Cognitive Improvement through early Restoration of cirCADian rhythms in very preterm Infants via Environmental Modification: The CIRCA DIEM Study

Abstract

Circadian rhythms are vital to normal fetal development but the fetus is dependent on maternal circadian rhythms until near-term. Preterm infants spend the first months of postnatal life in the disruptive setting of constant environmental light and noise, without maternal circadian inputs. In animals, disturbed circadian rhythms are associated with impaired brain development. Cognitive impairment remains the primary morbidity associated with extremely preterm birth and increases health care costs. Therefore, we aim to establish if individual diurnal cycling of environmental light and noise levels improves cognitive outcomes of very preterm infants compared to more constant background lighting and noise. We are undertaking a multicentre, prospective, randomised, open, blinded end-point (PROBE) parallel controlled trial that assesses the effect of non-invasive application of eye masks and ear muffs for 10 hours per night via measurements of neurodevelopmental, social, psychological, physiological, and economic outcomes. We hypothesise that diurnal cycling of light and noise commenced from birth and continued until discharge home will improve the cognitive score (Bayley Scales of Infant Development (BSID) 4th edition), in infants born at < 32 w gestation. Primary outcome will be a mean difference of 4 points in the cognitive score on BSID-4 at 2 years corrected postnatal age. Sample size to achieve 90 % power and alpha 0.05 is 954 infants, assuming a standard deviation of 15 points, a 10 % loss to follow-up and a 30 % adjustment for multiple births. Secondary outcomes will target survival, anthropometry and growth, key neonatal morbidities (BPD/NEC/ROP/Sepsis/IVH), length of hospital stay, survival, Bayley 4 subscores, infant behaviour, sleep, hormonal and clock gene circadian profiles, health service utilisation, core health economic analyses and primary carer mental health and sleep, .