Background: In Australia about 16,000 infants are born preterm each year. Despite an increase in survival, developmental morbidity has not improved, with more than half of surviving infants born < 28 weeks of gestation growing up with significant neurodevelopmental impairment. Even infants born moderately or late preterm (> 32 weeks of gestation) are at double the risk for neurodevelopmental disability compared to term born peers. There is an urgent need to understand the mechanisms involved in these impairments, so that outcomes can be improved. We hypothesise that short apnoeas and periodic breathing in infancy, which are currently thought to be benign, may significantly contribute to these developmental impairments.
Progress: 32 babies born between 28-32 weeks of gestational age have been recruited. All infants completed the first sleep study at 32-36 weeks postmenstrual age (PMA). 20 infants completed the second study at 36-40 weeks PMA, 18 infants at 3 months corrected age (CA) and 19 infants at 6 months CA. Recruitment was suspended in early March 2020 due to COVID-19 restrictions. Ethical approval to study the babies already recruited in their own home between Stage 4 lockdowns in Melbourne was obtained. As a result one study at 3 months was missed and three infants were studied at 7 months CA (instead of 6). The Growth and Development Clinic which conducts the developmental assessments at 6 months was closed and only re-opened in December 2020. All 19 infants who completed the final sleep study have now been assessed (including one baby who had moved to Auckland during COVID – this was done by liaising with the University of Auckland). Recruitment commenced at the beginning of March and have studied 3 babies with a further 2 to be studied on 29 March 2021. All physiological data from the sleep studies have been analysed the 89 studies completed before or during 2020.
Results: The amount of total sleep time with periodic breathing decreased with increasing postnatal age from 12 ± 3% at Study 1, to 9 ± 2% at Study 2, to 2 ± 1% at Study 3 to 3 ± 1% at Study 4. 91% and 90 % of babies had episodes of periodic breathing at Studies 1 and 2 respectively, 55% at Study 3 and 37% at Study 4. Respiratory control was assessed using loop gain. When assessed across total sleep time loop gain decreased (i.e. respiratory control improved) with increasing postnatal age from 36-40 weeks, although this did not reach statistical significance between studies. However, loop gain measured in quiet sleep significantly decreased from 36-40 weeks to 6 months and from 3 months to 6 months. Loop gain significantly predicted the change in the % total sleep time spent in periodic breathing. The presence/absence of periodic breathing was a significant predictor of loop gain where studies with periodic breathing were associated with higher loop gain (more unstable respiratory control) compared to those studies without periodic breathing. Importantly loop gain measured at 32-36 weeks (Study 1), predicted the presence/absence of periodic breathing at 6 months.
Conclusions: Loop gain may be a useful tool to predict those infants with unstable respiratory control while in the neonatal unit who are likely to continue to periodic breath and thus be exposed to prolonged fluctuations in brain oxygen levels. Changes in brain oxygen levels which occur during periodic breathing are currently being relating to developmental outcomes.