Episode 93: Finding out more about preterm births, fetal surgery, and fetal gene therapy!

This week, Dr. Bahijja talks more about preterm births, fetal surgery and fetal gene therapy with Professor Anna David, consultant at UCLH and leader of the UCL Institute of Women’s Health.

What is preterm birth?

“A preterm birth is when a baby is born before 37 weeks of pregnancy” – Professor David

Usually, pregnancy lasts about 40 weeks – however preterm births occur a few weeks earlier. Preterm births can be accompanied by complications ranging from short-term problems with breathing, keeping warm and blood sugar, to more long-term problems such as being at greater risk of suffering from a heart attack, or from diabetes. The earlier you are born, the more of a problem it is.

Globally, 15 million births a year are preterm – in the UK, the rate of preterm birth is about 7%. It’s an expensive problem, costing the public sector around 3 billion per year. If delivery could be delayed by just one week, the cost would be reduced to 2 billion. Preterm birth is such a costly issue due to both the short and long-term problems it causes – preterm babies must stay in special care for a few weeks, but in the long-term, they are also more likely to have problems in school, have a greater risk of having ADHD and are less likely to stay in employment.

“It is the second leading cause of childhood death” – Professor David

There are multiple reasons that women may deliver early – sometimes they go into labour themselves in what is called ‘spontaneous preterm birth’, the most common cause. However, illness can also result in early delivery, such as pre-eclampsia which causes high blood pressure and protein in urine, affecting up to 5% of women in their first pregnancy. Such illnesses are more related to the way in which the placenta develops, and placental insufficiency, which causes the baby to be growth restricted.

How can preterm birth be prevented?

Preterm birth is a pressing but difficult issue to tackle as it is multifactorial; social deprivation, racism, employment status, smoking, drug taking and the state of health at conception all influence the chance of preterm birth. In particular, obesity during pregnancy has been associated with a greater risk of pre-eclampsia, gestational diabetes and preterm birth. However, it isn’t all about weight – rather, overall fitness.

“Pre-conception care is key” – Professor David

The best way to increase the chance of positive pregnancy outcome is to improve fitness 6-9 months beforehand. Eliminating smoking and drug taking, reducing alcohol intake, managing weight and taking folic acid will all help to increase fitness, producing an optimal state for pregnancy outcome. Professor David emphasises that it isn’t just mothers that need to maintain their fitness – fathers have a very important role to play, and the state of their own fitness is essential for pregnancy outcome.

Healing after fetal surgery

When a hole is made in the amniotic membrane around the baby during surgery, it will still be visible 10 weeks later. Professor David’s team have been investigating whether there is any way to encourage the hole to heal on its own, and following experiments conducted on donated membranes, they found that the hole can heal up, but it depends on how big it is. Cells called myofibroblasts migrate to the site of the hole and contract to seal it back together, Professor David’s team are currently looking into potential techniques to enhance this natural process.

Membranes which rupture early in what is called ‘preterm premature rupture of membranes’ affect about 40% of women who deliver preterm. The fluid around the baby leaks out, and infections can enter, causing women to go into early labour. If the hole could be sealed, and the fluid refilled, the pregnancy could go on a lot further. Plugging these holes with collagen, for example, has been previously attempted, however amniotic fluid contains enzymes which break down collagen. Professor David’s team are currently working with bioengineers to develop protein plugs which can self-assemble inside the amniotic fluid.

What is fetal gene therapy?

Fetal gene therapy aims to treat genetic diseases in babies before they are born. Individually, inherited diseases are quite rare, but when looking at them as a whole, they represent a big problem and cost.

“1/3 of hospital admissions for children are due to a single gene disorder” – Professor David

Gene therapy consists of manipulating and correcting the defective gene that is causing the abnormality: an area which looks promising for genetic metabolic disorders in relation to targeting conditions before birth. However, it is a difficult procedure to conduct before birth, especially when considering the effects on the genome as a whole, and the genes contained in the egg and sperm.

Conducting fetal gene therapy poses additional issues, such as those concerning diagnostic techniques to determine whether the baby definitely has a genetic disease, such as taking samples of the amniotic fluid or placenta. It is very easy, however, to administer an injection into the umbilical vein in the umbilical cord, so stem cells or targeted gene therapy can effectively be injected as the blood travels to the placenta. This procedure is riskier if it is conducted too early, so timing is critical for safety and outcome.

Fetal gene therapy has been successful in mouse models but has not yet been conducted in humans, although stem cell transplantation is currently being carried out before birth to treat genetic disease. It is still a very experimental area with many clinical trials being conducted to determine whether it is both safe and effective enough to be implemented as a proper treatment.

Surgery during COVID-19

“The mum is the priority when it comes to fetal surgery” – Professor David

Pregnant women represent a group who suffers greatly with COVID-19, and Professor David’s team take many precautions while conducting fetal surgery during this pandemic to reduce the risk of infection as much as possible, including swabbing the mother beforehand – not much is known about conducting fetal surgery while the mother is infected with COVID-19, so it is avoided to ensure their safety.

Professor David describes her experience during the pandemic, including stepping up to fill the places of junior doctors on the labour ward and doing extra clinical work. During the second wave of the pandemic, more pregnant women were in the Intensive Therapy Unit (ITU), and stayed for a long time, which posed a challenge for Professor David and her team, however, their recoveries were all successful.

Professor David’s take-home message

Professor David highlights that parents and parents-to-be are willing to take part in clinical trials and the new terminology that Professor David and her team created will transform the way that trials are conducted. Treating the fetus before birth is difficult, and the mother’s wellbeing should always be prioritised, but it is possible and can have a huge impact on their future lives.

Want to find out more? Check out these links:

Fetal membrane repairment

Prenatal gene therapy

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