Oral Presentation 46th Annual Meeting of the Fetal and Neonatal Physiological Society 2019

Characterising the development of molecular and hormonal circadian rhythm development in preterm infants  (#23)

Natasha Sorensen 1 2 , Jane J Pillow 1 , Shane Maloney 1 , Peter Mark 1
  1. School of Human Sciences, University of Western Australia, Crawley, WA, Australia
  2. Neonatal Clinical Care Unit, King Edward Memorial Hospital, Subiaco, WA, Australia

Contemporary NICU environments now target constant dim lighting instead of constant bright light. We hypothesised that emergence of endogenous circadian rhythms remains delayed in infants cared for under contemporary NICU lighting conditions, regardless of gestational age. We aimed to elucidate the ontogeny of circadian rhythms of salivary melatonin and cortisol and buccal cell clock gene expression in newborn infants across a range of gestations.

Design: prospective observational study (Mar 2017-Jul2019) in extremely preterm, very preterm, moderate-late preterm and term born infants. Saliva swabs (Salimetrics®) were collected immediately prior to feeds 4-6 times/day and stored at -800C. Salivary cortisol and melatonin were measured by enzyme immunoassay. Buccal swabs were immersed in guanidine thiocyanate (Copan DiagnoticsTM) for a minimum of 24h then stored at -800C prior to RNA extraction. Gene expression of BMAL1, Per2, Rev-ErbA (genes of interest), PPIA, RNA Pol II, and SDHA (housekeeping genes) was performed using RT-qPCR. The presence of circadian rhythms was determined using Cosinor analysis. ANOVA was used to determine the influence of gestation group on mean postconceptional age at emergence of significant circadian rhythms.

Forty-five infants were recruited. Measurements were obtained on 7 occasions between birth and 3 months correct postnatal age (cPNA). Mean (SD) cPNA of emergence of circadian rhythms (R2>0.6) was 7.1 (±3.5) weeks corrected postnatal age and wasn’t associated with gestation (r=-0.07; p=0.9687). Both the cortisol (p=0.001) and melatonin (p=0.002) profiles of preterm infants (<32w) were damped immediately prior to hospital discharge compared with infants born at term. Infants born <32w still had a dampened rhythm for cortisol (p=0.001) but not melatonin (p=0.169) when compared with more mature infants at 3 months cPNA. Clock gene results will be presented.

Preterm infants cared for using contemporary lighting protocols have delayed emergence of circadian rhythms compared with term babies.