Fetal Medicine

Work in fetal medicine led by Professor Nicholas Fisk and Dr Helena Gardiner aims to develop fetal therapies. Building on our clinical research foundation (first reports of pleuro-amniotic shunting, combined intravascular and intraperitoneal transfusion, fetal analgesia, pulmonary valvoplasty, interstitial laser, cord occlusion for twin-twin transfusion syndrome (TTTS), serial amnio-infusion, maternal sulindac therapy in monoamniotic twins), the clinical focus will be to reduce the high incidence of perinatal death and brain injury in unbalanced monochorionic inter-twin transfusion (1 in 400 pregnancies). After characterising the placental vascular basis and circulatory consequences of TTTS, we developed Doppler techniques for visualising functional anastomoses, which protect against TTTS and improve survival, and are now applied clinically to determine prognosis and treatment. We are major contributors to the international registry of TTTS and a large multicentre randomised trial. Although major improvements in outcome have been achieved, two-thirds of affected pregnancies still suffer at least one dead or brain-injured child, with treatment-related complications problematic. Our five-year plan aims to develop better therapeutic methods. The shorter- term surgical approach comprises leading a multicentre trial of aggressive versus palliative therapy to address the controversy in Stage I disease, while the longer-term approach aims to interrupt the paradoxical discordant placental RAS activation we have shown in TTTS.

 

Another major component of this programme in experimental fetal medicine is developing treatment in utero for disabling genetic conditions such as osteogenesis imperfecta, muscular dystrophy and mucopolysaccharidoses, using stem cell populations which we have characterised in the early human fetus and have shown engraft mothers for life.

Translational proof-of-principle studies are planned to build on our promising animal work showing a two-thirds reduction in fractures in osteogenesis imperfecta.

Patient-based studies will also involve development of ultrasound-guided and endoscopic techniques for feto-placental stem cell harvest in early pregnancy.