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Funder: National Institute for Health Research (NIHR), INTRODUCTION: There has been an increase in the birth prevalence of congenital hypothyroidism (CH) since the introduction of newborn screening, both globally and in the UK. This increase can be accounted for by an increase in CH with gland in situ (CH-GIS). It is not known why CH-GIS is becoming more common, nor how it affects the health, development and learning of children over the long term. Our study will use linked administrative health, education and clinical data to determine risk factors for CH-GIS and describe long-term health and education outcomes for affected children. METHODS AND ANALYSIS: We will construct a birth cohort study based on linked, administrative data to determine what factors have contributed to the increase in the birth prevalence of CH-GIS in the UK. We will also set up a follow-up study of cases and controls to determine the health and education outcomes of children with and without CH-GIS. We will use logistic/multinomial regression models to establish risk factors for CH-GIS. Changes in the prevalence of risk factors over time will help to explain the increase in birth prevalence of CH-GIS. Multivariable generalised linear models or Cox proportional hazards regression models will be used to assess the association between type of CH and school performance or health outcomes. ETHICS AND DISSEMINATION: This study has been approved by the London Queen Square Research Ethics Committee and the Health Research Authority's Confidentiality Advisory Group CAG. Approvals are also being sought from each data provider. Obtaining approvals from CAG, data providers and information governance bodies have caused considerable delays to the project. Our methods and findings will be published in peer-reviewed journals and presented at academic conferences.

Aim Azathioprine is an effective immunosuppressive agent for the management of a wide spectrum of diseases, including systemic lupus erythematosus, vasculitis and in renal transplantation. Myelosuppression is a known major side-effect so some authors advocate that erythrocyte thiopurine transmethyltransferase (TPMT) activity is required to identify those patients at increased risk. In such cases, the azathioprine dosage can be adjusted prior to prescribing. However, there is a lack of data to support routine TPMT monitoring in paediatric patients. Methods Retrospective study in a single paediatric centre of all patients who had TPMT enzyme assay measured over a three year period prior to the commencement of azathioprine therapy. Patients with TPMT enzyme activities of 26-50, 10-25 and Results 363 (51% female) patients aged 1-19 (median 10.2) years were tested for TPMT activity of whom 228 patients were subsequently commenced on azathioprine. Erythrocyte TPMT activities were 14-76 (median 33.7) pmol/h/mgHb with 88% and 12% of patient having normal and intermediate activity respectively (none were deficient). The initial prescribed dosage of azathioprine was 0.7-3.5 (median 2.0) mg/kg/day. Only two patients required reduction of azathioprine dosage due to mild neutropenia in this cohort. Conclusion This is the first large paediatric cohort study which demonstrates that the majority of paediatric patients had normal TMPT activities and no patients developed severe neutropenia as a result of azathioprine treatment. We estimate the cost for testing this patient cohort was £16,000 without clinical benefit. We would recommend close monitoring of full blood counts after instituting azathioprine therapy but would question the value of pre-treatment TPMT activity in paediatric practice.