My Research on PPROM by David Barrett
PPROM remains a devastating complication for expectant mothers of the 21st century; affecting 2% of all pregnancies and complicating 40% of preterm births. It has many causes such as excessive vaginal bleeding that appears to weaken the membrane, and uterine contractions that stretch the fetal membranes.
Fetal surgery is increasingly being offered to surgically repair structural problems in the baby before birth. This requires a small hole to be made in the fetal membranes for access to the amniotic cavity.
The hole never seals as the fetal membranes have very limited healing powers, and PPROM frequently complicates these pregnancies. The fetal membranes have been studied by several research groups over the past 30 years, but we are only now beginning to understand why the fetal membranes respond differently than other types of tissue to trauma.
Why don’t fetal membranes heal?
During the past 3 years I have worked with clinicians at UCLH and scientists at Queen Mary University of London to ask the question: Why do fetal membranes fail to heal? This multidisciplinary approach has increased our understanding why this is at a molecular level and to develop new ways to seal the defect using biomaterials and nanotechnology.
We have discovered that there are high levels of a protein called connexin-43 in certain types of cells at the leading wound edge of the amniotic membrane. Comparisons can be drawn with other types of tissue that fail to self-heal. Diabetic skin wounds that heal poorly also show high amounts of this protein.
When I have looked at fetal membranes taken even 10 weeks after fetal surgery, the connexin-43 protein remains at high levels. We believe that this protein alters the normal behaviour of healing cells. Microscopy techniques have enabled us to identify different patterns in collagen, which is the main component of fetal membrane tissue. At the wound edge, collagen is deposited in highly aligned bundles that circle the wound edge. This is likely to further reduce the ability of cells to mount a normal healing response.
Working with researchers from a variety of backgrounds is vital to this kind of translational research. I am now working with material scientists to develop effective ways to seal fetal membrane defects. By using small molecules designed in our lab we can grow new biomaterials that mimic fetal membrane architecture at the defect using nanotechnology.
UCLH Charity registration no. 229771
This effectively seals the hole and provides a barrier to prevent amniotic fluid leakage.
Over the next few years our research is developing a novel bioengineering solution for PPROM prevention and treatment, with funding from SPARKS and GOSH Children’s charity and the UCLH Prenatal Therapy charity.
You can help support this project by either donating to the Little Heartbeats UCLH Prenatal Therapy charity by texting PROM49 £2 to 70070 or by joining the Little Heartbeats UCLH fundraising team by opening a Just Giving page
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