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Objectives To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the second wave of the COVID-19 pandemic in England, and describe the impact of corticosteroids on outcomes. Methods Hospital Episode Statistics data were used to identify people alive on 1 August 2020 with ICD-10 codes for RAIRD from the whole population of England. Linked national health records were used to calculate rates and rate ratios of COVID-19 infection and death up to 30 April 2021. Primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. NHS Digital and Office for National Statistics general population data were used for comparison. The association between 30-day corticosteroid usage and COVID-19-related death, COVID-19-related hospital admissions and all-cause deaths was also described. Results Of 168 330 people with RAIRD, 9961 (5.92%) had a positive COVID-19 PCR test. The age-standardized infection rate ratio between RAIRD and the general population was 0.99 (95% CI: 0.97, 1.00). 1342 (0.80%) people with RAIRD died with COVID-19 on their death certificate and the age–sex-standardized mortality rate for COVID-19-related death was 2.76 (95% CI: 2.63, 2.89) times higher than in the general population. There was a dose-dependent relationship between 30-day corticosteroid usage and COVID-19-related death. There was no increase in deaths due to other causes. Conclusions During the second wave of COVID-19 in England, people with RAIRD had the same risk of COVID-19 infection but a 2.76-fold increased risk of COVID-19-related death compared with the general population, with corticosteroids associated with increased risk.

ObjectivesTo investigate the prevalence of spike-protein antibodies following at least 3 COVID-19 vaccine doses in immunocompromised individuals.DesignCross-sectional study using UK national disease registries of individuals with solid organ transplants (SOT), rare autoimmune rheumatic diseases (RAIRD) and lymphoid malignancies (LM).SettingParticipants were identified, invited and recruited at home by accessing the NHS Blood and Transplant Registry for those UK individuals who had received a SOT; and the National Disease Registration Service at NHS Digital for identifying individuals within England with RAIRD or LM.Participants101972 people were invited, 28411 recruited, and 23036 provided serological data, comprising 9927 SOT recipients, 6516 with RAIRD, and 6593 with LM.InterventionsParticipants received a lateral flow immunoassay for spike-protein antibodies to perform at home together with an online questionnaire.Main outcome measuresOdds of detectable IgG spike-protein antibodies in immunosuppressed cohorts following at least three COVID-19 vaccine doses by participant demographic, disease type, and treatment related characteristicsResultsIgG spike-protein antibodies were undetectable in 23.3%, 14.1% and 20.7% of the SOT, RAIRD and LM cohorts, respectively. Participants had received three, four or ≥five vaccine doses at the time of testing in 28.5%, 61.8%, and 9.6%, respectively. In all groups, seropositivity was associated with younger age, higher number of vaccine doses and previous COVID-19 infection. Immunosuppressive medication reduced the likelihood of seropositivity: the lowest odds of seropositivity were found in SOT recipients receiving an anti-proliferative agent, calcineurin inhibitor and steroid concurrently, and those treated with anti-CD20 in the RAIRD and LM cohorts.ConclusionsApproximately one in five individuals with SOT, RAIRD and LM have no detectable IgG spike-protein antibodies despite three or more vaccines, but this proportion reduces with sequential booster doses. Choice of immunosuppressant and disease-type is strongly associated with serological response. Antibody testing could enable rapid identification of individuals who are most likely to benefit from additional COVID-19 interventions.Trial registrationClinicaltrials.gov,NCT05148806

Objective To describe the incidence of Kawasaki Disease (kDa) between 2006 and 2021 in England. Methods We identified all cases in hospital episode statistics with an ICD-10 diagnostic code M303 (for kDa) between 1 April 2006 and 31 March 2021. We validated 83 diagnoses using hospital medical records and found >97% accuracy. We calculated incidence rate ratios (IRRs) using Poisson regression and assessed the influence of age, sex, ethnicity and index of multiple deprivation (IMD). We used Office for National Statistics population estimates for England as the denominator. Results We identified a total of 5908 cases of kDa in all children under the age of 16 (mean age 3.8, s.d.=3.2, 95% CI: 3.7, 3.9). Incidence in children aged Conclusions Incidence rates of kDa derived from hospital admission data in England were higher than in studies relying on clinician reporting. We confirm previous findings on the influence of sex and ethnicity on kDa incidence and observe that there was a higher incidence of kDa within more deprived socioeconomic groups.

We assessed the validity of coded healthcare data to identify cases of haemophagocytic lymphohistiocytosis (HLH). Hospital Episode Statistics (HES) identified 127 cases within five hospital Trusts 2013-2018 using ICD-10 codes D76.1, D76.2 and D76.3. Hospital records were reviewed to validate diagnoses. Out of 74 patients, 73 were coded D76.1 or D76.2 (positive predictive value 89·0% [95% Confidence Interval {CI} 80·2-94·9%]) with confirmed/probable HLH. For cases considered not HLH, 44/53 were coded D76.3 (negative predictive value 97·8% [95% CI 88·2-99·9%]). D76.1 or D76.2 had 68% sensitivity in detecting HLH compared to an established active case-finding HLH register in Sheffield. Office for National Statistics (ONS) mortality data (2003-2018) identified 698 patients coded D76.1, D76.2 and D76.3 on death certificates. Five hundred and forty-one were coded D76.1 or D76.2 of whom 524 (96·9%) had HLH in the free-text cause of death. Of 157 coded D76.3, 66 (42·0%) had HLH in free text. D76.1 and D76.2 codes reliably identify HLH cases, and provide a lower bound on incidence. Non-concordance between D76.3 and HLH excludes D76.3 as an ascertainment source from HES. Our results suggest electronic healthcare data in England can enable population-wide registration and analysis of HLH for future research.

This analysis is the largest population-based study to date to provide contemporary and comprehensive epidemiological estimates of all third edition of the International Classification of Diseases for Oncology (ICD-O-3) coded Langerhans cell histiocytosis (LCH) from England. People of all ages were identified from the National Cancer Registration Dataset using ICD-O-3 morphologies 9751–9754 for neoplasms diagnosed in 2013–2019. A total of 658 patients were identified, of whom 324 (49%) were children aged

Objective Hospital episode statistics (HES) are routinely recorded at every hospital admission within the National Health Service (NHS) in England. This study validates diagnostic ICD-10 codes within HES as a method of identifying cases of idiopathic inflammatory myopathies (IIMs). Methods All inpatient admissions at one NHS Trust between 2010 and 2020 with relevant diagnostic ICD-10 codes were extracted from HES. Hospital databases were used to identify all outpatients with IIM, and electronic care records were reviewed to confirm coding accuracy. Total hospital admissions were calculated from NHS Digital reports. The sensitivity and specificity of each code and code combinations were calculated to develop an optimal algorithm. The optimal algorithm was tested in a sample of admissions at another NHS Trust. Results Of the 672 individuals identified by HES, 510 were confirmed to have IIM. Overall, the positive predictive value (PPV) was 76% and sensitivity 89%. Combination algorithms achieved PPVs between 89 and 94%. HES can also predict the presence of IIM-associated interstitial lung disease (ILD) with a PPV of 79% and sensitivity of 71%. The optimal algorithm excluded children (except JDM code M33.0), combined M33.0, M33.1, M33.9, M36.0, G72.4, M60.8 and M33.2, and included M60.9 only if it occurred alongside an ILD code (J84.1, J84.9 or J99.1). This produced a PPV of 88.9% and sensitivity of 84.2%. Retesting this algorithm at another NHS Trust confirmed a high PPV (94.4%). Conclusion IIM ICD-10 code combinations in HES have high PPVs and sensitivities. Algorithms tested in this study could be applied across all NHS Trusts to enable robust and cost-effective whole-population research into the epidemiology of IIM.

Background/Aims Takayasu arteritis (TAK) is a chronic, inflammatory vasculitis of the aorta and primary branches, particularly prevalent in women of childbearing age. We studied pregnancy outcomes for women with TAK compared to the general population. Methods All people in England with an ICD-10 diagnostic code for TAK 1997/98 to 2020/21 were identified from Hospital Episode Statistics (HES) using National Congenital Abnormality and Rare Disease Registration Service (NCARDRS) data (CAG 10-02(d)/2015). To improve precision of estimated date of diagnosis, we used an English hospital case register of 122 TAK patients. We analysed all HES admissions occurring after their clinician-confirmed diagnosis date and before their first TAK ICD code in HES to identify codes which indicated likely TAK-related activity, and then applied these to the whole NCARDRS cohort. Maternity-related ICD-10 and OPCS-4 code admissions after the estimated diagnosis date were extracted and age-specific values were calculated for number of births, TAK patient years and birth rates. ONS published national data was used for comparison. Results We identified 1,437 people with TAK. Between 2001 and 2021, there were 133 babies born (129 singleton, 2 twin births, no stillbirths) to 85 mothers. Mean maternal age at first delivery was 32.2 years (SD 5.3, median 33.2), above the UK mean of 27.8, with age-specific birth rates compared to the 2019 general population (see table). Overall birth rate in women with TAK was 68% of the national England/Wales rate. Gestational diabetes (GDM) was present in 13/131 (9.9%) but large variation in UK prevalence estimates makes national comparison difficult. Mothers with GDM had a median age of 37 and delivery was by C-section in 9/13 cases. For non-GDM, 50% (95% CI: 41%, 59%) were C-section; this is significantly higher than the UK level of 26%. 12% were vacuum and/or forceps assisted deliveries, approximately equal to the general population. Conclusion The birth rate in women with TAK is lower than the general population and C-section rates higher. Causes are complex and might include patient choice, reduced fertility related to cytotoxic treatment, or physician recommendation, highlighting the importance of equitable access to specialist pre-conception counselling for people with rare autoimmune diseases. Disclosure D.J. Groves: None. M. Rutter: None. P.C. Lanyon: None. M. Odingo: None. M.J. Grainge: None. M. Bythell: None. J. Aston: None. S. Stevens: None. J.R. Hannah: None. J. Mason: None. F.A. Pearce: None.

Background/Aims People with ANCA-associated vasculitis (AAV) have high rates of hospital admissions. They may have emergency admissions at the time of diagnosis, or day case admissions to receive immunosuppressive treatment. We describe the trends in emergency and day case admissions over the past 9 years, and the effect of the COVID-19 pandemic. Methods We extracted hospital episode statistics available publicly from NHS Digital for 2012/13 to 2019/20 and added provisional data from the National Congenital Anomaly and Rare Disease Registration Service for 2020/21 under their legal permissions (CAG 10-02(d)/2015) because the publicly available data had not yet been released. We extracted all emergency and day-case admission rates with ICD codes for each AAV subtype (M301, M313 and M317, in the primary position denoting main admission diagnosis). We used England population estimates from the Office for National Statistics as the denominator for rates. We calculated Poisson confidence intervals to quantify the difference in rates between 2019/20 and 2020/21 financial years. Results Rates of day case admissions per 1,000,000 for AAV increased from 49.1 (47.2 - 50.9) in 2012/13 to 63.3 (61.2 - 65.4) in 2019/20, then decreased by 26.4% to 48.6 (46.7 - 50.4) in 2020/21 (Table). The trends in emergency admissions were relatively unchanged between 2012/13 and 2019/20 (mean 6.7 per 1,000,000), and there was no significant decrease in emergency admissions during the COVID-19 pandemic. Conclusion Day case admission rates increased between 2012/13 and 2019/20 but decreased during the COVID-19 pandemic. Emergency admission rates for patients with AAV remained relatively unchanged, despite the context of the significant disruption and reconfiguration of healthcare services. Further work on patient-level data is needed to establish whether the day case reduction is due to fewer new patients or relapsing patients being diagnosed (and therefore fewer remission induction infusions) during this period or altered clinical practice leading to postponement of planned remission maintenance treatment that would have usually been given. Alternatively, this change may reflect a change in clinical practice to preferentially use oral rather than IV agents. All of this may have future consequences both for clinical practice and individual patient care and outcomes post-pandemic. Disclosure M. Odingo: None. M. Rutter: None. P. Lanyon: Grants/research support; Grants/research support; PCL has received funding for research from Vifor Pharma. M. Grainge: None. D. Groves: None. M. Bythell: None. J. Aston: None. S. Stevens: None. F. Pearce: Grants/research support; Grants/research support; FAP has received funding for research from Vifor Pharma.

Background: Haemophagocytic lymphohistiocytosis (HLH) is a rare hyper-inflammatory condition with poor outcomes. Objectives: Few population-based estimates of the incidence and survival in adults exist. We aimed to provide these data for England. Methods: We used population-based linked data from primary care, secondary care, cancer registries and mortality databases in England to identify people diagnosed with HLH between 1 January 2000 and 31 December 2016. We calculated annual incidence rates by age and sex, modelled change in incidence over time with Poisson regression, calculated overall 1-year survival using Kaplan–Meier methods and estimated adjusted hazard ratios (HRs) of death using a Cox proportional hazards model. Results: We identified 214 patients with HLH. The reported age and sex-adjusted incidence increased twofold over the period, from around one to around two per million. Incidence was highest in those below 1 year (14.6 per million) and ≥75 years (2.2 per million), and lowest in those aged 15–44 years (0.8 per million). One-year survival varied by age and sex from 77% (95% confidence interval [CI] 63%–86%) in those

Objectives To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the first wave of the COVID-19 pandemic in England compared with the general population. Methods We used Hospital Episode Statistics to identify all people alive on 1 March 2020 with ICD-10 codes for RAIRD from the whole population of England. We used linked national health records (demographic, death certificate, admissions and PCR testing data) to calculate rates of COVID-19 infection and death up to 31 July 2020. Our primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. General population data from Public Health England and the Office for National Statistics were used for comparison. We also describe COVID-19-related hospital admissions and all-cause deaths. Results We identified a cohort of 168 680 people with RAIRD, of whom 1874 (1.11%) had a positive COVID-19 PCR test. The age-standardized infection rate was 1.54 (95% CI: 1.50, 1.59) times higher than in the general population. A total of 713 (0.42%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.41 (2.30–2.53) times higher than in the general population. There was no evidence of an increase in deaths from other causes in the RAIRD population. Conclusions During the first wave of COVID-19 in England, people with RAIRD had a 54% increased risk of COVID-19 infection and more than twice the risk of COVID-19-related death compared with the general population. These increases were seen despite shielding policies.

SummaryWe assessed the validity of coded health care data to identify cases of haemophagocytic lymphohistiocytosis (HLH). Hospital Episode Statistics (HES) identified 127 cases within five hospital Trusts 2013-2018 using ICD-10 codes D76.1, D76.2 and D76.3. Hospital records were reviewed to validate diagnoses. 73/74 patients with confirmed/probable HLH were coded D76.1 or D76.2 (positive predictive value 89.0% [95% CI 80.2-94.9%]). For cases considered not HLH, 44/53 were coded D76.3 (negative predictive value 97.8% [95% CI 88.2%-99.9%]). D76.1 or D76.2 had 68% sensitivity in detecting HLH compared to an established active case finding HLH register in Sheffield. Office for National Statistics (ONS) mortality data (2003-2018) identified 698 patients coded D76.1, D76.2 and D76.3 on death certificates. 541 were coded D76.1 or D76.2 of whom 524(96.9%) had HLH in the free text cause of death. Of 157 coded D76.3, 66(42.0%) had HLH in free text.D76.1 and D76.2 codes reliably identify HLH cases, and provide a lower bound on incidence. Non-concordance between D76.3 and HLH excludes D76.3 as an ascertainment source from HES. Our results suggest electronic health care data in England can enable population wide registration and analysis of HLH for future research.

Background/Aims Understanding real-world usage of high cost drugs and subsequent outcomes are crucial to support high quality care, adoption of innovation, and reduce unwarranted variation in treatment. Hospital Episode Statistics (HES) contain diagnoses (coded by ICD-10) and procedures/treatment (coded by OPCS) for admissions in England. However, OPCS codes are not specific for individual drugs, for example X921 (cytokine inhibitors band 1) includes rituximab and 15 other drugs. We aimed to validate the accurate identification of patients treated with rituximab for ANCA-associated vasculitis (AAV) using HES data. Methods We used data available to the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS), part of NDRS at Public Health England and their legal permissions (CAG 10-02(d)/2015). We extracted from HES all patients treated at one hospital who ever had a coded diagnosis of either granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis, polyarteritis nodosa or 'arteritis unspecified’, which is applied by coders to several clinical terms including “systemic vasculitis” and “ANCA associated vasculitis”. Enabled by data sharing agreements, we reviewed hospital records of those patients who had a Finished Consultant Episode (FCE) during 2018/19, to validate diagnoses and whether X921 reliably identified rituximab. Results Initially using codes only for granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, or microscopic polyangiitis we identified 65 people, 60 of whom had AAV confirmed in their medical notes (Positive predictive value (PPV) 92.3%; 95% CI 83.0-97.5). When we expanded our search to include in addition people with codes for polyarteritis nodosa or ‘arteritis unspecified’ who had rheumatology or renal follow up, we identified an additional 13 people with AAV and 10 who had other types of systemic vasculitis (PPV for AAV 79.5, 95% CI 69.6-87.4; PPV for systemic vasculitis 90.9%, 95% CI 82.9-96.0). Among patients identified only by the specific ICD-10 codes for the 3 subtypes of AAV there were 51 episodes coded as X921, of which 50 correctly identified a rituximab infusion (and 1 was tocilizumab). No additional infusions for these patients were missed by the coding. The PPV was 98.0% (95% CI 89.6-100). Among patients identified by the more inclusive algorithm, there were 61 episodes coded as X921 in that year. Of these, 59 were for rituximab treatment for AAV and an additional 4 rituximab infusions occurred but were not coded. The PPV was 96.7% (95% CI 88.7-99.6), and the sensitivity was 93.7% (95% CI 84.5-98.2). Conclusion This pilot study demonstrates how the use of novel algorithms within the NDRS RECORDER project can enable the identification and registration of people with AAV and their high-cost treatment at whole-population level. Further work is now underway to study this national cohort, and to apply this methodology to other rare autoimmune diseases and high cost drugs. Disclosure M. Chakravorty: None. F. Pearce: Grants/research support; Recipient of research grant from Vifor Phama. Vifor Pharma had no influence on the design, interpretation or reporting of this work. M. Rutter: None. P. Lanyon: Grants/research support; Recipient of research grant from Vifor Phama. Vifor Pharma had no influence on the design, interpretation or reporting of this work. J. Aston: None. M. Bythell: None. S. Stevens: None.

ObjectivesTo quantify the risk of death among people with rare autoimmune rheumatic diseases (RAIRD) during the UK 2020 COVID-19 pandemic compared to the general population, and compared to their pre-COVID risk.MethodsWe conducted a cohort study in Hospital Episode Statistics for England 2003 onwards, and linked data from the NHS Personal Demographics Service. We used ONS published data for general population mortality rates.ResultsWe included 168,691 people with a recorded diagnosis of RAIRD alive on 01/03/2020. Their median age was 61.7 (IQR 41.5-75.4) years, and 118,379 (70.2%) were female. Our case ascertainment methods had a positive predictive value of 85%. 1,815 (1.1%) participants died during March and April 2020. The age-standardised mortality rate (ASMR) among people with RAIRD (3669.3, 95% CI 3500.4-3838.1 per 100,000 person-years) was 1.44 (95% CI 1.42-1.45) times higher than the average ASMR during the same months of the previous 5 years, whereas in the general population of England it was 1.38 times higher. Age-specific mortality rates in people with RAIRD compared to the pre-COVID rates were higher from the age of 35 upwards, whereas in the general population the increased risk began from age 55 upwards. Women had a greater increase in mortality rates during COVID-19 compared to men.ConclusionThe risk of all-cause death is more prominently raised during COVID-19 among people with RAIRD than among the general population. We urgently need to quantify how much risk is due to COVID-19 infection and how much is due to disruption to healthcare services.Key messagesPeople with RAIRD had an increased risk of dying during COVID-19 from age 35 years onwards, whereas in the general population it increased from the age of 55 onwards.Women had a greater increase in their risk of death during COVID-19 compared to men.The risk of working age people with RAIRD dying during COVID-19 was similar to that of someone 20 years older in the general population.

Background/Aims To quantify the risk of death among people with vasculitis during the UK 2020 COVID-19 epidemic compared with baseline risk, risk during annual influenza seasons and risk of death in the general population during COVID-19. Methods We performed a cohort study using data from the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) under their legal permissions (CAG 10-02(d)/2015). Coded diagnoses for vasculitis (ANCA-associated vasculitis, Takayasu arteritis, Behçet's disease, and giant cell arteritis) were identified from Hospital Episode Statistics from 2003 onwards. Previous coding validation work demonstrated a positive predictive value >85%. The main outcome measure was age-standardised mortality rates (ASMRs) for all-cause death. ONS published data were used for general population mortality rates. Results We identified 55,110 people with vasculitis (median age 74.9 (IQR 64.1-82.7) years, 68.0% female) alive 01 March 2020. During March-April 2020, 892 (1.6%) died of any cause. The crude mortality rate was 9773.0 (95% CI 9152.3-10,435.9) per 100,000 person-years. The ASMR was 2567.5 per 100,000 person-years, compared to 1361.1 (1353.6-1368.7) in the general population (see table). The ASMR in March-April 2020 was 1.4 times higher than the mean ASMR for March-April 2015-2019 (1965.6). The increase in deaths during March-April 2020 occurred at a younger age than in the general population. We went on to investige the effect of previous influenza seasons. The 2014/15 season saw the greatest excess all-cause mortality nationally in recent years, and there were 624 deaths in 38,888 people (6472.5 person-years) with vasculitis in our data (crude mortality rate 9640.8 (8913.3-10427.7); The ASMR was 2657.6, which was marginally higher than the ASMR among people with vasculitis recorded during March-April 2020 during the COVID-19 pandemic. Conclusion People with vasculitis are at increased risk of death during circulating COVID-19 and influenza epidemics. The ASMR among people with vasculitis was high both during the 2014/15 influenza season and during the first wave of the COVID-19 epidemic. COVID-19 vaccination and annual influenza vaccination for people with vasculitis are both important, regardless of patient age. Disclosure M. Rutter: None. P.C. Lanyon: Grants/research support; PCL has received funding for research from Vifor Pharma.. M.J. Grainge: None. R.B. Hubbard: None. E.J. Peach: Grants/research support; EJP has received funding for research from Vifor Pharma. M. Bythell: None. J. Aston: None. S. Stevens: None. F.A. Pearce: Grants/research support; FAP has received funding for research from Vifor Pharma..

Background/Aims To quantify the risk of death among people with rare autoimmune rheumatic diseases (RAIRD) during the UK 2020 COVID-19 epidemic compared with baseline risk and the risk of death in the general population during COVID-19. Methods A cohort study was performed using data from the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS). Coded diagnoses for RAIRD were identified from Hospital Episode Statistics from 2003 onwards. Previous coding validation work demonstrated our case ascertainment methods had a positive predictive value >85%. ONS published data were used for general population mortality rates. The main outcome measure was age-standardised mortality rates (ASMRs) for all-cause death. Secondary outcome measures were age-sex standardised mortality rates, and age-stratified mortality rates. Results 168,691 people with RAIRD were alive on 1 March 2020. Their median age was 61.7 (IQR 41.5-75.4) years, and 118,379 (70.2%) were female. 1,815 (1.1%) people with RAIRD died during March and April 2020. The ASMR among people with RAIRD was 3669.3 (95% CI 3500.4-3838.1) per 100,000 person-years, which was 1.44 (95% CI 1.42-1.45) times higher than the average ASMR during the same months of the previous 5 years. In the whole population of England, the ASMR during March and April 2020 was 1361.1 (1353.6- 1368.7) per 100,000 people, which was 1.38 times higher than the average ASMR during the same months of the previous 5 years (see related abstract about influenza seasons). Unlike in the general population, sex-specific rates in RAIRD were similar in males and females. When comparing risk of death during COVID-19 to pre-COVID-19, people with RAIRD had an increased risk of death from age 35 upwards, compared to around age 55 upwards in the general population. As the protective effect of being female was not seen in RAIRD, the group at the largest increased risk compared to their pre-COVID-19 risk were women aged 35 upwards. The absolute risk of all-cause death for someone aged 20-29 with RAIRD was similar to someone in the general population aged >20 years older, someone aged 40-49 years with RAIRD similar to someone in the general population 20 years older, and someone aged 60-69 with RAIRD similar to someone in the general population aged >10 years older. Conclusion The excess risk of all-cause death during COVID-19 occurs at a younger age among people with RAIRD than among the general population, and particularly affects females. . We urgently need to quantify how much risk is due to COVID-19 infection and how much due to disruption to healthcare services to inform better guidance about shielding, access to healthcare and vaccine priorities for people with rare diseases. Disclosure M. Rutter: None. P.C. Lanyon: None. E. Peach: None. M.J. Grainge: None. R.B. Hubbard: None. J. Aston: None. M. Bythell: None. S. Stevens: None. F.A. Pearce: None.

Background/Aims The National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) aims to register all patients in England with congenital or rare diseases. Maintaining ongoing contemporaneous registers requires substantial time and resource, so novel methodologies for identification and registration of rare disorders such as the idiopathic inflammatory myopathies (IIMs) need development. Hospital Episode Statistics (HES) are routinely recorded data from every hospital admission within the National Health Service (NHS) England. This study aims to validate diagnostic ICD-10 codes within HES as a method of identifying and recording cases of IIM. Methods In collaboration with the Registration of Complex Rare Diseases - Exemplars in Rheumatology (RECORDER) project we extracted all Finished Consultant Episodes (FCE) at one hospital trust between 2010-2019 with diagnostic ICD-10 codes indicating either dermatomyositis or polymyositis under NCARDRS section 251 legal permissions (CAG 10-02(d)/2015). Co-occurring interstitial lung disease (ILD) was also considered due to ILDs association with IIMs. Hospital rheumatology and immunology databases were interrogated to identify all outpatients with IIM. Hospital electronic care records were reviewed to confirm coding accuracy. The total number of FCEs at the trust was calculated from NHS Digital reports. Sensitivity and specificity of each code and various code combination algorithms were calculated. Results HES ICD-10 codes identified 530 individuals, of whom 388 had records confirming IIM diagnosis. 146 additional patients were found through hospital records. This gives these codes a positive predictive value (PPV) of 73.1% and sensitivity of 72.7%. Due to the rarity of IIM coded FCEs compared to all FCEs, the specificity is 100.0% for every code. Dermatomyositis codes M331 and M339 had PPV 94.8% and 93.4% respectively. Juvenile DM (M330) and paraneoplastic myositis (M360) whilst rarely used had a high PPV of 91.6% and 100% respectively. Myositis unspecified (M609), was the worst performing code with PPV 61.4%. Excluding M609 from the analysis, PPV improved to 85.9%. Adding an ILD code made specificity 94.2% and sensitivity 15.5%, however it did find 51.5% of the known IIM-ILD patients. Strategies to improve PPV without impacting sensitivity were attempted. The highest PPV of 95.3% was found by selecting patients who had at least 2 different codes recorded, however sensitivity was only 30.7%. By then adding patients who also had one of the high performing codes the PPV dropped to 91.73% but sensitivity improved to 60.7%. Conclusion This is the first validation cohort to show that IIM ICD code combinations in HES have high positive predictive values, and sensitivities of up to 72.7%. The relative importance of sensitivity, specificity and PPV vary according to the research question being asked, but algorithms tested in this study could be applied across all NHS trusts to enable robust and cost-effective whole-population research into the epidemiology of IIM. Disclosure J.R. Hannah: None. P. Gordon: None. J. Galloway: None. E.J. Peach: Grants/research support; Vifor Pharma. P.C. Lanyon: Grants/research support; Vifor Pharma. M. Bythell: None. F.A. Pearce: Grants/research support; Vifor Pharma.

Background Wilson Disease (WD) is a rare genetic disorder of copper metabolism. Without appropriate treatment it can progress to liver failure and death. The National Congenital Anomaly and Rare Disease Registration Service (NCARDRS), with support from the Wilson Disease Special Interest Group, has established registration of WD in England. We aim to provide a descriptive study of mortality, including multiple cause of death and transplant status, of those with WD. Method Confirmed cases of WD were reported by 20 hospital trusts and registered with NCARDRS enabled by their legal permissions (CAG 10-02(d)/2015) to collect patient data without consent. Vital status of all cases were determined and linkage with Office of National Statistics (ONS) mortality data was undertaken to obtain death certificate data. Cases of E83.0 Disorders of copper metabolism, between 2008–2018, were extracted from ONS mortality data. Cause of death free text was manually searched to identify deaths that mentioned WD. All deaths were linked to Hospital Episode Statistics (HES) inpatient data to determine transplant status. Results Death records were identified for 52 patients, 65% were male, with a mean age of 45.5 years (range 17–82). Complications related to cirrhosis or liver failure were assigned as the underlying cause of death (UCOD) in 44%. Hepatocellular carcinoma (HCC) was the UCOD in 5.8%. Of the 21% of patients who were recorded as having a liver transplant, transplant complications or graft failure were recorded as a cause of death in 8%. Sepsis was mentioned on the death certificate in 42% and recorded as the UCOD in 21%. Conclusion The contribution of WD to mortality in England will be underestimated unless multiple cause of death analysis is undertaken. The number of deaths resulting from complications related to cirrhosis or liver failure suggests that there might be missed opportunity for liver grafting. HCC was the cause of death in 5.8% of cases suggesting the prevalence of HCC in WD may be higher than previously thought. This project demonstrates the utility of the NCARDRS’ for WD in England.

Background The true incidence of Kawasaki disease (KD) in England is unknown. In KD treatment with intravenous immunoglobulin (IVIG) can be lifesaving, but it is both expensive and in limited supply. In collaboration with Public Health England’s National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) we aimed to determine the incidence of KD in England. Methods We worked within NCARDRS to access patient-identifiable Hospital Episode Statistics (HES) data, enabled by their legal permissions (CAG 10-02(d)/2015). We extracted all patients receiving a primary or additional diagnostic code for KD between April 2003 -March 2017. For patients identified in Nottingham University Hospitals Trust, we reviewed the coding accuracy in their medical records. We calculated incidence with 95% Poisson confidence intervals among children in England using the total number of cases newly diagnosed in the study period. We used the ONS mid-year estimates for 2016 for the denominator. Results 37 patients were coded as having KD in our Trust. All had a clinical diagnosis of KD (positive predictive value 100%). 32 patients were paediatric cases treated for KD; the remaining 5 patients were diagnosed in adult life on the basis of pathognomonic angiogram findings. It was not possible to apply classification criteria because the required information was not always available. During the 13-year study period we identified 3345 cases in children aged Conclusion Analysis of HES data within NCARDRS has provided population-based estimates of incidence of KD for the whole of England. Our estimates are higher than in previous studies. Validation of coding accuracy has shown our methods were specific, and they are likely to be sensitive given KD is always treated in hospital. Accurate incidence estimates are essential for appropriate resource allocation, given the limited availability of lifesaving IVIG treatment. Disclosures M. Rutter None. P.C. Lanyon None. M. Bythell None. S. Stevens None. J. Aston None. F.A. Pearce None.

Background The contemporary prevalence of ANCA-associated vasculitis (AAV) in England is unknown. Hospital Episode Statistics (HES) contain data on every hospital and day case NHS admission in England since 1997. In collaboration with the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) we validated the diagnosis of AAV using ICD codes in HES. The positive predictive value of these codes was 86%, which compares favourably to a median coding accuracy of 80% in a recent systematic review of NHS coding studies. This justifies using this novel dataset for population-based epidemiology with coverage of the whole population of England. Methods We worked within NCARDRS enabled by their Section 251 legal permissions (CAG 10-02(d)/2015). We extracted all cases of AAV from HES 2011/12 to 2016/17 using ICD-10 codes M313 Granulomatosis with polyangiitis (GPA), M317 Microscopic polyangiitis (MPA), and M301 Eosinophilic granulomatosis with polyangiitis (EGPA). We used the Summary Care Record to check vital status and record date of death where appropriate. We estimated point prevalence on 1 July 2016 using ONS mid-year population estimates for England in 2016 as the denominator. Standardised mortality ratio (SMR) was calculated using the Office for National Statistics death summary tables 2016 to provide expected number of deaths for each 5-year age-band and sex. Results We identified 9,890 patients who were coded as having AAV during a hospital admission 2011-2017. This included 6,856 (69.3%) with GPA, 964 (9.8%) with MPA and 2,070 (20.9%) with EGPA. On 1 July 2016, our dataset found 8,040 people in England were living with ANCA associated vasculitis. We estimate the prevalence was 14.55 (95% CI: 14.23-14.87)/100,000 adult population. The median age of these patients was 65.3 years (interquartile range 52.3-74.2). 47% were female. The prevalence of GPA was 9.97/100.000 (95% CI: 9.71-10.24), MPA was 1.40/100,000 (95% CI: 1.30-1.50), and EGPA was 3.18/100,000 (95% CI: 3.03-3.33). People with AAV were 4.6 times more likely to die than the background population of the same age and sex (Standardised Mortality Ratio = 4.58). Conclusion There are no recent UK prevalence estimates for all types of ANCA-associated vasculitis. Studies in Australia, Germany, Southern Sweden and the USA have found estimated prevalence to be between 4.6-18.4 cases per 100,000 individuals. Our estimate of 14.6/100,000 in England is consistent with this, and towards the higher end of the range. However, our estimates underestimate the prevalence of MPA compared to other studies, and further work is needed to increase the routine identification of cases of MPA. Further work within NCARDRS using their unique data linkages will enable more specific AAV case ascertainment as well as nationwide population-based studies on cause of death and studies using the database of English prescriptions dispensed in the community. Disclosures F.A. Pearce None. B. Griffiths None. C. Mukhtyar None. R. Al-Jayoussi None. R.A. Watts None. J. Aston None. M. Bythell None. S. Stevens None. P.C. Lanyon None.

Background The National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) records those people with congenital anomalies and rare diseases across the whole of England. The NCARDRS Rare Rheumatology Project is establishing methodologies to identify and register people with rare rheumatic diseases. Hospital Episode Statistics (HES), comprising data from all admitted-patient NHS care in England, provides a promising source for case ascertainment. We aimed to confirm the reliability of diagnostic ICD codes for rare autoimmune rheumatic diseases within HES. Methods We used NCARDRS’ legal permissions (CAG 10-02(d)/2015) to extract cases who had at least one inpatient or daycase admission recorded in HES during 2003 to 2017 with a primary or additional diagnostic code for Kawasaki disease, Takayasu’s arteritis, Adult-onset Still’s disease, Relapsing polychondritis, Polyarteritis nodosa, Granulomatosis with polyangiitis (GPA), Microscopic polyangiitis (MPA) or Eosinophilic granulomatosis with polyangiitis (EGPA). Using Data Sharing Agreements between NCARDRS and NHS Trusts, we reviewed medical records for all cases admitted to one NHS Trust to confirm diagnoses. For ANCA-associated vasculitis (AAV), up to 20 randomly selected cases admitted to 5 Trusts with a diagnostic code of GPA, MPA and EGPA were reviewed. Results Table 1 shows the positive predictive value (PPV) of each diagnosis at one Trust: Kawasaki disease 100%, Takayasu’s arteritis 91.7%, Adult-onset Still’s disease 42.8%, Relapsing polychondritis 40.0%, and Polyarteritis nodosa 5.0%. For AAV, which had a PPV at the index Trust of 92.0%, the PPV across the 5 Trusts varied from 92.9% to 74.0%. Combining all 5 Trusts PPV for AAV was 85.9%. It was higher in MPA (PPV=98.4%) than in GPA (PPV=83.3%) and EGPA (PPV=77.4). Conclusion This is the first study to validate the coding of rare rheumatic disease diagnoses within HES data. Our results highlight heterogeneity in coding accuracy both between conditions and between NHS Trusts. Further work is needed to develop and validate algorithms for conditions where HES coding alone has poor positive predictive value, and test sensitivity. National rare disease registration will enable robust, cost-effective and reproducible population-based epidemiology of rare rheumatic diseases across England which is needed to inform service provision and aid development of new treatments. Disclosures F.A. Pearce None. M. Rutter None. B. Griffiths None. C. Mukhtyar None. R. Al-Jayoussi None. R.A. Watts None. J. Aston None. M. Bythell None. S. Stevens None. P.C. Lanyon None.

OBJECTIVE: To examine the influence of fetal and maternal characteristics on the survival of children born with Down syndrome. METHODS: We used prospectively collected population-based data on Down syndrome extracted from the UK Northern Congenital Abnormality Survey (NorCAS), January 1, 1985–December 31, 2003, matched to hospital and national mortality records to January 29, 2008, to determine survival status of liveborn children. Survival to 20 years was estimated by using Kaplan-Meier methods. Cox proportional hazards regression was used to examine factors that predict survival. RESULTS: A total of 1115 Down syndrome pregnancies were notified to NorCAS during the 19 years, a total prevalence of 16.8 (95% CI, 15.8–17.8) per 10 000 live births and stillbirths. Of these, 5.4% resulted in a spontaneous fetal loss (late miscarriage ≥20 weeks and stillbirth), 31.7% in a termination of pregnancy, and 63.0% in a live birth. Survival status was known for 95.3% of live births; 16.6% resulted in a death. Year of birth (P < .001), gestational age at delivery (P < .001), standardized birth weight (P < .001), karyotype (P < .01), and presence of additional structural anomalies (P < .001) were significant predictors of survival. Infant gender, plurality, maternal age, and maternal deprivation were not significant predictors of survival. CONCLUSIONS: These robust estimates of predictors of survival are important for the prenatal counseling of parents whose pregnancy is affected by Down syndrome and for health care planning for the future care needs of these children.

INTRODUCTION Hirschsprung's disease is the commonest congenital gut motility disorder, characterized by the absence of the enteric ganglion cells along the distal gut, which causes intestinal obstruction. Few publications report its epidemiology and temporal trends. METHODS Cases of Hirschsprung's disease delivered during 1990 to 2008 in the North of England reported to the Northern Congenital Abnormality Survey (NorCAS) formed this population-based case series. RESULTS Of 612,916 live births, 105 cases were reported to NorCAS. After excluding one diabetic and four multiple pregnancies, the live birth prevalence was 1.63 (95% confidence interval [CI], 1.33–1.98) per 10,000 live births. There was a significant temporal increase in the prevalence of Hirschsprung's disease (p = 0.020), from 1.26 (95% CI, 0.80–1.89) in 1990 to 1994 to 2.29 (95% CI, 1.53–3.29) in 2005 to 2008. The ratio of male to female cases was 2:1. Ten (10.0%) cases occurred with Down syndrome, one with Smith-Lemli-Opitz Syndrome, and six (6.0%) with associated structural anomalies. The remaining 83 (83.0%) cases were isolated. All cases were live born, but nine (9.0%) died in the first year of life. Hirschsprung's disease was not prenatally suspected in any case. Half the cases were diagnosed within 5 days postpartum, but time of diagnosis ranged from birth to 5 years of age. CONCLUSION This study confirmed a male predominance and an association with Down syndrome, but also founda temporal increase in Hirschsprung's disease prevalence. No cases were suspected prenatally, but half were diagnosed within 5 days of life. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.

We describe the prevalence, associated anomalies, prenatal diagnosis and survival of patients with bladder exstrophy-epispadias complex.Data were extracted from the Northern Congenital Abnormality Survey for patients delivered during 1985 to 2008. This survey collects data on congenital anomalies in fetuses, stillbirths and live-born infants of mothers residing in Northern England (Northumberland, North Cumbria, Tyne and Wear Durham, Darlington and Teesside).A total of 43 cases were identified from 824,368 registered births for a total prevalence of 5.22 per 100,000 (95% CI 3.77-7.03). Excluding 1 twin with cloacal exstrophy, 42 cases occurred in singleton pregnancies. A total of 29 cases (69%) were isolated and 13 (31%) were associated with other anomalies, of which 11 (26%) were other structural and 2 (5%) were chromosomal. Male-to-female ratio was 2.2:1 for all singleton cases and 1.4:1 for isolated cases. Total prevalence of bladder exstrophy-epispadias complex singleton cases was 5.10 per 100,000 registered births (95% CI 3.67-6.89) and overall live birth prevalence was 4.63 per 100,000 live births (95% CI 3.28-6.36). Total prevalence of isolated cases of bladder exstrophy-epispadias complex was 3.52 per 100,000 births (95% CI 2.36-5.05) and live birth prevalence was 3.29 per 100,000 (95% CI 2.17-4.79). Accuracy of prenatal diagnosis was low, with 4 cases (10%) being detected prenatally by routine ultrasound (bladder exstrophy in 3, cloacal exstrophy in 1). Overall survival of all infants at 1 year was 95%.This population based study demonstrates a prevalence rate similar to other studies, a low prenatal diagnosis rate and high survival.

Congenital anomalies are a leading cause of perinatal and infant mortality. Advances in care have improved the prognosis for some congenital anomaly groups and subtypes, but there remains a paucity of knowledge about survival for many others, especially beyond the first year of life. We estimated survival up to 20 years of age for a range of congenital anomaly groups and subtypes.Information about children with at least one congenital anomaly, delivered between 1985 and 2003, was obtained from the UK Northern Congenital Abnormality Survey (NorCAS). Anomalies were categorised by group (the system affected), subtype (the individual disorder), and syndrome according to European Surveillance of Congenital Anomalies (EUROCAT) guidelines. Local hospital and national mortality records were used to identify the survival status of liveborn children. Survival up to 20 years of age was estimated by use of Kaplan-Meier methods. Cox proportional hazards regression was used to examine factors that affected survival.13,758 cases of congenital anomaly were notified to NorCAS between 1985 and 2003. Survival status was available for 10 850 (99.0%) of 10 964 livebirths. 20-year survival was 85.5% (95% CI 84.8-86.3) in individuals born with at least one congenital anomaly, 89.5% (88.4-90.6) for cardiovascular system anomalies, 79.1% (76.7-81.3) for chromosomal anomalies, 93.2% (91.6-94.5) for urinary system anomalies, 83.2% (79.8-86.0) for digestive system anomalies, 97.6% (95.9-98.6) for orofacial clefts, and 66.2% (61.5-70.5) for nervous system anomalies. Survival varied between subtypes within the same congenital anomaly group. The proportion of terminations for fetal anomaly increased throughout the study period (from 12.4%, 9.8-15.5, in 1985 to 18.3%, 15.6-21.2, in 2003; p0.0001) and, together with year of birth, was an independent predictor of survival (adjusted hazard ratio [HR] for proportion of terminations 0.95, 95% CI 0.91-0.99, p=0.023; adjusted HR for year of birth 0.94, 0.92-0.96, p0.0001).Estimates of survival for congenital anomaly groups and subtypes will be valuable for families and health professionals when a congenital anomaly is detected, and will assist in planning for the future care needs of affected individuals.BDF Newlife.

Objectives Pregnant women are a highly mobile group, yet studies suggest exposure error due to migration in pregnancy is minimal. We aimed to investigate the impact of maternal residential mobility on exposure to environmental variables (urban fabric, roads and air pollution (PM10 and NO 2 )) and socio-economic factors (deprivation) that varied spatially and temporally. Methods We used data on residential histories for deliveries at ≥24 weeks gestation recorded by the Northern Congenital Abnormality Survey, 2000–2008 ( n = 5399) to compare: (a) exposure at conception assigned to maternal postcode at delivery versus maternal postcode at conception, and (b) exposure at conception assigned to maternal postcode at delivery versus mean exposure based on residences throughout pregnancy. Results In this population, 24.4% of women moved during pregnancy. Depending on the exposure variable assessed, 1–12% of women overall were assigned an exposure at delivery >1SD different to that at conception, and 2–25% assigned an exposure at delivery >1SD different to the mean exposure throughout pregnancy. Conclusions To meaningfully explore the subtle associations between environmental exposures and health, consideration must be given to error introduced by residential mobility.

Aim: Infection is an important cause of neonatal and infant mortality. We evaluatedchanges in infant deaths from infections from 1988 to 2008 in the North of England. Methods: We interrogated a population-based survey and reviewed infant deaths frominfection. Proportional contribution to deaths, pathogens identified and risk factors wereanalysed. Results: Thirteen percentage of 4366 infant deaths from a population of 704 536livebirths were infectious. The absolute numbers of infant deaths from infection fell overtime but the proportion of deaths from infection increased (12.1%, 13.6% and 14.9%).Significantly preterm infants were increasingly represented in successive epochs (14%,24% and 38%). Infant mortality rate (IMR) from meningococcus and Group BStreptococcus (GBS) fell in the latest epoch, but there was a corresponding increase fromEscherichia coli and candida. Discussion: This large study shows that infections have become proportionately moreimportant causes of death especially in very preterm infants. Recent significant reductionsin death from meningococcus and GBS are likely to represent successful achievements ofvaccination and antibiotic prophylactic policies. Increases in IMR from E. coli may relate toGBS prophylaxis and increases in candida to the increase from preterm populations.Further efforts to understand these changing patterns and develop additional preventionand treatment strategies and vaccines remain an urgent priority.INTRODUCTIONDespite medical advances data suggest that infectionscontinue to have a significant impact on neonatal andinfant mortality even in developed countries (1,2). Deathcertificate studies in the United Kingdom (UK) (3,4)highlight the total burden and the large number of causesof infections on neonatal and infant mortality. However,detailed clinical data that might help focus efforts atreduction in cases are currently lacking.Data currently suggests that all-cause neonatal and infantmortality rates have steadily decreased in the UK in the last25 years. A proportion of these reductions are accountedfor by changes in vaccine preventable diseases particularlymeningococcus, Haemophilus influenzae type b and pneu-mococcus (5), but there is little data available describinghow all-cause infectious neonatal and infant mortality rateshave changed in this time period. There are many factorsthat affect the observed epidemiological patterns includingchanges to immunization schedules, improvements indiagnostic techniques and medical management, and anincreasing preterm population, in part as a consequence ofincreasing survival of the most immature.There are few long-term population-based data describ-ing the epidemiology of infectious death in infancy. Weaimed to describe the contribution of infections to infantmortality in a well-defined population in the UK andexplore how this has changed over a 21-year period.METHODSWe used the Perinatal Mortality Survey (PMS) database,coordinated by the Regional Maternity Survey Office(RMSO) in the North of England. This well-validatedpopulation-based survey captures the death of all live-borninfants of mothers resident in the North East and NorthCumbria within the first post-natal year, including infantswho were born or died outside the region. Deaths are

Objective To determine the role of viral infections in causing fetal and infant death. Study design We assessed a well-validated population database of fetal (≥20 weeks gestation) and infant death for infective deaths and deaths from viruses over a 21-year period (1988-2008). We analyzed by specific viral cause, timing (late fetal loss [20-23 weeks], stillbirth [≥24 weeks], neonatal death [0-27 days], and post-neonatal infant death [28-364 days]) and across time. Results Of the 989 total infective deaths, 108 were attributable to viral causes (6.5% of late fetal losses, 14.5% of stillbirths, 6.5% of neonatal deaths, and 19.4% of postneonatal infant deaths). Global loss (combined fetal and infant losses per 100 000 registerable births) was 139.6 (95% CI, 130.9-148.3) for any infective cause and 15.2 (95% CI, 12.3-18.1) for viral infections. More than one-third (37%) of viral-attributed deaths were before live birth, from parvovirus (63%) or cytomegalovirus (33%). Parvovirus accounted for 26% (28 of 108) of all viral deaths. Cytomegalovirus was associated with a global loss rate of 3.1 (95% CI, 1.8-4.4) and an infant mortality rate of 1.3 (95% CI, 0.4-2.1) per 100 000 live births; 91% of cases were congenital infections. Herpes simplex virus caused death only after live births (infant mortality rate, 1.4; 95% CI, 0.5-2.3). No changes in rates were seen over time. Conclusion We have identified a substantial contribution of viral infections to global fetal and infant losses. More than one-third of these losses occurred before live births. Considering our methodology, our estimates represent the minimum contribution of viral illness. Strategies to reduce this burden are needed.

Compared to catastrophic impacts from storms, disease epidemics and bleaching events, little is known about the effects of more routine chronic mortality in reef corals. To monitor this ongoing mortality, monthly visual assessments of the cause of tissue damage were related to mortality rates (changes in planar surface area) of tagged colonies of three common reef corals: Montastrea annularis, Porites astreoides and Diploria strigosa at Buck Island Reef National Monument, St. Croix, US Virgin Islands. During the study Hurricane Hugo, the most powerful cyclone to affect the area in at least 60 y, made a direct impact on the site. Effects of the hurricane were extremely localized, with certain exposed sites being almost completely razed while others showed no detectable changes in community structure. Mortality caused both by the hurricane and by other factors during the 26 month study varied between species and also between site locations around the island. Differences in susceptibility were not dependent solely on gross morphology, because two robust, massive species showed opposite responses to hurricane damage and chronic mortality. Diploria strigosa was virtually unaffected by chronic factors, but was heavily damaged at exposed sites during the hurricane. In contrast, mortality from predation and tissue necrosis was high in Montastrea annularis, but it largely escaped damage from the hurricane because it was absent from the most severely scoured locations. Porites astreoides, with populations dominated by much smaller colonies, was affected by both chronic and hurricanerelated mortality. Differences in susceptibility to the various types of natural disturbance among species, coupled with high spatial and temporal variability in the effects of such disturbances, may be critical to the maintenance of species diversity on the reef.

Fixed position linear transects were established in early 1989 at Buck Island Reef National Monument, St. Croix, U.S. Virgin Islands. On September 17–18 of that year Hurricane Hugo, the most severe cyclone to impact the area in over 60 years, passed directly over the island bringing hurricane-force winds for over 12 h and maximum estimated wind speeds of 70 m · s −1 (160 mph). Despite the severity of the storm, damage to coral reefs was extremely localised and concentrated mainly on reefs open to its southeasterly direction of approach. The southeast reef front at Buck Island was razed to substrate level between the surface and 7 m depth and the reef crest behind it was smothered in a 1 m deep berm of broken coral rubble. At a site on the north backreef, however, only a slight loss of coral cover was detected which was more than compensated for during 1990–1991. At a south reef site which was in 8–10 m depth, just outside the region of severe damage, coral cover was reduced by 40–46% on three out of four transects. Shifts in community structure were detected by multi-dimensional scaling of Bray-Curtis similarity measures and by k -dominance curves, but not by the Shannon diversity statistic (H′). Coral cover had returned to approximate pre-hurricane levels by June 1991, but community composition remained distinct. One of the four transects at this south site was apparently not significantly damaged during the hurricane. Such spatial variability may affect recovery rates, since pockets of relatively undisturbed benthos may provide seed populations for recruitment into adjacent, more severely damaged areas. Hurricane Hugo did not appear to cause an immediate increase in species diversity by differential mortality of the dominant species in the community. This result is consistent with previous studies of the impact of less severe storms on St. Croix, but contrary to several reports of hurricane impact in other areas.

To investigate the association between maternal body mass index (BMI) and major, structural congenital anomalies.Cohort study using prospectively collected data.Data on all singleton pregnancies booked at five maternity units in the north of England between 01 January 2003 and 31 December 2005 and data on congenital anomalies notified to the Northern Congenital Abnormality Survey were linked using key variables. Maternal pre-gestational diabetic status was derived from the Northern Diabetes in Pregnancy Survey. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated by maximum-likelihood logistic regression models, with missing values modelled as explicit categories.There was a total of 41,013 singleton pregnancies during the study period, of which 682 were affected by a structural congenital anomaly, a total prevalence of 166 (95% CI: 154, 179) per 10,000 registered births. Overall, the risk of a congenital anomaly was significantly increased among the maternal underweight (BMIor= 18.5 kg m(-2); aOR = 1.60, 95% CI: 1.09, 2.36; P = 0.02) and maternal obese groups (BMIor = 30 kg m(-2); aOR = 1.30, 95% CI: 1.03, 1.63; P = 0.03), but not for maternal overweight (BMI = 25-29.9 kg m(-2); aOR = 0.85, 95% CI: 0.68, 1.06; P=0.15), compared with mothers of recommended BMI. Maternal obesity was associated with significantly increased risk of ventricular septal defect (aOR=1.56, 95% CI: 1.01, 2.40; P = 0.04), cleft lip (aOR = 3.71, 95% CI: 1.05, 13.10; P = 0.04) and eye anomalies (aOR = 11.36, 95% CI: 2.25, 57.28; P=0.003). Maternal underweight was associated with significantly increased risks of atrial septal defect (aOR = 2.86, 95% CI: 1.18, 6.96; P=0.02), genital anomalies (aOR = 6.30, 95% CI: 1.58, 25.08; P = 0.009) and hypospadias (aOR = 8.77, 95% CI: 1.42, 54.29; P = 0.02).We found an overall increased risk of congenital anomalies in women who are obese and women who are underweight compared with women of recommended weight. Women should be made aware of these risks and supported to optimize their weight before pregnancy.

Background Many epidemiological studies assign exposure to an individual's residence at a single time point, such as birth or death. This approach makes no allowance for migration and may result in exposure error, leading to reduced study power and biased risk estimates. Pregnancy outcomes are less susceptible to this bias, however data from North American populations indicate that pregnant women are a highly mobile group. We assessed mobility in pregnant women in the north of England using data from the Northern Congenital Abnormality Survey (NorCAS). Methods Data were extracted from NorCAS for 1985 to 2003. Eligible cases had a gestational age at delivery of ≥ 24 weeks (a viable delivery) (n = 11 559). We assessed mobility between booking appointment (average gestational age 13 weeks) and delivery for pregnancies where the address at booking appointment and delivery were known. The impacts on mobility of maternal age and area-level socio-economic indicators were explored using standard descriptive statistics. A sensitivity analysis and a small validation exercise were undertaken to assess the impact of missing data on the estimate of mobility. Results Out of 7 919 eligible cases for whom addresses at booking and delivery were known, 705 (8.9% (95% CI 8.3 - 9.5)) moved between booking and delivery; the mean and median moving distance was 9.7 and 1.4 km respectively. Movers were significantly younger (25.4 versus 27.3 years, p < 0.01) and lived in more deprived areas (index of multiple deprivation score 38.3 versus 33.7, p < 0.01) than non movers. Conclusion Mobility in the north of England (9%) is considerably lower than that reported in North America and the only other study from the UK (23%). Consistent with other studies, mobility was related to maternal age and socio-economic status, and the majority of moves were over a relatively short distance. Although this population appears relatively stable, the mobility we have observed may still introduce misclassification or error into an exposure assessment relying solely on postcode at delivery, and migration should still therefore be considered a potential source of bias in future studies.

The impact of late terminations (or = 24 weeks) on the overall stillbirth rate was determined for the 12-year period from 1994 to 2005 using data collected by the Regional Maternity Survey Office in the north of England. It is a legal requirement to register late terminations, and this may lead to an overestimation of the true stillbirth rate. In our region, terminations resulting in stillbirth increased the registered stillbirth rate by nearly 10%. The impact remained stable for the period 1998-2005. This suggests that the failure of the national (and regional) stillbirth rate to decline in recent years is not due to an increase in late terminations.

Background Infection is an important cause of neonatal/infant mortality. Antenatal care, neonatal intensive care and immunisation practices affect infectious mortality, but no good data show how these deaths have changed over time. Understanding this will help direct future medical priorities. Objective To evaluate changes in neonatal/infant mortality from infection over 2 decades (1988–2008) in a geographical population. Design and Methods We used a population database (Perinatal Mortality Survey, Northern region UK) and reviewed infant deaths coded as infection. Proportional contribution to deaths, pathogens identified and risk factors were analysed. To demonstrate changes over time, three 7-year epochs were created. Results 625 deaths from infection were identified. Absolute numbers of deaths fell with time but the proportion from infection increased. Significantly preterm infants were increasingly represented in successive epochs. Deaths from GBS fell, and a fall in meningoccal (MEN) infections follows universal immunisation (1999). Infections from staphylococcus aureus (SA) were unchanged. Conclusions Despite better care and immunisations, the proportion of infant mortality from infections has increased. Term infants have benefited from changes in management but preterm infants have not, and deserve urgent prioritisation.

Background Spina bifida is associated with life-long disability and reduced survival, but the determinants of survival for those born with spina bifida remain poorly understood. This study describes the impact of several factors on the survival of children born with spina bifida, up to age 10 years. Methods Cases of isolated spina bifida, delivered during 1985–2003, were identified from the population-based Northern Congenital Abnormality Survey (NorCAS). Survival status was determined from local and national mortality records. Cox regression models were used to examine the potential influences of survival. Results 500 cases of spina bifida were identified during the study, a prevalence of 7.5 (95% CI 6.9 to 8.2) per 10 000 total births. 10-year survival among live born cases was 66.6% (95% CI 59.8 to 72.6), increasing significantly with time (p=0.002) from 60.2% (95% CI 51.1 to 68.0) in 1985–1990 to 83.3% (95% CI 64.5 to 92.7) in 1997–2003. The proportion of terminations of pregnancy also increased from 40.2% (95% CI 34.0 to 46.6) in 1985–1990 to 72.4% (95% CI 64.5 to 79.3) in 1997–2003 (p The presence of hydrocephalus significantly reduced survival (p Conclusions Survival of children born with spina bifida has improved significantly over time, but prognosis remains poor for children born with hydrocephalus or preterm. These data are important for counselling families and for health service planning.

Background Infection is a major cause of perinatal, neonatal and infant deaths, but the viral contribution to these deaths is poorly described. Objective To describe the contribution of viruses to perinatal, neonatal and infant deaths in one Region of the UK (1985–2008). Methods Using Regional Perinatal Mortality Survey – a population based database of fetal deaths ≥20 weeks gestation and in live-born individuals within the first year. Deaths from viral infection were identified, verified and specified. Results From 819 890 live births and 4478 stillbirths (>24 weeks) 1123 deaths were infectious: 585 bacterial, 102 viral. Of viral deaths 29% were parvovirus (mostly stillbirths); 23% were cytomegalovirus (CMV) (mostly stillbirths). 92% of CMV cases were congenital (cCMV). 23 infant deaths were due to respiratory viruses (table 1). Conclusions Viruses caused 9% of all infective deaths: 6% of fetal losses 24 weeks, 5% of neonatal deaths and 15% of non-neonatal infant deaths. In this population viral deaths occur in ∼7:100 000 live-births and 6:1000 stillbirths ≥24 weeks, most commonly from parvovirus or CMV. By comparison 13% of these deaths were attributed to GBS infection. Morbidity from cCMV is more common than mortality: this population has considerable burden from cCMV.

Although survival rates for infants of less than 26 weeks' gestation have increased, rates for those born at less than 24 weeks do not appear to have changed. While there are good data on overall survival, it is unclear how many infants are offered active resuscitation but do not survive. The study objectives were to describe the numbers receiving active treatment and the length of survival in infants live born at 22 or 23 weeks' gestation but who did not survive, and any changes over the last 15 years.The authors used a well-validated population-based database to identify deaths among live born infants born at 22 or 23 weeks' completed gestation between 1993 and 2007 from a single region in the north of England. The study period was divided into three 5-year cohorts. Survivors were identified from regional databases and individual case notes reviewed.During the study period, there were 480 662 total live births, of which 229 were live born at 22-23 weeks' gestation (birth prevalence of 0.05%). Of the 210 infants who did not survive, 71 (34%) survived for longer than 6 h. The median survival of those who died but had received active resuscitation and were still alive at 6 h of age was 11 h in 1993-1997 (n=17), 20 h in 1998-2002 (n=28) and 3.7 days (n=26) in 2003-2007.Over the last 15 years, increasing numbers of babies24 weeks received active resuscitation. Overall survival has not changed, but non-survivors endured significantly longer durations of intensive care.

Aims To establish whether there is variation in health care for children and young people with cerebral palsy (CP) across the north of England. Methods Retrospective case note review of 389 children and young people registered on the North of England Collaborative Cerebral Palsy Survey (NECCPS) living in 15 geographical districts, born 1995-2002, with subsequent data validation by clinicians involved in their care. Data was collected on magnetic resonance imaging (MRI) of brain (marker of aetiological assessment), hips, spines, pain, growth, and nutrition. Results The audit sample was representative of all children and young people registered with the NECCPS across a range of clinical and demographic factors. 221/389 (56.8%) children and young people had an MRI overall, with significant variation (p 259/389 (66.6%) had a discussion about pain recorded within the last 2 years. 110/126 (87.3%) cases where pain was present, had a management plan (figure 2). Those from the socio-economically most deprived quintile were significantly (p 69/373 (18.5%) had some degree of hip migration, of which 20.3% had complete hip dislocation. There was no record of hip status in 16/389 (4.1%). There was significant (p 31/66 (47%) of those with a spinal curvature were monitored by a spinal surgeon and 54/353 (33.1%) had their hips monitored by an orthopaedic surgeon, with inter-district variation in access to spinal and orthopaedic surgeons. 35/383 (9.1%) had received gastrostomy for feeding but there was no difference in Body Mass Index between this group and the rest of the sample. Only for 60% of the sample, weight was recorded within the last year. 119/389 (31%) had weight percentiles ascertained and recorded with a significant (p Conclusion There is variation in important aspects of health care for children and young people with cerebral palsy across the north of England. There is a need to work towards more equitable health care for the best health outcomes.

Introduction There are very few population-based data on congenital brain anomalies. The aim of this study is to provide estimates of associated anomalies, prevalence and clinical outcomes in pregnancies where a brain anomaly has been detected. Methods Data on all cases with a confirmed brain anomaly notified to the Northern Congenital Abnormality Survey 2000-09, formed this population-based case-series. Higher ascertainment was achieved by contacting neuroradiologists for confirmation of cases. Cases associated with multiple pregnancies, teratogenic syndromes, associations and skull anomalies were excluded. Results 470 cases were notified to NorCAS during the 10 years. 43 (9%) were associated with syndromes or microdeletions and 70 (15%) with chromosomal anomalies, of which 28 (40%) were with trisomy 13. There were 229 (49%) isolated brain anomalies giving a total prevalence of 7.3 (95% confidence interval (95%CI): 6.4-8.3) per 10,000 births. Termination of pregnancy occurred in 72 (31%) cases and fetal death in five. The live birth prevalence was 4.9 (95%CI: 4.1-5.7) per 10,000 live births. Hydrocephalus, cerebral cysts\schizencephaly, encephalocele and holprosencephaly were the most common with total prevalences of 2.0, 0.8, 0.7 and 0.7 per 10,000 births respectively. There was a male predominance (56%) overall and in most subgroups, except holoprosencephaly (41%). Conclusion This study is the first register based study to describe the prevalence of congenital brain anomalies. We found an association with trisomy 13 and identified hydrocephalus as the most common isolated anomaly. This information will help inform prenatal counselling when a brain anomaly is diagnosed.

Bladder Exstrophies and Epispadias Complex: Prevalence, Associated Anomalies, Prenatal Diagnosis and Survival in the North of England

Introduction Spina bifida is a serious congenital anomaly associated with life-long disability. This study describes trends in the prevalence and survival of spina bifida, to 10 years, using data from a long-standing congenital anomaly register in Northern England. Methods Cases of isolated spina bifida, delivered during 1985–2003, were identified from the population-based Northern Congenital Abnormality Survey (NorCAS). Survival status was determined from local to national records. Trends in prevalence and survival were examined by the Cochran-Armitage test and by Cox regression respectively. Results 500 cases of spina bifida were identified during the study, including 196 (39%) live born cases. The total prevalence of spina bifida was 7.5 (95% CI 6.9 to 8.2) per 10 000 total births, while the live born prevalence was 3.0 (95% CI 2.6 to 3.4) per 10 000 live births. Total prevalence decreased over time from 9.6 (95% CI 8.4 to 11.0) per 10 000 total births in 1985–1990 to 5.8 (95% CI 4.8 to 6.9) per 10 000 total births in 1997–2003 (p Conclusions The prevalence of spina bifida has decreased over time while survival for live born cases has significantly increased. These data are important for counselling families when a spina bifida is detected and for health service planning.

Correction to: International Journal of Obesity (2010) 34, 1371–1380; doi:10.1038/ijo.2010.66; published online 6 April 2010 After the publication of the article, the authors noticed a couple of minor errors in Table 2 , in Fetal characteristics section. The correct table is reproduced below. The authors would like to apologize for this mistake.

Objective To investigate the influences of survival in children born with Down Syndrome. Design Population-based case-series derived from the Northern Congenital Abnormality Survey. Setting A geographically distinct area of Northeast England, incorporating North Cumbria, Northumberland, Tyne and Wear, Country Durham, and the Tees Valley. Participants 1101 individuals with Down Syndrome delivered between 01 January 1985 and 31 December 2003, of whom 697 were live born and 664 (95%) were traced for their survival status on 28 January 2008. Main outcome measures Overall prevalence of Down Syndrome. Frequency of additional structural anomalies among cases of Down Syndrome. 10-year survival for all cases of Down Syndrome, by time-period, and by presence, and type, of additional structural anomalies. Independent influence of year of birth, sex, plurality, gestational age, birthweight (standardised for sex, plurality, and gestational age), maternal age, index of multiple deprivation, prenatal diagnosis, and presence, and type, of additional structural anomalies on survival. Results Overall prevalence of Down Syndrome was 16.7 per 10 000 registered births (95% CI 15.6 to 17.6). 697 (63%) cases had no additional structural anomalies, 320 (29%) had isolated cardiovascular anomalies, 27 (2%) had isolated digestive system anomalies, 26 (2%) had both cardiovascular and digestive system anomalies, and 31 (3%) had at least one other structural congenital anomaly. 10-year survival among children born with Down syndrome was 83.9% (95% CI 80.9 to 86.5). Survival increased significantly with time (p Conclusion Independent of significant improvement over time, survival of children born with Down syndrome is influenced by gestational age, birthweight, and the presence of additional structural anomalies. This information will be valuable for families and health care professionals when Down Syndrome is detected, and will assist in planning, assessing, and aiding, the future care needs of those affected.

Background While the association between maternal age and the risk of chromosomal anomalies is well established, uncertainty remains for structural (ie, non-genetic) anomalies. This study used data from North East England and North Cumbria to investigate the relationship between maternal age, young or advanced and the risk of structural congenital anomalies. Method Congenital anomaly cases without known chromosomal or genetic features, delivered between 1985 and 2004, were identified from the population-based Northern Congenital Abnormality Survey. The age distribution of case mothers and the general maternal population were compared using χ 2 tests. The relative odds of a structural anomaly for young maternal age (below 20 years) and advanced maternal age (30 years or over), were determined for all groups and subtypes with at least 100 cases. Results 11 422 pregnancies were affected by a structural congenital anomaly. The odds of a pregnancy affected by a structural anomaly were significantly greater among young mothers (OR 1.13 (95% CI 1.07 to 1.20), p Conclusion This study found evidence of an association between maternal age, young and advanced and the risk of certain structural congenital anomalies.