David BarrattPreterm premature rupture of membranes (PPROM) is the rupture of fetal membranes prior to 37 weeks development and before the onset of labour. It can occur spontaneously after bleeding or contractions in pregnancy, or it can occur after fetal surgery, which is increasingly offered to treat life-threatening conditions in the baby before birth.

Fetal membranes surround the baby in the womb protecting it from harm. Once they rupture, they almost never heal, leaving the baby vulnerable to infection and preterm birth. In fact 40% of preterm births are due to PPROM.

Preterm birth can be fatal. When babies are born with immature vital organs, they often cannot survive outside the womb, and those that do, will more likely experience complications such as problems with breathing, gut and brain development.

Professor Anna David, a leading consultant in obstetrics and fetal medicine at UCLH, says that there is very little research into PPROM and scientists are yet to understand why fetal membranes fail to heal after they rupture.

“The lack of research and treatment for PPROM is exactly why it is so important to fund”, says Anna. “I frequently see pregnant women who have ruptured their membranes and it is frustrating that we cannot offer them a treatment.” She adds that developments in this field have the potential to save lives and prevent major complications associated with PPROM and subsequent preterm birth.

Now, under the supervision of Anna, PhD student, David Barrett will develop a plug to repair fetal membrane defects following fetal surgery to prevent PPROM. Scientists at UCL found that slow healing skin wounds, for example in diabetic skin, had high levels of a protein called connexin 43. Reducing the levels of this protein in skin using a gel called NexagonTM can accelerate the wound healing process. David wants to test out if this might heal defects in the fetal membranes. In the past, collagen plugs have been trialled to seal fetal membranes, but when tested in pregnant women, the plug failed as it dissolved in the amniotic fluid after only a few hours, and did not seal the defect. David’s new plug formulation, developed with researchers from Queen Mary University of London, is more resistant to amniotic fluid, so does not break down when exposed to it.

Enthused by the potential that his project brings, David says “cross-disciplinary research is essential for tackling many healthcare problems. In this instance, working with tissue engineers, material scientists, cell biologists, and clinicians from UCLH, UCL and Queen Mary University of London, has helped design a novel approach to an old problem within fetal surgery.”  David claims that his new plug is created “using three-dimensional architectures that mimic tissue structure within the fetal membrane. Importantly, the plug must provide a barrier to prevent amniotic fluid leakage and allow the pregnancy to progress until it is safe to deliver.”

David is supervised by Dr Tina Chowdhury from the School of Engineering and Material Sciences at Queen Mary University of London, who says, “To have potentially found a way to reduce pre-term births and prevent early deaths of young babies worldwide is incredibly exciting. The unique bioengineering tools at QMUL and UCL have allowed us to test the tissue in a way that has never been done before. This gives us an understanding of both the mechanical as well as biological mechanisms involved and will help us to develop therapies that will reduce the number of pre-term births.”

With financial support from Professor David’s Prenatal Therapy Fund held at UCLH Charity, along with a grant from the Rosetrees Trust, David has begun trialling the plug, and so far, has shown that it can seal holes in samples of human fetal membranes taken at delivery. Further work is needed to optimise the plug and then to test the safety and effectiveness in PPROM. “If this is successful we will then need to trial it in women before it is possible to come in to NHS provision.”

To find out more about UCLH Fetal Medicine Unit, visit http://www.uclh.nhs.uk/ourservices/servicea-z/wh/mat2/yourpregnancy/FMU/Pages/Home.aspx. To donate to this project, visit the UCLH Prenatal Therapy Just Giving page: https://www.justgiving.com/fundraising/UCLH-Prenatal-Therapy-Fund.

Since publication of this article, David has won the young investigators Malcolm Ferguson-Smith Award for the best paper by a junior scientist. His work is published in the Prenatal Diagnosis Journal.