Elucidating the relationship between the neonatal cerebral connectome and immune dysregulation in preterm infants

Primary supervisor: James P. Boardman

Secondary supervisor: Manuel Blesa-Cábez, Riccardo Marioni (CGEM)

Lay abstract

The problem

In the UK, around 6-7% of babies are premature, meaning born at less than 37 weeks of pregnancy. Compared to children and young people born after a complete pregnancy, those born prematurely are eight times more likely to be diagnosed with autism, and they have higher rates of attention deficit hyperactivity disorder, emotional problems, learning difficulties and psychiatric problems. These challenges prevent children from reaching their full potential, impact family life, and affect health and wealth across the life course. There are no treatments to prevent these challenges.

We know that premature birth often changes the way the brain develops because differences in brain connections (‘wiring’) are frequently seen on MRI scans, which give very detailed pictures of the body, at the time the baby leaves the neonatal intensive care unit. These changes predict atypical child development. Now, we want to understand what causes different brain ‘wiring’ to develop in some premature babies and what makes others resilient.

Previous research points to problems in the immune system of premature babies as a key driver of abnormal brain development. We have developed a new way to measure baby immunity from genetic material (DNA) in saliva.

The solution

To discover which aspects of the immune system lead to abnormal brain development after premature birth. This essential understanding is needed to design new treatments designed to reduce the adverse impact of premature birth on child development. To achieve this, we have recruited a large group of families into a research study that includes the collection of baby brain MRI and DNA from saliva, along with detailed information about other influences on child development, such as illness severity in early life, nutrition, and parental wellbeing. The PhD candidate will develop sophisticated new ways to analyse MRI scans using computers to produce very detailed pictures of brain wiring. Then, by looking at the DNA samples, the student will discover which aspects of altered immune function predict atypical and typical brain development in premature babies. We expect these studies to pave the way to designing treatments based on changing the immune system that could help restore healthier brain development to children born too soon.