Fetal therapy: progress made and lessons learnt.

Fetal therapy began more than half a century ago when Liley reported the first intraperitoneal transfusion for the treatment of fetal anaemia in Rhesus disease (Liley, 1963). This was to be replaced with intravascular transfusion, initially by fetoscopy and subsequently by ultrasound-guided cordocentesis. This is now a wellestablished therapy and one which was never subjected to rigorous evaluation. In this issue of Prenatal Diagnosis, we focus on fetal therapy, exploring how far it has developed since these early reports and discuss how new approaches might further change management, highlighting the need for rigorous evaluation of any new technology prior to clinical implementation. The widespread use of ultrasound scanning in the 1980s and the prenatal detection of fetal defects stimulated the development of a wide range of techniques for intrauterine interventions. The aim was to improve the outcome for conditions that were traditionally treated by postnatal surgery because it was thought that prenatal surgery could reduce irreversible damage to the developing organs. However, for the large part the absolute benefit in terms of improved longer term outcome for affected fetuses remains unknown. It is only in the last few decades or so that we have realised that the only way to properly assess many of these therapies is with randomised trials, which must include structured long-term follow-up to determine the true benefits and costs. A good example is the management of lower urinary tract obstruction where shunting initially seemed to improve outcome as more babies survived the neonatal period. However, most studies were small and had no control group, thus making it impossible to define any benefit resulting from the intervention and longer term follow-up was patchy and inconsistently collected (Ruano, 2011). Furthermore, because of the rarity of many of these conditions, much of this research must be multicentre and multinational, raising an issue in itself as these techniques will be concentrated in centres of excellence, thereby limiting equity of access and focussing expertise in a few centres (Ville, 2011).