Galit Levi Dunietz

Sleep-Disordered Breathing During Pregnancy: Future Implications for Cardiovascular Health

Importance Cardiovascular disease (CVD) is a common condition in postreproductive females. Key risk factors for later-life CVD include gestational hypertension (GHTN) and preeclampsia (PE). Although several risk factors of hypertension in pregnancy are well recognized, a novel risk factor that has emerged recently is sleep-disordered breathing (SDB), a condition characterized by repeated closure of the upper airway during sleep with disrupted ventilation and sleep fragmentation. In the nonpregnant population, SDB is now known to play a causal role in future CVD. Objective The aim of this study was to propose the hypothesis that occult SDB during pregnancy may play a role in long-term CVD in women who had hypertensive disorders of pregnancy. Evidence Acquisition This study is a review and synthesis of empirical evidence that links SDB to GHTN/PE and GHTN/PE to future CVD. Results An increasing body of evidence supports the relationship between SDB and hypertensive disorders of pregnancy via mechanisms of inflammation, oxidative stress, and endothelial dysfunction. It is well established that hypertensive disorders of pregnancy are associated with long-term risk for CVD via similar mechanisms. However, no studies have addressed the potential role of SDB in long-term outcomes of women with GHTN/PE during pregnancy. Conclusions Given the suggested mechanisms that explain these associations, it is plausible that SDB during pregnancy may increase long-term cardiovascular morbidity and mortality. Relevance Pregnancy may offer a window of opportunity for identification and treatment of SDB, which could provide substantial health benefit for many years to come. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives After completing this CME activity, physicians should be better able to evaluate the current evidence regarding the frequency of SDB in pregnancy, its risk factors, subsequent outcomes, and treatment.

Moderately elevated blood pressure during pregnancy and odds of hypertension later in life: the POUCHmoms longitudinal study

Hypertensive disorders in pregnancy signal an increased risk of cardiovascular disease for women. However, future hypertension risk among pregnant women with moderately elevated blood pressure (BP) is unknown. We examined associations among moderately elevated BP or hypertensive disorders during pregnancy and later prehypertension or hypertension.

Restless Legs Syndrome and Sleep-Wake Disturbances in Pregnancy

STUDY OBJECTIVES To estimate the association of restless legs syndrome (RLS) and its frequency with sleep-wake disturbances in pregnancy. METHODS A cohort of 1,563 women in their third trimester of pregnancy were recruited from prenatal clinics between March 2007 and December 2010. Demographic, pregnancy, and delivery data were extracted from medical records and sleep information was collected with questionnaires. To diagnose RLS, we used standardized criteria of RLS symptoms and frequency that were developed by the International Restless Legs Study Group. Logistic regression models were constructed to investigate the association of RLS and its frequency with sleep-wake disturbances (poor sleep quality, daytime sleepiness, poor daytime function) and delivery outcomes. RESULTS Overall 36% of the pregnant women had RLS, and half had moderate to severe symptoms. Compared to women without RLS, those with RLS were more likely to have poor sleep quality (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.7-2.9), poor daytime function (OR 1.9, 95% CI 1.4-2.4), and excessive daytime sleepiness (OR 1.6, 95% CI 1.3-2.0). A dose-response relationship also was evident between RLS frequency and each of the sleep-wake disturbances. There was no evidence for any association between RLS and delivery outcomes. CONCLUSIONS RLS is a significant contributor to poor sleep quality, daytime sleepiness, and poor daytime function, all common and often debilitating conditions in pregnancy. Obstetric health care providers should be aware of these associations and screen women for RLS. COMMENTARY A commentary on this article appears in this issue on page 857.

Assisted reproductive technology and newborn size in singletons resulting from fresh and cryopreserved embryos transfer

Objectives and Study Design The aim of this study was two-fold: to investigate the association of Assisted Reproductive Technology (ART) and small newborn size, using standardized measures; and to examine within strata of fresh and cryopreserved embryos transfer, whether this association is influenced by parental infertility diagnoses. We used a population-based retrospective cohort from Michigan (2000–2009), Florida and Massachusetts (2000–2010). Our sample included 28,946 ART singletons conceived with non-donor oocytes and 4,263,846 non-ART singletons. Methods Regression models were used to examine the association of ART and newborn size, measured as small for gestational age (SGA) and birth-weight-z-score, among four mutually exclusive infertility groups: female infertility only, male infertility only, combined female and male infertility, and unexplained infertility, stratified by fresh and cryopreserved embryos transfer. Results We found increased SGA odds among ART singletons from fresh embryos transfer compared with non-ART singletons, with little difference by infertility source [adjusted odds-ratio for SGA among female infertility only: 1.18 (95% CI 1.10, 1.26), male infertility only: 1.20 (95% CI 1.10, 1.32), male and female infertility: 1.18 (95% CI 1.06, 1.31) and unexplained infertility: 1.24 (95% CI 1.10, 1.38)]. Conversely, ART singletons, born following cryopreserved embryos transfer, had lower SGA odds compared with non-ART singletons, with mild variation by infertility source [adjusted odds-ratio for SGA among female infertility only: 0.56 (95% CI 0.45, 0.71), male infertility only: 0.64 (95% CI 0.47, 0.86), male and female infertility: 0.52 (95% CI 0.36, 0.77) and unexplained infertility: 0.71 (95% CI 0.47, 1.06)]. Birth-weight-z-score was significantly lower for ART singletons born following fresh embryos transfer than non-ART singletons, regardless of infertility diagnoses.

Recognition and Diagnosis of Obstructive Sleep Apnea in Older Americans: Obstructive sleep apnea in older Americans

To estimate the proportion of older Americans at risk for obstructive sleep apnea (OSA) who receive OSA evaluations, diagnosis, and treatment.

Adiposity in Adolescents: The Interplay of Sleep Duration and Sleep Variability

Objective To assess whether adiposity measures differed according to joint categories of sleep duration and sleep variability in a sample of Mexican adolescents. Study design A sample of 528 Mexico City adolescents aged 9‐17 years wore wrist actigraphs for 6‐7 days. Average sleep duration was categorized as age‐specific sufficient or insufficient. Sleep variability, the standard deviation of sleep duration, was split at the median into stable versus variable. Adiposity measures—body mass index (BMI)‐for‐age Z score (BMIz), triceps skinfolds, waist circumference, and percent body fat—were collected by trained assistants. We regressed adiposity measures on combined sleep duration and variability categories. Log binomial models were used to estimate prevalence ratios and 95% CI for obesity (>2 BMIz) by joint categories of sleep duration and variability, adjusting for sex, age, and maternal education. Results Approximately 40% of the adolescents had insufficient sleep and 13% were obese. Relative to sufficient‐stable sleepers, adolescents with insufficient‐stable sleep had higher adiposity across all 4 measures (eg, adjusted difference in BMIz was 0.68; 95% CI, 0.35‐1.00) and higher obesity prevalence (prevalence ratio, 2.54; 95% CI, 1.36‐4.75). Insufficient‐variable sleepers had slightly higher BMIz than sufficient‐stable sleepers (adjusted difference, 0.30; 95% CI, 0.00‐0.59). Conclusions Adolescents with consistently insufficient sleep could be at greater risk for obesity. The finding that insufficient‐variable sleepers had only slightly higher adiposity suggests that opportunities for “catch‐up” sleep may be protective.

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.

Lack of Worsening of Sleep-Disordered Breathing After Recurrent Stroke in the BASIC Project

STUDY OBJECTIVES To investigate the difference in sleep-disordered breathing (SDB) prevalence and severity after an index and recurrent stroke. METHODS In a sample of 40 subjects, home sleep apnea tests were performed a median of 10 days after an index ischemic stroke and 14 days after a recurrent ischemic stroke. A respiratory event index (REI) of ≥ 10 events/h (apneas plus hypopneas per hour of recording) was used to define clinically significant SDB. The relative difference in REI or relative SDB prevalence was used to compare the post-recurrent stroke measurement with that made after the index stroke, and was expressed as a rate ratio (RR) or prevalence ratio (PR). Adjusted regression models (negative binomial for REI and log binomial for SDB) included change in body mass index and time between the events. RESULTS The median time from index to recurrent stroke was 330.5 days (interquartile range [IQR]: 103.5, 766.5). The median REI was 17.5 (IQR: 9.0, 32.0) after the index stroke and 18.0 (IQR: 11.0, 25.5) after the recurrent stroke. The within-subject median difference was zero (IQR: -9, 7.5). The relative difference in REI was not significant in unadjusted or adjusted (RR: 0.97 [95% confidence interval: 0.76, 1.24]) models. The prevalence of SDB was not different after the recurrent stroke compared with the index stroke, in unadjusted or adjusted (PR: 1.10 [95% confidence interval: 0.91, 1.32]) models. CONCLUSIONS In this within-subject, longitudinal study, neither severity nor prevalence of SDB worsened after recurrent stroke.

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.

Sleep and Gastrointestinal Symptoms in a Community-Based Survey of Children:

We examined whether gastrointestinal (GI) symptoms were associated with sleep disturbances in a community-based sample of 337 school-aged children from Ypsilanti, Michigan. Parents completed the sleep-related breathing disorder scale of the Pediatric Sleep Questionnaire and the Conners’ parents rating scale, which included questions concerning GI symptoms. One fifth of the children screened positive for sleep-disordered breathing; the same fraction had sleepiness, and one-quarter snored more than half the time. Similarly, one quarter of children had 2 or more GI symptoms. Children with positive sleep-disordered breathing scores were 2.22 times as likely to have 2 or more GI symptoms in the past month after confounder adjustment (95% confidence interval = 1.39-3.55). In particular, this relationship appeared to be driven by daytime sleepiness, as children with sleepiness had about a 2-fold higher prevalence of 2 or more GI symptoms (adjusted prevalence ratio = 1.96, 95% confidence interval = 1.18-3.26). Neither snoring nor sleep duration were associated with GI symptoms.