Oxytocin and women's health in midlife.

Menopause marks the cessation of fertility and the transition to post-reproductive years. Nearly 1M US women experience menopause annually, but despite the significant impact it has on their physical and mental health, menopause has been insufficiently studied. Oxytocin is a neurohormone that regulates emotionality, social behaviors, and fundamental physiological systems. Localization of oxytocin receptors in the brain, reproductive tissues, bone, and heart support their role in mental health and potentially sleep, along with reproductive and cardiovascular functions. While experimental data linking oxytocin to behavior and physiology in animals are largely consistent, human data are correlative and inconclusive. As women transition into menopause, oxytocin levels decrease while their susceptibility to mood disorders, poor sleep, osteoporosis, and cardiovascular diseases increases. These concurrent changes highlight oxytocin as a potential influence on the health and mood of women along their reproductive lifespan. Here we summarize experimental rodent studies that link oxytocin to reproductive aging and metabolic health and highlight the inconclusive findings in studies of women. Most human studies relied on a single oxytocin assessment in plasma or on intranasal oxytocin administration. The pulsatile release and short half-life of plasma oxytocin limits the validity of these methods. We discuss the need for oxytocin assessments in stable bio-samples, such as urine, and to use valid assays for assessment of associations between changing oxytocin levels and well-being across the reproductive lifespan. This work has the potential to guide therapeutic strategies that will one day alleviate adverse health outcomes for many women.

Patterns of Sleep Duration and Metabolic Biomarkers Across the Menstrual Cycle.

CONTEXT: Along the menstrual cycle, associations between inconsistent sleep duration and levels of metabolic biomarkers are uncertain and could involve fluctuations in estrogen concentrations. OBJECTIVE: To examine associations between patterns of sleep duration and metabolic biomarkers across two menstrual cycles within a cohort of premenopausal women. METHODS: The BioCycle Study was conducted in New York between 2005-2007, enrolling 259 premenopausal women over two menstrual cycles. This micro-longitudinal cohort study involved intensive data collection including daily sleep diaries and biomarker assessments of leptin, insulin, and glucose at 16 key points timed to menstrual cycle phases. We considered dynamic sleep duration, as hours slept one night or as mean hours slept during the two nights prior to each biomarker assessment. Variability in habitual sleep duration, i.e., reported daily sleep duration, summarized across both menstrual cycles. Variation in habitual sleep duration was computed using L-moments, a robust version of dispersion, skewness, and kurtosis. To examine associations between patterns of sleep duration and metabolic biomarkers, we fitted a series of linear mixed models with random intercepts and inverse probability weighting. These models were adjusted for potential demographic, lifestyle, health confounders, and menstrual cycle phase. RESULTS: Sleep duration one night or two nights prior to clinic visits were not associated with metabolic biomarker measures we assessed. However, overall variability (dispersion) in habitual sleep duration was associated with lower mean insulin HOMA-IR levels, but not glucose. Moreover, extreme short or long bouts of sleep duration was associated with higher mean levels of leptin, insulin, and HOMA-IR. CONCLUSIONS: These data suggest that variation in habitual sleep duration along the menstrual cycle may be associated with metabolic function.

Delayed Sleep Midpoint Across Pregnancy Is Associated with Excessive Gestational Weight Gain.

Background: Changes in sleep patterns and body weight occur during pregnancy, yet it is unclear whether sleep patterns are related to gestational weight gain (GWG). This study examined the relationship between maternal sleep across pregnancy and excessive GWG. Methods: Participants from the Michigan Archive for Research on Child Health (MARCH) cohort study, who had singleton births and provided information on fall-asleep and wake-up times during early (first or second) and the third trimesters, were included (n = 372). Changes in sleep duration and sleep midpoints throughout pregnancy were calculated. Prepregnancy weight and the last maternal weight before delivery were used to calculate GWG, which was categorized into groups (inadequate, adequate, and excessive). Poisson regression models were used to examine associations between sleep changes and excessive GWG, adjusted for age, race, gestational age, prepregnancy body mass index, income, fetus gender, physical activity, added sugar, and fruit and vegetable intake. Results: Excessive GWG was observed in 46.5% of women, and was more common among those with prepregnancy obesity (p < 0.001). Women who delayed sleep midpoint by 1 hour (or more) from the early trimester assessment to the third trimester experienced higher risk of excessive GWG (Risk ratio: 1.3; 95% confidence interval: 1.1-1.7). Single time points of sleep duration and sleep midpoint or changes in sleep duration were not related to GWG. Conclusions: Delay in sleep midpoint from early-mid pregnancy to the third trimester was associated with excessive GWG. Health professionals should consider changes in sleep patterns during pregnancy to identify those prone to excessive GWG.

Disparities in sleep-wake patterns by labor force status: Population-based findings.

Sleep disturbances have been associated with unemployment, but variation in sleep-wake patterns by labor force status has rarely been examined. With a population-based sample, we investigated differences in sleep-wake patterns by labor force status (employed, unemployed, and not-in-the-labor-force) and potential disparities by sociodemographic variables. The analysis included 130,602 adults aged 25-60 y, who participated in the American Time Use Survey between 2003 and 2019. Individual sleep-wake pattern was extracted from time use logs in a strict 24-h period (04:00 h-03:59 h). Functional nonparametric regression models based on dimensionality reduction and neighborhood matching were applied to model the relationship between sleep-wake patterns and labor force status. Specifically, we predicted changes in intra-person sleep-wake patterns under hypothetical changes of labor force status from employed to unemployed or not-in-the-labor-force. We then studied moderations of this association by gender, race/ethnicity and educational attainment. In comparison to the employed state, unemployed and not-in-the-labor-force states were predicted to have later wake-times, later bedtimes, and higher tendency for taking midday naps. Changes in labor force status led to more apparent shifts in wake-times than in bedtimes. Additionally, sleep schedules of Hispanics and those with higher education level were more vulnerable to the change of labor force status from employed to unemployed.

Early-to-mid pregnancy sleep and circadian markers in relation to birth outcomes: An epigenetics pilot study.

Maternal sleep and circadian health during pregnancy are emerging as important predictors of pregnancy outcomes, but examination of potential epigenetic mechanisms is rare. We investigated links between maternal leukocyte DNA methylation of circadian genes and birth outcomes within a pregnancy cohort. Women (n = 96) completed a questionnaire and provided a blood sample at least once during early-to-mid pregnancy (average gestation weeks = 14.2). Leukocyte DNA was isolated and DNA methylation (average percent of methylation) at multiple CpG sites within BMAL1, PER1, and MTNR1B genes were quantified by pyrosequencing. Birth outcomes including gestational age at delivery, birthweight, and head circumference were abstracted from medical charts. Linear regression analyses were run between each CpG site with birth outcomes, adjusting for important confounders. Sleep duration and timing were assessed as secondary exposures. Higher methylation of a CpG site in PER1 was associated with smaller log-transformed head circumference (ß=-0.02 with 95% CI -0.02 to 0.01; P, trend = 0.04). Higher methylation of MTNR1B (averaged across sites) was associated with lower log-transformed birthweight (-0.08 with 95% CI -0.16 to -0.01; P, trend = 0.0495). In addition, longer sleep duration was associated with higher birthweight (0.10 with 95% CI 0.02 to 0.18 comparing > 9 h to < 8 h; P, trend = 0.04). This pilot investigation revealed that higher methylation of PER1 and MTNR1B genes, and sleep duration measured in early-to-mid pregnancy were related to birth outcomes.

Does fetal size affect maternal perception of fetal movements? Evidence from an individual participant data meta-analysis.

INTRODUCTION: Maternal perception of fetal movements during pregnancy are reassuring; however, the perception of a reduction in movements are concerning to women and known to be associated with increased odds of late stillbirth. Prior to full term, little evidence exists to provide guidelines on how to proceed unless there is an immediate risk to the fetus. Increased strength of movement is the most commonly reported perception of women through to full term, but perception of movement is also hypothesized to be influenced by fetal size. The study aimed to assess the pattern of maternal perception of strength and frequency of fetal movement by gestation and customized birthweight quartile in ongoing pregnancies. A further aim was to assess the association of stillbirth to perception of fetal movements stratified by customized birthweight quartile. MATERIAL AND METHODS: This analysis was an individual participant data meta-analyses of five case-control studies investigating factors associated with stillbirth. The dataset included 851 cases of women with late stillbirth (>28 weeks' gestation) and 2257 women with ongoing pregnancies who then had a liveborn infant. RESULTS: The frequency of prioritized fetal movement from 28 weeks' gestation showed a similar pattern for each quartile of birthweight with increased strength being the predominant perception of fetal movement through to full term. The odds of stillbirth associated with reduced fetal movements was increased in all quartiles of customized birthweight centiles but was notably greater in babies in the lowest two quartiles (Q1: adjusted OR: 9.34, 95% CI: 5.43, 16.06 and Q2: adjusted OR: 6.11, 95% CI: 3.11, 11.99). The decreased odds associated with increased strength of movement was present for all customized birthweight quartiles (adjusted OR range: 0.25-0.56). CONCLUSIONS: Increased strength of fetal movements in late pregnancy is a positive finding irrespective of fetal size. However, reduced fetal movements are associated with stillbirth, and more so when the fetus is small.

Society of Anesthesia and Sleep Medicine and the Society for Obstetric Anesthesia and Perinatology Consensus Guideline on the Screening, Diagnosis, and Treatment of Obstructive Sleep Apnea in Pregnancy.

The Society of Anesthesia and Sleep Medicine and the Society for Obstetric Anesthesia and Perinatology tasked an expert group to review existing evidence and to generate recommendations on the screening, diagnosis, and treatment of patients with obstructive sleep apnea during pregnancy. These recommendations are based on a systematic review of the available scientific evidence and expert opinion when scientific evidence is lacking. This guideline may not be appropriate for all clinical situations and patients, and physicians must decide whether these recommendations are appropriate for their patients on an individual basis. We recognize that not all pregnant people may identify as women. However, data on non-cisgendered pregnant patients are lacking, and many published studies use gender-binary terms; therefore, depending on the study referenced, we may refer to pregnant individuals as women. This guideline may inform the creation of clinical protocols by individual institutions that consider the unique considerations of their patient populations and the available resources.

Sleep Disparities Across Pregnancy: A Michigan Cohort Study.

Introduction: Poor sleep health during pregnancy is related to adverse pregnancy outcomes. This study aims to identify sociodemographic characteristics associated with sleep health during pregnancy and to examine how they relate to changes in sleep during pregnancy. Materials and Methods: Participants (n = 458) were from the Michigan Archive for Research on Child Health, which is a prospective pregnancy cohort. Sociodemographic characteristics and self-reported sleep timing and quality were collected in phone interviews. This longitudinal study collected sleep parameters once during the early trimesters and once during the third trimester. Fall asleep and wake-up times were used to calculate sleep duration and sleep midpoint. Results: Compared to the third trimester, sleep duration was 12 minutes longer (p = 0.02), fall asleep time was 21 minutes earlier (p < 0.001), and the midpoint of sleep was 12 minutes earlier (p = 0.01) in early trimesters. Shorter sleep duration was noted in younger women. Sleep midpoint was later in those who were younger, overweight, or obese, racial minorities, unmarried, and with lower educational levels or socioeconomic status, and who smoked before pregnancy after adjusting for covariates. After controlling for confounders, women who were not working for pay had higher likelihood of reduced sleep duration, and women who were unmarried were more likely to have a delayed sleep midpoint in the third trimester compared to the early trimesters. Conclusions: This study suggests that sleep parameters changed during pregnancy and sleep health differed by sociodemographic characteristics. Understanding sleep disparities could help with early detection of at-risk populations during prenatal care.

Racial/ethnic disparities in sleep-disordered breathing during pregnancy in the nuMoM2b study.

OBJECTIVE: The aim of this study was to assess the prevalence and severity of sleep-disordered breathing (SDB) across racial/ethnic groups in 3702 pregnant people at 6 to 15 and 22 to 31 weeks gestational age, examine whether BMI modifies the association between race/ethnicity and SDB, and investigate whether interventions to reduce weight might reduce racial/ethnic disparities in SDB. METHODS: Differences by race/ethnicity in SDB prevalence and severity were quantified via linear, logistic, or quasi-Poisson regression. Controlled direct effect was used to estimate whether intervening on BMI would remove/diminish differences by race/ethnicity in SDB severity. RESULTS: This study comprised 61.2% non-Hispanic White (nHW), 11.9% non-Hispanic Black (nHB), 18.5% Hispanic, and 3.7% Asian people. SDB prevalence was higher for nHB compared with nHW pregnant people at 6 to 15 weeks (odds ratio [OR] 1.81, 95% CI [1.07, 2.97]), whereas at 21 to 32 weeks, Asian pregnant people had a higher SDB prevalence than nHW (OR 2.2, 95% CI [1.1, 4.0]). The severity of SDB differed across racial/ethnic groups in early pregnancy, with nHB pregnant people having a higher apnea-hypopnea index (AHI) (OR 1.35, 95% CI [1.07, 1.69]) compared with nHW. Having overweight/obesity was associated with a higher AHI (ß = 2.36, 95% CI [1.97, 2.84]). Controlled direct effect analyses indicated that in early pregnancy, nHB and Hispanic pregnant people would have a lower AHI compared with nHW people had they had normal weight. CONCLUSIONS: This study extends knowledge on racial/ethnic disparities in SDB to a pregnant population.

Variability in Sleep Duration and Biomarkers of Cardiovascular Disease Across the Menstrual Cycle.

Variability in sleep duration and cardiovascular health have been infrequently investigated, particularly among reproductive-age women. We examined these associations across the menstrual cycle among a cohort of 250 healthy premenopausal women, aged 18-44 years. The BioCycle study (New York, 2005-2007) collected cardiovascular biomarkers (serum high- and low-density lipoprotein (HDL, LDL), total cholesterol, triglycerides, and C-reactive protein (CRP)) at key time points along the menstrual cycle (follicular, ovulatory, and luteal phases). Women also recorded sleep duration in daily diaries. From these data, we computed L-moments, robust versions of location, dispersion, skewness, and kurtosis. We fitted linear mixed models with random intercepts and inverse probability weighting to estimate associations between sleep variability and cardiovascular biomarkers, accounting for demographic, lifestyle, health, and reproductive factors. Sleep dispersion (any deviation from mean duration) was associated with lower mean LDL for nonshift workers and non-White women. Skewed sleep duration was associated with higher mean CRP and lower mean total cholesterol. Sleep durations with extreme short and long bouts (kurtosis) were associated with a lower mean HDL, but not mean CRP, LDL, or triglycerides. Sleep duration modified associations between sleep dispersion and LDL, HDL, and total cholesterol. Even in young and healthy women, sleep duration variability could influence cardiovascular health.

Risk factors for late preterm and term stillbirth: A secondary analysis of an individual participant data meta-analysis.

OBJECTIVE: Identify independent and novel risk factors for late-preterm (28-36 weeks) and term (≥37 weeks) stillbirth and explore development of a risk-prediction model. DESIGN: Secondary analysis of an Individual Participant Data (IPD) meta-analysis investigating modifiable stillbirth risk factors. SETTING: An IPD database from five case-control studies in New Zealand, Australia, the UK and an international online study. POPULATION: Women with late-stillbirth (cases, n = 851), and ongoing singleton pregnancies from 28 weeks' gestation (controls, n = 2257). METHODS: Established and novel risk factors for late-preterm and term stillbirth underwent univariable and multivariable logistic regression modelling with multiple sensitivity analyses. Variables included maternal age, body mass index (BMI), parity, mental health, cigarette smoking, second-hand smoking, antenatal-care utilisation, and detailed fetal movement and sleep variables. MAIN OUTCOME MEASURES: Independent risk factors with adjusted odds ratios (aOR) for late-preterm and term stillbirth. RESULTS: After model building, 575 late-stillbirth cases and 1541 controls from three contributing case-control studies were included. Risk factor estimates from separate multivariable models of late-preterm and term stillbirth were compared. As these were similar, the final model combined all late-stillbirths. The single multivariable model confirmed established demographic risk factors, but additionally showed that fetal movement changes had both increased (decreased frequency) and reduced (hiccoughs, increasing strength, frequency or vigorous fetal movements) aOR of stillbirth. Poor antenatal-care utilisation increased risk while more-than-adequate care was protective. The area-under-the-curve was 0.84 (95% CI 0.82-0.86). CONCLUSIONS: Similarities in risk factors for late-preterm and term stillbirth suggest the same approach for risk-assessment can be applied. Detailed fetal movement assessment and inclusion of antenatal-care utilisation could be valuable in late-stillbirth risk assessment.

Sleep duration and timing are prospectively linked with insulin resistance during late adolescence.

OBJECTIVE: The aim of this study was to evaluate whether short sleep duration or later sleep timing is a risk factor for insulin resistance (IR) in late adolescence. METHODS: Mexico City adolescents enrolled in a longitudinal birth cohort (ELEMENT) took part in two study visits during peri-puberty that occurred approximately 2 years apart. IR was assessed with serum glucose and insulin. Four groups were defined using puberty-specific cut points: no IR over the follow-up period, transition from normal to IR, transition from IR to normal, and IR at both time points. Baseline sleep assessments were measured with 7-day wrist actigraphy. Multinomial logistic regression models were used to evaluate associations between sleep duration and timing with homeostatic model assessment of insulin resistance categories, adjusting for age, sex, and baseline pubertal status. RESULTS: Adolescents who were ≥ 1 hour below the sleep duration recommendations-for-age were 2.74 times more likely to develop IR (95% CI: 1.0-7.4). Similarly, adolescents who were in the latest category of sleep midpoint (>4:33 a.m.) were more likely than those with earliest midpoints (1 a.m.-3 a.m.) to develop IR (odds ratio = 2.63, 95% CI: 1.0-6.7). Changes in adiposity over follow-up did not mediate sleep and IR. CONCLUSIONS: Insufficient sleep duration and late sleep timing were associated with development of IR over a 2-year period in late adolescence.

Preconception sleep duration, sleep timing, and shift work in association with fecundability and live birth among women with a history of pregnancy loss.

OBJECTIVE: To evaluate the associations between preconception sleep characteristics and shift work with fecundability and live birth. DESIGN: Secondary analysis of the Effects of Aspirin in Gestation and Reproduction study, a preconception cohort. SETTING: Four US academic medical centers. PATIENT(S): Women aged 18-40 with a history of 1-2 pregnancy losses who were attempting to conceive again. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURES(S): We evaluated baseline, self-reported sleep duration, sleep midpoint, social jetlag, and shift work among 1,228 women who were observed for ≤6 cycles of pregnancy attempts to ascertain fecundability. We ascertained live birth at the end of follow up via chart abstraction. We estimated fecundability odds ratios (FORs) using discrete, Cox proportional hazards models and risk ratios (RRs) for live birth using log-Poisson models. RESULT(S): Sleep duration ≥9 vs. 7 to <8 hours (FOR: 0.81, 95% confidence interval [CI], 0.61; 1.08), later sleep midpoints (3rd tertile vs. 2nd tertile: FOR: 0.85; 95% CI, 0.69, 1.04) and social jetlag (continuous per hour; FOR: 0.93, 95% CI: 0.86, 1.00) were not associated with reduced fecundability. In sensitivity analyses, excluding shift workers, sleep duration ≥9 vs. 7 to <8 hours (FOR: 0.62; 95% CI, 0.42; 0.93) was associated with low fecundability. Night shift work was not associated with fecundability (vs. non-night shift work FOR: 1.17, 95% CI, 0.96; 1.42). Preconception sleep was not associated with live birth. CONCLUSION(S): Overall, there does not appear to be a strong association between sleep characteristics, fecundability, and live birth. Although these findings may suggest weak and imprecise associations with some sleep characteristics, our findings should be evaluated in larger cohorts of women with extremes of sleep characteristics. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT00467363.

Novel treatment for hypotonic airway obstruction and severe obstructive sleep apnea using a nasopharyngeal airway device with 3D printing innovation.

STUDY OBJECTIVES: Pediatric obstructive sleep apnea impacts child and familial well-being. Airway management in patients with hypotonic pharyngeal conditions is complex. Some patients may benefit from continuous positive airway pressure or bilevel positive airway pressure, others may require further invasive measures for treatment. There is critical need for treatment alternatives for patients with pharyngeal hypotonia. METHODS: This is a retrospective case series. Collaboratively with patients, families, biomedical engineers, and medical professionals, a long-term nasopharyngeal airway (NPA) was created to bypass upper airway obstruction. Two patients used a safety pin and tape attachment, and two patients used a novel 3D-printed, self-supporting nasal securement. All 4 patients had polysomnography before and during NPA use. Paired 1-tailed t-tests were conducted to compare apnea-hypopnea index, hypopnea index, obstructive index, and oxygen nadir. RESULTS: Compared to baseline polysomnography, repeat polysomnography with the NPA in place demonstrated statistically significant improvement for apnea-hypopnea index (75.8 ± 36.6 events/h to 8.9 ± 2.9 events/h, P = .03), hypopnea index (45.4 ± 25.8 events/h to 7.7 ± 3.2 events/h, P = .04), and oxygen saturation nadir (60.3 ± 13.0% to 79.3 ± 8.7%, P = .01). The NPA had been used for over 1 year in 3 of the 4 children. Those using the safety pin and tape did report skin irritation due to adhesive required to keep device in place. CONCLUSIONS: Current management of severe upper airway obstruction and obstructive sleep apnea in hypotonic pharyngeal conditions requires a team-based approach to care. A long-term NPA device may be an alternative or temporizing option to continuous positive airway pressure, upper airway surgery, or tracheostomy in children with pharyngeal hypotonia and severe obstructive sleep apnea. Larger studies of this approach are underway to assess efficacy in a range of obstructive sleep apnea severity in this population. CITATION: Powell AR, Srinivasan S, Helman JL, et al. Novel treatment for hypotonic airway obstruction and severe obstructive sleep apnea using a nasopharyngeal airway device with 3D printing innovation. J Clin Sleep Med. 2022;18(10):2497-2502.

Cell-autonomous Hedgehog signaling controls Th17 polarization and pathogenicity.

Th17 cells are key drivers of autoimmune disease. However, the signaling pathways regulating Th17 polarization are poorly understood. Hedgehog signaling regulates cell fate decisions during embryogenesis and adult tissue patterning. Here we find that cell-autonomous Hedgehog signaling, independent of exogenous ligands, selectively drives the polarization of Th17 cells but not other T helper cell subsets. We show that endogenous Hedgehog ligand, Ihh, signals to activate both canonical and non-canonical Hedgehog pathways through Gli3 and AMPK. We demonstrate that Hedgehog pathway inhibition with either the clinically-approved small molecule inhibitor vismodegib or genetic ablation of Ihh in CD4+ T cells greatly diminishes disease severity in two mouse models of intestinal inflammation. We confirm that Hedgehog pathway expression is upregulated in tissue from human ulcerative colitis patients and correlates with Th17 marker expression. This work implicates Hedgehog signaling in Th17 polarization and intestinal immunopathology and indicates the potential therapeutic use of Hedgehog inhibitors in the treatment of inflammatory bowel disease.

Racial/ethnic disparities in subjective sleep duration, sleep quality, and sleep disturbances during pregnancy: an ECHO study.

In the United States, racial/ethnic minoritized groups experience worse sleep than non-Hispanic Whites (nHW), but less is known about pregnant people. This is a key consideration since poor sleep during pregnancy is common and associated with increased risk of adverse perinatal outcomes. This study reports the prevalence of subjective sleep measures in a multi-racial/ethnic pregnant population from the Environmental influences on Child Health Outcomes (ECHO) program. Participants' self-reported race and ethnicity were grouped into: nHW, non-Hispanic Black/African American (nHB/AA), Hispanic, non-Hispanic Asian (nHA). Analyses examined trimester-specific (first (T1), second (T2), third (T3)) nocturnal sleep duration, quality, and disturbances (Pittsburgh Sleep Quality Index and ECHO maternal sleep health questionnaire). Linear or multinomial regressions estimated the associations between race/ethnicity and each sleep domain by trimester, controlling for body mass index and age, with nHW as reference group. We repeated analyses within maternal education strata. nHB/AA participants reported shorter sleep duration (T2: ß = -0.55 [-0.80,-0.31]; T3: ß = -0.65 [-0.99,-0.31]) and more sleep disturbances (T2: ß = 1.92 [1.09,2.75]; T3: ß = 1.41 [0.09,2.74]). Hispanic participants reported longer sleep duration (T1: ß = 0.22 [0.00004,0.44]; T2: ß = 0.61 [0.47,0.76]; T3: ß = 0.46 [0.22,0.70]), better sleep quality (Reference group: Very good. Fairly good T1: OR = 0.48 [0.32,0.73], T2: OR = 0.36 [0.26,0.48], T3: OR = 0.31 [0.18,0.52]. Fairly bad T1: OR = 0.27 [0.16,0.44], T2: OR = 0.46 [0.31, 0.67], T3: OR = 0.31 [0.17,0.55]), and fewer sleep disturbances (T2: ß = -0.5 [-1.0,-0.12]; T3: ß = -1.21 [-2.07,-0.35]). Differences persisted within the high-SES subsample. Given the stark racial/ethnic disparities in perinatal outcomes and their associations with sleep health, further research is warranted to investigate the determinants of these disparities.

Later sleep timing and social jetlag are related to increased inflammation in a population with a high proportion of OSA: findings from the Cleveland Family Study.

STUDY OBJECTIVES: To examine the association between sleep midpoint and inflammation in a population with a large proportion of individuals diagnosed with obstructive sleep apnea syndrome (OSAS), a group that is already prone to increased inflammation. METHODS: Subjects from the Cleveland Family Study underwent overnight polysomnography and completed surveys on sleep habits. Morning and evening blood samples were collected and assayed for proinflammatory biomarkers interleukin (IL)-1, IL-6, and tumor necrosis factor α (TNF-α). Linear regression models were used, adjusting for potential confounders and sleep duration. RESULTS: The study population included 587 adults (52.3% with OSAS). Mean ± standard deviation weekday sleep midpoint was 3.52 ± 2.09 (3:31 am) and weekend sleep midpoint was 4.46 ± 1.69 (4:28 am). The Mean difference between weekday and weekend sleep midpoint (social jetlag) was 0.94 ± 2.08 hours. After adjusting for OSA severity, greater social jetlag was associated with higher levels of the inflammatory cytokine IL-1 (beta: 0.435 pg/mL, 95% confidence interval [CI]: 0.091 to 0.779). Additionally, later timing of sleep during both the weekdays and the weekends was associated with increased levels of IL-6 (weekday beta: 0.182 pg/mL; 95% CI: 0.013 to 0.350; and weekend beta: 0.188 pg/mL; 95% CI: 0.004 to 0.373). No trends were observed with TNF-α and any sleep exposure. CONCLUSIONS: Later sleep timing was associated with elevated levels of IL-6 while increased social jetlag was associated with elevated levels of IL-1. Our results indicate that later sleep schedules and increased social jetlag may lead to higher inflammation, even after controlling for OSA severity. CITATION: Girtman KL, Baylin A, O'Brien LM, Jansen EC. Later sleep timing and social jetlag are related to increased inflammation in a population with a high proportion of OSA: findings from the Cleveland Family Study. J Clin Sleep Med. 2022;18(9):2179-2187.

DSM-5 insomnia disorder in pregnancy: associations with depression, suicidal ideation, and cognitive and somatic arousal, and identifying clinical cutoffs for detection.

Study Objectives: The study had three primary goals. First, we estimated survey-assessed DSM-5 insomnia disorder rates in pregnancy, and described associated sociodemographics, and sleep-wake and mental health symptoms. Second, we derived cutoffs for detecting DSM-5 insomnia disorder using common self-report measures of sleep symptoms. Third, we identified clinically relevant cut-points on measures of nocturnal cognitive and somatic arousal. Methods: Ninety-nine women (85.9% in the 2nd trimester) completed online surveys including DSM-5 insomnia disorder criteria, the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Presleep Arousal Scale's Cognitive (PSASC) and Somatic (PSASS) factors, and Edinburgh Postnatal Depression Scale. Results: DSM-5 insomnia disorder rate was 19.2%. Insomnia was associated with depression, suicidality, nocturnal cognitive and somatic arousal, and daytime sleepiness. An ISI scoring method that aligns with DSM-5 criteria yielded excellent metrics for detecting insomnia disorder and good sleep. Regarding quantitative cutoffs, ISI ≥ 10 and ISI ≥ 11 (but not ISI ≥ 15) were supported for detecting DSM-5 insomnia, whereas ISI ≤ 7 and ISI ≤ 9 performed well for detecting good sleep. PSQI cutoff of 5 was supported for detecting insomnia and good sleep. The optimal cutoff for nocturnal cognitive arousal was PSASC ≥ 18, whereas the optimal cutoff for somatic arousal was PSASS ≥ 13. Conclusions: Insomnia disorder affects a large segment of pregnant women. Empirically derived cutoffs for insomnia, good sleep, cognitive arousal, and somatic arousal may inform case identification and future perinatal sleep research methodology.

Risk of obstructive sleep apnea after treatment of head and neck squamous cell carcinoma: a cross-sectional study.

STUDY OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) or its treatment may be associated with an increased risk of obstructive sleep apnea (OSA). However, reported relationships between OSA risk factors and HNSCC are inconsistent. This study examined associations between tumor variables and risk of OSA at least 1 year after completion of treatment for HNSCC. METHODS: This cross-sectional study included HNSCC patients of a large academic medical center. Inclusion criteria were age ≥ 18 years, cancer free for at least 1 year, and absence of tracheostomy or mental impairment. The STOP-BANG questionnaire, with a threshold ≥ 3, was used to classify HNSCC patients into elevated and low OSA risk. Tumor characteristics and treatment types were obtained from medical records. Descriptive statistics were used to compare characteristics between OSA risk groups. Unadjusted and age-adjusted logistic and linear regression models were used to explore associations between exposures and OSA risk. RESULTS: Among 67 participants, 85% were males, mean age was 62.0 years (8.0 standard deviation), mean body mass index was 28.7 kg/m2 (4.6 standard deviation), and mean neck circumference was 16.3 inches (1.2 standard deviation). Three-quarters of participants received chemoradiation only. Elevated OSA risk was observed in 60% of the participants. Tumor location, tumor stage, and type of cancer treatment were not different between OSA risk groups. Hyperlipidemia was more common in the elevated OSA risk group vs the low-risk group (n = 16, 40% vs n = 2, 7%, P = .004). Age-adjusted analysis showed a trend toward 2-fold increased odds of elevated OSA risk in patients with tumors at the base of the tongue in comparison to other locations (odds ratio = 2.3, 95% confidence interval 0.9, 6.4). No associations between tumor stage, cancer treatment, and elevated OSA risk were observed. CONCLUSIONS: Elevated OSA risk was common after HNSCC treatment. However, measured HNSCC characteristics generally were not different between elevated and low OSA risk groups. Given the high frequency of OSA that appears likely to exist in HNSCC patients, clinicians should inquire about OSA features in patients with a history of HNSCC. CITATION: Gavidia R, Dunietz GL, O'Brien LM, et al. Risk of obstructive sleep apnea after treatment of head and neck squamous cell carcinoma: a cross-sectional study. J Clin Sleep Med. 2022;18(6):1681-1686.

Parent-Reported Sleep Profile of Children With Early-Life Epilepsies.

BACKGROUND: Sleep comorbidities are common, and sometimes severe, for children with early-life epilepsies (ELEs). Yet, there is a paucity of data regarding the profile of these sleep disturbances and their complications. METHODS: Participants registered with the Rare Epilepsy Network (REN) were queried about sleep via online questionnaires. Descriptive statistics and logistic regression were performed. RESULTS: Median age of the 356 children was 56 months (interquartile range 30 to 99), 56% were female, and 53% (188/356) endorsed a sleep concern. Frequent nighttime awakenings (157 of 350; 45%), difficulty falling asleep (133 of 350; 38%), and very restless sleep (118 of 345; 34%) were most endorsed. Nocturnal seizures were associated with sleep concerns and were reported in 75% (268 of 356) of children. Of the children with nocturnal seizures, 56% (118 of 268) had sleep concerns. Of the children without nocturnal seizures, 43% (38 of 88) had sleep concerns. Sleep concerns were most common in dup15q syndrome (16 of 19; 84%). Children aged 4 to ≤10 years (adjusted odds ratio [aOR] 16.1; 95% confidence interval [CI] 2.0, 131.0) and 10 to <13 years (aOR 22.2; 95% CI 2.6, 188.6) had a greater odds of having a sleep concern compared with children aged ≤6 months. Female sex appeared protective for sleep concerns (aOR 0.6; 95% CI 0.4, 0.9). The association between sleep concerns and nocturnal seizures was weaker when adjusted for sex and age category in a logistic regression model. CONCLUSIONS: Reported sleep concerns are highly prevalent in children with ELEs and persist with age, in contrast to what is expected in healthy children. There may be unmet sleep-related clinical needs in children with ELEs.