All the commonly used drugs that produce general anaesthesia have been shown to increase brain cell death in young laboratory animals and lead to abnormal function later on. Mounting concern about the potentially toxic effects of anaesthetic drugs on the young brain has led to 76 studies since 1990 which have attempted to measure the brain development and functioning of humans who were given general anaesthetics for surgery or procedures in early childhood. Aspects of brain development which have been examined include measures of intelligence, movement and co-ordination, behaviour, language and speech, literacy and numeracy. Other measures have included academic achievement in school and diagnoses of learning disability, autism and attention deficit hyperactivity disorder (ADHD). Unfortunately, these human studies are frequently of limited quality, with: too few children (on average 130 cases), no method to account for other causes of adverse brain development which could bias the results, no information on the duration and type of general anaesthetic drugs given and not specifically designed to assess children's brain development. Their results are conflicting and somewhat difficult to interpret. At present, it remains uncertain whether anaesthetic drugs are harming young childrens' brains. The definitive results of a single clinical trial specifically designed to address this important question are not due for several years. In the meantime, the number of published review articles, commentaries, consensus statements and statements by regulatory bodies continues to grow. The United States Food and Drug Association urges careful consideration of the risks and benefits of a general anaesthetic in young children and pregnant women undergoing anaesthesia which may last longer than three hours or require multiple procedures.

Our project will determine whether there is evidence of impaired long-term brain development in ALSPAC data, specifically those children who had general anaesthetics for surgery or procedures before the age of four. We anticipate that the detailed information recorded about these children and their parents, as well as the quality of assessment of their brain development throughout childhood and adolescence, will allow us to better investigate this important issue than previous human studies have been able to do. We also propose to collect new information from childrens' medical records in order to describe the types and duration of general anaesthetics which were given in the early 1990s for different surgeries or unpleasant procedures. This will help us to determine whether increased duration of anaesthesia is associated with additionally worse brain development, and will allow us to place the findings of the ALSPAC study in context with changes to paediatric anaesthetic practice in the last two decades, as well as enhancing the utility of the ALSPAC resource to future anaesthetic research.