Researchers will fit nearly 500 preterm babies with tiny eye masks and earplugs at night-time in a bid to kickstart their circadian rhythms – a crucial biological process they fail to develop during extended stays in neonatal intensive care units (NICUs).
The study team – led by The Kids Research Institute Australia and University of Western Australia preterm health researcher Professor Jane Pillow – believes the simple intervention, which will cost just $66 per baby, could result in improved brain development and earlier discharge from hospital, as well as help prevent a range of later health problems.
The CIRCA DIEM study, which will involve NICUs in WA, Victoria, New South Wales, Queensland and South Australia, recently received $3.077 million in funding via the National Health and Medical Research Council as part of the Australian Government’s $74 million investment to find better ways to prevent, detect and treat disease.
The randomised controlled trial will focus on very preterm (born at 28–31 weeks+6 days’ gestation) and extremely preterm babies (less than 28 weeks’ gestation).
Half of the 954 babies to be recruited will receive routine care and the other half will be fitted with eye masks and earplugs between 8pm and 6am, while being exposed to a comfortable level of lighting and noise during the daytime. Those receiving the intervention will do so until they are discharged from hospital.
Researchers will then follow the babies’ progress for two years, to see whether the simple intervention leads to better health and developmental outcomes.
Professor Pillow said circadian rhythms did much more than control waking and sleeping.
“Circadian rhythms are vital for healthy development,” Professor Pillow said. “They’re present in most cells and drive up to 20 per cent of the genes in your body, so they actually control many developmental processes.”
She said babies received time-of-day signals from their mother for most of a pregnancy but typically developed their own circadian rhythm very late in the third trimester, shortly before birth.
“Preterm babies are born before that intrinsic rhythm has developed, when they’re still reliant on the mother’s time-of-day signals – and then suddenly the mum’s not there any more,” Professor Pillow said.
Some of these babies are then in a noisy hospital environment with constant lighting for 3–5 months – and we know from recent studies that they don’t develop a circadian rhythm before they go home. That’s a concern, because without circadian rhythms, development doesn’t proceed normally and it may be that the brain and other vital organs are not receiving the right signals for normal development.
“Unless we help them experience the difference between night and day – effectively teach them to develop a circadian rhythm – they don’t get it until 6–8 weeks after getting home.”
Dr Peter Mark, a circadian biologist at The University of Western Australia and cofounder of the project, said a disrupted circadian rhythm could affect processes including sleep, organ development, and behaviour; and was associated with cardiovascular disease, obesity, metabolic syndrome, motor problems such as cerebral palsy, and neuropsychiatric conditions.
“If you have a disrupted circadian rhythm you often have disrupted immune function, too, and we know that preterm babies are susceptible to infection,” Dr Mark said.
Professor of Autism at The Kids Research Institute Australia and The University of Western Australia, Professor Andrew Whitehouse – who is also involved in the study – said the intervention may also help support child development.
“Critical brain development occurs in the last prenatal trimester, and there is reason to believe that these small adjustments may make a big difference,” Professor Whitehouse said.
For example, autism is a developmental disorder that is around 4–7 times more frequent in preterm children compared to term children. Establishing sleep-wake cycles as early as possible in postnatal life may provide critical contributions to the brain growth of preterm babies and support their early social and intellectual development.
Professor Pillow said a pilot of the approach which commenced at King Edward Memorial Hospital in 2019, supported by a WA Child Research Fund grant, had seen babies develop a circadian rhythm within just three days.
“The big question is, will that early development of a circadian rhythm result in shorter stays in hospital?” she said. “Will they get home sooner and will they have less severe disease? Or they may be in hospital just as long, because they have to grow and get to a certain maturity level before they can go home, but they may not have such severe lung disease, infections, or other problems.”
Thanks to the NHMRC funding, the pilot can now move to a full trial and will commence recruitment in other states and some neonatal units overseas within the next few months.