Antenatal carrier screening for cystic fibrosis
This thesis explores the advantages and disadvantages of various aspects of antenatal carrier screening for cystic fibrosis, taking into account both psychological and economic factors. It also provides information specific to the implementation of screening within Grampian region. Following the introductory literature review, a population genetic study of CF in Grampian region is described. In addition to giving information about the incidence and prevalence of the disease itself, the relative frequencies of the common CF mutations are detailed. Next, there is an assessment of different molecular methods for CF mutation detection. The remainder of the thesis comprises a comparative evaluation of two different approaches to antenatal CF carrier screening, namely step-wise (disclosure) and couple (non-disclosure) testing. The evaluation covers both psychological and economic aspects of screening. Grampian was found to have a higher prevalence of the common CF mutation F508 than the southern Scottish population. Thus testing for the four commonest mutations allows detection of 92% of carriers. The use of multiplex ARMS, dot-blotting and a deletion/digest/PAGE method were compared. The multiplex ARMS system was sensitive, specific and robust, and required less labour than the other methods. Step-wise antenatal carrier screening was found to be associated with transiently high levels of anxiety amongst carriers, which dissipates when a negative partner's result is received. For the majority of screenees who will test negative, couple screening is associated with more anxiety and false reassurance. Step-wise screening was found to be slightly less expensive than couple screening. When asked to state their preferred method, more women chose step-wise than couple screening.