Research in fetal medicine

The Problem The sanctity of the fetal environment provides a formidable barrier to research endeavour. The fetus appears to lie inaccessible within the pregnant abdomen, vulnerable to exogenous insults causing teratogenicity, miscarriage and premature delivery. Mothers understandably regard their babies as ‘precious’, and ethical constraints preclude all but so-called low-risk research. Whereas adult medicine advances swiftly owing to modern technology, fetal medicine lags behind, denied the progress in knowledge that would accrue from positron emission tomography, nuclear medicine, interventional radiology, metabolic challenge, cardiac catheterisation, direct drug therapy, invasive circulatory monitoring, chronic arterial or venous access and serial tissue biopsy. The Field The modern subspecialty of fetal medicine owes its origins to two parallel developments: the advent of high-resolution ultrasound, and the access to the fetus provided by invasive procedures. In particular, fetal blood sampling has allowed biochemical and haematological investigation as well as direct therapy by transfusion. Despite considerable research activity using these tools over the last 25-30 years, many questions remain. In physiological terms, for instance, we do not fully understand what causes circulatory redistribution (‘brain sparing’) in response to hypoxaemia, while in clinical terms, despite progress, to date there have been only a small number of randomised controlled trials (RCT) published for invasive fetal therapy. A greater understanding of fetal physiology is needed to advance the field of fetal therapy, with its expanding scope from open surgery through fetoscopic and percutaneous approaches, as well as stem cell and gene therapy. At the moment, however, knowledge of pathological states, obtained through such techniques, is advancing much faster than knowledge of physiology, for the over-riding ethical reasons mentioned above. Fetal medicine, however, is by no means limited to ultrasound and invasive procedures. A glance at the index of any of the mainstream journals in obstetrics and gynaecology reveals that around half of the published articles deal with the fetus and/or placenta. The ‘big three’ problems in obstetric practice - preterm labour, growth restriction and pre-eclampsia - are arguably more fetal than maternal, their origins lying with impaired trophoblastic invasion or altered signalling between the fetus and placenta/membranes.