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1.  Use of Sleep Aids During the First Year of Life 
Pediatrics  2002;109(4):594-601.
Objective.
In an attempt to foster self-soothing during the night, a novel sleep aid infused with maternal odor was introduced to 4 groups of infants ranging in age from 3 to 12 months. Infants’ use of parent-provided sleep aids also was examined.
Methodology.
Nighttime sleep and waking behaviors were videotaped for 2 consecutive nights on 3 occasions over a 3-month interval. Using all-night video recording, the study examined the infant’s use of a novel sleep aid and parent-provided sleep aids during sleep onset and after nighttime awakenings.
Results.
Results indicated that infants of different ages differed in the types of sleep aids used when falling asleep either at the beginning of the night or after awakenings in the middle of the night. More 3-month-olds used their thumbs/fingers/hands, whereas more 6-month-olds used soft objects. The 6-month-olds were most likely to use the novel sleep aid. Almost all of the infants at all 4 ages used some type of object during the night. Intra-individual analyses showed that infants tended to change their pattern of sleep aid use over the 3-month study period.
Conclusions.
The data provide evidence that infants during the first year of life use sleep aids frequently and interchangeably rather than a specific favorite object.
PMCID: PMC1351014  PMID: 11927702
2.  Nighttime sleep-wake patterns and self-soothing from birth to one year of age: a longitudinal intervention study 
Background
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.
Methods
Eighty infants’ nighttime sleep-wake patterns and associated variables were studied at 5 times across the first year of life using videosomnography and questionnaires.
Results
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.
Conclusions
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
3.  Maternal Caffeine Consumption and Infant Nighttime Waking: Prospective Cohort Study 
Pediatrics  2012;129(5):860-868.
OBJECTIVE:
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.
METHODS:
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.
RESULTS:
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.
CONCLUSIONS:
Caffeine consumption during pregnancy and by nursing mothers seems not to have consequences on sleep of infants at the age of 3 months.
doi:10.1542/peds.2011-1773
PMCID: PMC3566755  PMID: 22473365
sleep; sleep duration; infant sleeping; night waking; infant; caffeine; coffee
4.  Defective Awakening Response to Nocturnal Hypoglycemia in Patients with Type 1 Diabetes Mellitus 
PLoS Medicine  2007;4(2):e69.
Background
Nocturnal hypoglycemia frequently occurs in patients with type 1 diabetes mellitus (T1DM). It can be fatal and is believed to promote the development of the hypoglycemia-unawareness syndrome. Whether hypoglycemia normally provokes awakening from sleep in individuals who do not have diabetes, and whether this awakening response is impaired in T1DM patients, is unknown.
Methods and Findings
We tested two groups of 16 T1DM patients and 16 healthy control participants, respectively, with comparable distributions of gender, age, and body mass index. In one night, a linear fall in plasma glucose to nadir levels of 2.2 mmol/l was induced by infusing insulin over a 1-h period starting as soon as polysomnographic recordings indicated that stage 2 sleep had been reached. In another night (control), euglycemia was maintained.
Only one of the 16 T1DM patients, as compared to ten healthy control participants, awakened upon hypoglycemia (p = 0.001). In the control nights, none of the study participants in either of the two groups awakened during the corresponding time. Awakening during hypoglycemia was associated with increased hormonal counterregulation. In all the study participants (from both groups) who woke up, and in five of the study participants who did not awaken (three T1DM patients and two healthy control participants), plasma epinephrine concentration increased with hypoglycemia by at least 100% (p < 0.001). A temporal pattern was revealed such that increases in epinephrine in all participants who awakened started always before polysomnographic signs of wakefulness (mean ± standard error of the mean: 7.5 ± 1.6 min).
Conclusions
A fall in plasma glucose to 2.2 mmol/l provokes an awakening response in most healthy control participants, but this response is impaired in T1DM patients. The counterregulatory increase in plasma epinephrine that we observed to precede awakening suggests that awakening forms part of a central nervous system response launched in parallel with hormonal counterregulation. Failure to awaken increases the risk for T1DM patients to suffer prolonged and potentially fatal hypoglycemia.
A study of 16 patients with type 1 diabetes and 16 healthy participants showed that the normal awakening response provoked by a fall in plasma glucose was impaired in diabetic individuals.
Editors' Summary
Background.
Hypoglycemia (low blood sugar) is a frequent complication of insulin-treated diabetes, affecting patients with type 1 diabetes mellitus in particular. In individuals who do not have diabetes, insulin secretion is modified naturally and continuously by the body's own regulatory systems, depending on the blood sugar. However, in diabetes patients there is a lack of natural insulin and so manufactured insulin has to be given by injection after blood sugar testing. Hence, it is not possible for patients with diabetes to modify insulin secretion naturally in response to a change in glucose levels, and so blood glucose levels can rise and fall beyond healthy levels. In individuals who have intensive insulin therapy, hypoglycemia can be a particular problem; each year about 25% of patients on intensive insulin therapy have at least one episode of severe hypoglycemia—which requires the assistance of another person.
When hypoglycemia occurs during the day, diabetes patients can recognize it by a variety of symptoms, e.g., feeling sweaty and lightheaded, and they may either seek help from another person or treat themselves with sugar. Hypoglycemia during sleep may be very common—it has been observed to occur in up to half of the nights when patients with diabetes were monitored. The particular problem with hypoglycemia occurring during sleep is that diabetes patients may not be aware of it and hence may not be able to treat themselves or to seek assistance. It is believed to contribute to some instances of sudden death during sleep in patients with diabetes.
Why Was This Study Done?
It has not been clear whether there is a certain level of blood glucose below which a signal is triggered that provokes awakening from sleep in either diabetes patients or in individuals who do not have diabetes. The authors of this study wanted to compare responses to lowered blood glucose in diabetes patients and in individuals who do not have diabetes and to see whether the responses differed. They also wanted to look at whether there were any other hormonal changes that preceded or followed awakening after hypoglycemia.
What Did the Researchers Do and Find?
They treated two groups; 16 type 1 diabetes mellitus patients and 16 healthy control participants. With careful monitoring, on one night once stage 2 sleep (as measured by a method known as polysomnography) had been reached, they gave insulin to lower the blood glucose to a specific level (2.2 mmol/l), which would when awake give symptoms of hypoglycemia. On another night (the control night) normal blood sugar levels were maintained.
They found that only one of the 16 diabetes patients, as compared to ten healthy control participants, woke when hypoglycemia occurred. In the control nights, none of the study participants in either of the two groups awakened during the corresponding time. Awakening during hypoglycemia was associated with substantial hormonal changes, especially with an increase in one hormone, epinephrine (also known as adrenaline), and the increases in this hormone occurred before polysomnographic signs of wakefulness.
What Do These Findings Mean?
It appears that patients with type 1 diabetes mellitus do not awake at a level of hypoglycemia that triggers waking in normal individuals. The hormonal responses that were seen in individuals who awoke may be part of a crucial response system to hypoglycemia. These results help us to understand how diabetes patients respond to hypoglycemia, but further work will need to be done to determine whether it is possible to improve the response. It should be noted, however, that the results are probably not generalizable to patients with type 2 diabetes mellitus, who represent the majority of patients with diabetes.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040069.
A related PLoS Medicine Perspective article by Ilan Gabriely and Harry Shamoon discusses this study and more about hypoglycemia in T1DM
MedlinePlus, the encyclopedia of health information from the US National Library of Medicine, has a collection of pages on hypoglycemia
Wikipedia pages on hypoglycemia (note that Wikipedia is a free online encyclopedia that anyone can edit)
National Diabetes Information Clearinghouse, a service of the US National Institute of Diabetes and Digestive and Kidney Diseases, has information on hypoglycemia
doi:10.1371/journal.pmed.0040069
PMCID: PMC1808097  PMID: 17326710
5.  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.
doi:10.1111/j.1365-2869.2010.00866.x
PMCID: PMC2958223  PMID: 20629937
Intra-individual variability; sleep; physical activity; intervention; unpredictability; sleep-onset latency
6.  Mini-KiSS Online: an Internet-based intervention program for parents of young children with sleep problems – influence on parental behavior and children’s sleep 
Purpose
Behavioral sleep problems are highly common in early childhood. These sleep problems have a high tendency to persist, and they may have deleterious effects on early brain development, attention, and mood regulation. Furthermore, secondary effects on parents and their relationship are documented. Negative parental cognition and behavior have been found to be important influencing factors of a child’s behavioral sleep problems. Therefore, in the current study we examined the acceptance and efficacy of a newly developed Internet-based intervention program called Mini-KiSS Online for sleep disturbances for children aged 6 months to 4 years and their parents.
Patients and methods
Fifty-five children (54.54% female; aged 8–57 months) suffering from psychophysiological insomnia or behavioral insomnia participated in the 6-week online treatment. Sleep problems and treatment acceptance were examined with a sleep diary, anamnestic questionnaires, a child behavior checklist (the Child Behavior Checklist 1.5–5), and treatment evaluation questionnaires.
Results
The evaluation questionnaires showed a high acceptance of Mini-KiSS Online. Parents would recommend the treatment to other families, were glad to participate, and reported that they were able to deal with sleep-related problems of their child after Mini-KiSS Online. Parental behavior strategies changed with a reduction of dysfunctional strategies, such as staying or soothing the child until they fell asleep, allowing the child to get up again and play or watch TV, or reading them another bedtime story. Frequency and duration of night waking decreased as well as the need for external help to start or maintain sleep. All parameters changed significantly, not only in the questionnaires but also in the sleep diary.
Conclusion
Mini-KiSS Online is shown to be a highly accepted and effective treatment to change parental behavior and reduce behavioral sleep problems in early childhood.
doi:10.2147/NSS.S28337
PMCID: PMC3630970  PMID: 23620677
insomnia; childhood; behavioral insomnia of childhood; online treatment; parental behavior
7.  The Intervention Nurses Start Infants Growing on Healthy Trajectories (INSIGHT) study 
BMC Pediatrics  2014;14:184.
Background
Because early life growth has long-lasting metabolic and behavioral consequences, intervention during this period of developmental plasticity may alter long-term obesity risk. While modifiable factors during infancy have been identified, until recently, preventive interventions had not been tested. The Intervention Nurses Starting Infants Growing on Healthy Trajectories (INSIGHT). Study is a longitudinal, randomized, controlled trial evaluating a responsive parenting intervention designed for the primary prevention of obesity. This “parenting” intervention is being compared with a home safety control among first-born infants and their parents. INSIGHT’s central hypothesis is that responsive parenting and specifically responsive feeding promotes self-regulation and shared parent–child responsibility for feeding, reducing subsequent risk for overeating and overweight.
Methods/Design
316 first-time mothers and their full-term newborns were enrolled from one maternity ward. Two weeks following delivery, dyads were randomly assigned to the “parenting” or “safety” groups. Subsequently, research nurses conduct study visits for both groups consisting of home visits at infant age 3–4, 16, 28, and 40 weeks, followed by annual clinic-based visits at 1, 2, and 3 years. Both groups receive intervention components framed around four behavior states: Sleeping, Fussy, Alert and Calm, and Drowsy. The main study outcome is BMI z-score at age 3 years; additional outcomes include those related to patterns of infant weight gain, infant sleep hygiene and duration, maternal responsiveness and soothing strategies for infant/toddler distress and fussiness, maternal feeding style and infant dietary content and physical activity. Maternal outcomes related to weight status, diet, mental health, and parenting sense of competence are being collected. Infant temperament will be explored as a moderator of parenting effects, and blood is collected to obtain genetic predictors of weight status. Finally, second-born siblings of INSIGHT participants will be enrolled in an observation-only study to explore parenting differences between siblings, their effect on weight outcomes, and carryover effects of INSIGHT interventions to subsequent siblings.
Discussion
With increasing evidence suggesting the importance of early life experiences on long-term health trajectories, the INSIGHT trial has the ability to inform future obesity prevention efforts in clinical settings.
Trial registration
NCT01167270. Registered 21 July 2010.
doi:10.1186/1471-2431-14-184
PMCID: PMC4105401  PMID: 25037579
Obesity; Prevention; Infancy; Responsiveness; Home visitation; Feeding; Parenting
8.  Effects of Filtering Visual Short Wavelengths During Nocturnal Shiftwork on Sleep and Performance 
Chronobiology International  2013;30(8):951-962.
Circadian phase resetting is sensitive to visual short wavelengths (450–480 nm). Selectively filtering this range of wavelengths may reduce circadian misalignment and sleep impairment during irregular light-dark schedules associated with shiftwork. We examined the effects of filtering short wavelengths (<480 nm) during night shifts on sleep and performance in nine nurses (five females and four males; mean age ± SD: 31.3 ± 4.6 yrs). Participants were randomized to receive filtered light (intervention) or standard indoor light (baseline) on night shifts. Nighttime sleep after two night shifts and daytime sleep in between two night shifts was assessed by polysomnography (PSG). In addition, salivary melatonin levels and alertness were assessed every 2 h on the first night shift of each study period and on the middle night of a run of three night shifts in each study period. Sleep and performance under baseline and intervention conditions were compared with daytime performance on the seventh day shift, and nighttime sleep following the seventh daytime shift (comparator). On the baseline night PSG, total sleep time (TST) (p < 0.01) and sleep efficiency (p = 0.01) were significantly decreased and intervening wake times (wake after sleep onset [WASO]) (p = 0.04) were significantly increased in relation to the comparator night sleep. In contrast, under intervention, TST was increased by a mean of 40 min compared with baseline, WASO was reduced and sleep efficiency was increased to levels similar to the comparator night. Daytime sleep was significantly impaired under both baseline and intervention conditions. Salivary melatonin levels were significantly higher on the first (p < 0.05) and middle (p < 0.01) night shifts under intervention compared with baseline. Subjective sleepiness increased throughout the night under both conditions (p < 0.01). However, reaction time and throughput on vigilance tests were similar to daytime performance under intervention but impaired under baseline on the first night shift. By the middle night shift, the difference in performance was no longer significant between day shift and either of the two night shift conditions, suggesting some adaptation to the night shift had occurred under baseline conditions. These results suggest that both daytime and nighttime sleep are adversely affected in rotating-shift workers and that filtering short wavelengths may be an approach to reduce sleep disruption and improve performance in rotating-shift workers. (Author correspondence: casper@lunenfeld.ca)
doi:10.3109/07420528.2013.789894
PMCID: PMC3786545  PMID: 23834705
Melatonin; shiftwork; short-wavelength light; sleep efficiency; total sleep time; wake after sleep onset
9.  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.
doi:10.1113/jphysiol.2010.197517
PMCID: PMC3039272  PMID: 21059762
10.  Preventing Obesity during Infancy: A Pilot Study 
Obesity (Silver Spring, Md.)  2010;19(2):353-361.
More than 20% of US children between ages 2 and 5 years are overweight suggesting efforts to prevent obesity must begin earlier. This study tested the independent and combined effects of two behavioral interventions delivered to parents, designed to promote healthy infant growth in the first year. Mother–newborn dyads intending to breastfeed were recruited from a maternity ward. With a 2 × 2 design, 160 dyads were randomized into one of four treatment cells to receive both, one, or no interventions delivered at two nurse home visits. The first intervention (“Soothe/Sleep”) instructed parents on discriminating between hunger and other sources of infant distress. Soothing strategies were taught to minimize feeding for non-hunger-related fussiness and to prolong sleep duration, particularly at night. The second intervention (“Introduction of Solids”) taught parents about hunger and satiety cues, the timing for the introduction of solid foods, and how to overcome infants’ initial rejection of healthy foods through repeated exposure. A total of 110 mother–infant dyads completed the year-long study. At 1 year, infants who received both interventions had lower weight-for-length percentiles (P = 0.009). Participants receiving both interventions had a mean weight-for-length in the 33rd percentile; in contrast, those in other study groups were higher first intervention only—50th percentile; second intervention only—56th percentile; control group—50th percentile).This suggests that multicomponent behavioral interventions may have potential for long-term obesity prevention (ClinicalTrials.gov number, NCT00359242).
doi:10.1038/oby.2010.182
PMCID: PMC3477360  PMID: 20725058
11.  Sleep and breathing in premature infants at 6 months post-natal age 
BMC Pediatrics  2014;14(1):303.
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1186/s12887-014-0303-6
PMCID: PMC4272529  PMID: 25510740
Sleep questionnaire; Sleep-disordered breathing; Prematurity; Full-term infant
12.  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.
doi:10.1177/0748730408318081
PMCID: PMC3130065  PMID: 18663242
circadian rhythm; cognitive performance; grogginess; jet lag; shift work; sleep; sleep inertia
13.  Longitudinal study of self-awakening and sleep/wake habits in adolescents 
Nature and Science of Sleep  2012;4:103-109.
Self-awakening is the ability to awaken without external assistance at a predetermined time. Cross-sectional studies reported that people who self-awaken have sleep/wake habits different from those of people who use external means to wake from sleep. However, no longitudinal study has examined self-awakening. The present study investigated self- awakening, both habitual and inconsistent, compared to awakening by external means in relation to sleep/wake schedules for five consecutive years in 362 students (starting at mean age 15.1 ± 0.3 years). Students who self-awakened consistently for five consecutive years (5% of all students) went to bed earlier than those who inconsistently self-awakened (mixed group, 40%) or consistently used forced awakening by external means (56%). Awakening during sleep was more frequent and sleep was lighter in the consistently self-awakened group than in the mixed and consistently forced-awakened groups. However, daytime dozing was less frequent and comfort immediately after awakening was greater for the consistently self-awakened group than for the mixed and consistently forced-awakened groups. These results indicate that the three groups have different sleep/wake habits. Previous studies of self-awakening using cross-sectional survey data may have confounded both consistent and inconsistent self-awakening habits. A longitudinal study is necessary to clarify the relationship between the self-awakening habit and sleep/wake patterns.
doi:10.2147/NSS.S33861
PMCID: PMC3630977  PMID: 23620684
habitual self-awakening, sleep; wake pattern; adolescent
14.  Sleep patterns and habits in high school students in Iran 
Background
Sleep patterns and habits in high school students in Iran have not been well studied to date. This paper aims to re-address this balance and analyse sleep patterns and habits in Iranian children of high school age.
Methods
The subjects were 1,420 high school students randomly selected by stratified cluster sampling. This was a self-report study using a questionnaire which included items about usual sleep/wake behaviours over the previous month, such as sleep schedule, falling asleep in class, difficulty falling asleep, tiredness or sleepiness during the day, difficulty getting up in the morning, nightmares, and taking sleeping pills.
Results
The mean duration of night sleep was 7.7 h, with no difference between girls, boys, and school year (grade). The mean time of waking in the morning was not different between genders. About 9.9% of the girls and 4.6% of the boys perceived their quality of sleep as being bad, and 58% of them reported sleepiness during the day. About 4.2% of the subjects had used medication to enhance sleep. The time of going to bed was associated with grade level and gender. Sleep latency was not associated with gender and grade leve, l and 1.4% experienced bruxism more than four times a week.
Conclusion
Our results are in contrast with that of previous studies that concluded sleep duration is shorter in Asia than in Europe, that boys woke-up significantly later than girls, and that the frequency of sleep latency category was associated with gender and grade level. The magnitude of the daytime sleepiness, daytime sleepiness during classes, sleep latency, and incidences of waking up at night represent major public health concerns for Iran.
doi:10.1186/1744-859X-7-5
PMCID: PMC2292723  PMID: 18339201
15.  Nighttime maternal responsiveness and infant attachment at one year 
Attachment & human development  2009;11(4):347-363.
This study examined associations between mother–infant nighttime interactions and mother–infant attachment when infants were 12 months old. Forty-four mother–infant pairs participated in this study. For three consecutive nights at home, babies were observed in their cribs using a digital video system. Mothers reported on their nighttime interactions with their babies using a self-report diary and completed a questionnaire regarding child temperament. Attachment was assessed in the Strange Situation (Ainsworth, Blehar, Waters, & Wall, 1978). Mothers of securely attached infants had nighttime interactions that were generally more consistent, sensitive and responsive than those of insecurely attached infants. Specifically, in secure dyads, mothers generally picked up and soothed infants when they fussed or cried after an awakening.
doi:10.1080/14616730903016979
PMCID: PMC3422632  PMID: 19603300
maternal responsiveness; attachment; infants; nighttime; sleep
16.  Does sleep aggravate tension-type headache?: An investigation using computerized ecological momentary assessment and actigraphy 
Background
Both insufficient sleep and oversleeping have been reported as precipitating and aggravating factors of tension-type headache (TTH). However, previous studies relied on recalled self-reports, and the relationship has not been confirmed prospectively and objectively in a daily life situation. Recently, ecological momentary assessment (EMA) using electronic diaries, i.e., computerized EMA, is used to record subjective symptoms with the advantages of avoiding recall bias and faked compliance in daily settings. In addition, actigraphy has become an established method to assess sleep outside laboratories. Therefore, the aim of this study was to investigate the within-individual effect of sleep on the following momentary headache intensity in TTH patients during their daily lives utilizing EMA and actigraphy.
Methods
Twenty-seven patients with TTH wore watch-type computers as electronic diaries for seven consecutive days and recorded their momentary headache intensity using a visual analog scale of 0-100 approximately every six hours, on waking up, when going to bed, and at the time of headache exacerbations. They also recorded their self-report of sleep quality, hours of sleep and number of awakenings with the computers when they woke up. Physical activity was continuously recorded by an actigraph inside the watch-type computers. Activity data were analyzed by Cole's algorithm to obtain total sleep time, sleep efficiency, sleep latency, wake time after sleep onset and number of awakenings for each night. Multilevel modeling was used to test the effect of each subjective and objective sleep-related variable on momentary headache intensity on the following day.
Results
Objectively measured total sleep time was significantly positively associated with momentary headache intensity on the following day, while self-reported sleep quality was significantly negatively associated with momentary headache intensity on the following day.
Conclusions
Using computerized EMA and actigraphy, longer sleep and worse sleep quality were shown to be related to more intense headache intensity on within-individual basis and they may be precipitating or aggravating factors of TTH.
doi:10.1186/1751-0759-5-10
PMCID: PMC3163177  PMID: 21835045
17.  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.
Background
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.
Methods/Design
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.
Discussion
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
ISRCTN: ISRCTN63834603
doi:10.1186/1471-2431-12-13
PMCID: PMC3292472  PMID: 22309617
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.
doi:10.3389/fnbeh.2014.00182
PMCID: PMC4032881  PMID: 24904334
orexin; DORA; hypocretin; sleep; arousal; auditory discrimination
19.  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.
doi:10.1016/j.socscimed.2012.05.043
PMCID: PMC3505270  PMID: 22818487
infant sleep; sleep-related risks; Sudden Infant Death Syndrome (SIDS); nighttime parenting; USA
20.  Chronic Insomnia 
The American journal of psychiatry  2008;165(6):678-686.
Ms. F, a 42-year-old divorced woman, presents for evaluation of chronic insomnia. She complains of difficulty falling asleep, often 30 minutes or longer, and difficulty maintaining sleep during the night, with frequent awakenings that often last 30 minutes or longer. These symptoms occur nearly every night, with only one or two “good” nights per month. She typically goes to bed around 10:00 p.m. to give herself adequate time for sleep, and she gets out of bed around 7:00 a.m. on work days and as late as 9:00 a.m. on weekends. Her nighttime sleep problems result in daytime irritability and difficulty focusing and organizing her thoughts, which subjectively impair her work as an administrative assistant, although her performance evaluations have been satisfactory. She says that she has “no energy for anything extra,” that her house is a mess, and that she routinely declines invitations to join social and even family activities. Her insomnia began approximately 5 years ago during a period of increased life stress related to a difficult divorce and a job change. At that time she was diagnosed with major depression and was started on a successful trial of escitalopram, which she continues at a dose of 10 mg/day. Her current symptoms are distinct from those that were associated with her episode of major depression. She denies pervasive sadness or loss of interest, but she is very frustrated with her inability to function more effectively, which she attributes to her insomnia. In fact, she believes that her cognitive difficulties and irritability are most noticeable after nights of particularly poor sleep. Her medical history is unremarkable other than a past history of Graves’ disease. She has been treated with levothyroxine for the past 15 years.
How should Ms. F be evaluated? What medical testing, if any, would be appropriate? What factors should be considered in formulating a treatment plan? What treatments would be appropriate?
doi:10.1176/appi.ajp.2008.08010129
PMCID: PMC2859710  PMID: 18519533
21.  Sleep Quality after Initial Chemotherapy for Breast Cancer 
Goals of Work
To characterize sleep quality and quantity prior to and in the first 3 nights after initial chemotherapy for breast cancer.
Patients and Methods
Secondary analysis of data from two separate randomized clinical trials (RCT) of behavioral interventions to improve fatigue and sleep. Patients came from two comprehensive cancer centers, three clinical cancer centers, and 10 community clinics in five states. Participants were women with stage I-IIIA breast cancer treated with anthracycline and/or cyclophosphamide based regimens.
Main Results
Baseline data from each RCT were used in the analysis. Sixty-five percent of women self-reported poor sleep in the month preceding chemotherapy using the Pittsburgh Sleep Quality Index (PSQI) score >5. Three nights of actigraphy data indicated a wide range of sleep experience with an average of 10 awakenings and time (minutes) awake after sleep onset (WASO-M) averaging 61 minutes per night. The first night’s sleep was the worst. There was no statistically significant relationship between self-reported poor sleep and sleep measures obtained by actigraphy. Women with poor sleep at baseline (global PSQI >5) had significantly lower (p<.001) physical (MOS PCS) and mental (MOS MCS) health status. However neither the PCS nor MCS was associated with any of the average actigraphy sleep parameters or Night 1 parameters in the aggregated sample. Increasing age was also associated with poorer sleep.
Conclusions
A high percent of women with breast cancer begin chemotherapy with disturbed sleep and the initial nights after chemotherapy are characterized by sleep fragmentation that disrupts sleep maintenance. Interventions should focus on strategies to decrease the number and duration of night awakenings. Further research is needed to identify predictors of poor sleep during this time.
doi:10.1007/s00520-009-0662-y
PMCID: PMC2874643  PMID: 19521723
sleep; chemotherapy; breast cancer; actigraphy; neoplasm; function
22.  Temporal daily associations between pain and sleep in adolescents with chronic pain versus healthy adolescents 
Pain  2010;151(1):220-225.
Adolescents with chronic pain frequently report sleep disturbances, particularly short sleep duration, night wakings, and poor sleep quality. Prior research has been limited by assessment of subjectively reported sleep only and lack of data on daily relationships between sleep and pain. The current study utilized multilevel modeling to compare daily associations between sleep and pain in adolescents with chronic pain and healthy adolescents. Ninety-seven adolescents (n=39 chronic pain; n=58 healthy) aged 12–18, 70.1% female participated. Adolescents completed pain diary ratings (0–10 NRS) and actigraphic sleep monitoring for 10 days. Actigraphic sleep variables (duration, efficiency, WASO) and self-reported sleep quality were tested as predictors of next-day pain, and daytime pain was tested as a predictor of sleep that night. Effects of age, gender, study group, and depressive symptoms on daily associations between sleep and pain were also tested. Multivariate analyses revealed that nighttime sleep (p<.001) and minutes awake after sleep onset (WASO) (p<.05) predicted next-day pain, with longer sleep duration and higher WASO associated with higher pain. Contrary to hypotheses, neither nighttime sleep quality nor sleep efficiency predicted pain the following day. The interaction between nighttime sleep efficiency and study group was significant, with adolescents with pain showing stronger associations between sleep efficiency and next day pain than healthy participants (p=.05). Contrary to hypotheses, daytime pain did not predict nighttime sleep. Daily associations between pain and sleep suggest that further work is needed to identify specific adolescent sleep behaviors (e.g., compensatory sleep behaviors) that may be targeted in interventions.
doi:10.1016/j.pain.2010.07.016
PMCID: PMC2939216  PMID: 20719433
pain; chronic pain; actigraphy; adolescents; sleep; multilevel-modeling
23.  Coparenting Quality During the First Three Months After Birth: The Role of Infant Sleep Quality 
The transition to parenthood can be stressful for new parents, as parents must learn to take on new roles and responsibilities. Sleep disruption—which has been linked in prior research to parent distress and fatigue—is common in the early months. The current study is the first to our knowledge to examine infant sleep and its potential indirect influence on parents’ perceptions of coparenting quality at 1 and 3 months of infant age. Participants included 150 families. Mothers reported more night waking, poorer sleep quality, more depressive symptoms, and worse perceptions of coparenting quality as compared with fathers. We tested a structural model of infant and parent night waking and sleep quality as predictors of parent distress and coparenting using maximum likelihood estimation. The frequency of infant night waking predicted father and mother night waking, which in turn predicted parent sleep quality. Poor parent sleep quality predicted elevated depressive symptoms, and finally depressive symptoms were negatively related to perceptions of coparenting quality. Significant indirect effects between infant night waking and parent depression and coparenting quality were found. In summary, both mothers’ and fathers’ perceptions of coparenting were related to the unfolding parental dynamics that take place surrounding infant sleep difficulties. This held true even after controlling for parent education, family income, and infant temperament. Therefore, parenting may indirectly benefit from interventions targeting infant sleep difficulties.
doi:10.1037/a0030707
PMCID: PMC3562740  PMID: 23244456
Transition to parenthood; coparenting; parent sleep; infant sleep; depression
24.  SLEEP FOLLOWING ALCOHOL INTOXICATION IN HEALTHY, YOUNG ADULTS: EFFECTS OF SEX AND FAMILY HISTORY OF ALCOHOLISM 
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1111/j.1530-0277.2010.01417.x
PMCID: PMC3083467  PMID: 21323679
alcohol; sleep; polysomnography; sex; family history
25.  Effects of L-serine ingestion on human sleep 
SpringerPlus  2014;3:456.
To investigate the effects of L-serine intake on human sleep, we conducted two randomized double-blinded crossover studies. In Study 1, healthy subjects who were dissatisfied with their sleep were given L-serine or a placebo 30 min before going to bed. After waking the next morning, subjective sleep quality was rated using the Ogri-Shirakawa-Azumi subjective sleep rating scale. In Study 2, subjective sleep quality was rated using the St. Mary’s Hospital sleep questionnaire, and objective parameters, including sleep initiation time, number of nighttime awakenings, and hours of sleep, were evaluated using actigraphy. In Study 1, factors related to “sleep initiation” and “sleep maintenance” during the L-serine intake period were significantly improved compared to the placebo intake period (p = 0.02 and p = 0.008, respectively). In Study 2, scores for “How well did you sleep last night?” and “How satisfied were you with last night’s sleep?” were significantly better during L-serine intake compared to placebo (p = 0.04 and p = 0.03, respectively). Subjective evaluation of sleep quality on waking was thus improved. In addition, objective evaluation using actigraphy showed that the “number of nighttime awakenings” tended to be decreased (p = 0.08). These findings suggest that intake of L-serine before going to bed may improve human sleep.
doi:10.1186/2193-1801-3-456
PMCID: PMC4155056  PMID: 25197619
Human sleep; L-serine; Amino acid

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