Louise M. O’Brien

Assessment and Management of Sleep Problems in Youths With Attention-Deficit/Hyperactivity Disorder

OBJECTIVE To provide evidence- or consensus-based recommendations concerning the assessment and management of sleep problems in youths with attention-deficit/hyperactivity disorder (ADHD). METHOD PubMed, Ovid, EMBASE, and Web of Knowledge were searched through October 31, 2012. When no evidence was available, consensus of the authors was achieved. The evidence-level of the recommendations on the management of sleep disturbances was based on the Scottish Intercollegiate Guidelines Network (SIGN) system. RESULTS A total of 139 original articles on sleep and childhood ADHD were retrieved, including 22 on treatment of sleep disturbances. This review focuses on behaviorally based insomnia, circadian rhythm disorder, sleep-disordered breathing, restless legs syndrome/periodic limb movement disorder, and sleep disturbances due to comorbid psychiatric disorders or ADHD medications. Healthy sleep practices are recommended as the foundation of management strategies. Behavioral interventions should be considered as first-line treatment of insomnia, although further evidence from randomized controlled trials (RCTs) is needed to prove their efficacy in ADHD. Among pharmacological treatments, RCTs support the use of melatonin to reduce sleep-onset delay, whereas there is more limited evidence for other medications. CONCLUSION Growing empirical evidence is informing assessment/management strategies of sleep problems in youths with ADHD. However, further RCTs are warranted to support current recommendations.

Sleep and quality of life in children with cerebral palsy

OBJECTIVE To examine the associations between sleep problems and quality of life (QoL) in children with cerebral palsy (CP). METHODS Prospective correlational study using parent-report forms to measure QoL and sleep disorder symptoms. Two groups comprised of 41 children with CP and 91 typically developing (TD) controls age 8-12years participated in a prospective correlational study. RESULTS Measures were the PedsQL-4.0 Generic scales and the Pediatric Sleep Questionnaire, with subscales of interest including sleep disordered breathing (SDB), excessive daytime sleepiness (EDS), insomnia (INS) and snoring (SNOR). Hierarchical regression analyses indicated that EDS contributed unique variance in physical QoL, and INS contributed unique variance in psychosocial QoL in children with CP; for TD children, sleep disorder symptoms were infrequent and not associated with physical or psychosocial QoL. CONCLUSIONS Findings highlight the importance of assessing sleep difficulties when addressing the needs of children with CP.

Sleep disruption and adverse pregnancy outcomes

A recent meta-analysis reported the most important and potentially modifiable risk factors for stillbirth [1]. Approximately half of these risk factors are likely influenced by maternal sleep disruption. Poor sleep occurs for many reasons although the most common sleep problems include: • sleep restriction (short sleep duration), which is often self-imposed because of busy lifestyles; • sleep-disordered breathing (SDB), a term which describes a spectrum of breathing problems during sleep from habitual snoring to obstructive sleep apnea, resulting in oxygen desaturation and sleep fragmentation; and • poor sleep quality. Emerging literature now suggests that sleep disruption during pregnancy is associated with poor pregnancy outcomes for both mother and infant [2]. There are emerging associations between maternal sleep and several major risk factors for stillbirth: maternal obesity, gestational hypertension/pre-eclampsia, gestational diabetes, and intra-uterine growth restriction (IUGR). In recent years, sleep duration has drastically fallen and has been paralleled by a rise in the prevalence of obesity. Chronic sleep restriction (such as self-imposed short sleep duration) plays a pivotal role in the pathophysiology of overweight and obesity via the modulation of neuroendocrine function. Sleep disruption, including short sleep duration and sleep fragmentation, has emerged as a major determinant of metabolic health, independently of weight and is implicated in poor glucose control [3] and possibly gestational diabetes. Of note, approximately half of all Western women of childbearing age are overweight or obese and obesity can lead to increased risk for sleep disorders such as SDB. Habitual snoring is the main symptom of SDB and its frequency reaches a peak in the third trimester, affecting approximately one third of pregnant women in general, and the majority of those with pre-eclampsia. Habitual snoring is independently associated with gestational hypertension and pre-eclampsia [4]. Although the pathogenesis of pre-eclampsia is not completely understood, the biological pathways include endothelial dysfunction, oxidative stress, and inflammation. The pathogenic process likely originates in the placenta during early pregnancy with abnormal implantation and vasculature development. This leads to oxidative stress and inflammation with subsequent release of anti-angiogenic factors and widespread endothelial dysfunction. Sleep disruption, including poor sleep quality, in early pregnancy has been suggested to adversely impact implantation [5] which has the potential to accelerate the cascade of inflammation and oxidative stress described above. Notably, the mechanisms of sleep disruption that affect cardiovascular morbidity are remarkably similar to the biological pathways for pre-eclampsia. Poor sleep quality during pregnancy is already evident in the first trimester and has been associated with increased risk for longer labors and Caesarean section delivery [6], as well as preterm delivery [5], likely via its impact on neuroendocrine, metabolic, and inflammatory pathways. In women with SDB, case reports have shown that maternal obstructive apneas are associated with fetal heart rate decelerations, perhaps due to uteroplacental hypoperfusion, a mechanism implicated in intrauterine growth restriction (IUGR). In summary, maternal sleep disruption is emerging as a significant factor in adverse pregnancy outcomes. Future research should consider maternal sleep when investigating stillbirth.

Postsurgical behaviors in children with and without symptoms of sleep-disordered breathing

BackgroundAlthough some children undergo formal preoperative testing for obstructive sleep apnea, it is likely that many children present for surgery with undetected sleep-related disorders. Given that these children may be at increased risk during the perioperative period, this study was designed to compare postoperative behaviors between those with and without symptoms of sleep-disordered breathing (SDB).MethodsThis study represents a secondary analysis of data from a study examining the effect of SDB on perioperative respiratory adverse events in children. Parents of children aged 2–14 years completed the Sleep-Related Breathing Disorder (SRBD) subscale of the Pediatric Sleep Questionnaire prior to surgery. Children were classified as having SDB if they had a positive score (≥0.33) on the SRBD subscale. Seven to ten days following surgery, the SRBD subscale was re-administered to the parents who also completed the Children’s Post Hospitalization Behavior Questionnaire. Children were classified as exhibiting increased problematic behaviors if their postoperative behaviors were considered to be “more/much more” relative to normal.ResultsThree hundred thirty-seven children were included in this study. Children with SDB were significantly more likely to exhibit problematic behaviors following surgery compared with children without SDB. Logistic regression identified adenotonsillectomy (OR 9.89 [3.2–30.9], P < 0.01) and posthospital daytime sleepiness (OR 2.8 [1.3–5.9], P < 0.01) as risk factors for postoperative problematic behaviors.ConclusionsChildren presenting for surgery with symptoms of SDB have an increased risk for problematic behaviors following surgery. These results are potentially important in questioning whether the observed increase in problematic behaviors is biologically grounded in SDB or simply a response to poor sleep habits/hygiene.

Sleep-Related Breathing Disorder, Cognitive Functioning, and Behavioral-Psychiatric Syndromes in Children.

Childhood sleep disordered breathing (SDB) is strongly associated with a range of cognitive and behavioral disturbances, including some psychiatric diagnoses. Despite this, the majority of children with symptoms of SDB go unrecognized, even though simple screening could identify children in need of further evaluation. Definitive evidence showing that SDB causes cognitive and behavioral impairment has yet to emerge, although a randomized controlled trial evaluating neuropsychological and health outcomes of treatment for SDB in children is currently underway.

Maternal sleep position: what do we know where do we go?

Good sleep is an essential component to health and wellbeing. It consumes one third of human existence; unhealthy sleep can severely impair the other two-thirds. An increasing amount of data now shows that poor sleep – such as sleep disordered breathing, poor sleep quality, and insomnia - has a negative impact on pregnancy outcomes [1-5]. Indeed, over half of the most important risk factors for stillbirth, such as maternal hypertension, gestational diabetes, and fetal growth restriction, have been shown to be associated with maternal sleep disruption [1,2,6-9]. Findings from recent studies have also suggested that maternal sleep position may be a risk factor for stillbirth [10,11]. It has long been recognized that posture in late pregnancy can have a profound effect on maternal hemodynamics. Studies in awake pregnant women have demonstrated reduced ejection fraction and cardiac output in the supine position compared to the left lateral position [12] that may reduce utero-placental blood flow to the fetus since the gravid uterus compresses the inferior vena cava. Failure to prevent this compression can lead to maternal supine hypotensive syndrome [13] and to an adverse effect on umbilical artery blood flow and gas exchange between mother and fetus, with consequent fetal heart rate decelerations [14] and fetal growth restriction [15]. For over 60 years it has been standard of care to place laboring pregnant women in the left lateral tilt position to displace the uterus from the inferior vena cava and improve maternal hemodynamics. Despite this knowledge, little attention has been paid to maternal sleep position during pregnancy even though we spend about one third of our life asleep. Given the known effects of inferior vena cava compression it is very possible that supine sleep could be a risk for stillbirth. Recent studies in Auckland, New Zealand [10], and Ghana, Africa [11] have both shown that supine sleep is independently associated with stillbirth; indeed Owusu et al [11] found that the effect of supine sleep on stillbirth was mediated via low birth weight. Both of the latter studies suggested that if supine sleep plays a causal role in stillbirth, altering the sleep position of pregnant women may reduce stillbirth by approximately 25%. Of note, we have recently demonstrated that the majority of pregnant women (about 80%) spend some time sleeping supine, with the median time being approximately one quarter of the night [16].Supine sleep may therefore represent a maternal stressor in the unexplained late stillbirth triple risk model [17]. Thus, if supine sleep plays a role in stillbirth, the majority of pregnant women would benefit from education and potential intervention. Several potential methods to reduce supine sleep include the use of mattress wedges or pillows [18] or other interventions such as the ‘tennis ball’ technique [19] or even novel devices that could alert a pregnant women to change position. However, before intervention studies are launched, it is pertinent that the findings regarding sleep position are repeated and confirmed in other studies; several such studies are currently underway including small studies monitoring the fetus during maternal sleep (O’Brien and Warland, personal communication) and large studies such as the MiNESS study in the UK [20] that will either support or refute the sleep position hypothesis.

The effect of repeated light-dark shifts on uterine receptivity and early gestation in mice undergoing embryo transfer

ABSTRACT Female shift workers are at increased risk for negative reproductive outcomes, and animal evidence suggests that manipulation of the light-dark cycle is detrimental to early gestation in female mice. Specifically, failure of implantation may be responsible for these findings. The objective of this study was to better delineate which reproductive processes are vulnerable to detrimental effects of maternal circadian disturbance. We exposed mice undergoing embryo transfer to repetitive phase advances of the photoperiod. Embryos were derived from donor sperm and eggs from mice living in normal light-dark conditions to isolate the effects of photoperiod disruption on uterine receptivity and early gestation. Twenty-eight mice receiving embryo transfer underwent an experimental light-dark condition (advance of lights on and lights off by 6 hours every 4 days). Twenty-eight mice remained in a normal light-dark condition. Animals lived in their assigned light-dark condition beginning 2 weeks prior to embryo transfer and ending the day of uterine necropsy (post-coitus day 14.5). Wilcoxon-Mann-Whitney test demonstrated no significant differences between control and experimental light-dark conditions in pups (Z=0.10, p=.92), resorptions (Z=0.20, p=.84), or implantations (Z=-0.34, p=.73). Pup and placental weights were similar between groups. In this investigation, uterine receptivity and maintenance of early gestation were preserved despite recurrent phase advances in photoperiod. This finding, in the context of the current literature, suggests that the negative effects of circadian disruption are mediated by reproductive processes upstream of implantation.

Key insomnia symptoms and incident pain in older adults: direct and mediated pathways through depression and anxiety

Pain is common among older adults and negatively impacts functioning. Sleep disturbances and mood disorders, specifically depression and anxiety, are closely associated with pain in older individuals, but the directionality of these associations remains unclear. In this study, we deconstruct long-term temporal effects of two key insomnia symptoms on incident pain into direct and indirect pathways, with focus on depression and anxiety symptoms, within a nationally representative sample. We utilized 2011-2013 data from the National Health and Aging Trends Study, a longitudinal survey of 2239 community-dwelling Medicare beneficiaries. Participants completed annual in-person interviews with assessments of sleep initiation and maintenance; depression, and anxiety (using the Patient Health Questionnaire-2 [PHQ-2] and the Generalized Anxiety Disorder Scale-2 [GAD-2] respectively); and bothersome pain. Causal mediation analysis was applied to examine direct effects of the two insomnia symptoms at baseline on incident pain, and their indirect effects through depression and anxiety symptoms. Almost one-third of the study participants were 69 years old or younger. A similar proportion reported bothersome pain in 2013. The two baseline insomnia symptoms predicted the development of pain. Adjusted analyses suggested that compared to older adults without the two baseline insomnia symptoms, participants with sleep initiation or maintenance difficulties had 24% (95% confidence interval [CI] 2%,51%) and 28% (95% CI 4%,55%) higher odds of incident pain, respectively. Anxiety symptoms partially mediated the relationship between the insomnia symptoms and incident pain, accounting for up to 17% of the total effect, but depressive symptoms did not. These results suggest that improved sleep or anxiety could reduce the risk for future pain.

Effects of maternal obstructive sleep apnea on fetal growth: a case-control study

ObjectiveTo investigate whether maternal obstructive sleep apnea (OSA) is associated with changes in fetal growth trajectory.Study designRetrospective review of pregnant women who underwent overnight polysomnography. Fetal growth was estimated using sonographic biometric measurements obtained during routine prenatal care. Customized estimated fetal weight and birth weight centiles were calculated and impaired fetal growth was defined as birth weight <10th centile or a slowing of fetal growth by >33% during the last trimester. Logistic regression models were used to determine the relationship between maternal OSA and altered fetal growth after adjusting for potential covariates.ResultsThere were 48 women without and 31 women with OSA. There were no differences in the proportion of infants with birth weight <10th centile between women with and without OSA (23 vs. 25%, p = 1.0), However, the presence of maternal OSA was predictive of impaired fetal growth (aOR 3.9, 95% CI 1.2–12.6). Logistic regression models were repeated using only a slowing of fetal growth in the 3rd trimester (excluding birth weight <10th centile) and OSA predicted a slowing in fetal growth across the 3rd trimester (aOR 3.6, 95% CI 1.4–9.4). Fourteen additional women were treated with positive airway pressure during pregnancy; fetal growth was not significantly different in these women compared to controls.ConclusionObstructive sleep apnea is independently associated with altered fetal growth, which appears to be ameliorated with use of positive airway pressure.

Sleep, Diet, and Cardiometabolic Health Investigations: a Systematic Review of Analytic Strategies

Purpose of ReviewPoor sleep is a risk factor for cardiometabolic morbidity. The relationship of sleep and cardiometabolic health could be confounded, mediated, or modified by diet, yet the incorporation of diet in sleep-cardiometabolic health studies is inconsistent. This rapid systematic literature review evaluates the conceptualization of diet as a confounder, mediator, or effect modifier within sleep-cardiometabolic health investigations, and the statistical approaches utilized.Recent FindingsOf 4692 studies identified, 60 were retained (28 adult, 32 pediatric). Most studies included diet patterns, quality, or energy intake as confounders, while a few examined these dietary variables as mediators or effect modifiers. There was some evidence, mostly in pediatric studies, that inclusion of diet altered sleep-cardiometabolic health associations.SummaryDiet plays a diverse role within sleep-cardiometabolic health associations. Investigators should carefully consider the conceptualization of diet variables in these relationships and utilize contemporary statistical approaches when applicable.