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1.  Night Waking, Sleep-Wake Organization, and Self-Soothing in the First Year of Life 
Few objective data are available regarding infants’ night waking behaviors and the development of self-soothing during the first year of life. This cross-sectional study examined 80 infants in one of four age groups (3, 6, 9, or 12 mo) for four nights by using videosomnography to code nighttime awakenings and parent-child interactions. A large degree of variability was observed in parents’ putting the infant to bed awake or asleep and in responding to vocalizations after nighttime awakenings. Most infants woke during the night at all ages observed. Younger infants tended to require parental intervention at night to return to sleep, whereas older infants exhibited a greater proportion of self-soothing after nighttime awakenings. However, even in the 12-month-old group, 50% of infants typically required parental intervention to get back to sleep after waking. Results emphasize the individual and contextual factors that effect the development of self-soothing behavior during the first year of life.
PMCID: PMC1201414  PMID: 11530895
2.  Sleep and breathing in premature infants at 6 months post-natal age 
BMC Pediatrics  2014;14:303.
Poor sleep contributes to the developmental problems seen in preterm infants. We evaluated sleep problems in preterm infants 6 months of post-gestational age using the subjective Brief Infant Sleep Questionnaire (BISQ) and objective sleep tests. We also compared the sleep of premature infants with that of full-term infants.
The study included 68 6-month-old full-term healthy infants and 191 premature infants born at <37 weeks gestation. All parents completed the BISQ-Chinese version and sleep diaries. At the same time, all premature infants were submitted to one night of polysomnography (PSG) in the sleep laboratory and also were set up with an actigraph kept for 7 days. Statistical analyses were performed using correlation coefficients and the t-test with SPSS version 18 to compare questionnaire responses with other subjective and objective measures of sleep.
The sleep problems indicated in the subjective questionnaire for the premature infants, particularly: “the nocturnal sleep duration, number of night awakenings, daytime sleep duration, duration of time with mouth breathing, and loud-noisy breathing” had significant correlations with sleep diaries, actigraphy and PSG results. The BISQ showed that duration of infant’s sleeping on one side, nocturnal sleep duration, being held to fall asleep, number of nighttime awakenings, daytime sleep duration, subjective consideration of sleep problems, loud-noisy breathing, and duration spent crying during the night were significantly different between the premature infants and the term infants. PSG confirmed the presence of a very high percentage (80.6%) of premature infants with AHI > 1 event/hour as indicated by the questionnaire.
Premature infants have more sleep problems than full-term infants, including the known risk of abnormal breathing during sleep, which has been well demonstrated already with the BISQ-Chinese (CBISQ).
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-014-0303-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4272529  PMID: 25510740
Sleep questionnaire; Sleep-disordered breathing; Prematurity; Full-term infant
3.  Nighttime sleep-wake patterns and self-soothing from birth to one year of age: a longitudinal intervention study 
The objectives of this study were to: (1) describe the longitudinal development of sleep-wake patterns of solitary-sleeping infants from 1 to 12 months of age, (2) identify effects on sleep patterns and on self-soothing behaviors of introducing a novel sleep aid, and (3) identify predictive factors of self-soothing at 12 months using a transactional model as a guide.
Eighty infants’ nighttime sleep-wake patterns and associated variables were studied at 5 times across the first year of life using videosomnography and questionnaires.
Sleep-wake state developmental changes, as reported in investigations of infant sleep, were replicated, although a great deal of individual variability in the development of all sleep-related variables was noted. No major effects on sleep or on self-soothing behavior were evident from the introduction of the novel sleep aid. Three variables were identified as significant predictors of self-soothing at 12 months: decreasing amounts of time spent out of crib across the first year, high levels of quiet sleep at birth, and longer parental response times to infant awakenings at 3 months.
These data lend preliminary support for the transactional model and suggest that infant and parental factors interact to influence the development of self-soothing.
PMCID: PMC1201415  PMID: 12236607
Infancy; normal development; parent-child interaction; paediatrics; sleep; temperament; AS: active sleep; AW: wakefulness; BDI: Beck Depression Inventory; GLM: general linear modeling; LSP: longest sleep period; OOC: out of crib; PSOCS: Parenting Sense of Competence Scale; QS: quiet sleep; RSA: representational sleep aid; SC: sham control; SS: self-soothed; TST: total sleep time
4.  Video Evidence That London Infants Can Resettle Themselves Back to Sleep After Waking in the Night, as well as Sleep for Long Periods, by 3 Months of Age 
This article has supplementary material on the Web site:
Most infants become settled at night by 3 months of age, whereas infants not settled by 5 months are likely to have long-term sleep-waking problems. We assessed whether normal infant development in the first 3 months involves increasing sleep-period length or the ability to resettle autonomously after waking in the night.
One hundred one infants were assessed at 5 weeks and 3 months of age using nighttime infrared video recordings and parental questionnaires.
The clearest development was in sleep length; 45% of infants slept continuously for ≥5 hours at night at 3 months compared with 10% at 5 weeks. In addition, around a quarter of infants woke and resettled themselves back to sleep in the night at each age. Autonomous resettling at 5 weeks predicted prolonged sleeping at 3 months suggesting it may be a developmental precursor. Infants reported by parents to sleep for a period of 5 hours or more included infants who resettled themselves and those with long sleeps. Three-month olds fed solely breast milk were as likely to self-resettle or have long sleep bouts as infants fed formula or mixed breast and formula milk.
Infants are capable of resettling themselves back to sleep in the first 3 months of age; both autonomous resettling and prolonged sleeping are involved in “sleeping through the night” at an early age. Findings indicate the need for physiological studies of how arousal, waking, and resettling develop into sustained sleeping and of how environmental factors support these endogenous and behavioral processes.
PMCID: PMC4459553  PMID: 26035139
infant sleeping; infant crying; settling; parenting
5.  Maternal Caffeine Consumption and Infant Nighttime Waking: Prospective Cohort Study 
Pediatrics  2012;129(5):860-868.
Coffee and other caffeinated beverages are commonly consumed in pregnancy. In adults, caffeine may interfere with sleep onset and have a dose-response effect similar to those seen during insomnia. In infancy, nighttime waking is a common event. With this study, we aimed to investigate if maternal caffeine consumption during pregnancy and lactation leads to frequent nocturnal awakening among infants at 3 months of age.
All children born in the city of Pelotas, Brazil, during 2004 were enrolled on a cohort study. Mothers were interviewed at delivery and after 3 months to obtain information on caffeine drinking consumption, sociodemographic, reproductive, and behavioral characteristics. Infant sleeping pattern in the previous 15 days was obtained from a subsample. Night waking was defined as an episode of infant arousal that woke the parents during nighttime. Multivariable analysis was performed by using Poisson regression.
The subsample included 885 of the 4231 infants born in 2004. All but 1 mother consumed caffeine in pregnancy. Nearly 20% were heavy consumers (≥300 mg/day) during pregnancy and 14.3% at 3 months postpartum. Prevalence of frequent nighttime awakeners (>3 episodes per night) was 13.8% (95% confidence interval: 11.5%–16.0%). The highest prevalence ratio was observed among breastfed infants from mothers consuming ≥300 mg/day during the whole pregnancy and in the postpartum period (1.65; 95% confidence interval: 0.86–3.17) but at a nonsignificant level.
Caffeine consumption during pregnancy and by nursing mothers seems not to have consequences on sleep of infants at the age of 3 months.
PMCID: PMC3566755  PMID: 22473365
sleep; sleep duration; infant sleeping; night waking; infant; caffeine; coffee
6.  Prevalence, Patterns, and Persistence of Sleep Problems in the First 3 Years of Life 
Pediatrics  2012;129(2):e276-e284.
Examine the prevalence, patterns, and persistence of parent-reported sleep problems during the first 3 years of life.
Three hundred fifty-nine mother/child pairs participated in a prospective birth cohort study. Sleep questionnaires were administered to mothers when children were 6, 12, 24, and 36 months old. Sleep variables included parent response to a nonspecific query about the presence/absence of a sleep problem and 8 specific sleep outcome domains: sleep onset latency, sleep maintenance, 24-hour sleep duration, daytime sleep/naps, sleep location, restlessness/vocalization, nightmares/night terrors, and snoring.
Prevalence of a parent-reported sleep problem was 10% at all assessment intervals. Night wakings and shorter sleep duration were associated with a parent-reported sleep problem during infancy and early toddlerhood (6–24 months), whereas nightmares and restless sleep emerged as associations with report of a sleep problem in later developmental periods (24–36 months). Prolonged sleep latency was associated with parent report of a sleep problem throughout the study period. In contrast, napping, sleep location, and snoring were not associated with parent-reported sleep problems. Twenty-one percent of children with sleep problems in infancy (compared with 6% of those without) had sleep problems in the third year of life.
Ten percent of children are reported to have a sleep problem at any given point during early childhood, and these problems persist in a significant minority of children throughout early development. Parent response to a single-item nonspecific sleep query may overlook relevant sleep behaviors and symptoms associated with clinical morbidity.
PMCID: PMC3357046  PMID: 22218837
sleep problems; infants; toddlers; prevalence; persistence
7.  A Comparison of Actigraphy and Sleep Diaries for Infants’ Sleep Behavior 
Detecting the effectiveness of behavioral interventions to reduce infant night-waking requires valid sleep measures. Although viewed as an objective measure, actigraphy has overestimated night-waking. Sleep diaries are criticized for only documenting night-waking with infant crying. To support potential outcome measure validity, we examined differences between sleep diaries and actigraphy in detecting night-waking and sleep duration. We recruited 5.5 to 8-month-old infants for a behavioral sleep intervention trial conducted from 2009 to 2011. Intervention (sleep education and support) and control groups (safety education and support) collected infant diary and actigraphy data for 5 days. We compared night-time sleep actigraphy with diary data at baseline (194 cases), and 6 weeks (166 cases) and 24 weeks post-education (118 cases). We hypothesized numbers of wakes and wakes of ≥20 min would be higher and longest sleep time and total sleep time shorter by actigraphy compared with diaries. Using paired t-tests, there were significantly more actigraphy night wakes than diary wakes at baseline (t = 29.14, df = 193, p < 0.001), 6 weeks (t = 23.99, df = 165, p < 0.001), and 24 weeks (t = 22.01, df = 117, p < 0.001); and significantly more night wakes of ≥20 min by actigraphy than diary at baseline (t = 5.03, df = 183, p < 0.001), and 24 weeks (t = 2.19, df = 107, p < 0.05), but not 6 weeks (t = 1.37, df = 156, n.s.). Longest sleep duration was significantly higher by diary than actigraphy at baseline (t = 14.71, df = 186, p < 0.001), 6 weeks (t = 7.94, df = 158, p < 0.001), and 24 weeks (t = 17.18, df = 114, p < 0.001). Night sleep duration was significantly higher by diary than actigraphy at baseline (t = 9.46, df = 185, p < 0.001), 6 weeks (t = 13.34, df = 158, p < 0.001), and 24 weeks (t = 13.48, df = 114, p < 0.001). Discrepancies in actigraphy and diary data may indicate accurate actigraphy recording of movement but not sleep given active infant sleep and self-soothing.
PMCID: PMC4325935  PMID: 25729371
infant; sleep problems; actigraphy; sleep diaries; behavioral symptoms
8.  Nighttime Parenting Strategies and Sleep-Related Risks to Infants 
A large social science and public health literature addresses infant sleep safety, with implications for infant mortality in the context of accidental deaths and Sudden Infant Death Syndrome (SIDS). As part of risk reduction campaigns in the USA, parents are encouraged to place infants supine and to alter infant bedding and elements of the sleep environment, and are discouraged from allowing infants to sleep unsupervised, from bed-sharing either at all or under specific circumstances, or from sofa-sharing. These recommendations are based on findings from large-scale epidemiological studies that generate odds ratios or relative risk statistics for various practices; however, detailed behavioural data on nighttime parenting and infant sleep environments are limited. To address this issue, this paper presents and discusses the implications of four case studies based on overnight observations conducted with first-time mothers and their four-month old infants. These case studies were collected at the Mother-Baby Behavioral Sleep Lab at the University of Notre Dame USA between September 2002 and June 2004.Each case study provides a detailed description based on video analysis of sleep-related risks observed while mother-infant dyads spent the night in a sleep lab. The case studies provide examples of mothers engaged in the strategic management of nighttime parenting for whom sleep-related risks to infants arose as a result of these strategies. Although risk reduction guidelines focus on eliminating potentially risky infant sleep practices as if the probability of death from each were equal, the majority of instances in which these occur are unlikely to result in infant mortality. Therefore, we hypothesise that mothers assess potential costs and benefits within margins of risk which are not acknowledged by risk-reduction campaigns. Exploring why mothers might choose to manage sleep and nighttime parenting in ways that appear to increase potential risks to infants may help illuminate how risks occur for individual infants.
PMCID: PMC3505270  PMID: 22818487
infant sleep; sleep-related risks; Sudden Infant Death Syndrome (SIDS); nighttime parenting; USA
9.  Obstructive Sleep Apnea and Risk of Cardiovascular Events and All-Cause Mortality: A Decade-Long Historical Cohort Study 
PLoS Medicine  2014;11(2):e1001599.
Tetyana Kendzerska and colleagues explore the association between physiological measures of obstructive sleep apnea other than the apnea-hypopnea index and the risk of cardiovascular events.
Please see later in the article for the Editors' Summary
Obstructive sleep apnea (OSA) has been reported to be a risk factor for cardiovascular (CV) disease. Although the apnea-hypopnea index (AHI) is the most commonly used measure of OSA, other less well studied OSA-related variables may be more pathophysiologically relevant and offer better prediction. The objective of this study was to evaluate the relationship between OSA-related variables and risk of CV events.
Methods and Findings
A historical cohort study was conducted using clinical database and health administrative data. Adults referred for suspected OSA who underwent diagnostic polysomnography at the sleep laboratory at St Michael's Hospital (Toronto, Canada) between 1994 and 2010 were followed through provincial health administrative data (Ontario, Canada) until May 2011 to examine the occurrence of a composite outcome (myocardial infarction, stroke, congestive heart failure, revascularization procedures, or death from any cause). Cox regression models were used to investigate the association between baseline OSA-related variables and composite outcome controlling for traditional risk factors. The results were expressed as hazard ratios (HRs) and 95% CIs; for continuous variables, HRs compare the 75th and 25th percentiles. Over a median follow-up of 68 months, 1,172 (11.5%) of 10,149 participants experienced our composite outcome. In a fully adjusted model, other than AHI OSA-related variables were significant independent predictors: time spent with oxygen saturation <90% (9 minutes versus 0; HR = 1.50, 95% CI 1.25–1.79), sleep time (4.9 versus 6.4 hours; HR = 1.20, 95% CI 1.12–1.27), awakenings (35 versus 18; HR = 1.06, 95% CI 1.02–1.10), periodic leg movements (13 versus 0/hour; HR = 1.05, 95% CI 1.03–1.07), heart rate (70 versus 56 beats per minute [bpm]; HR = 1.28, 95% CI 1.19–1.37), and daytime sleepiness (HR = 1.13, 95% CI 1.01–1.28).The main study limitation was lack of information about continuous positive airway pressure (CPAP) adherence.
OSA-related factors other than AHI were shown as important predictors of composite CV outcome and should be considered in future studies and clinical practice.
Please see later in the article for the Editors' Summary
Editors' Summary
Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder, particularly among middle-aged and elderly people. It is characterized by apnea—a brief interruption in breathing that lasts at least 10 seconds—and hypopnea—a decrease of more than 50% in the amplitude of breathing that lasts at least 10 seconds or clear but smaller decrease in amplitude associated with either oxygen desaturation or an arousal. Patients with OSA experience numerous episodes of apnea and hypopnea during the night; severe OSA is defined as having 30 or more episodes per hour (an apnea-hypopnea index [AHI] of >30). These breathing interruptions occur when relaxation of the upper airway muscles decreases the airflow, which lowers the amount of oxygen in the blood. As a result, affected individuals frequently wake from deep sleep as they struggle to breathe. Symptoms of OSA include loud snoring and daytime sleepiness. Treatments include lifestyle changes such as losing weight (excess fat around the neck increases airway collapse) and smoking cessation. For severe OSA, doctors recommend continuous positive airway pressure (CPAP), in which a machine blows pressurized air through a face mask into the airway to keep it open.
Why Was This Study Done?
OSA can be life-threatening. Most directly, daytime sleepiness can cause accidents, but OSA is also associated with an increased risk of developing cardiovascular disease (CVD, disease that affects the heart and the circulation). To date, studies that have investigated the association between OSA and the risk of myocardial infarction (heart attack), congestive heart failure, stroke, and other CVDs have used the AHI to diagnose and categorize the severity of OSA. However, by focussing on AHI, clinicians and researchers may be missing opportunities to improve their ability to predict which patients are at the highest risk of CVD. In this historical cohort study, the researchers investigate the association between other OSA-related variables (for example, blood oxygen saturation and sleep fragmentation) and the risk of cardiovascular events and all-cause mortality (death). A historical cohort study examines the medical records of groups of individuals who have different characteristics at baseline for the subsequent occurrence of specific outcomes.
What Did the Researchers Do and Find?
The researchers used administrative data (including hospitalization records and physicians' claims for services supplied to patients) to follow up adults referred for suspected OSA who underwent diagnostic polysomnography (a sleep study) at a single Canadian hospital between 1994 and 2010. A database of the polysomnography results provided information on OSA-related variables for all the study participants. Over an average follow-up of about 6 years, 11.5% of the 10,149 participants were hospitalized for a myocardial infarction, stroke, or congestive heart failure, underwent a revascularization procedure (an intervention that restores the blood supply to an organ or tissue after CVD has blocked a blood vessel), or had died from any cause. After adjusting for multiple established risk factors for CVD such as smoking and age in Cox regression models (a statistical approach that examines associations between patient variables and outcomes), several OSA-related variables (but not AHI) were significant predictors of CVD. The strongest OSA-related predictor of cardiovascular events or all-cause mortality was total sleep time spent with oxygen saturation below 90%, which increased the risk of a cardiovascular event or death by 50%. Other statistically significant OSA-related predictors (predictors that were unlikely to be associated with the outcome through chance) of cardiovascular events or death included total sleep time, number of awakenings, frequency of periodic leg movements, heart rate, and daytime sleepiness.
What Do These Findings Mean?
These findings indicate that OSA-related factors other than AHI are important predictors of the composite outcome of a cardiovascular event or all-cause mortality. Indeed, although AHI was significantly associated with the researchers' composite outcome in an analysis that did not consider other established risk factors for CVD (“confounders”), the association became non-significant after controlling for potential confounders. The accuracy of these findings, which need to be confirmed in other settings, is likely to be limited by the lack of information available about the use of CPAP by study participants and by the lack of adjustment for some important confounders. Importantly, however, these findings suggest that OSA-related factors other than AHI should be considered as predictors of CVD in future studies and in clinical practice.
Additional Information
Please access these websites via the online version of this summary at
The US National Heart Lung and Blood Institute has information (including several videos) about obstructive sleep apnea (in English and Spanish), sleep studies, heart disease, and other cardiovascular diseases (some information in English and Spanish)
The UK National Health Service Choices website provides information (including personal stories) about sleep apnea and about cardiovascular disease
The not-for-profit American Sleep Apnea Association provides detailed information about sleep apnea for patients and health-care professionals, including personal stories about the condition
The MedlinePlus encyclopedia has pages on obstructive sleep apnea and on polysomnography; MedlinePlus provides links to further information and advice about obstructive sleep apnea, heart diseases, and vascular diseases (in English and Spanish)
PMCID: PMC3913558  PMID: 24503600
10.  Sleep and energy intake in early childhood 
Background And Objectives:
Shorter sleep is associated with higher weight in children, but little is known about the mechanisms. The aim of this study was to test the hypothesis that shorter sleep was associated with higher energy intake in early childhood.
Participants were 1303 families from the Gemini twin birth cohort. Sleep duration was measured using the Brief Infant Sleep Questionnaire when the children were 16 months old. Total energy intake (kcal per day) and grams per day of fat, carbohydrate and protein were derived from 3-day diet diaries completed by parents when children were 21 months old.
Shorter nighttime sleep was associated with higher total energy intake (P for linear trend=0.005). Children sleeping <10 h consumed around 50 kcal per day more than those sleeping 11–<12 h a night (the optimal sleep duration for children of this age). Differences in energy intake were maintained after adjustment for confounders. As a percentage of total energy intake, there were no significant differences in macronutrient intake by sleep duration. The association between sleep and weight was not significant at this age (P=0.13).
This study provides the first evidence that shorter nighttime sleep duration has a linear association with higher energy intake early in life. That the effect is observed before emergence of associations between sleep and weight indicates that differences in energy intake may be a mechanism through which sleep influences weight gain.
PMCID: PMC4088945  PMID: 24667887
sleep; diet; child
Background & Objectives
Shorter sleep is associated with higher weight in children, but little is known about the mechanisms. The aim of this study was to test the hypothesis that shorter sleep was associated with higher energy intake in early childhood.
Participants were 1303 families from the Gemini twin birth cohort. Sleep duration was measured using the Brief Infant Sleep Questionnaire (BISQ) when the children were 16 months old. Total energy intake (kcal/day) and grams/day of fat, carbohydrate and protein were derived from 3-day diet diaries completed by parents when children were 21 months old.
Shorter nighttime sleep was associated with higher total energy intake (p for linear trend=0.005). Children sleeping <10 hours consumed around 50 kcals/day more than those sleeping 11-<12 hours a night (the optimal sleep duration for children of this age). Differences in energy intake were maintained after adjustment for confounders. As a percentage of total energy intake, there were no significant differences in macronutrient intake by sleep duration. The association between sleep and weight was not significant at this age (p=0.13).
This study provides the first evidence that shorter nighttime sleep duration has a linear association with higher energy intake early in life. That the effect is observed before emergence of associations between sleep and weight indicates that differences in energy intake may be a mechanism through which sleep influences weight gain.
PMCID: PMC4088945  PMID: 24667887
sleep; diet; obesity; child
12.  Exercise Effects on Night-to-Night Fluctuations in Self-rated Sleep among Older Adults with Sleep Complaints 
Journal of sleep research  2011;20(1 Pt 1):28-37.
Sleep interventions have rarely explored reductions in night-to-night fluctuations (i.e., intra-individual variability [IIV]) in sleep, despite the negative impacts of such fluctuations on affective states and cognitive and physical symptoms. In a community-based randomized controlled trial we evaluated whether physical exercise reduced IIV in self-rated sleep outcomes among middle-aged and older adults with sleep complaints. Under-active adults 55 years and older (N=66, 67% women) with mild to moderate sleep complaints were randomized to 12mos of a moderate-intensity endurance exercise (n=36) or a health education control group (n=30). Daily sleep logs, Pittsburgh Sleep Quality Index (PSQI), and in-home polysomnographic sleep recordings (PSG) were collected at baseline, 6mos, and 12mos. Sleep log-derived means and IIV were computed for sleep-onset latency (SOL), time in bed (TIB), feeling rested in the morning, number of nighttime awakenings, and wake after final awakening (WAFA). Using intent-to-treat methods, at 6mos no differences in IIV were observed by group. At 12mos, SOL-based IIV was reduced in the exercise group compared to the control (difference=23.11, 95% CI: 3.04–47.18, p=.025, Cohen’s d=0.57). This change occurred without mean-level or IIV changes in sleep-wake schedules. For all sleep variables except SOL and WAFA, IIV changes and mean-level changes in each variable were negatively correlated (r’s=−.312 to −.691, p’s<.05). Sleep log-derived IIV changes were modestly correlated with mean-level PSQI and PSG-based changes at 12mos. Twelve months of moderate-intensity exercise reduced night-to-night fluctuations in self-rated time to fall asleep, and this relationship was independent of mean-level time to fall asleep.
PMCID: PMC2958223  PMID: 20629937
Intra-individual variability; sleep; physical activity; intervention; unpredictability; sleep-onset latency
13.  A Multicenter, Placebo-controlled Trial of Melatonin for Sleep Disturbance in Alzheimer’s Disease 
Sleep  2003;26(7):893-901.
To determine the safety and efficacy of 2 dose formulations of melatonin for the treatment of insomnia in patients with Alzheimer’s disease.
A multicenter, randomized, placebo-controlled clinical trial of 2 dose formulations of oral melatonin coordinated by the National Institute of Aging-funded Alzheimer’s Disease Cooperative Study. Subjects with Alzheimer’s disease and nighttime sleep disturbance were randomly assigned to 1 of 3 treatment groups: placebo, 2.5-mg slow-release melatonin, or 10-mg melatonin.
Private homes and long-term care facilities.
157 individuals were recruited by 36 Alzheimer’s disease research centers. Subjects with a diagnosis of Alzheimer’s disease were eligible if they averaged less than 7 hours of sleep per night (as documented by wrist actigraphy) and had 2 or more episodes per week of nighttime awakenings reported by the caregiver.
Nocturnal total sleep time, sleep efficiency, wake-time after sleep onset, and day-night sleep ratio during 2- to 3-week baseline and 2-month treatment periods. Sleep was defined by an automated algorithmic analysis of wrist actigraph data.
No statistically significant differences in objective sleep measures were seen between baseline and treatment periods for the any of the 3 groups. Nonsignificant trends for increased nocturnal total sleep time and decreased wake after sleep onset were observed in the melatonin groups relative to placebo. Trends for a greater percentage of subjects having more than a 30-minute increase in nocturnal total sleep time in the 10-mg melatonin group and for a decline in the day-night sleep ratio in the 2.5-mg sustained-release melatonin group, compared to placebo, were also seen. On subjective measures, caregiver ratings of sleep quality showed improvement in the 2.5-mg sustained-release melatonin group relative to placebo. There were no significant differences in the number or seriousness of adverse events between the placebo and melatonin groups.
Based on actigraphy as an objective measure of sleep time, melatonin is not an effective soporific agent in people with Alzheimer’s disease.
PMCID: PMC4418658  PMID: 14655926
14.  An Endogenous Circadian Rhythm in Sleep Inertia Results in Greatest Cognitive Impairment upon Awakening during the Biological Night 
Journal of biological rhythms  2008;23(4):353-361.
Sleep inertia is the impaired cognitive performance immediately upon awakening, which decays over tens of minutes. This phenomenon has relevance to people who need to make important decisions soon after awakening, such as on-call emergency workers. Such awakenings can occur at varied times of day or night, so the objective of the study was to determine whether or not the magnitude of sleep inertia varies according to the phase of the endogenous circadian cycle. Twelve adults (mean, 24 years; 7 men) with no medical disorders other than mild asthma were studied. Following 2 baseline days and nights, subjects underwent a forced desynchrony protocol composed of seven 28-h sleep/wake cycles, while maintaining a sleep/wakefulness ratio of 1:2 throughout. Subjects were awakened by a standardized auditory stimulus 3 times each sleep period for sleep inertia assessments. The magnitude of sleep inertia was quantified as the change in cognitive performance (number of correct additions in a 2-min serial addition test) across the first 20 min of wakefulness. Circadian phase was estimated from core body temperature (fitted temperature minimum assigned 0°). Data were segregated according to: (1) circadian phase (60° bins); (2) sleep stage; and (3) 3rd of the night after which awakenings occurred (i.e., tertiary 1, 2, or 3). To control for any effect of sleep stage, the circadian rhythm of sleep inertia was initially assessed following awakenings from Stage 2 (62% of awakening occurred from this stage; n = 110). This revealed a significant circadian rhythm in the sleep inertia of cognitive performance (p = 0.007), which was 3.6 times larger during the biological night (circadian bin 300°, ~2300–0300 h in these subjects) than during the biological day (bin 180°, ~1500–1900 h). The circadian rhythm in sleep inertia was still present when awakenings from all sleep stages were included (p = 0.004), and this rhythm could not be explained by changes in underlying sleep drive prior to awakening (changes in sleep efficiency across circadian phase or across the tertiaries), or by the proportion of the varied sleep stages prior to awakenings. This robust endogenous circadian rhythm in sleep inertia may have important implications for people who need to be alert soon after awakening.
PMCID: PMC3130065  PMID: 18663242
circadian rhythm; cognitive performance; grogginess; jet lag; shift work; sleep; sleep inertia
15.  The Effects of Iron and/or Zinc Supplementation on Maternal Reports of Sleep in Infants from Nepal and Zanzibar 
There is some evidence that sleep patterns may be affected by iron deficiency anemia but the role of iron in sleep has not been tested in a randomized iron supplementation trial.
We investigated the effect of iron supplementation on maternal reports of sleep in infants in 2 randomized, placebo-controlled trials from Pemba Island, Zanzibar, and Nepal.
In both studies, which had parallel designs and were carried out in years 2002 to 2003, infants received iron–folic acid with or without zinc daily for 12 months, and assessments of development were made every 3 months for the duration of the study. Eight hundred seventy-seven Pemban (12.5 ± 4.0 months old) and 567 Nepali (10.8 ± 4.0 months) infants participated. Maternal reports of sleep patterns (napping frequency and duration, nighttime sleep duration, frequency of night waking) were collected.
Mean Hb concentration was 9.2 ± 1.1 for Pemban and 10.1 ± 1.2 g/dL for Nepali infants. Approximately, one-third of the children were stunted. Supplemental iron was consistently associated with longer night and total sleep duration. The effects of zinc supplementation also included longer sleep duration.
Micronutrient supplementation in infants at high risk for iron deficiency and iron deficiency anemia was related to increased night sleep duration and less night waking.
PMCID: PMC2771202  PMID: 19322104
infants; sleep; iron deficiency anemia; iron supplementation; developing countries
This study evaluated sex and family history of alcoholism as moderators of subjective ratings of sleepiness/sleep quality and polysomnography following alcohol intoxication in healthy, young adults.
Ninety-three healthy adults (mean age 24.4 ± 2.7 years, 59 women, 29 subjects with a positive family history of alcoholism (FH+)) were recruited. Following screening polysomnography, participants consumed alcohol (sex/weight adjusted dosing) to intoxication (peak breath alcohol concentration [BrAC] of 0.11 ± 0.01 g% for men and women) or matching placebo between 2030 and 2200 hours. Sleep was monitored with polysomnography between 2300 and 0700 hours. Participants completed the Stanford Sleepiness Scale and Karolinska Sleepiness Scale at bedtime and on awakening and a validated post-sleep questionnaire.
Following alcohol, total sleep time, sleep efficiency, nighttime awakenings, and wake after sleep onset were more disrupted in women than men, with no differences by family history status. Alcohol reduced sleep onset latency, sleep efficiency, and REM sleep while increasing wakefulness and Slow Wave Sleep across the entire night compared to placebo. Alcohol also generally increased sleep consolidation in the first half of the night, but decreased it during the second half. Sleepiness ratings were higher following alcohol, particularly in women at bedtime. Morning sleep quality ratings were lower following alcohol than placebo.
Alcohol intoxication increases subjective sleepiness and disrupts sleep objectively more in healthy women than in men, with no differences evident by family history of alcoholism status. Evaluating moderators of alcohol effects on sleep may provide insight into the role of sleep in problem drinking.
PMCID: PMC3083467  PMID: 21323679
alcohol; sleep; polysomnography; sex; family history
17.  A Comparison of the Sleep–Wake Patterns of Cosleeping and Solitary-Sleeping Infants 
This study examined whether 3–15 month-old cosleeping infants displayed differences in time spent in active versus quiet sleep, and in the number/duration of nighttime awakenings when compared with solitary-sleeping infants; and also whether they spent the majority of the night sleeping face-to-face, as previously reported. Nine cosleeping and nine solitary-sleeping infants were matched on age, gender, ethnicity, maternal age, and family SES. Video recordings of nighttime sleep yielded percentage of time in active sleep, quiet sleep, and awake, number of awakenings, and the percentage of time cosleeping infants and mothers spent face-to-face. Across age, cosleeping infants had more awakenings per night (mean 5.8(1.50) versus 3.2(1.95); t = 3.16, p = .006). The percent of the nighttime spent awake did not differ between groups, suggesting that cosleeping infants had shorter awakenings. Cosleeping infants spent 40% of the night face-to-face with their mothers.
PMCID: PMC1201416  PMID: 15577276
cosleeping; infants; sleep
18.  Orexin receptor antagonist-induced sleep does not impair the ability to wake in response to emotionally salient acoustic stimuli in dogs 
The ability to awaken from sleep in response to important stimuli is a critical feature of normal sleep, as is maintaining sleep continuity in the presence of irrelevant background noise. Dual orexin receptor antagonists (DORAs) effectively promote sleep across species by targeting the evolutionarily conserved wake-promoting orexin signaling pathway. This study in dogs investigated whether DORA-induced sleep preserved the ability to awaken appropriately to salient acoustic stimuli but remain asleep when exposed to irrelevant stimuli. Sleep and wake in response to DORAs, vehicle, GABA-A receptor modulators (diazepam, eszopiclone and zolpidem) and antihistamine (diphenhydramine) administration were evaluated in telemetry-implanted adult dogs with continuous electrocorticogram, electromyogram (EMG), electrooculogram (EOG), and activity recordings. DORAs induced sleep, but GABA-A modulators and antihistamine induced paradoxical hyperarousal. Thus, salience gating studies were conducted during DORA-22 (0.3, 1, and 5 mg/kg; day and night) and vehicle nighttime sleep. The acoustic stimuli were either classically conditioned using food reward and positive attention (salient stimulus) or presented randomly (neutral stimulus). Once conditioned, the tones were presented at sleep times corresponding to maximal DORA-22 exposure. In response to the salient stimuli, dogs woke completely from vehicle and orexin-antagonized sleep across all sleep stages but rarely awoke to neutral stimuli. Notably, acute pharmacological antagonism of orexin receptors paired with emotionally salient anticipation produced wake, not cataplexy, in a species where genetic (chronic) loss of orexin receptor signaling leads to narcolepsy/cataplexy. DORA-induced sleep in the dog thereby retains the desired capacity to awaken to emotionally salient acoustic stimuli while preserving uninterrupted sleep in response to irrelevant stimuli.
PMCID: PMC4032881  PMID: 24904334
orexin; DORA; hypocretin; sleep; arousal; auditory discrimination
19.  Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial 
Objective To assess the effectiveness and safety of melatonin in treating severe sleep problems in children with neurodevelopmental disorders.
Design 12 week double masked randomised placebo controlled phase III trial.
Setting 19 hospitals across England and Wales.
Participants 146 children aged 3 years to 15 years 8 months were randomised. They had a range of neurological and developmental disorders and a severe sleep problem that had not responded to a standardised sleep behaviour advice booklet provided to parents four to six weeks before randomisation. A sleep problem was defined as the child not falling asleep within one hour of lights out or having less than six hours’ continuous sleep.
Interventions Immediate release melatonin or matching placebo capsules administered 45 minutes before the child’s bedtime for a period of 12 weeks. All children started with a 0.5 mg capsule, which was increased through 2 mg, 6 mg, and 12 mg depending on their response to treatment.
Main outcome measures Total sleep time at night after 12 weeks adjusted for baseline recorded in sleep diaries completed by the parent. Secondary outcomes included sleep onset latency, assessments of child behaviour, family functioning, and adverse events. Sleep was measured with diaries and actigraphy.
Results Melatonin increased total sleep time by 22.4 minutes (95% confidence interval 0.5 to 44.3 minutes) measured by sleep diaries (n=110) and 13.3 (−15.5 to 42.2) measured by actigraphy (n=59). Melatonin reduced sleep onset latency measured by sleep diaries (−37.5 minutes, −55.3 to −19.7 minutes) and actigraphy (−45.3 minutes, −68.8 to −21.9 minutes) and was most effective for children with the longest sleep latency (P=0.009). Melatonin was associated with earlier waking times than placebo (29.9 minutes, 13.6 to 46.3 minutes). Child behaviour and family functioning outcomes showed some improvement and favoured use of melatonin. Adverse events were mild and similar between the two groups.
Conclusions Children gained little additional sleep on melatonin; though they fell asleep significantly faster, waking times became earlier. Child behaviour and family functioning outcomes did not significantly improve. Melatonin was tolerable over this three month period. Comparisons with slow release melatonin preparations or melatonin analogues are required.
Trial registration ISRCT No 05534585.
PMCID: PMC3489506  PMID: 23129488
20.  Baby Business: a randomised controlled trial of a universal parenting program that aims to prevent early infant sleep and cry problems and associated parental depression 
BMC Pediatrics  2012;12:13.
Infant crying and sleep problems (e.g. frequent night waking, difficulties settling to sleep) each affect up to 30% of infants and often co-exist. They are costly to manage and associated with adverse outcomes including postnatal depression symptoms, early weaning from breast milk, and later child behaviour problems. Preventing such problems could improve these adverse outcomes and reduce costs to families and the health care system. Anticipatory guidance-i.e. providing parents with information about normal infant sleep and cry patterns, ways to encourage self-settling in infants, and ways to develop feeding and settling routines before the onset of problems-could prevent such problems. This paper outlines the protocol for our study which aims to test an anticipatory guidance approach.
750 families from four Local Government Areas in Melbourne, Australia have been randomised to receive the Baby Business program (intervention group) or usual care (control group) offered by health services. The Baby Business program provides parents with information about infant sleep and crying via a DVD and booklet (mailed soon after birth), telephone consultation (at infant age 6-8 weeks) and parent group session (at infant age 12 weeks). All English speaking parents of healthy newborn infants born at > 32 weeks gestation and referred by their maternal and child health nurse at their first post partum home visit (day 7-10 postpartum), are eligible. The primary outcome is parent report of infant night time sleep as a problem at four months of age and secondary outcomes include parent report of infant daytime sleep or crying as a problem, mean duration of infant sleep and crying/24 hours, parental depression symptoms, parent sleep quality and quantity and health service use. Data will be collected at two weeks (baseline), four months and six months of age. An economic evaluation using a cost-consequences approach will, from a societal perspective, compare costs and health outcomes between the intervention and control groups.
To our knowledge this is the first randomised controlled trial of a program which aims to prevent both infant sleeping and crying problems and associated postnatal depression symptoms. If effective, it could offer an important public health prevention approach to these common, distressing problems.
Trial registration number
PMCID: PMC3292472  PMID: 22309617
21.  Exploring Socioeconomic Differences in Bedtime Behaviours and Sleep Duration in English Preschool Children 
Infant and Child Development  2014;23(5):518-531.
Children's sleep is critical for optimal health and development; yet sleep duration has decreased in recent decades, and many children do not have adequate sleep. Certain sleep behaviours (‘sleep hygiene’) are commonly recommended, and there is some evidence that they are associated with longer nighttime sleep. Parents of 84 British 3-year-old children were interviewed about their children's sleep and completed five-night/four-day sleep diaries documenting their children's sleep, from which daily sleep duration was estimated. Diaries were validated by actigraphy in a subgroup of children. Sleep hygiene behaviours (regular bedtime, reading at bedtime, falling asleep in bed) were associated with each other, and were more common in the high socioeconomic status compared to the low socioeconomic status group. Parents' reasons for not practicing sleep hygiene included difficulty, inability or inconvenience. Sleep hygiene behaviours were associated with significantly longer child sleep at night but not over 24 h. Longer daytime napping compensated for shorter nighttime sleep in children whose parents did not implement sleep hygiene behaviours. Parents may need to be advised that certain behaviours are associated with longer nighttime sleep and given practical advice on how to implement these behaviours. © 2014 The Authors. Infant and Child Development published by John Wiley & Sons, Ltd.
PMCID: PMC4283760  PMID: 25598710
sleep; preschool children; sleep hygiene; England; mixed methods; anthropology
22.  Energy expenditure during sleep, sleep deprivation and sleep following sleep deprivation in adult humans 
The Journal of Physiology  2010;589(1):235-244.
Non-technical summary One of the proposed functions of sleep is to conserve energy. We determined the amount of energy conserved by sleep in humans, how much more energy is expended when missing a night of sleep, and how much energy is conserved during recovery sleep. Findings support the hypothesis that a function of sleep is to conserve energy in humans. Sleep deprivation increased energy expenditure indicating that maintaining wakefulness under bed-rest conditions is energetically costly. Recovery sleep after sleep deprivation reduced energy use compared to baseline sleep suggesting that human metabolic physiology has the capacity to make adjustments to respond to the energetic cost of sleep deprivation. The finding that sleep deprivation increases energy expenditure should not be interpreted that sleep deprivation is a safe or effective strategy for weight loss as other studies have shown that chronic sleep deprivation is associated with impaired cognition and weight gain.
Sleep has been proposed to be a physiological adaptation to conserve energy, but little research has examined this proposed function of sleep in humans. We quantified effects of sleep, sleep deprivation and recovery sleep on whole-body total daily energy expenditure (EE) and on EE during the habitual day and nighttime. We also determined effects of sleep stage during baseline and recovery sleep on EE. Seven healthy participants aged 22 ± 5 years (mean ±s.d.) maintained ∼8 h per night sleep schedules for 1 week before the study and consumed a weight-maintenance diet for 3 days prior to and during the laboratory protocol. Following a habituation night, subjects lived in a whole-room indirect calorimeter for 3 days. The first 24 h served as baseline – 16 h wakefulness, 8 h scheduled sleep – and this was followed by 40 h sleep deprivation and 8 h scheduled recovery sleep. Findings show that, compared to baseline, 24 h EE was significantly increased by ∼7% during the first 24 h of sleep deprivation and was significantly decreased by ∼5% during recovery, which included hours awake 25–40 and 8 h recovery sleep. During the night time, EE was significantly increased by ∼32% on the sleep deprivation night and significantly decreased by ∼4% during recovery sleep compared to baseline. Small differences in EE were observed among sleep stages, but wakefulness during the sleep episode was associated with increased energy expenditure. These findings provide support for the hypothesis that sleep conserves energy and that sleep deprivation increases total daily EE in humans.
PMCID: PMC3039272  PMID: 21059762
23.  Armodafinil for Treatment of Excessive Sleepiness Associated With Shift Work Disorder: A Randomized Controlled Study 
Mayo Clinic Proceedings  2009;84(11):958-972.
OBJECTIVE: To assess the effect of armodafinil, 150 mg, on the physiologic propensity for sleep and cognitive performance during usual night shift hours in patients with excessive sleepiness associated with chronic (≥3 months) shift work disorder (SWD) of moderate or greater severity.
PATIENTS AND METHODS: This 12-week, randomized controlled study was conducted at 42 sleep research facilities in North America from April 2 through December 23, 2004, and enrolled 254 permanent or rotating night shift workers with SWD. Entry criteria included excessive sleepiness during usual night shifts for 3 months or longer (corroborated by mean sleep latency of ≤6 minutes on a Multiple Sleep Latency Test), insomnia (sleep efficiency ≤87.5% during daytime sleep), and SWD that was judged clinically to be of moderate or greater severity. Patients received armodafinil, 150 mg, or placebo 30 to 60 minutes before each night shift. Physiologic sleep propensity during night shift hours, clinical impression of severity, patient-reported sleepiness, and cognitive function were assessed during laboratory night shifts at weeks 4, 8, and 12.
RESULTS: Armodafinil significantly improved mean (SD) sleep latency from 2.3 (1.6) minutes at baseline to 5.3 (5.0) minutes at final visit, compared with a change from 2.4 (1.6) minutes to 2.8 (2.9) minutes in the placebo group (P<.001). Clinical condition ratings improved in more patients receiving armodafinil (79%) vs placebo (59%) (P=.001). As reported by patients' diaries, armodafinil significantly reduced sleepiness during laboratory nights (P<.001), night shifts at work (P<.001), and the commute home (P=.003). Armodafinil improved performance on standardized memory (P<.001) and attention (power, P=.001; continuity, P<.001) tests compared with placebo. Armodafinil was well tolerated and did not affect daytime sleep, as measured by polysomnography.
CONCLUSION: In patients with excessive sleepiness associated with chronic SWD of moderate or greater severity, armodafinil significantly improved wakefulness during scheduled night work, raising mean nighttime sleep latency above the level considered to indicate severe sleepiness during the daytime. Armodafinil also significantly improved measures of overall clinical condition, long-term memory, and attention.
Trial Registration: Identifier: NCT00080288
In patients with excessive sleepiness associated with chronic shift work disorder of moderate or greater severity, armodafinil significantly improved wakefulness during scheduled night work, raising mean nighttime sleep latency above the level considered to indicate severe sleepiness during the daytime. Armodafinil also significantly improved measures of overall clinical condition, long-term memory, and attention.
PMCID: PMC2770907  PMID: 19880686
24.  A Transactional Model of Sleep–Wake Regulation in Infants Born Preterm or Low Birthweight 
Journal of Pediatric Psychology  2008;34(8):837-849.
Objective To test a transactional model of sleep–wake development in infants born preterm or low birthweight (PT LBW), which may inform clinical practice, interventions, and future research in this at risk population. Methods One hundred and twenty-eight mother–infant dyads participated from hospital discharge to 4 months postterm. Assessments of prematurity, infant sleep–wake patterns, maternal interaction quality, depression, feeding route, and sociodemographic factors were conducted. Results Path analyses revealed that maternal interactions directly related to infant sleep patterns and family sociodemographic risks related to less optimal parenting. In addition, bottle fed infants experienced fewer night wakings and more nighttime sleep. Conclusions Two potential pathways to sleep patterns in PT LBW infants were identified. The findings suggest directions for clinical work, such as supporting healthy infant sleep through parenting interventions or supporting interpersonal relations between parents and their PT LBW infants by encouraging more daytime naps. Additionally, clinicians should assess parents’ nighttime sleep concerns within the larger sociodemographic and feeding context.
PMCID: PMC2729680  PMID: 19098064
low birthweight; preterm; sleep; transactional development
25.  Reducing postnatal depression, anxiety and stress using an infant sleep intervention 
BMJ Open  2012;2(5):e001662.
To examine the psychological well-being of mothers following participation in a behavioural modification programme previously shown to improve infant sleep.
Design, setting and participants
A 45 min consultation with either a general practitioner (GP) or trained nurse providing verbal and written information describing sleep physiology in infants and strategies to improve infant sleep. Eighty mothers of infants 6−12 months of age with established infant sleep problems at a single general practice, Adelaide, South Australia.
Main outcome measures
The Depression Anxiety Stress Scale 21 (DASS21) immediately prior to the first consultation and again at follow-up approximately 3 weeks later. The number of infant nocturnal awakenings requiring parental support was also reported by mothers on both occasions.
All measures of maternal well-being and infant nocturnal awakenings improved significantly. The mean number of maximum nocturnal awakenings decreased from 5.0 to 0.5 (mean difference 4.4, 95% CI 3.4 to 5.5). All measures of DASS21 improved significantly. The mean total DASS21 decreased from 29.1 to 14.9 (mean decrease 14.2, 95% CI 10.2 to 18.2); mean depression decreased from 7.9 to 2.8 (mean difference 5.2, 95% CI 3.7 to 6.7); mean anxiety decreased from 4.6 to 2.6 (mean difference 2.0, 95% CI 0.7 to 3.2); mean stress decreased from 16.6 to 9.5 (mean difference 7.0, 95% CI 5.1 to 9.0). The proportion of mothers assessed as having any degree of depression decreased by 85% from 26/80 (32.5%) to 4/80 (5%).
The number of nocturnal awakenings requiring parental support among infants aged 6−12 months significantly decreased following a single consultation on infant sleep physiology and teaching behavioural strategies to improve sleep. Significant improvements in maternal stress, anxiety and depression were also observed.
PMCID: PMC3467591  PMID: 22983788
Mental Health; Sleep Medicine

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