Lost in translation: a narrative review and synthesis of the published international literature on mental health research and translation priorities (2011-2023).

BACKGROUND: Priority setting in mental health research is arguably lost in translation. Decades of effort has led to persistent repetition in what the research priorities of people with lived-experience of mental ill-health are. AIM: This was a narrative review and synthesis of published literature reporting mental health research priorities (2011-2023). METHODS: A narrative framework was established with the questions: (1) who has been involved in priority setting? With whom have priorities been set? Which priorities have been established and for whom? What progress has been made? And, whose priorities are being progressed? RESULTS: Seven papers were identified. Two were Australian, one Welsh, one English, one was from Chile and another Brazilian and one reported on a European exercise across 28 countries (ROAMER). Hundreds of priorities were listed in all exercises. Prioritisation mostly occured from survey rankings and/or workshops (using dots, or post-it note voting). Most were dominated by clinicians, academics and government rather than people with lived-experience of mental ill-health and carer, family and kinship group members. CONCLUSION: One lived-experience research led survey was identified. Few studies reported lived-experience design and development involvement. Five of the seven papers reported responses, but no further progress on priorities being met was reported.

This review followed PRISMA guidance for search strategy development and systematic review and reporting. This was not a systematic review with or without meta-analysis and the method did not fit for registration with PROSPERO.

Integrative genomics reveals pathogenic mediator of valproate-induced neurodevelopmental disability.

Prenatal exposure to the anti-seizure medication sodium valproate (VPA) is associated with an increased risk of adverse postnatal neurodevelopmental outcomes, including lowered intellectual ability, autism spectrum disorder and attention-deficit hyperactivity disorder. In this study, we aimed to clarify the molecular mechanisms underpinning the neurodevelopmental consequences of gestational VPA exposure using integrative genomics. We assessed the effect of gestational VPA on foetal brain gene expression using a validated rat model of valproate teratogenicity that mimics the human scenario of chronic oral valproate treatment during pregnancy at doses that are therapeutically relevant to the treatment of epilepsy. Two different rat strains were studied-inbred Genetic Absence Epilepsy Rats from Strasbourg, a model of genetic generalized epilepsy, and inbred non-epileptic control rats. Female rats were fed standard chow or VPA mixed in standard chow for 2 weeks prior to conception and then mated with same-strain males. In the VPA-exposed rats maternal oral treatment was continued throughout pregnancy. Foetuses were extracted via C-section on gestational Day 21 (1 day prior to birth) and foetal brains were snap-frozen and genome-wide gene expression data generated. We found that gestational VPA exposure via chronic maternal oral dosing was associated with substantial drug-induced differential gene expression in the pup brains, including dysregulated splicing, and observed that this occurred in the absence of evidence for significant neuronal gain or loss. The functional consequences of VPA-induced gene expression were explored using pathway analysis and integration with genetic risk data for psychiatric disease and behavioural traits. The set of genes downregulated by VPA in the pup brains were significantly enriched for pathways related to neurodevelopment and synaptic function and significantly enriched for heritability to human intelligence, schizophrenia and bipolar disorder. Our results provide a mechanistic link between chronic foetal VPA exposure and neurodevelopmental disability mediated by VPA-induced transcriptional dysregulation.

Interventions to reduce falls in hospitals: a systematic review and meta-analysis.

BACKGROUND: Falls remain a common and debilitating problem in hospitals worldwide. The aim of this study was to investigate the effects of falls prevention interventions on falls rates and the risk of falling in hospital. DESIGN: Systematic review and meta-analysis. PARTICIPANTS: Hospitalised adults. INTERVENTION: Prevention methods included staff and patient education, environmental modifications, assistive devices, policies and systems, rehabilitation, medication management and management of cognitive impairment. We evaluated single and multi-factorial approaches. OUTCOME MEASURES: Falls rate ratios (rate ratio: RaR) and falls risk, as defined by the odds of being a faller in the intervention compared to control group (odds ratio: OR). RESULTS: There were 43 studies that satisfied the systematic review criteria and 23 were included in meta-analyses. There was marked heterogeneity in intervention methods and study designs. The only intervention that yielded a significant result in the meta-analysis was education, with a reduction in falls rates (RaR = 0.70 [0.51-0.96], P = 0.03) and the odds of falling (OR = 0.62 [0.47-0.83], P = 0.001). The patient and staff education studies in the meta-analysis were of high quality on the GRADE tool. Individual trials in the systematic review showed evidence for clinician education, some multi-factorial interventions, select rehabilitation therapies, and systems, with low to moderate risk of bias. CONCLUSION: Patient and staff education can reduce hospital falls. Multi-factorial interventions had a tendency towards producing a positive impact. Chair alarms, bed alarms, wearable sensors and use of scored risk assessment tools were not associated with significant fall reductions.

Antiepileptic Drug Teratogenicity and De Novo Genetic Variation Load.

OBJECTIVE: The mechanisms by which antiepileptic drugs (AEDs) cause birth defects (BDs) are unknown. Data suggest that AED-induced BDs may result from a genome-wide increase of de novo variants in the embryo, a mechanism that we investigated. METHODS: Whole exome sequencing data from child-parent trios were interrogated for de novo single-nucleotide variants/indels (dnSNVs/indels) and de novo copy number variants (dnCNVs). Generalized linear models were applied to assess de novo variant burdens in children exposed prenatally to AEDs (AED-exposed children) versus children without BDs not exposed prenatally to AEDs (AED-unexposed unaffected children), and AED-exposed children with BDs versus those without BDs, adjusting for confounders. Fisher exact test was used to compare categorical data. RESULTS: Sixty-seven child-parent trios were included: 10 with AED-exposed children with BDs, 46 with AED-exposed unaffected children, and 11 with AED-unexposed unaffected children. The dnSNV/indel burden did not differ between AED-exposed children and AED-unexposed unaffected children (median dnSNV/indel number/child [range] = 3 [0-7] vs 3 [1-5], p = 0.50). Among AED-exposed children, there were no significant differences between those with BDs and those unaffected. Likely deleterious dnSNVs/indels were detected in 9 of 67 (13%) children, none of whom had BDs. The proportion of cases harboring likely deleterious dnSNVs/indels did not differ significantly between AED-unexposed and AED-exposed children. The dnCNV burden was not associated with AED exposure or birth outcome. INTERPRETATION: Our study indicates that prenatal AED exposure does not increase the burden of de novo variants, and that this mechanism is not a major contributor to AED-induced BDs. These results can be incorporated in routine patient counseling. ANN NEUROL 2020;87:897-906.

Benefits and risks of non-slip socks in hospitals: a rapid review.

BACKGROUND: Non-slip socks are sometimes used in an attempt to prevent falls in hospitals despite limited evidence of benefit. We critique the current literature on their risks, benefits and effects. METHODS: A rapid review was conducted following the Cochrane Rapid Review Methods Group Guidelines. To be included, studies needed to have data on single or multifactorial interventions that used non-slip socks in hospitals or their safety, risks or effects in a laboratory setting. Six electronic databases were searched: Medline, Embase, Cinahl, Cochrane, Allied and Medical Health Database (AMED) and Proquest Central. RESULTS: Fourteen articles met the inclusion criteria. Nine used non-slip socks as an intervention in hospitals. Three assessed their effects in laboratory settings. Two reported risks in relation to bacterial transfer. Most studies that used non-slip socks to prevent hospital falls had negative or equivocal results and were of comparatively low method quality, with a high risk of bias. Two of the laboratory tests reported traction socks to be no safer than walking barefoot and to have similar slip resistance. The laboratory studies had a low risk of bias and showed that bacteria can sometimes be acquired from socks. CONCLUSION: Non-slip socks have the potential to carry an infection control risk that requires careful management. There was no strong or conclusive evidence that they prevent hospital falls.

A rat model of valproate teratogenicity from chronic oral treatment during pregnancy.

OBJECTIVE: Sodium valproate (VPA), the most effective antiepileptic drug for patients with genetic generalized epilepsy (GGE), is a potent human teratogen that increases the risk of a range of congenital malformations, including spina bifida. The mechanisms underlying this teratogenicity are not known, but may involve genetic risk factors. This study aimed to develop an animal model of VPA-induced birth defects. METHODS: We used three different rat strains: inbred Genetic Absence Epilepsy Rats From Strasbourg (GAERS), a model of GGE with absence seizures; inbred Non-Epileptic Controls (NEC); and outbred nonepileptic Wistars. Female rats were fed standard chow or VPA (20 g/kg food) mixed in standard chow for 2 weeks prior to conception, and then mated with same-strain males. Treatment continued throughout pregnancy. Fetuses were extracted via C-section on gestational day 21 and examined for birth defects, including external assessment and spinal measurements. RESULTS: VPA-exposed pups showed significant reductions in weight, length, and whole-body development compared with controls of all three strains (P < .0001). Gestational VPA treatment altered intravertebral distances, and resulted in underdeveloped vertebral arches between thoracic region T11 and caudal region C2 in most pups (GAERS, 100%; NEC, 95%; Wistar, 80%), more frequently than in controls (9%, 13%, 19%). SIGNIFICANCE: Gestational VPA treatment results in similar developmental and morphological abnormalities in three rat strains, including one with GGE, indicating that the genetic underpinnings of epilepsy do not contribute markedly to VPA-induced birth defects. This model may be used in future studies to investigate mechanisms involved in the pathogenesis of antiepileptic drug-induced birth defects.

Hospital falls prevention with patient education: a scoping review.

BACKGROUND: Hospital falls remain a frequent and debilitating problem worldwide. Most hospital falls prevention strategies have targeted clinician education, environmental modifications, assistive devices, hospital systems and medication reviews. The role that patients can play in preventing falls whilst in hospital has received less attention. This critical review scopes patient falls education interventions for hospitals. The quality of the educational designs under-pinning patient falls education programmes was also evaluated. The outcomes of patient-centred falls prevention programs were considered for a range of hospital settings and diagnoses. METHODS: The Arksey and O'Malley (2005) framework for scoping reviews was adapted using Joanna Briggs Institute and PRISMA-ScR guidelines. Eight databases, including grey literature, were searched from January 2008 until February 2020. Two reviewers independently screened the articles and data were extracted and summarised thematically. The quality of falls prevention education programs for patients was also appraised using a modified quality metric tool. RESULTS: Forty-three articles were included in the final analysis. The interventions included: (i) direct face-to-face patient education about falls risks and mitigation; (ii) educational tools; (iii) patient-focussed consumer materials such as pamphlets, brochures and handouts; and (iv) hospital systems, policies and procedures to assist patients to prevent falls. The included studies assessed falls or education related outcomes before and after patient falls prevention education. Few studies reported incorporating education design principles or educational theories. When reported, most educational programs were of low to moderate quality from an educational design perspective. CONCLUSIONS: There is emerging evidence that hospital falls prevention interventions that incorporate patient education can reduce falls and associated injuries such as bruising, lacerations or fractures. The design, mode of delivery and quality of educational design influence outcomes. Well-designed education programs can improve knowledge and self-perception of risk, empowering patients to reduce their risk of falling whilst in hospital.

A functional correlate of severity in alternating hemiplegia of childhood.

OBJECTIVE: Mutations in ATP1A3, the gene that encodes the α3 subunit of the Na(+)/K(+) ATPase, are the primary cause of alternating hemiplegia of childhood (AHC). Correlations between different mutations and AHC severity were recently reported, with E815K identified in severe and D801N and G947R in milder cases. This study aims to explore the molecular pathological mechanisms in AHC and to identify functional correlates for mutations associated with different levels of disease severity. METHODS: Human wild type ATP1A3, and E815K, D801N and G947R mutants were expressed in Xenopus laevis oocytes and Na(+)/K(+) ATPase function measured. Structural homology models of the human α3 subunit containing AHC mutations were created. RESULTS: The AHC mutations examined all showed similar levels of reduction in forward cycling. Wild type forward cycling was reduced by coexpression with any mutant, indicating dominant negative interactions. Proton transport was measured and found to be selectively impaired only in E815K. Homology modeling showed that D801 and G947 lie within or near known cation binding sites while E815 is more distal. Despite its effect on proton transport, E815K was also distant from the proposed proton transport route. INTERPRETATION: Loss of forward cycling and dominant negativity are common and likely necessary pathomechanisms for AHC. In addition, loss of proton transport correlated with severity of AHC. D801N and G947R are likely to directly disrupt normal Na(+)/K(+) binding while E815K may disrupt forward cycling and proton transport via allosteric mechanisms yet to be elucidated.

Implementation of Virtual Communities of Practice in Healthcare to Improve Capability and Capacity: A 10-Year Scoping Review.

Virtual communities of practice consist of individuals who use a common online platform to share professional expertise and experiences. In healthcare settings a virtual community of practice (VCoP) can optimise knowledge, skills, and the implementation of evidence-based practice. To ensure effective knowledge synthesis and translation into practice, it is essential to clarify the best methods for designing and implementing VCoPs within healthcare organisations. This scoping review aimed to identify the methods used to establish and facilitate online or digitally enabled communities of practice within healthcare organisations across the globe. Six online databases identified papers published from January 2010 to October 2020. Papers were independently screened by two reviewers using Covidence. Data were captured and analysed using a data extraction chart in Covidence. Twenty-four publications that detail methods for establishing a VCoP in healthcare were included. Few studies used a framework to establish a VCoP. It was difficult to identify details regarding methods of development and key elements such as roles, how they were coordinated, and types of technology used. Healthcare organisations can benefit from using a standardised framework for the establishment, implementation and evaluation of VCoPs to improve practice, staff engagement, and knowledge sharing.

Implementing Patient Falls Education in Hospitals: A Mixed-Methods Trial.

Patient education is key to preventing hospital falls yet is inconsistently implemented by health professionals. A mixed methods study was conducted involving a ward-based evaluation of patients receiving education from health professionals using a scripted conversation guide with a falls prevention brochure, followed by semi-structured qualitative interviews with a purposive sample of health professionals involved in delivering the intervention. Over five weeks, 37 patients consented to surveys (intervention n = 27; control n = 10). The quantitative evaluation showed that falls prevention education was not systematically implemented in the trial ward. Seven individual interviews were conducted with health professionals to understand the reasons why implementation failed. Perceived barriers included time constraints, limited interprofessional collaboration, and a lack of staff input into designing the research project and patient interventions. Perceived enablers included support from senior staff, consistent reinforcement of falls education by health professionals, and fostering patient empowerment and engagement. Recommended strategies to enhance implementation included ensuring processes were in place supporting health professional accountability, the inclusion of stakeholder input in designing the falls intervention and implementation processes, as well as leadership engagement in falls prevention education. Although health professionals play a key role in delivering evidence-based falls prevention education in hospitals, implementation can be compromised by staff capacity, capability, and opportunities for co-design with patients and researchers. Organisational buy-in to practice change facilitates the implementation of evidence-based falls prevention activities.

Healthcare professional perspectives on barriers and enablers to falls prevention education: A qualitative study.

In hospitals, patient falls prevention education is frequently delivered by nurses and allied health professionals. Hospital falls rates remain high globally, despite the many systems and approaches that attempt to mitigate falling. The aim of this study was to investigate health professional views on the enablers and barriers to providing patient falls education in hospitals. Four focus groups with 23 nursing and allied health professionals were conducted at 3 hospitals. Three researchers independently coded the data and findings were analysed thematically with a descriptive qualitative approach to identify and develop themes according to barriers and enablers. Barriers included (i) limited interprofessional communication about patient falls; (ii) sub-optimal systems for falls education for patients and health professionals, and (iii) perceived patient-related barriers to falls education. Enablers to providing patient falls education included: (i) implementing strategies to increase patient empowerment; (ii) ensuring that health professionals had access to effective modes of patient education; and (iii) facilitating interprofessional collaboration. Health professionals identified the need to overcome organisational, patient and clinician-related barriers to falls education. Fostering collective responsibility amongst health professionals for evidence-based falls prevention was also highlighted.

Virtual communities of practice to improve clinical outcomes in healthcare: protocol for a 10-year scoping review.

INTRODUCTION: Virtual communities of practice (VCoPs) use a common online platform to provide healthcare professionals with the opportunity to access highly specialised knowledge, build a professional support network and promote the translation of research evidence into practice. There is limited reporting of how best to design and administer VCoPs within healthcare organisations. The primary aim of this scoping review is to identify the best methods used to establish and maintain VCoPs. Findings shall be used to develop a flexible framework to guide the establishment and facilitation of a VCoP for healthcare professionals to ensure the translation of falls prevention clinical guidelines into practice. METHODS AND ANALYSIS: A five-stage scoping review process will be followed based on Arksey and O'Malley's framework and refined by the Joanna Briggs Institute Methodology. An initial limited search of PubMed and Cumulative Index to Nursing and Allied Health Literature will identify relevant studies and assist with search term development. This will be followed by a search of five online databases to identify papers published from January 2010 until November 2020. Papers will be independently screened by two reviewers, and data extracted and analysed using a reporting framework. Qualitative data will be analysed thematically and numerical synthesis of the data will be conducted. RESULTS AND DISSEMINATION: The results of this scoping review will highlight the best ways to design and manage VCoPs in healthcare organisations. The findings will be presented at relevant stakeholder workshops, conferences and published in peer-reviewed journals.

Dance Is an Accessible Physical Activity for People with Parkinson's Disease.

OBJECTIVE: To evaluate the outcomes of face-to-face, digital, and virtual modes of dancing for people living with Parkinson's disease (PD). DESIGN: Systematic review informed by Cochrane and PRIMSA guidelines. Data Sources. Seven electronic databases were searched: AMED, Cochrane, PEDro, CINHAL, PsycINFO, EMBASE, and MEDLINE. METHODS: Eligible studies were randomised controlled trials (RCT) and other trials with quantitative data. The PEDro scale evaluated risk of bias for RCTs. Joanna Briggs Institute instruments were used to critically appraise non-RCTs. The primary outcome was the feasibility of dance interventions, and the secondary outcomes included gait, balance, quality of life, and disability. RESULTS: The search yielded 8,327 articles after duplicates were removed and 38 met the inclusion criteria. Seven were at high risk of bias, 20 had moderate risk of bias, and 11 had low risk of bias. There was moderately strong evidence that dance therapy was beneficial for balance, gait, quality of life, and disability. There was good adherence to digital delivery of dance interventions and, for people with PD, online dance was easy to access. CONCLUSION: Dancing is an accessible form of exercise that can benefit mobility and quality of life in people with PD. The COVID-19 pandemic and this review have drawn attention to the benefits of access to digital modes of physical activity for people living with chronic neurological conditions.

Patient Perspectives on Hospital Falls Prevention Education.

Hospital falls remain an intractable problem worldwide and patient education is one approach to falls mitigation. Although educating patients can help their understanding of risks and empower them with prevention strategies, patient experiences of hospital falls education are poorly understood. This study aimed to understand the perspectives and preferences of hospitalized patients about falls prevention education. Three focus groups were conducted in Australian hospitals. A phenomenological approach was used to explore patient perspectives and data were analyzed thematically. The focus groups revealed that most people did not realize their own risk of falling whilst an inpatient. Experiences of falls prevention education were inconsistent and sometimes linked to beliefs that falls were not relevant to them because they were being cared for in hospital. Other barriers to falls mitigation included poor patient knowledge about hospital falls risk and inconsistencies in the delivery of falls prevention education. A strong theme was that individualized, consistent education, and small interactive groups were helpful.

Divesting from a Scored Hospital Fall Risk Assessment Tool (FRAT): A Cluster Randomized Non-Inferiority Trial.

BACKGROUND/OBJECTIVES: We investigated the impact of ceasing routine falls risk assessment tool (FRAT) completion and instead used clinical reasoning to select fall mitigation strategies. DESIGN: Two-group, multi-site cluster-randomized active-control non-inferiority trial. SETTING: Hospital wards. PARTICIPANTS: Adult inpatients admitted to participating hospitals (n = 10 hospitals, 123,176 bed days). INTERVENTION: Hospitals were randomly assigned (1:1) to a usual care control group that continued to use a historical FRAT to assign falls risk scores and accompanying mitigation strategies, or an experimental group whereby clinicians did not assign risk scores and instead used clinical reasoning to select fall mitigation strategies using a decision support list. MEASUREMENTS: The primary measure was between-group difference in mean fall rates (falls/1000 bed days). Falls were identified from incident reports supplemented by hand searches of medical records over three consecutive months at each hospital. The incidence rate ratio (IRR) of monthly falls rates in control versus experimental hospitals was also estimated. RESULTS: The experimental clinical reasoning approach was non-inferior to the usual care FRAT that assigned fall risk ratings when compared to a-priori stakeholder derived and sensitivity non-inferiority margins. The mean fall rates were 3.84 falls/1000 bed days for the FRAT continuing sites and 3.11 falls/1000 bed days for experimental sites. After adjusting for historical fall rates at each hospital, the IRR (95%CI) was 0.78 (0.64, 0.95), where IRR < 1.00 indicated fewer falls among the experimental group. There were 4 and 3 serious events in the control and experimental groups, respectively. CONCLUSION: Replacing a FRAT scoring system with clinical reasoning did not lead to inferior fall outcomes in the short term and may even reduce fall incidence.

Educating hospital patients to prevent falls: protocol for a scoping review.

INTRODUCTION: Falls prevention in hospitals is an ongoing challenge worldwide. Despite a wide variety of recommended falls mitigation strategies, few have strong evidence for effectiveness in reducing falls and accompanying injuries. Patient education programmes that promote engagement and enable people to understand their heightened falls risk while hospitalised are one approach. The aim of this scoping review is to examine the content, design and outcomes of patient education approaches to hospital falls prevention. As well as critiquing the role of patient education in hospital falls prevention, strategies that can be used in clinical practice shall be recommended. METHODS AND ANALYSIS: The analysis will apply the methodological framework developed by Arksey and O'Malley and refined by the Joanna Briggs Institute. An initial limited search of Cumulative Index to Nursing and Allied Health Literature (CINAHL) and PubMed will be completed to identify keywords and index terms. A developed search strategy of Medical Subject Headings and text words will be conducted of PubMed, CINAHL, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database, PsychINFO, Education Resources Information Center and grey literature databases from January 2008 to current. The reference lists of included articles will be hand searched for additional studies. Two reviewers will screen the titles and abstracts independently and analyse the full text of potential articles based on the inclusion and exclusion criteria. The data will be extracted using a structured data form. Thematic analysis and numerical synthesis of the data will be conducted, and key themes will be identified. ETHICS AND DISSEMINATION: Results of this scoping review will illuminate the designs and outcomes of patient education research for hospital falls prevention in the current literature. It is anticipated that the findings will highlight best-practice educational design to inform the development of future patient-focused education for falls prevention. Study findings will be presented at relevant conferences and public forums, and published in peer-reviewed journals. Ethics approval is not required.

Boxing for Parkinson's Disease: Has Implementation Accelerated Beyond Current Evidence?

Background: Exercise and physical activity are argued to promote neural plasticity in Parkinson's disease (PD), with potential to slow disease progression. Boxing for PD is rapidly growing in popularity. Objectives: (i) To evaluate evidence on benefits and risks of boxing exercises for people living with PD and (ii) to appraise websites for evidence of global implementation of this intervention. Data Sources: We searched AMED, CINAHL, Cochrane, EMBASE, EMCARE, Health and Medical Collection via ProQuest, MEDLINE, and PEDro electronic databases for the research literature. Websites were also searched for evidence of successful implementation of boxing for PD. Study Selection: Published research and websites were considered if they reported data on adults with PD and boxing as an intervention. Data Extraction: For the literature review, two reviewers independently extracted data on study characteristics and intervention content. Risk of bias was assessed with the PEDro scale and Joanna Briggs Checklist. We conducted a quality appraisal of websites using the QUality Evaluation Scoring Tool (QUEST). Data Synthesis: Two studies, with a total of 37 participants, met the review eligibility criteria for the literature review. Risk of bias was low in these trials. Balance confidence, mobility, and quality of life were reported to improve with community-based boxing training programs delivered in 24-36 sessions over 12 weeks. PD medications were not always documented and some elements of the boxing interventions were incompletely reported against the CERT (Consensus on Exercise Reporting Template). Nine websites advocating boxing programs for PD were also evaluated. The QUEST analysis showed low-level quality, and little scientific evidence verifying findings, despite positive reports. Limitations: In the published literature, findings were limited due to the small number of included studies and participants. Websites were numerous yet often lacked verifiable data. Conclusions: Despite the recent growth in the popularity of boxing for PD and some positive findings, there is limited evidence of efficacy. Risks and disease-specific modifications have not been reported. Safety guidelines and health professional training are key considerations for implementation.

Outcomes of pregnancies in women taking antiepileptic drugs for non-epilepsy indications.

PURPOSE: Antiepileptic drugs (AEDs), particularly valproate (VPA), are known to be teratogens when taken by women with epilepsy (WWE), but the risk in women who take these drugs for indications other than epilepsy have been little studied. This study aims to investigate the incidence of birth defects in children born to mothers taking AEDs for non-epilepsy indications. METHODS: The Australian Pregnancy Register (APR), established in 1998, is a prospective observational study operating with ethical approval and informed written consent for participation. Of the 2066 pregnancies enrolled in the Register, 98% are WWE and the remainder received AEDs for other indications. Data from this Register was analysed to study the rates of congenital malformations (CM) in infants exposed to AEDs in utero in WWE compared to those women taking AEDs for other indications. RESULTS: The malformation rates in pregnancies of WWE taking AEDs (5%), is higher than the rates of infants born to untreated WWE (2%). There were 32 pregnancies enrolled from 29 mothers taking AEDs for indications other than epilepsy (2 women/2 pregnancies were lost to follow up). Out of 30 pregnancies, 9 of which were exposed to VPA, 1 resulted in a child with a malformation (3%) (cleft palate) on 1700 mg/day of valproate. CONCLUSIONS: This is the first attempt to assess the use of AEDs in a prospective study of women who are pregnant but do not have active epilepsy. Although underpowered, this study suggests that women taking AEDs for non-epilepsy indications have a similar risk of having a child with a CM as compared with women taking AEDs for epilepsy. Larger numbers are required to investigate the risk of AED-associated malformations in this important group.