Preterm Labour

Preterm labour is the major cause of infant deaths and long-term handicap, particularly <32 weeks, with 8000 births p.a. in the UK at birthweights under 1500g.

Infection and inflammation are important causes of both preterm labour and cerebral palsy.

Laboratory research, which depends on accurate clinical-phenotyping linked to tissue collection, focuses on the mechanisms by which labour begins, in particular regulation of gene expression changes with labour onset and identification of ways in which these could be inhibited clinically.

Earlier basic findings, such as the central role of COX-2 in parturition and the effects of progesterone on uterine gene expression, have led to large clinical trials, both completed (TOCOX for COX-2 inhibitors), current (OPPTIMUM for progesterone) and future.

In the next five years Professor Phil Bennett’s group plans translational studies arising from our demonstration of key roles for the NF kappaB and AP-1 transcription factor systems in both preterm labour and neonatal brain injury, with the role of inhibitors currently being explored in an animal model.

Mr Mark Johnson’s group have focussed on the role of stretch in preterm labour, particularly in multiple pregnancy. His group has identified an essential role for mitogen activated protein kinases in stretch-induced pro-labour gene expression and are planning in vivo studies to investigate the efficacy of specific inhibitors. Clinical research findings, especially relating to cervical length and cervical cerclage, have become applied clinically both in our ‘prematurity clinic’ and by obstetricians generally, resulting in better targeting of patients for in-patient care and thus reduced cost.

We will complete our current trial of cervical cerclage (CIRCLE), which will impact practice as soon as reported.  Pivotal negative studies of non-steroidal drugs have translated into discontinuation of their use. The focus in the next five years will be on improving selection of women at high risk of preterm labour by combining biochemical tests with transvaginal ultrasound, and targeting preventative therapy using progesterone and novel inhibitors under development.