Sleep position alters arousal processes maximally at the high-risk age for sudden infant death syndrome.

An impaired ability to arouse from sleep may play an important role in the pathogenesis of sudden infant death syndrome (SIDS). This study aimed to investigate the effects of prone sleeping on the nature of both induced and spontaneous arousal responses in infants. Thirteen healthy term infants were studied longitudinally at 2-4 weeks, 2-3 months and 5-6 months postnatal age. A pulsatile jet of air to the nostrils was used to induce arousal from both active sleep and quiet sleep in both prone and supine positions. For each stimulus, arousals were classified as sub-cortical activations and cortical arousals, scored using physiological and electroencephalogram changes and expressed as a percentage of the total number of arousals. Spontaneous arousals were similarly analysed. Increased proportions of cortical arousals, hence decreased proportions of sub-cortical activations, were observed in the prone position at 2-3 months. This distinct peak in the proportion of cortical arousals occurred regardless of sleep state and regardless of whether the arousal occurred spontaneously or was induced by air-jet stimulation. The nature of arousal responses in healthy term infants is altered in the prone sleeping position at 2-3 months after birth, the age where SIDS incidence is highest. We postulate that a greater propensity for cortical arousal may be a protective mechanism to promote complete arousal in a vulnerable sleeping position and/or a vulnerable period of maturation. Inadequate or incomplete cortical arousals may explain the increased risk of SIDS associated with the prone position at this age.

The impact of melatonin on the sleep patterns of women undergoing IVF: a double blind RCT.

STUDY QUESTION: Does melatonin result in a dose-response effect on sleep quality and daytime sleepiness in women undergoing IVF? SUMMARY ANSWER: Melatonin, even when given at high doses twice per day, does not cause significant daytime sleepiness or change night time sleep quantity or quality. WHAT IS KNOWN ALREADY: Melatonin is being increasingly used as an adjuvant therapy for women undergoing IVF owing to its antioxidative effects. It is widely considered to be sedative but there are scant objective data on the effects of melatonin on sleep in the setting of IVF. STUDY DESIGN SIZE DURATION: The study was a double-blind placebo-controlled randomized trial of 116 women recruited between September 2014 and September 2016. PARTICIPANTS/MATERIALS SETTING METHOD: Women who were undergoing their first cycle of IVF at private IVF centers were recruited into the RCT and randomized to receive either placebo, 2 mg, 4 mg or 8 mg of melatonin, twice per day (BD) from Day 2 of their cycle until the day before oocyte retrieval. Each participant wore an accelerometer that provides an estimate of sleep and wake activity for up to 1 week of baseline and throughout treatment (up to 2 weeks). They also kept sleep diaries and completed a Karolinska sleepiness score detailing their night time sleep activity and daytime sleepiness, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 116 women were included in the intention-to-treat analysis (placebo BD (n = 32), melatonin 2 mg BD (n = 29), melatonin 4 mg BD (n = 26), melatonin 8 mg BD (n = 29)). There were no significant differences in daytime Karolinska sleepiness score between groups (P = 0.4), nor was there a significant dose-response trend (ß=0.05, 95% CI -0.22-0.31, P = 0.7). There were no differences in objective measures of sleep quantity or quality, including wake after sleep onset time, sleep onset latency, and sleep efficiency before and after treatment or between groups. There was an improvement in subjective sleep quality scores from baseline to during treatment in all groups, except 8 mg BD melatonin: placebo (percentage change -13.3%, P = 0.01), 2 mg (-14.1%, P = 0.03), 4 mg (-8.6%, P = 0.01) and 8 mg (-7.8%, P = 0.07). LIMITATIONS REASONS FOR CAUTION: As this was a subset of a larger trial, the melatonin in ART (MIART) trial, it is possible that the sample size was too small to detect statistically significant differences between the groups. WIDER IMPLICATIONS OF THE FINDINGS: While this study suggests that melatonin can be used twice per day at high doses to achieve sustained antioxidation effects, with the reassurance that this will not negatively impact daytime sleepiness or night time sleep habits, the sample size is small and may have missed a clinically significant difference. Nevertheless, our findings may have implications not only for future studies of fertility treatments (including meta-analyses), but also in other medical fields where sustained antioxidation is desired. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Monash IVF Research and Education Foundation (PY12_15). S.F. is supported by the National Health and Medical Research Council (Postgraduate Scholarship APP1074342) and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists Ella Macknight Memorial Scholarship. E.W. is supported by an National Health and Medical Research Council Program Grant (APP1113902). S.F., E.W., R.H., B.V., N.L., N.H., M.W., M.L., A.L., P.T., K.L. have nothing to declare. L.R. is a Minority shareholder in Monash IVF Group, has unrestricted grants from MSD®, Merck-Serono® and Ferring® and receives consulting fees from Ferring®. S.N.B. reports consulting fees from Johnson & Johnson Consumer Inc®, outside the submitted work. TRIAL REGISTRATION NUMBER: This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (Project ID: ACTRN12613001317785). TRIAL REGISTRATION DATE: 27/11/2013. DATE OF FIRST PATIENT'S ENROLMENT: 1/9/2014.