens with valid measurements. Data are provided in the Table. African Americans were more likely to be vitamin D deficient than other races (24.5% versus 3.7%, p 0.0001) as were women with specimens drawn between Oct and Apr (20.9% versus 9.2%, p 0.011). Mean midtrimester 25-OH D levels were similar between cases and controls. After adjusting for age, race, parity, weight, and season of specimen collection, neither vitamin D insufficiency (Adjusted OR: 0.8; 0.4-1.4) www.AJOG.org Doppler Assessment, Fetus, Prematurity Poster Session III

630: Comparing international guidelines on hypertensive disorders in pregnancy

630 Comparing international guidelines on hypertensive disorders in pregnancy Melanie Wiegerinck, Sigrid Huigen, Teus van Barneveld, Ben Willem Mol, Hans Duvekot Academic Medical Centre, Obstetrics and Gynaecology, Amsterdam, Netherlands, Erasmus Medical Center, Obstetrics and Gynaecology, Rotterdam, Netherlands, Netherlands Association of Medical specialists, Department of guideline development, Utrecht, Netherlands, Dutch consortium AMPHIA trial, Netherlands, Erasmus Medical Center, Department of Obstetrics and Gynaecology, Rotterdam, Netherlands OBJECTIVE: To compare international guidelines on Hypertensive disorders in pregnancy in order to assess the quality of guideline development in this field. STUDY DESIGN: We contacted the official Obstetric Societies of all European countries, the US, Canada and Australia, regarding the availability of a guideline on Hypertensive disorders in pregnancy. All retrieved guidelines were systematically reviewed on 7 topics that were identified as important by professionals: definitions of hypertensive disorders, methods for assessing proteinuria, top 3 antihypertensive agents, criteria for starting treatment (antihypertensive, anticonvulsive, termination of pregnancy), and target blood pressure after delivery. In addition, the methodologic quality of the guidelines was assessed using the Appraisal of Guidelines for Research & Evaluation (AGREE-II) Instrument. RESULTS: We approached professional societies in 41 European countries, and obtained guidelines from the US, Canada, and Australia (figure 1). Since 21 European countries did not reply and 4 had no guidelines, we analyzed a total of 19 guidelines. Nearly all countries had developed these guidelines themselves, and 17 dated from the last 4 years. Even though most guidelines refer to the same references, only 6 (32%) use the exact same definition for hypertension. All guidelines use the same cut-off values for proteinuria (0.3g/24 hours), but the accepted methods for assessing proteinuria differ (3 quantative 24 hour measure, 1 automated dipstick, 5 also accept protein/kreatinin ratio and visual dipstick, and in 10 it was not stated). Five guidelines agreed on initiation of antihypertensive treatment when the bloodpressure exceeds 160/110 mmHg, whereas 14 used other criteria. The remaining topics were comparable among the included guidelines. Methodological rigour and transparency of the guidelines also differed significantly. CONCLUSION: We found a wide variation in used definitions, clinical recommendations and methodology. This study emphasizes the need for international collaboration in the field of guideline development. 631 The impact of postpartum hemorrhage drill training at a single institution Noel Strong, Angela Bianco, Joanne Stone, Pozharny Zhenya, Luca Lambertini Mount Sinai Medical Center, Maternal Fetal Medicine, New York, NY, Mount Sinai School of Medicine, Maternal Fetal Medicine, New York, NY, North Shore-Long Island Jewish Health System, Maternal Fetal Medince, Manhasset, NY, Mount Sinai School of Medicine, Department of Preventive Medicine, New York, NY OBJECTIVE: To evaluate the impact of standardized postpartum hemorrhage drill training. STUDY DESIGN: In June of 2009 our institution mandated that all obstetrical providers participate in standardized postpartum hemorrhage training drills. The purpose of these drills was to improve recognition and management of post partum hemorrhage (PPH). Each drill consisted of a didactic session which emphasized accurate estimation of blood loss, early intervention, use of misoprostol as a first line agent and increased use of the Bakri Balloon and B-lynch suture. Each didactic session was followed by a simulated postpartum hemorrhage utilizing a female anthropomorphic robotic simulator. A retrospective chart review was preformed comparing all cases of PPH identified by the Labor & Delivery Quality Assurance Committee in the year preceding this mandate to all cases of PPH identified by the same committee in the year following this mandate. RESULTS: 160 patients with PPH were identified over the 2 year study period: 57 cases in the year preceding the PPH drills and 103 cases in the year following the PPH drills. The demographics of these two groups did not differ statistically, nor did their labor courses or etiologies of hemorrhage. In the first six months following the PPH training drills a trend toward increased use of misoprostol (26 %v 33% p 0.069) and Bakri Balloon (7% v 17% p 0.087) was noted. Although the rate of c-hysterectomy appeared to be reduced during this time period no trend toward significance was seen (19% v 8% p 0.220). At 6-12 months following the mandated drills these findings were no longer seen. No significant differences were noted in mean estimated blood loss, change in hemoglobin or rate of transfusion between any of the studied time periods. CONCLUSION: Training appears to improve recognition and reporting of PPH. While no statistically significant changes were noted, a trend towards increased use of misoprostol and Bakri Balloon was initially seen following the PPH training drills. This trend dissipated after 6 months. These findings seem to support a need for re-education.