Background:Obstructive sleep apnea (OSA) is associated with a wide range of comorbidities, but large-scale phenome-wide analyses in clinical biobanks remain under-reported. In this study, we identified common comorbidities enriched in patients with OSA, tested the temporality of these associations, and analyzed relevant associations with summary sleep recording data. Methods:48,251 participants with OSA in the Mass General Brigham healthcare system were identified using a natural language processing phenotyping algorithm and/or evidence of an elevated apnea-hypopnea index (AHI). Controls were matched (2:1) on demographics, body mass index (BMI), and healthcare utilization. Associations with 358 incident and 563 cross-sectional diseases were tested using Modified Poisson regression, adjusting for covariates. Sensitivity analyses examined timing by binning data in years relative to the first OSA diagnosis. Selected laboratory results were obtained based on associated diseases. Associated diseases were tested with sleep recording statistics (n ≤18,348). Findings:179 incident and 421 cross-sectional diseases were associated with OSA at Bonferroni significance. 37 diseases had Bonferroni-significant sex interactions. Several associations were significant years before the first recorded OSA diagnosis. Four red blood cell laboratory measures were significant ten years prior to the first diagnosis. One incident and 47 cross-sectional diseases were associated with the AHI and/or chronic hypoxemia. Interpretation:Obstructive sleep apnea is associated with enrichment of hundreds of diseases, several of which are supported by orthogonal polysomnographic evidence. Leveraging early signs of OSA in clinical data may help to identify at-risk patients.

OBJECTIVES:Exposure to allergens may trigger inflammatory pathways contributing to poor sleep. We investigated the associations between indoor allergen concentrations with multiple sleep dimensions in children. METHODS:Bedroom dust aeroallergens were collected in participants' homes. The outcomes were caregiver-reported sleep-related daytime impairment and sleep disturbance (pediatric PROMIS instruments), sleep-disordered breathing (SDB; apnea-hypopnea index or oxygen desaturation index >5), and actigraphy-based short sleep (<8 hours) duration and poor sleep continuity (sleep fragmentation index > 75th percentile). Logistic regression was used to examine associations between aeroallergens (>50% detectable levels) and sleep outcomes, adjusting for potential confounders (i.e., sociodemographic, environmental, and health-related). RESULTS:The sample included an urban cohort of 256 children (41% Hispanic, 29% Black; 43% female) aged 6-12 years. Mouse (Mus m 1), cat (Fel d 1), and dog (Can f 1) allergens were detected in 81%, 72%, and 53% of households, respectively. Elevated mouse allergen exposure (>0.55 μg/g-75th percentile) was associated with a 2.6-fold (95% CI: 1.34, 5.03) increased odds for sleep-related daytime impairment (PROMIS T-score > 55) after adjusting for demographic factors. This association persisted after further adjusting for inflammatory-related health factors (asthma, allergic rhinitis, obesity, and environmental tobacco smoke), neighborhood disadvantage, and SDB. There was attenuation of this association with poor sleep consolidation. Associations were not observed for other allergens or other sleep outcomes. CONCLUSIONS:Exposure to elevated mouse dust was associated with increased sleep-related daytime impairment symptoms. The role of household pest exposure as a potentially modifiable target for improving sleep health should be further studied.

The phenotypic similarities between exfoliation syndrome (XFS)/exfoliation glaucoma (XFG) and pigment dispersion syndrome (PDS)/pigmentary glaucoma (PG), particularly their association with material deposition in the eye’s anterior segment, have prompted investigations into genetic commonalities. This study focuses on the LOXL1 gene, conducting a comprehensive meta-analysis of three candidate gene association studies. We analyzed three single nucleotide polymorphisms (SNPs) of LOXL1: rs1048661, rs3825942, and rs2165241. Our results reveal nominal significance for the exonic SNPs rs1048661 and rs3825942 (p ≤ 0.01), but show no significant association for the intronic SNP rs2165241 (p = 0.83) with PDS/PG. There was homogeneity across study cohorts (I2 = 0), and sensitivity analyses and funnel plots confirmed a lower likelihood of bias in our findings. The lack of a statistically significant association between LOXL1 variants and PDS/PG at p < 0.05 was attributable to the insufficient statistical power of the pooled data, which ranged from 5% to 37% for the three SNPs. This study suggests no association between LOXL1 variants and PDS/PG. Further validation and exploration of XFS/XFG-associated genes in larger and more diverse cohorts would be helpful to determine the genetic correlation or distinctiveness between these conditions.

Pigment Dispersion Syndrome (PDS) and Pigmentary Glaucoma (PG) comprise a spectrum of ocular disorders characterized by iris pigment dispersion and trabecular meshwork changes, resulting in increased intraocular pressure and potential glaucomatous optic neuropathy. This review summarizes recent progress in PDS/PG genetics including rare pathogenic protein coding alterations (PMEL) and susceptibility loci identified from genome-wide association studies (GSAP and GRM5/TYR). Areas for future research are also identified, especially the development of efficient model systems. While substantial strides have been made in understanding the genetics of PDS/PG, our review identifies key gaps and outlines the future directions necessary for further advancing this important field of ocular genetics.

AbstractBackgroundThis study reports the outcomes of Communities for Healthy Living (CHL), a cluster randomized obesity prevention trial implemented in partnership with Head Start, a federally-funded preschool program for low-income families.MethodsUsing a stepped wedge design, Head Start programs (n = 16; Boston, MA, USA) were randomly assigned to one of three intervention start times. CHL involved a media campaign and enhanced nutrition support. Parents were invited to join Parents Connect for Healthy Living (PConnect), a 10-week wellness program. At the beginning and end of each school year (2017-2019), data were collected on the primary outcome of child Body Mass Index z-score (BMIz) and modified BMIz, and secondary outcomes of child weight-related behaviors (diet, physical activity, sleep, media use) and parents’ weight-related parenting practices and empowerment. Data from 2 years, rather than three, were utilized to evaluate CHL due to the COVID-19 pandemic. We used mixed effects linear regression to compare relative differences during intervention vs. control periods (n = 1274 vs. 2476 children) in (1) mean change in child BMIz and modified BMIz, (2) the odds of meeting child health behavior recommendations, (3) mean change in parenting practices, and (4) mean change in parent empowerment. We also compared outcomes among parents who chose post-randomization to participate in PConnect vs. not (n = 55 vs. 443).ResultsDuring intervention periods (vs. control), children experienced greater increases in BMIz and modified BMIz (b = 0.06, 95% CI = 0.02,0.10;b = 0.07, 95% CI = 0.03, 0.12), yet were more likely to meet recommendations related to three of eight measured behaviors: sugar-sweetened beverage consumption (i.e., rarely consume; Odds Ratio (OR) = 1.5, 95% CI = 1.2,2.3), water consumption (i.e., multiple times per day; OR = 1.6, 95% CI = 1.2,2.3), and screen time (i.e., ≤1 hour/day; OR = 1.4, 95% CI = 1.0,1.8). No statistically significant differences for intervention (vs. control) periods were observed in parent empowerment or parenting practices. However, parents who enrolled in PConnect (vs. not) demonstrated greater increases in empowerment (b = 0.17, 95% CI = 0.04,0.31).ConclusionsInterventions that emphasize parent engagement may increase parental empowerment. Intervention exposure was associated with statistically, but not clinically, significant increases in BMIz and increased odds of meeting recommendations for three child behaviors; premature trial suspension may explain mixed results.Trial registrationClinicalTrials.gov,NCT03334669, Registered October 2017.

The present study aimed to summarize and validate the genomic association signals for diabetic retinopathy (DR), proliferative DR, and diabetic macular edema/diabetic maculopathy. A systematic search of the genome-wide association study (GWAS) catalog and PubMed/MELINE databases was conducted to curate a comprehensive list of significant GWAS discoveries. The top signals were then subjected to meta-analysis using established protocols. The results indicate the need for improved consensus among DR GWASs, highlighting the importance of validation efforts. A subsequent meta-analysis confirmed the association of two SNPs, rs4462262 (ZWINT-MRPS35P3) (odds ratio = 1.38, p = 0.001) and rs7903146 (TCF7L2) (odd ratio = 1.30, p < 0.001), with DR in independent populations, strengthening the evidence of their true association. We also compiled a list of candidate SNPs for further validation. This study highlights the importance of consistent validation and replication efforts in the field of DR genetics. The two identified gene loci warrant further functional investigation to understand their role in DR pathogenesis.

The phenotypic and genetic links between body fat phenotypes and primary open-angle glaucoma (POAG) are unclear. We conducted a meta-analysis of relevant longitudinal epidemiological studies to evaluate the phenotypic link. To identify genetic links, we performed genetic correlation analysis and pleiotropy analysis of genome-wide association study summary statistics datasets of POAG, intraocular pressure (IOP), vertical cup-to-disc ratio, obesity, body mass index (BMI), and waist-to-hip ratio. In the meta-analysis, we first established that obese and underweight populations have a significantly higher risk of POAG using longitudinal data. We also discovered positive genetic correlations between POAG and BMI and obesity phenotypes. Finally, we identified over 20 genomic loci jointly associated with POAG/IOP and BMI. Among them, the genes loci CADM2, RP3-335N17.2, RP11-793K1.1, RPS17P5, and CASC20 showed the lowest false discovery rate. These findings support the connection between body fat phenotypes and POAG. The newly identified genomic loci and genes render further functional investigation.

BACKGROUND:Pediatric sleep-disordered breathing (SDB) disproportionately affects children with low socioeconomic status (SES). The multilevel risk factors that drive these associations are not well understood.RESEARCH QUESTION:What are the associations between SDB risk factors, including individual health conditions (obesity, asthma, and allergies), household SES (maternal education), indoor exposures (environmental tobacco smoke [ETS] and pests), and neighborhood characteristics (neighborhood disadvantage), and pediatric SDB symptoms?STUDY DESIGN AND METHODS:Cross-sectional analyses were performed on 303 children (aged 6-12 years) enrolled in the Environmental Assessment of Sleep Youth study from 2018 to 2022. Exposures were determined by caregiver reports, assays of measured settled dust from the child's bedroom, and neighborhood-level Census data (deriving the Childhood Opportunity Index to characterize neighborhood disadvantage). The primary outcome was the SDB-related symptom burden assessed by the OSA-18 questionnaire total score. Using linear regression models, we calculated associations between exposures and SDB-related symptom burden, adjusting for sociodemographic factors, then health conditions, indoor environment, and neighborhood factors.RESULTS:The sample included 303 children (39% Hispanic, Latino, Latina, or Spanish origin; 30% Black or African American; 22% White; and 11% other). Increasing OSA-18 total scores were associated with low household SES after adjustment for demographic factors, and with asthma, allergies, ETS, pests (mouse, cockroach, and rodents), and an indoor environmental index (sum of the presence of pests and ETS; 0-2) after adjusting for sociodemographic factors. Even after further adjusting for asthma, allergies, and neighborhood disadvantage, ETS and pest exposure were associated with OSA-18 (ETS: β = 12.80; 95% CI, 7.07-18.53, also adjusted for pest; pest exposure: β = 3.69; 95% CI, 0.44-6.94, also adjusted for ETS).INTERPRETATION:In addition to associations with ETS, a novel association was observed for indoor pest exposure and SDB symptom burden. Strategies to reduce household exposure to ETS and indoor allergens should be tested as approaches for reducing sleep health disparities.

STUDY OBJECTIVES Suboptimal sleep is associated with obesity and its sequelae in children and adults. However, few studies have examined the association between sleep and physical growth in infants who experience rapid changes in sleep/wake patterns. We examined the longitudinal association of changes in objectively assessed sleep/wake patterns with changes in growth between ages 1 and 6 months. METHODS We studied 298 full-term infants in the longitudinal Rise & SHINE cohort study. Changes from 1 and 6 months in nighttime sleep duration, wake after sleep onset (WASO), and number of waking bouts ≥5 min were assessed using ankle actigraphy. Overweight was defined as age- and sex-specific weight for length ≥95th percentile. Generalized estimating equation analyses adjusted for infants' and mothers' characteristics. RESULTS The mean (SD) birth weight was 3.4 (0.4) kg; 48.7% were boys. In multivariable adjusted models, each 1-h increase in nighttime sleep duration between months 1 and 6 was associated with a 26% decrease in the odds of overweight from 1 to 6 months (odds ratio [OR] = 0.74; 95% confidence interval [CI, 0.56, 0.98]). Each 1-unit decrease in number of waking bouts was associated with a 16% decrease in the odds of overweight (OR = 0.84; 95% CI [0.72, 0.98]). Changes in WASO were not associated with the odds of overweight. CONCLUSIONS Greater increases in nighttime sleep duration and more consolidation of nighttime sleep were associated with lower odds of overweight from 1 to 6 months. Adverse sleep patterns as early as infancy may contribute to excess adiposity.

Abstract Introduction Pediatric obstructive sleep apnea (OSA) disproportionately affects children from minority groups and children living in disadvantaged neighborhoods, but the risk factors that drive this risk are not well understood. We investigated the relationship between minority race/ethnicity, household risk factors (smoking, socio-economic status [SES]), and neighborhood disadvantage with OSA-related quality of life (QOL) scores in participants in the Environmental Assessment of Sleep Youth (EASY) observational study. Methods Families of children 5-12 years old recruited from largely low-income Boston-area neighborhoods participated in an extensive in-home evaluation of OSA risk factors. OSA-related QOL was assessed with parent-reported OSA-18 questionnaire (values >37 indicative of negative impact of symptoms and signs of OSA on QOL). Secondhand smoking (SHS) was defined by parent-report of smoking in the home. Neighborhood disadvantage was characterized using geocoded addresses, calculating the Neighborhood Socioeconomic (NSES) index. We performed logistic regression with OSA-18 >37 as the dependent variable and age, gender, race/ethnicity, BMI, household smoking, household measures of SES and NSES index as independent variables. Results The sample included 256 children (40%-Hispanic ethnicity, 31%-Black, 20%-White, 9%-Other; 56% were female), with a mean age 9.1±1.9 and BMI percentile 69.9±29.8. 33% and 40% of children were from households with income <$25,000 and $25,000-$75,000, respectively, and 10% had SHS exposure. Mean NSES index was 47.9±15.4 (national average of 50). An elevated OSA-18 was reported for 35% of participants and significantly associated with Hispanic ethnicity and smoking exposure (OR=2.16, CI 1.01-4.62 and OR=2.71, CI 1.2-6.3) after adjusting for age, gender, and BMI percentile. Further adjustment for family income attenuated the association of OSA-18 with Hispanic ethnicity, but a significant association with household smoking persisted. NSES index and BMI percentile were not associated with OSA-18. Conclusion High symptoms and signs of OSA impacting QOL were associated with Hispanic ethnicity, household smoking and SES in this diverse cohort of children living in urban and predominantly low-income communities. The study points to the need for strategies to reduce household smoking as one strategy for decreasing sleep health disparities, and the further need to understand other factors associated with low SES that increase risk for poor sleep health. Support (If Any) NIH-NHLBI/T32HL007901, R35HL1358181, P30ES000002, K24AI106822, R01Hl137192, K23ES031663

Objective: To characterize family and environmental correlates of sleep patterns that may contribute to differences in infant sleep. Methods: We studied 313 infants in the Rise & SHINE (Sleep Health in Infancy & Early Childhood study) cohort. Our main exposures were the parent-reported sleep environment, feeding method and sleep parenting strategies at infant age one month. The main outcomes were nighttime sleep duration, longest nighttime sleep and number of awakenings measured by actigraphy at age six months. We used multivariable linear regression models to examine associations, and secondarily also explored the role of sleep-related environmental exposures in mediating previously observed associations of racial/ethnicity and parental education with infant sleep characteristics. Results: In adjusted models, a non-dark sleep environment (versus an always dark sleep location) and taking the baby to parent's bed when awake at night (versus no co-sleeping) were associated with 28 (95% CI, -45, -11) and 18 (95% CI, -33, -4) minutes less sleep at night, respectively. Bottle feeding at bedtime was associated with 62 (95% CI, 21, 103) minutes additional longest nighttime sleep period. Exploratory mediation analyses suggested a modest mediating role of a non-dark sleep environment on racial/ethnic and educational differences in sleep duration. Conclusions: Infant sleep duration was positively associated with a dark sleep environment and a focal feed at bedtime while taking the baby to the parent's bed was associated with reduced infant sleep. Modifying the sleep environment and practices may improve infant sleep and reduce sleep health disparities. (C) 2022 Elsevier B.V. All rights reserved.

The consumption of sugar-sweetened beverages (SSB) and 100% juice before age 12 months is discouraged. We examine racial/ethnic differences in SSB and 100% juice consumption when infants were 6- and 12-months old and examine links between fathers’ and infants’ beverage consumption. Participants were from a longitudinal cohort of infants and their parents (recruited 2016–2018), followed from birth until the child was 24 months. In 2020, we analyzed data collected when infants were 6- (N = 352 infants and 168 fathers) and 12-months (N = 340 infants and 152 fathers) old. Based on maternal report, 13% of infants consumed 100% juice at 6 months and 31% at 12 months. Two percent of infants consumed SSB at 6 months and 7% at 12 months. In models adjusting for income and education, Black/African American (Black/AA) and Hispanic infants were 5–6 times as likely at 6 months and 3 times as likely at 12 months to consume 100% juice compared with non-Hispanic white and Asian infants. At 12 months, Black/AA and Hispanic infants were 6–7 times as likely to consume SSB than non-Hispanic white and Asian infants after adjusting for covariates. In unadjusted models, infants were more likely to consume 100% juice and SSB at 12 months when their fathers were high consumers (>12times/month) of the beverage; effects were no longer significant after adjusting for income, race/ethnicity, education and maternal beverage consumption. Results highlight the need to implement culturally responsive interventions promoting healthy beverage consumption in infants prior to birth and should concurrently target fathers, in addition to mothers.

BACKGROUND:While research has examined prenatal to postnatal changes in women's weight, sleep, and diet, much less is known about these changes among fathers.PURPOSE:This study aimed to (a) examine changes in fathers' body mass index (BMI), sleep, and diet from 1 month before birth to 5-6 months following birth, and from 5-6 months to 11-12 months following birth and (b) explore the moderating roles of parenthood experience and coparenting support.METHODS:169 fathers (mean age 35.5 years, 58.9% White) participated. Fathers completed an intake survey shortly after their infant's birth to recall their height and weight, nighttime sleep hours, fruit and vegetable intake, soda intake, and fast food intake for the month prior to birth. When their child was 6 and 12 months old, fathers reported their weight, sleep, and diet again for the past 4 weeks (i.e., 4 week periods spanning 5-6 months and 11-12 months following birth). Generalized estimating equations were used to answer our research questions.RESULTS:Fathers reported higher BMI (Δ = 0.22 kg/m2; 95% confidence interval [CI] = 0.06, 0.38; p = .008) and less nighttime sleep duration (Δ = -0.21 hr; 95% CI = -0.38, -0.05; p = .012) at 5-6 months following birth compared to 1 month prior to birth. Fathers' diet remained stable over the three timepoints. No evidence was found to support the moderating roles of parenthood experience and coparenting support on fathers' weight and behavior changes.CONCLUSIONS:5-6 months following birth may be an important point of intervention for fathers to promote a return to prebirth BMI and sleep levels.

Objectives: Consistent with empowerment theory, parental empowerment acts as a mechanism of change in family-based interventions to support child health. Yet, there are no comprehensive, validated measures of parental health-related empowerment to test this important perspective. Informed by empowerment theory and in the context of a community-based obesity intervention, we developed a self-report measure of parental health-related empowerment and tested its preliminary validity with low-income parents. Methods: The Parental Empowerment through Awareness, Relationships, and Resources (PEARR) is a 21-item scale designed to measure three subdimensions of empowerment including resource empowerment, critical awareness, and relational empowerment. In the fall of 2017 or the fall of 2018, low-income parents (n = 770, 88% mothers) from 16 Head Start programs in Greater Boston completed the PEARR. The resulting data were randomly split into two equal samples with complete data. The factorial structure of the PEARR was tested in the first half of the sample using principal component analysis (PCA) and exploratory factor analysis (EFA) and subsequently confirmed with the second half of the sample using confirmatory factor analysis (CFA). Internal consistency coefficients were calculated for the final subscales. Results: Results from the PCA and EFA analyses identified three component factors (eigenvalues = 8.25, 2.75, 2.12) with all items loading significantly onto the hypothesized subdimension (β > 0.59 and p < 0.01). The three-factor model was subsequently confirmed with the second half of the sample using CFA (β > 0.54 and p < 0.01). Fit indices met minimum criteria (Comparative Fit Index = 0.95, Root Mean Square Error of Approximation = 0.05 (0.05, 0.06), Standardized Root-Mean-Square Residual = 0.05). Subscales demonstrated strong internal consistency (α= 0.83–0.90). Conclusions: Results support initial validity of a brief survey measuring parental empowerment for child health among Head Start parents. The PEARR can be utilized to measure changes in parental empowerment through interventions targeting empowerment as a mechanism of change.

Abstract Introduction Suboptimal sleep is associated with weight gain and related chronic diseases in adults, adolescents, and older children. However, little is known regarding the associations between sleep and physical growth in infants. We investigated prospectively the associations between objectively-measured sleep patterns at 1 month and physical growth in the first 6 months of life. Methods We studied 344 full term infants in the ongoing longitudinal Rise & SHINE (Sleep Health in Infancy & Early Childhood) birth cohort study. At 1 month, infants underwent 7-day ankle actigraphy, estimating average sleep duration (24-hour, nighttime, and daytime) and sleep fragmentation (number of nighttime awakenings). Weight and length were measured at birth and 6 months and used to calculate weight-for-length z (WFL-z) scores. We used linear and logistic regression analyses to examine the associations between sleep patterns at 1 month with WLF-z at 6 months and rapid weight gain from birth to 6 months, defined as an increase in WFL-z greater than or equal to 0.67, controlling for covariates. Results Each 1-hour increase in 24-hour sleep duration was associated with a 0.07-unit (95% CI [0.01, 0.12]) increase in WFL-z at 6 months. Daytime, but not nighttime, sleep duration was positively associated with WFL-z. Greater number of nighttime awakenings was associated with higher WFL-z (beta = 0.28; 95% CI [0.08, 0.49]). 24-hour and nighttime sleep duration were positively associated with a 18.5% (95% CI [1.04, 1.35]) and a 23.4% (95% CI [1.02, 1.49]) higher odds of rapid weight gain from birth to 6 months, respectively. Conclusion Longer 24-hour sleep duration was associated with higher 6-month WFL-z and more rapid increases in WFL-z from birth to 6 months. Greater nighttime sleep fragmentation was associated with higher 6-month WFL-z. Sleep at 1 month might provide modifiable targets to help avoid lifetime complications of excess weight. Support R01DK107972.

Background Process evaluation can illuminate barriers and facilitators to intervention implementation as well as the drivers of intervention outcomes. However, few obesity intervention studies have documented process evaluation methods and results. Community-based participatory research (CBPR) requires that process evaluation methods be developed to (a) prioritize community members’ power to adapt the program to local needs over strict adherence to intervention protocols, (b) share process evaluation data with implementers to maximize benefit to participants, and (c) ensure partner organizations are not overburdened. Co-designed with low-income parents using CBPR, Communities for Healthy Living (CHL) is a family-centered intervention implemented within Head Start to prevent childhood obesity and promote family well-being. We are currently undertaking a randomized controlled trial to test the effectiveness of CHL in 23 Head Start centers in the greater Boston area. In this protocol paper, we outline an embedded process evaluation designed to monitor intervention adherence and adaptation, support ongoing quality improvement, and examine contextual factors that may moderate intervention implementation and/or effectiveness. Methods This mixed methods process evaluation was developed using the Pérez et al. framework for evaluating adaptive interventions and is reported following guidelines outlined by Grant et al. Trained research assistants will conduct structured observations of intervention sessions. Intervention facilitators and recipients, along with Head Start staff, will complete surveys and semi-structured interviews. De-identified data for all eligible children and families will be extracted from Head Start administrative records. Qualitative data will be analyzed thematically. Quantitative and qualitative data will be integrated using triangulation methods to assess intervention adherence, monitor adaptations, and identify moderators of intervention implementation and effectiveness. Discussion A diverse set of quantitative and qualitative data sources are employed to fully characterize CHL implementation. Simultaneously, CHL’s process evaluation will provide a case study on strategies to address the challenges of process evaluation for CBPR interventions. Results from this process evaluation will help to explain variation in intervention implementation and outcomes across Head Start programs, support CHL sustainability and future scale-up, and provide guidance for future complex interventions developed using CBPR. Trial registration ClinicalTrials.gov, NCT03334669 . Registered on October 10, 2017