RMIT: Born too soon: Tackling the challenges and risks of preterm birth

Every year, 15 million babies worldwide are born preterm – before the 37th week of gestation – and thanks to advances in healthcare, survival rates are higher than ever.

Yet early birth can be damaging in many ways, disrupting the growth of the baby’s vital organs that would usually occur during the final stages of pregnancy.

Besides losing the support of the placenta, which produces growth factors to help the infant develop, the gut of the preterm baby isn’t ready to absorb nutrients to help them grow fully.

Even the lights and noises of the outside world can disrupt brain development and leave a lasting impact on a person’s ability to read, communicate, concentrate, or interact in social settings.

Preterm birth increases the likelihood of lifelong changes in growth and development, such as cerebral palsy, impaired cognitive function, and autism spectrum disorder.

RMIT’s Neurodevelopment in Health and Disease research program focuses on healthy brain development and the early origins of neurological disease.

“Many of us are investigating health issues relevant to children born too soon, related either to risk factors linked to preterm birth or to long-term health issues resulting from it,” said Professor David Walker, Program Leader.

The power of stem cells to repair brain injury

Walker, Dr Bobbi Fleiss and Associate Professor Mary Tolcos make up the RMIT team participating in PREMSTEM, an international research and innovation program funded by the European Union’s Horizon 2020 scheme.

Using stem cells from donated umbilical cord tissue, the international team is aiming to develop a new treatment for brain damage associated with preterm birth, known as encephalopathy of prematurity.

“We know that stem cells help to regenerate and rebuild damage to our body under the right conditions, with previous studies showing that they can play a part in repairing perinatal brain injury,” Walker said.

“We want to find the best way to unleash this potential – to determine the right moment to give the stem cells, the best way to deliver them into the body, and the correct dosage.”


Preventing abnormal brain development

Fetal growth restriction (FGR) occurs when a problem within the placenta stops the baby from growing properly during pregnancy, often leading to preterm delivery and a risk of abnormal brain development.

Associate Professor Mary Tolcos’ research group is studying the therapeutic potential of a thyroid hormone compound, DITPA, in preclinical models of FGR.

With funding from the NHMRC and Cerebral Palsy Alliance Research Foundation, they are testing whether DITPA can prevent abnormal brain development and injury when given either before birth (to the mum) or after birth (to the baby).

“It’s promising to see an enhanced development of myelin – the fatty insulation around nerve fibres – when we give DITPA for a short period of time in our FGR model after birth,” Tolcos said.

“We’re now investigating whether DITPA can prevent other forms of brain injury if given for longer, and if these positive effects continue into adolescence.”

Gut health and brain development

The gut and brain communicate with each other by sending signals back and forth along the vagus nerve as well as via the gut bacteria and immune system.

These complex connections, known as the gut-brain axis, link our emotions with the bacteria in our stomach – and are responsible for the butterflies you feel when you’re nervous.

Associate Professor Elisa Hill-Yardin’s research group is conducting preclinical research on the gut-brain axis and how it relates to neurodevelopmental disorders like autism, a risk for children born preterm.

“Complications occurring as the baby’s brain develops can have implications for gut function, including abdominal pain and discomfort, and lead to alternating constipation and diarrhoea in disorders such as autism,” Hill-Yardin said.

“There is evidence that improving gut health could reduce the severity of these issues.

“We aim to better understand the brain-gut interactions and their impact on gut contraction patterns and permeability to identify biological targets and find therapies to improve the quality of life for people with neurodevelopmental disorders.”


The impact of peri-pregnancy diets

Professor Sarah Spencer and her team are looking at why diet before and during pregnancy matters.

A particular focus is the link between unhealthy diets and inflammation in the central nervous system, which can weaken brain function in both mother and baby.

Parents’ eating habits can have lasting implications, with a consistently high intake of carbohydrates and saturated fats prior to pregnancy being a known risk for preterm birth.

Conversely, a healthy ‘Mediterranean’ diet rich in antioxidants and omega-3 fatty acids can lower the likelihood of preterm birth and reverse pro-inflammatory effects.

A healthy diet can also impact positively on after-effects of birth experienced by some women, including gestational weight gain and postnatal depression.

“Too much saturated fat and sugar before and during pregnancy not only leads to weight gain; it can also change the dynamics of neurogenesis – the process by which new neurons are formed – in the mother’s brain,” Spencer said.

Early detection of preeclampsia

As well as nourishing a baby during pregnancy, the placenta plays a key role in the development of pregnancy complications such as preeclampsia, affecting some expectant mothers and causing preterm birth.

One significant challenge in the management of preeclampsia is identifying pregnancies that are destined to develop this damaging condition before its clinical symptoms manifest.

Professor Guiying Nie, an expert in reproductive biology, and her team study how the placenta is involved in the development of preeclampsia and how to harness this knowledge for early detection.

“In some pregnancies, when preeclampsia sets in, the only option is to deliver the baby prematurely to avoid life-threatening complications,” Nie said.

“Finding a way to detect preeclampsia early in pregnancy is very important for these women and their babies.”

Retuning immune cells to build a healthy brain

The efforts of Dr Bobbi Fleiss and her team to improve outcomes for babies are focused on studying a dynamic type of brain immune cell, microglia.

These cells have various roles as the builders, gardeners, and protectors of the brain.

A frequent cause of preterm birth is infection originating inside the uterus.

As a response to the infection, the baby’s microglia switch from their healthy role of building the brain to protector mode, but this often does more harm than good, causing brain injury.

Overactivated microglia also cause brain damage in disorders such as Alzheimer’s, stroke, and traumatic injuries.

“Microglia are so powerful; understanding how they change during injury to the young brain, and how to switch them back to their healthy role of builder, opens up opportunities to improve brain health for many people, including babies born preterm,” Fleiss said.