National Congenital Anomaly Research Articles

Implementation of a national rapid prenatal exome sequencing service in England: evaluation of service outcomes and factors associated with regional variation.

Prenatal exome sequencing (pES) can enhance genetic diagnosis of fetuses with structural anomalies and has recently been introduced as a national service in England. We aimed to examine service outcomes such as diagnostic yield (definite final diagnosis), referral rate, and sources of referral, and explore variation in outcomes of pES by individual or service level factors between 01 October 2021 and 30 June 2022. pES testing results from the National Health Service laboratories performing testing were linked to National Congenital Anomaly and Rare Disease Registration Service data and the Maternity Services Data Set and descriptive statistics computed. There were 475,089 women who gave birth in England during the study period. The referral rate for pES was 8.6 (95% CI 7.8, 9.4) per 10,000 maternities. About 59% of those referred proceeded with pES testing and 35% of women who proceeded received a definite final diagnosis with a median turnaround time of 15days. Of those who had pES testing, 64.6% had a live birth, 25.3% underwent termination of pregnancy (median gestational age at termination: 26weeks), and 9.3% had a stillbirth. Among the 85 women who had a definite final diagnosis, 40% had a termination of pregnancy, 18% had a stillbirth, and 42% had a live birth. The corresponding figures among women without a definite final diagnosis were 18%, 5%, and 78%, respectively. Among women who had a termination of pregnancy, the median gestational age at final report was 24.9weeks and 26.2weeks at termination. Variation observed in some of the characteristics and outcomes between regional services were limited by small sample size. This study showed that of those referred, pES testing provided a diagnosis for one in three pregnancies with a fetal anomaly across England during the study period when other tests had been non-informative. Women who opted for a termination of pregnancy underwent the procedure at relatively late gestations. Earlier referral for pES, streamlining pathways, and faster turnaround times may help results to be available at an earlier gestation to allow families more time to make decisions around continuing or terminating their pregnancy. The variation in service outcomes between regional services needs to be investigated further to understand the reasons for these differences.

Prevalence of neural tube defects in England prior to the mandatory fortification of non-wholemeal wheat flour with folic acid: a population-based cohort study

ObjectivesTo determine the baseline trends in the total birth prevalence of neural tube defects (NTDs) in England (2000–2019) to enable the impact of folic acid fortification of non-wholemeal wheat flour...

Cohort profile: the National Congenital Anomaly Registration Dataset in England

PurposeThe National Congenital Anomaly and Rare Disease Registration Service (NCARDRS), part of National Disease Registration Service in National Health Service England, quality assures, curates and analyses individual data on the...

673 The Role of the First Postnatal Ultrasound Scan to Predict Outcome in Children with Antenatally Diagnosed Hydronephrosis

Abstract Aim We aimed to determine if the renal pelvic diameter on the first postnatal scan can predict the need for surgical intervention in children with antenatally diagnosed hydronephrosis. Method Data of all babies with antenatal hydronephrosis born in our centre from 2009–2015 were obtained from the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS). The medical records were analysed retrospectively for diagnosis, investigations, and interventions. Mean follow-up was 7 (4–10) years. The results were expressed as mean and percentage. Statistical data analysis was performed on GraphPad. Results 224 babies were included in the study. 162 (72%) were males, and 92 (39%) had bilateral hydronephrosis. 163 (73%) had spontaneous resolution of hydronephrosis. The resolution rates were similar for unilateral and bilateral cases. The mean renal pelvic diameter was 6.2mm in the resolved group and 16.2mm in the persistent group (p<0.01). The highest renal pelvic diameter undergoing spontaneous resolution was 24mm. Of the 61 (27%) children with persistent hydronephrosis, 38 (17%) children required surgery. Pyeloplasty for pelviureteric junction obstruction was the most common procedure. 23 (10%) patients continued to have persistent dilatation but needed no intervention. Renal duplex was the most common diagnosis in this group, followed by vesicoureteric reflux. All babies with a pelvic diameter of 25mm or above on their first postnatal ultrasound required surgical intervention. Conclusion The majority of antenatal hydronephrosis resolves spontaneously. However, interventions are necessary if the pelvic diameter is above 25mm.

P302 Trends in hospital admissions in patients with ANCA-associated vasculitis before and during the COVID-19 pandemic

Abstract 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.

My Heart Has Double Outlet What?

The aim of this case is to illustrate the rarity of this condition alongside complications that can occur post-surgical repair. In addition, the patient who generously consented for this case to be written has wished for increased awareness of double outlet right ventricle (DORV) among aspiring paediatricians, surgeons and cardiologists. A 40-year-old British Caucasian male presented with 2 concurrent episodes of chest pains. He has had a complex surgical repair of his DORV at age 32 with a pulmonary valve replacement which was complicated by endocarditis and an out of hospital ventricular tachycardia (VT) arrest at age 34 which resulted in hypoxic brain injury, permanent short term memory loss and an implantable cardioverterdefibrillator (ICD) insertion. Urgent ICD interrogation revealed evidence of spontaneous fast VT which were terminated back to sinus rhythm with 2 shocks. In view of recurring episodes of VT, commenced amiodarone and arranged further regular follow-up. With a birth prevalence of 0.02% based on the UK’s national congenital anomaly statistics, it is one of the less commonly occurring congenital heart defects in the UK. There has been massive advancement in our understanding of the condition and how to treat it which includes surgical intervention. However, the overall risks regarding mortality and complications post-surgery are still not well understood. Long term complications such as VT as demonstrated in this case carries a potential life-threatening risk and more research is needed in understanding how to effectively screen and prevent it.International Journal of Human and Health Sciences Supplementary Issue-2: 2021 Page: S14

POS1412 IDENTIFYING HIGH-COST DRUGS FOR RARE RHEUMATIC DISEASES IN ROUTINELY COLLECTED NHS DATA. RESULTS FROM A PILOT STUDY OF RITUXIMAB USE IN VASCULITIS USING DATA FROM THE NATIONAL DISEASE REGISTRATION SERVICE AND THE REGISTRATION OF COMPLEX RARE DISEASES-EXEMPLARS IN RHEUMATOLOGY (RECORDER) PROJECT

Background:Understanding real-world usage of high-cost drugs is crucial to support planning, adoption of innovation and reduce unwarranted variation in treatment. Hospital Episode Statistics (HES) contain diagnoses (coded by ICD-10) and procedures/treatments (coded by OPCS) for all daycase or inpatient care in England. However, OPCS codes are not specific for individual drugs, for example X921 (cytokine inhibitors band 1) includes rituximab (RTX) and 15 other drugs.Objectives:We aimed to validate the accurate identification of patients treated with RTX for ANCA-associated vasculitis (AAV) using HES data.Methods:We used data from the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) at Public Health England and their legal permissions (CAG 10-02(d)/2015). We extracted records from HES of all patients treated at two hospitals during financial year 2018/19 who ever had a coded diagnosis of granulomatosis with polyangiitis (GPA, M313), eosinophilic granulomatosis with polyangiitis (EGPA, M301), microscopic polyangiitis (MPA, M317), polyarteritis nodosa (PAN, M300) or arteritis unspecified (I776). Where people had multiple diagnoses of vasculitis, the most specific was considered their diagnosis. Enabled by data sharing agreements, we reviewed hospital records of those patients to validate diagnoses and whether X921 reliably identified RTX. We report the positive predictive value and sensitivity of the coding for X921 and GPA/EGPA/MPA for identifying people with AAV who are treated with RTX.Results:At Trust 1 records ever coded with GPA/EGPA/MPA identified 74 people, 69 of whom had AAV confirmed in their medical notes. Among these 74 patients there were 59 episodes coded with X921 procedure codes, of which 56 correctly identified a RTX infusion given for AAV. A total of 64 RTX infusions were given to people with AAV – 3 missed infusions were X921 procedures in patients who had coded diagnoses of PAN or I776 but never GPA/EGPA/MPA and 5 infusions were not coded as X921.The same analysis at Trust 2 identified 46 people, 44 of whom had AAV confirmed in their medical notes. Among patients identified with AAV there were 17 episodes coded as X921, of which 15 correctly identified a RTX infusion. A total of 23 infusions were given to people with AAV: 4 infusions were X921 procedures in patients who had coded diagnoses of PAN or I776 but never GPA/EGPA/MPA, and 4 infusions were not coded as X921.Table 1. Summary of Positive Predictive Values (PPV) applying our algorithm to identify AAV diagnoses and RTX useTrust 1Trust 2CombinedDiagnosis of AAV and coded as AAV6944113AAV coded7446120Diagnosis of AAV under any code7355128PPV AAV ascertainment (95% CI)93.2% (84.9-97.8)95.7% (85.2-99.5)94.2% (88.4-97.6)Sensitivity of AAV ascertainment (95% CI)94.5% (86.8-98.5)80.0% (67.0-89.6)88.3% (81.4-93.3)RTX given in people coded as AAV561571RTX coded in people coded as AAV591776RTX given for AAV under any diagnostic or procedure code642387PPV RTX ascertainment (95% CI)94.9% (85.9-98.9)88.2% (63.6-98.5)93.4% (85.3-97.8)Sensitivity of RTX ascertainment (95% CI)87.5% (76.8-94.4)65.2% (42.7-83.6)81.6% (71.9-89.1)Conclusion:HES data identified patients treated with RTX for AAV with a PPV of 93.4% (85.3-97.8) and sensitivity of 81.6% (71.9-89.1). This demonstrates the utility of national data to identify people receiving RTX for AAV. The RECORDER project, within the National Disease Registration Service plans to conduct real-world studies of the high-cost drug RTX, given for AAV, across the whole of England, and assess whether geography, demographics or socioeconomic factors influence frequency of prescription of this, and potentially other, high-cost drugs in line with the NHS long term plan.

O24 Risk of death during the 2020 UK COVID-19 epidemic and annual influenza seasons among people with vasculitis compared to the general population: a whole-population study using data from the NDRS and the RECORDER project

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..

P090 Validation of hospital episode statistics data to enable national registration of idiopathic inflammatory myopathies

Abstract 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.

P054 Risk of death during the 2020 UK COVID-19 epidemic among people with rare diseases compared to the general population

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.

P091 Can use of high cost drugs for rare rheumatic diseases be reliably identified within routinely collected NHS data? Results from a pilot study of rituximab use in vasculitis using data from the National Disease Registration Service (NDRS) and the Registration of Complex Rare Diseases - Exemplars in Rheumatology (RECORDER) project

Abstract 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.

An exploratory linkage and analysis of national congenital anomaly and medication dispensing data in the United Kingdom

An exploratory linkage and analysis of national congenital anomaly and medication dispensing data in the United Kingdom

P134 Collaborating with the National Congenital Anomaly and Rare Disease Registration Service to estimate national incidence of Kawasaki disease in England

Abstract 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 <5, and 4234 cases in children <16 in England. The incidence in children aged <5 years was 7.50 (95% CI: 7.25-7.76)/100,000 person-years, and 40.7% of cases were female. Incidence in children aged <16 was 3.09 (95% CI: 3.00-3.19)/100,000 person-years, and 41% of cases were female. 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.

P182 Prevalence and mortality of ANCA-associated vasculitis in England

Abstract 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.

O36 Validation of methods to enable national registration for rare autoimmune rheumatic diseases

Abstract 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.

Access to antenatal healthcare and the prevalence of oral clefts: a spatial analysis.

Congenital anomalies are caused by a variety of risk factors, including individual and environmental ones. This study estimated the prevalence of oral clefts and examined their area-level risk indicators using data from The National Congenital Anomaly Survey in South Korea. Disease mapping and ecological regression were used to assess the geographical variation and potential risk indicators for oral clefts, such as living in a rural area, material deprivation, and limited access to antenatal healthcare. In South Korea, 1.15 (95% CI, 1.08-1.23) children out of every 1,000 births were born with oral clefts during 2005 and 2006. The most common oral cleft type was cleft palate, followed by cleft lip, then cleft lip and palate. Disease mapping showed that the proportion of areas with a higher risk than the national average was relatively higher for oral clefts than for all congenital abnormalities among rural and healthcare underserved areas. The relative risk of oral cleft prevalence was higher in rural areas and healthcare underserved areas than in urban areas and areas with better access to healthcare. The findings suggest that access to antenatal healthcare as well as area-level risk indicators should be considered a priority when developing measures to decrease the occurrence of oral clefts.

The national congenital anomaly and rare disease registration service (NCARDRS)

The national congenital anomaly and rare disease registration service (NCARDRS)

Linking the National Down Syndrome Cytogenetic Register to Hospital Episode Statistics: Methods and challenges

BackgroundLinking national disease and congenital anomaly registers to other routinely collected data could provide multiple benefits. It could allow researchers to examine long-term outcomes for people with registered conditions and to explore synergies between services that are provided in different sectors, such as health and education. Linkage could also allow for the quality of diagnostic codes in electronic health records to be assessed using the national registers coverage and, conversely, for coverage of the national registers to be assessed using diagnostic codes.
 ObjectivesTo demonstrate the feasibility and value of creating a linked data resource to support research on health, social and educational services and outcomes for children with Down’s Syndrome.
 MethodsWe are currently linking the National Down’s Syndrome Cytogenetic Register (NDSCR), which includes all births with Down’s syndrome from 1989 to 2014 in England and Wales, to Hospital Episode Statistics (HES) for England and ONS Mortality data, and to the National Pupil Database (NPD). This requires a complex sequence of new linkages: (1) linkage of mothers to babies in HES, (2) linkage of mother-baby pairs to the NDSCR to identify a population cohort, (3) linkage of the cohort to the Personal Demographic Service to update address histories, and (4) linkage of updated cohort to NPD.
 FindingsEstablishment of this linked data resource has met with significant challenges. The main administrative challenge has been incompatible accreditation of information governance across government departments. Technical challenges have included overcoming issues with the internal linkage of contributing datasets, requiring additional linkage steps to be added, and the propagation of error and uncertainty across multiple linkages, which involves complex data structures that require novel ethods for analysis.
 ConclusionsWe hope this project will demonstrate that while the challenges to intersectoral data linkage are great, they are surmountable and the benefits outweigh the costs.

Development and progress of the National Congenital Anomaly and Rare Disease Registration Service

Public Health England (PHE) was formed in April 2013; at that time, regional congenital anomaly registers covered just 49% of births in England.1 A national congenital anomaly surveillance system managed...

613 Congenital Diaphragmatic Hernia Surveillance in Ireland

IntroductionThe incidence of Congenital Diaphragmatic Hernia (CDH) varies from 1 in 2,000 to 15,000 births per annum. Due to the legislation prohibiting termination of any pregnancy in the Republic of...