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Twin Research and Human Genetics

Cambridge University Press (CUP)

Preprints posted in the last 90 days, ranked by how well they match Twin Research and Human Genetics's content profile, based on 11 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

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Breastfeeding intentions and breastfeeding reality among first-time mothers living with obesity: A qualitative thematic analysis

Aubry, E. M.; Keller, D.

2026-08-18 nursing 10.64898/2026.08.17.26360590 medRxiv
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Background: Maternal obesity is associated with lower breastfeeding initiation, shorter breastfeeding duration and lower rates of exclusive breastfeeding. Although breastfeeding intention predicts initiation, little is known about how first-time mothers living with obesity experience the transition from antenatal intention to postpartum reality. Aim: This qualitative study explored breastfeeding expectations, intentions, attitudes and early breastfeeding challenges among first-time mothers living with obesity in Switzerland. Methods: Seven semi-structured interviews were conducted with first-time mothers living with obesity in German-speaking Switzerland. Interviews were audio-recorded, transcribed verbatim and analysed using reflexive thematic analysis according to Braun and Clarke. Results: All participants intended to breastfeed and described breastfeeding as part of motherhood. However, most experienced a postpartum reality that differed from their expectations. Three themes were developed: antenatal engagement with and expectations of breastfeeding, postpartum breastfeeding reality, and everyday breastfeeding life. Women received little antenatal breastfeeding counselling and faced challenges related to medicalised birth, delayed lactogenesis II, breast anatomy, pain, insufficient milk supply, pumping and inconsistent professional support. Several women described feelings of failure when breastfeeding did not work as hoped. Conclusion: First-time mothers living with obesity may have strong breastfeeding intentions but still experience major challenges after birth. Breastfeeding support should start during pregnancy and be realistic, respectful and weight-inclusive.

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Relations between prenatal sleep health and maternal weight retention 2 to 7 years after a first birth: the NuMoM2b-HHS

Hawkins, M. S.; Clifton, R. B.; Levine, M. D.; Kim, N.; Personette, C. M.; Davenport, M. A.; Kozai, A. B.; Kolko-Conlon, R. P.; Phan, D.; Grobman, W.; Ryan, J. T.; Ranzini, A. C.; Page, J.; Haas, D. M.; Bairey Merz, C. N.; Saade, G.; Yee, L. M.; Zee, P. C.; Chung, J.; Catov, J. M.

2026-08-26 epidemiology 10.64898/2026.08.23.26361117 medRxiv
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Background: Poor prenatal sleep health is associated with greater gestational weight gain, but the contributions to longer-term maternal weight retention remain unclear. Purpose: To examine associations between prenatal sleep health across multiple domains and maternal weight retention 2 to 7 years after a first birth. Methods: Participants were from the nuMoM2b-Heart Health Study. Self-reported sleep was assessed during early (6 to 13 6/7 weeks) and mid-pregnancy (22 to 28 6/7 weeks) across six domains: regularity, quality, sleepiness, timing, efficiency, and duration. A multidimensional sleep health (MSH) score reflected the number of domains meeting healthy thresholds. Outcomes included maternal weight retention, total and substantial (>11 lbs.), from pre-pregnancy to 2 to 7 years after a first birth. Associations were estimated using adjusted linear regression for total weight retention and Poisson regression with robust variance for substantial weight retention. Results: The sample included 3,661 individuals with data in early (n = 2,962) and mid-pregnancy (n = 3,210). In early pregnancy, healthy sleep duration was associated with lower total weight retention, whereas healthy sleep regularity was unexpectedly associated with greater retention. In contrast, during mid-pregnancy, a higher MSH score was associated with a lower risk of substantial weight retention (RR = 0.96, 95% CI: 0.93 to 0.99). Healthy sleep duration and quality were the two individual domains associated with lower weight retention (2 to 3 lbs.). Conclusions: In a prospective cohort of pregnant nulliparous individuals, healthy prenatal sleep, particularly during mid-pregnancy, was associated with less maternal weight retention 2 to 7 years after delivery. Future studies should estimate the causal effects of sleep health on long-term maternal weight retention.

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Psychosocial and socioeconomic vulnerability among caregivers of children with retinoblastoma: a cross-sectional latent profile study

Zhang, P.; Ge, X.

2026-07-17 nursing 10.64898/2026.07.15.26358190 medRxiv
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Background: Caregivers of children with retinoblastoma (RB) face substantial psychological and socioeconomic challenges. However, the factors independently associated with caregiver burden and the distribution of risk across caregiver subgroups remain incompletely characterized. We examined psychosocial and socioeconomic correlates of caregiver burden, identified distinct vulnerability profiles, and evaluated factors associated with high-risk profile membership. Methods: This cross-sectional study enrolled 413 primary caregivers of children with RB at a tertiary ophthalmic oncology center. Participants completed validated measures of caregiver burden (ZBI-22), anxiety (GAD-7), perceived social support (PSSS), family functioning (FAD-GF), and mental and physical quality of life (SF-12 MCS and PCS). Multivariable linear regression identified factors independently associated with caregiver burden and mental quality of life. Mediation analysis evaluated the indirect association between social support and burden through family functioning, and moderation analysis assessed whether household income modified the association between family dysfunction and burden. Latent profile analysis (LPA) identified caregiver risk profiles, and multinomial logistic regression examined factors associated with profile membership. Results: Anxiety showed the strongest independent association with greater caregiver burden (standardized coefficient beta = 0.641, 95% CI [1.46, 1.84], P < 0.001) and poorer mental quality of life (beta = -0.483, 95% CI [-0.12, -0.08], P < 0.001). Family debt was independently associated with greater burden (beta = 0.195, P = 0.040). Family functioning accounted for 32.19% of the total association between social support and burden. Household income modified the association between family dysfunction and burden (interaction B = -0.85, P < 0.001), with a steeper gradient in lower-income households. LPA identified three profiles: severe burden-high vulnerability (n = 82, 19.85%), moderate burden (n = 193, 46.73%), and mild burden-high resilience (n = 138, 33.41%). Low-to-moderate household income was associated with higher odds of severe-profile membership (OR = 31.50, 95% CI [6.56, 151.24], P < 0.001). Conclusions: Caregiver burden in pediatric RB was associated more strongly with psychosocial and socioeconomic factors than with the clinical indicators examined. Family functioning partly accounted for the association between social support and burden, while household income modified the association between family dysfunction and burden. These findings support prospective evaluation of family-centered and financial-support interventions and suggest that profile-based screening may help identify caregivers requiring more intensive support.

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Measuring Positive Stress Appraisal Among Nursing Students: Development and Psychometric Evaluation of the Nursing Student Positive Stress Scale (NSPSS)

Yan, H.; O'Brien, A. J.; Yoon, S. H.; Shaw, V.; vakavosaki, k.

2026-09-02 nursing 10.64898/2026.08.30.26361779 medRxiv
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Background: Stress research in nursing education has largely focused on distress, stressors, and negative outcomes, although challenging experiences may also support motivation, confidence, learning, and growth when appraised positively. Objective: To develop and evaluate the psychometric properties of the Nursing Student Positive Stress Scale (NSPSS). Design: A methodological instrument development and psychometric evaluation study. Methods: The NSPSS was developed using a deductive, theory-driven approach informed by the transactional theory of stress and coping and positive psychology perspectives. Content validity was assessed by an international nursing expert panel. Psychometric evaluation used national survey data from nursing students in New Zealand. Of 539 responses, 507 were analysed. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted using separate subsamples. Internal consistency was assessed using Cronbach's alpha and McDonald's omega, and convergent validity through correlation with Perceived Stress Scale-10 scores. Results: Content validity was strong (I-CVI = .88-1.00; S-CVI/Ave = .975; S-CVI/UA = .800). EFA identified a dominant factor explaining 41.38% of variance (loadings = .528-.735). CFA supported a two-context Academic and Clinical Positive Stress model with correlated residuals between five parallel item pairs, chi-square(29) = 60.49, CFI = .970, TLI = .954, RMSEA = .063, SRMR = .065. Internal consistency was good (alpha = .839; omega = .843). NSPSS scores correlated negatively with PSS-10 scores (r = -.298, p < .001). Conclusion: The NSPSS demonstrated strong content validity, preliminary evidence of structural and convergent validity, and good internal consistency reliability for assessing positive stress appraisal among nursing students. Further validation in independent samples is warranted.

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Associations between adult obesity and mid-life weight change patterns with cardiometabolic health in early old age: Evidence from the 1958 British birth cohort

Bridger Staatz, C.; Gimeno, L.; Sattar, N.; Chaturvedi, N.; Ploubidis, G. B.

2026-08-28 epidemiology 10.64898/2026.08.26.26361387 medRxiv
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Background: Cardiometabolic health typically declines with age and is worse among individuals living with obesity. Weight loss medications have modified the potential for weight loss across the life course, but it remains unclear whether weight reduction in later midlife contributes to improved cardiometabolic health, or if continuing to gain weight may continue to worsen cardiometabolic health. Methods: Using the nationally representative 1958 National Child Development Study (NCDS), a British birth cohort, associations were examined using lagged linear regression between weight change between ages 50-55 and health outcomes at age 62 (n=6,309 high-density lipoprotein (HDLc) and low-density lipoprotein (LDLc) cholesterol, systolic and diastolic blood pressure (SBP and DBP), heart rate, triglycerides, C-reactive protein (CRP), and glycated haemoglobin (HbA1c). Models accounted for prior biomarker levels at age 44. We also explored impacts of weight change on subsequent body composition. Results: Those who gained weight into or within obesity had less favourable cardiometabolic profiles and experienced faster deterioration of cardiometabolic markers between the ages of 44 and 62 than those remaining in healthy weight (e.g. SBP: 5.726, 95% CI: 2.660 to 8.793, p < 0.001; CRP: 0.802, 95% CI: 0.409 to 1.196, p < 0.001). Those who lost weight from obesity had similar rates of cardiometabolic biomarker deterioration to the healthy weight group (SBP: 0.947, 95%CI: -6.605 to 8.499, p=0.806; CRP: 0.140, 95% CI: -0.774 to 1.055, p= 0.764). Conclusion: Weight change in midlife tends towards increasing obesity and associated adverse cardiometabolic risk. Those who lose weight experienced improved cardiometabolic profiles. By viewing midlife as a modifiable stage of the life course, this study highlights opportunities to promote cardiometabolic health, and limit the speed of health decline.

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DNA methylation signal of birthweight generalizes to high-risk pregnancies and is independent of genetic, maternal, and obstetric factors: a twin study

Sulaiman, M.; Franken, L.; Spekman, J. A.; Groene, S. G.; van Zwet, E. W.; Roest, A. A. W.; Haak, M. C.; Kuipers, T.; Mei, H.; Neumann, A.; Cecil, C.; Heijmans, B. T.

2026-08-28 epidemiology 10.64898/2026.08.25.26361321 medRxiv
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Background. DNA methylation patterns in cord blood are robustly associated with birthweight in the general population. However, it remains unknown whether these associations extend to clinically relevant populations, such as preterm neonates or those born small for gestational age, and whether they directly reflect birthweight or are driven indirectly by genetic, familial, maternal, and obstetric factors. Methods. We calculated a birthweight methylation profile score (MPSBW) using weights of 835 CpGs previously associated with birthweight in the general population and evaluated its association with birthweight in 67 monochorionic (MC) twin pairs including 134 neonates (97% born preterm) from the Twinlife study. MC twin pairs are identical twins sharing a single placenta, often unequally, which can result in unequal resource distribution and differential fetal growth. Results. We examined the association between within-pair differences in birthweight and MPSBW, thereby estimating the association independent of factors shared equally by co-twins. A 500-gram increase in birthweight was associated with a 0.256 SD increase in MPSBW (p<0.005) in this population of preterm neonates. Adjustment for polygenic score for birthweight (PGSBW) confirmed that the observed epigenetic associations were not driven by common genetic variation underlying birthweight. Interestingly, a similar effect size (0.226 SD per 500 g birthweight increase; p<0.05) was observed in the within-pair analysis, which controls for all shared influences within a twin pair. Conclusion DNA methylation is associated with individual differences in birthweight in a high-risk clinical population of MC twins, independent of shared genetic, familial or maternal influences.

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Anticipatory nursing work and the co-construction of discharge readiness in coronary care units: A cross-national qualitative study

Rashidi, A.; Dunham, M.; KINLEY, E.; Bueser, T.; Glass, C.; Jones, I.; Makokha, M.; Whitehead, L.; Newson, L.

2026-08-05 nursing 10.64898/2026.08.03.26358968 medRxiv
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Abstract Background: Hospital discharge from coronary care units (CCUs) is commonly framed as a discrete clinical or administrative endpoint. This event-based conceptualisation obscures the ongoing nursing and interprofessional work undertaken across the admission to stabilise discharge readiness. Aim: To theorise discharge readiness in CCUs as anticipatory nursing and interprofessional work and to examine how professional roles, organisational systems and service contexts shape discharge across two national context. Design: Qualitative study utilising reflexive thematic analysis. Methods: Semi-structured interviews and focus groups were conducted with 37 clinicians (nurses, allied health professionals and medical staff) working in CCUs in Australia and the United Kingdom. Reflexive Thematic Analysis was undertaken inductively within each dataset, followed by higher-level interpretive integration. Results: Four interrelated themes conceptualised discharge readiness as: (1) anticipatory nursing work initiated at admission and sustained through ongoing assessment, coordination and documentation; (2) negotiated readiness achieved through interprofessional alignment and distributed expertise; (3) discharge documentation as a site of organisational tension shaping workflow and communication; and (4) discharge flow constrained by system-level pressures, downstream service availability and policy logics. Across both national contexts, nurses were positioned as custodians of discharge readiness through continuous monitoring, relational coordination and informal risk management, although enactment varied by organisational setting. Conclusion: This study contributes to nursing scholarship by positioning discharge readiness not as a single decision point, but as an emergent outcome of anticipatory nursing labour, interprofessional negotiation and organisational systems. By making visible the distributed and often hidden work underpinning discharge, the findings extend existing models of transitional care and provide a theoretically grounded foundation for strengthening discharge practice in coronary care nursing.

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The Inflammatory Cascade Through Discrimination, Socioeconomic Status, and Body-Mass Index

Espero, M.

2026-07-01 epidemiology 10.64898/2026.06.24.26356254 medRxiv
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C-Reactive Protein (hs-CRP) is a common marker for human inflammation, a response to perceived threat and precipitate to many compromising health conditions. Previous work demonstrated that in addition to other biological features that may be predictive and explanatory of variance in inflammation, psychosocial influences may play a role. The present work uses structural equation modeling to examine pathways including socioeconomic status (SES), psychological capital (PsyCap), and perceived discrimination (Discrim) -insofar as they explain variance in hs-CRP, potentially moderated by neurological lateralization (handedness). Body mass index (BMI), an indicator of body composition, stood as the strongest predictor of the obesity-related inflammatory marker (ORIM). On average, females are predicted to have higher hs- CRP scores than males. The psychosocial constructs were estimated to have little to no effect on inflammation (via hs-CRP) in the analysis sample (ADD Health Study) in either group (left and right-handers) although a small, statistically non-zero indirect path is found in the retained model for right-handed participants (given statistical power for estimation). With this finding, contextual effect estimates are provided with regard to the effect of perceived discrimination on hs-CRP given the range of SES and BMI.

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Care-Related Determinants of Adverse Outcomes among Low-Birth-Weight Neonates: Evidence from Newborn Unit Practice and Provider Perspectives in Kenya

Mukthar, V. K.; Cheptoo, J.; Shisanya, M. S.

2026-07-16 nursing 10.64898/2026.07.13.26357939 medRxiv
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Context. Survival of low-birth-weight (LBW) neonates depends heavily on modifiable nursing care processes at the bedside, making the newborn unit a decisive site for improvement. Evidence linking measurable care-process conditions to outcomes, and the provider experience that explains them, remains limited in Kenyan county referral settings. Aim. To examine the care-related determinants of severe adverse outcomes among LBW neonates and the provider perspectives that explain them, framed for newborn-unit nursing practice and quality improvement. Methods. A convergent mixed-methods design was applied at Kericho County Referral Hospital. Quantitatively, 169 LBW neonate-mother pairs were analysed; care-process indicators (skilled personnel at admission, warm-chain maintenance, shortage of essential drugs/feeds, and referral/outborn status) were related to a composite severe adverse outcome using Pearson chi-square tests and crude odds ratios (OR) with 95% confidence intervals (CI). Qualitatively, key-informant interviews with newborn-unit providers were analysed thematically and coded to care-process themes; strands were integrated for practice. Findings. A severe adverse outcome occurred in 136/169 neonates (80.5%). Skilled personnel (94.7%) and warm-chain practices (92.9%) were near-universal, whereas 58.6% of neonates faced shortages of essential drugs/feeds and 49.1% were referred (outborn). Shortage of essential drugs/feeds (OR = 2.26, 95% CI [1.04, 4.90], p = .036) and referral/outborn status (OR = 2.25, 95% CI [1.01, 5.00], p = .043) were significantly associated with higher odds of a severe outcome. Warm-chain care was statistically associated but in a counterintuitive direction (OR = 4.81, p = .006), consistent with confounding by indication, while skilled-personnel availability was not associated (p = .834). Provider narratives converged on seven care-process themes: staffing and workload, warm-chain maintenance, infection prevention, drug and equipment availability, referral coordination, monitoring and documentation, and caregiver/transport barriers around the first hour of care. Conclusion. Care-related conditions-commodity supply, referral readiness, thermal care, infection prevention, and monitoring-are clinically modifiable levers that shape whether vulnerable LBW neonates stabilize or deteriorate, even where they do not all retain independent statistical significance after adjustment. Recommendations. Newborn units should protect nurse staffing norms, secure consistent supply of essential neonatal commodities, standardize pre-referral stabilization and thermal-care protocols, and strengthen structured monitoring and documentation, supported by competency-based training and county-level policy. Keywords: low-birth-weight neonates; newborn unit; nursing care processes; warm chain; infection prevention; referral coordination; drug and equipment shortage; quality improvement; provider perspectives; mixed methods

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Chrononutrition and prenatal mental health: The relationship between food intake indicators and prenatal depressive symptomatology

Personette, C. M.; Phan, D. A.; Duan, D.; Kim, N.; Abebe, K. Z.; Scifres, C. M.; Costacou, T. M.; Catalano, P.; Simhan, H.; Davis, E. M.; Mendez, D. D.; Hawkins, M. S.

2026-08-22 epidemiology 10.64898/2026.08.19.26360839 medRxiv
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Abstract Aim: Examine cross-sectional associations between mid-pregnancy food intake indicators and prenatal depressive symptomatology. Methods: This secondary analysis of the Comparison of Two Screening Strategies for Gestational Diabetes trial (N = 718) examined domains of mid-pregnancy food intake (direct timing, energy timing, meal/snack structure, meal energy distribution, diet quality) derived from 24-hour dietary recalls. Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS). Generalized linear models examined associations between food intake indicators, total, and high (EPDS [&ge;]13) depressive symptoms. Results: Mean (SD) EPDS score was [6.3 (4.9)]; 12.4% (n = 89) had high depressive symptoms. Eating frequency (B = 0.08 [0.02, 0.14], p = 0.009), snack frequency (B = 0.06 [0.00, 0.12], p = 0.040), nighttime snacking frequency (B = 0.06 [0.00, 0.11], p = 0.041), and total daily energy intake (B = 0.06 [0.01, 0.12], p = 0.031) were positively associated with total depressive symptoms. Energy intake from breakfast (PR = 1.2 [1.0, 1.3], p = 0.017) was associated with a higher prevalence of high depressive symptoms. Energy intake from dinner (PR = 0.81 [0.69, 0.94], p = 0.007), later timing of the first eating episode (PR = 0.83 [0.70, 0.99], p = 0.034) and first energy quartile (PR = 0.84 [0.70, 1.0], p = 0.048), were associated with a lower prevalence of high depressive symptoms. Conclusion: These findings extend prior chrononutrition-depression literature to the prenatal period, implicating eating frequency, energy intake, and meal energy timing and distribution in depressive symptomatology during pregnancy, warranting further longitudinal investigation.

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Life course shaping of allostatic load across 17 countries: Evidence from England, the U.S., Europe, China and Indonesia

Li, G.; De Rubeis, V.; Cesari, M.; Sadana, R.; Jacob, C. M.; LEE, H.-Y.; Tampubolon, G.

2026-07-31 epidemiology 10.64898/2026.07.29.26359214 medRxiv
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Early life adversity is a recognised risk factor for poor health in later life, but its relationship with allostatic load (AL; a measure of cumulative physiological stress) remains underexplored across populations around the world. This study builds evidence to test a life course approach to AL using harmonised data from six longitudinal ageing cohorts: Health and Retirement Study (US, N=2,427), English Longitudinal Study of Ageing (England, N=2,038), The Irish Longitudinal Study on Ageing (Ireland, N=8,184), Survey of Health Ageing and Retirement in Europe (Europe, N=4,079), China Health and Retirement Longitudinal Study (China, N=5,220), and Indonesia Family Life Survey (Indonesia, N=1,243). Childhood information at aged ten to sixteen was collected retrospectively from adults aged 65 on average. An AL score is constructed using biomarker data and a latent construct of early life adversity constructed to address recall bias. Results show that early life poverty is significantly associated with raised AL in Ireland, China, and Indonesia, supporting the impact of early life experiences on older adulthood. However, studies from other countries do not confirm statistical significance. These findings document that experiencing poverty during development phase in some settings is associated with higher AL in later life, however further analyses are required to explore possible variations across different populations and their social and economic context. These results add further evidence that social determinants of health, including child poverty, in some settings, contribute to cumulative physiological stress across the life course, and that policies and actions to reduce child poverty can have beneficial effects not only as children, but also as older adults.

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Socioeconomic position, adverse childhood experiences, and menstrual symptoms in two generations of a prospective UK cohort.

Sawyer, G.; Farooq, B.; Birnie, K.; Fraser, A.; Lawlor, D. A.; Sharp, G. C.; Howe, L. D.

2026-08-31 epidemiology 10.64898/2026.08.27.26361513 medRxiv
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Background: Inequalities exist for many health outcomes, but there is limited evidence regarding menstrual symptoms despite their importance for health and wellbeing. We aimed to investigate inequalities in menstrual symptoms according to socioeconomic position and childhood adversity. Methods: In two generations (G0 mothers and G1 offspring) from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK prospective cohort study, we examined associations of multiple indicators of socioeconomic position (SEP) and adverse childhood experiences (ACEs) with menstrual symptoms (pain, abnormal uterine bleeding, and premenstrual syndrome (PMS) measured 3-8-years post-birth in G0 and 17-21-years-old in G1), using multivariable logistic regression. Samples ranged from 4,828 to 9,335 G0 participants and 1,288 to 2,757 G1 participants depending on the exposure-outcome association. Missing data were addressed using multiple imputation and inverse probability weighting. Results: Financial difficulties were associated with greater odds of menstrual pain (G1 OR 1.41; 95% CI 1.07, 1.86: G0 OR 1.55; 95% CI 1.36, 1.76) and irregular cycles (G1 OR 1.60; 95% CI 1.12, 2.29: G0 OR 1.48; 95% CI 1.27, 1.72) in both generations, as well as with short/long cycle lengths in G0 only. Lower education and manual social class were also associated with these three menstrual symptoms in at least one generation. Conversely, higher SEP was associated with PMS in both generations. Higher cumulative ACEs were consistently associated with menstrual pain (4+ compared to none: G1 OR 2.15; 95% CI 1.48, 3.11: G0 OR 1.52; 95% CI 1.29, 1.80) and irregular cycles (G1 OR 1.92; 95% CI 1.20, 3.09: G0 OR 1.54; 95% CI 1.26, 1.87) but not cycle length. Lower parental education, financial difficulties, and cumulative ACEs were associated with heavy bleeding in G1 offspring only, whereas financial difficulties, own manual social class, and cumulative ACEs were associated with prolonged bleeding in G0 mothers only. Higher cumulative ACEs were also associated with PMS in G1 offspring only. Conclusions: We found evidence of inequalities according to socioeconomic disadvantage and childhood adversity for multiple menstrual symptoms, although some associations were only observed in one generation. Findings suggest that menstrual symptoms are disproportionately experienced by socially and socioeconomically disadvantaged women.

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Association of Social Deprivation with Wait Time and Referral Attrition in Obstructive Sleep Apnea

McKinnon, G.; Tsai, W. H.; Ip-Buting, A.; Duff, N.; Fabreau, G. E.; McBrien, K.; David, O.; Donald, M.; Pendharkar, S. R.

2026-08-17 respiratory medicine 10.64898/2026.08.13.26360397 medRxiv
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Abstract Importance: Socially vulnerable patients have a high burden of obstructive sleep apnea, but the stage of the referral pathway at which access barriers arise is uncertain. Objective: To determine whether area-level social deprivation was associated with appointment scheduling, wait time, cancellations, or no-shows among adults referred for specialist obstructive sleep apnea care. Design: This was a cross-sectional study evaluating patients referred from December 1, 2016 through November 30, 2019. Data were analyzed from January 30, 2026 to May 16, 2026. Setting: Foothills Medical Centre Sleep Centre in Calgary, Canada. Participants: Adults referred to a tertiary academic sleep centre in Calgary, Alberta, Canada. Eligible patients had valid provincial health insurance and either a scheduled clinic appointment or home sleep apnea test data available. Exposures: Quintiles of the four Canadian Index of Multiple Deprivation domains: residential instability, economic dependency, ethnocultural composition, and situational vulnerability. Main Outcomes and Measures: The primary outcome was receipt of a scheduled specialist appointment. Secondary outcomes were time from referral to the first attended appointment and number of appointment cancellations or no-shows. Results: Among 3111 patients (mean [SD] age, 53.7 [14.3] years; 40.7% female), 1766 (56.7%) were scheduled and 1647 (52.9%) attended an appointment. Each quintile increase in situational vulnerability was associated with lower odds of scheduling (adjusted odds ratio [95% confidence interval] 0.86 [0.81-0.92]), whereas each quintile increase in ethnocultural composition was associated with higher odds (adjusted odds ratio [95% confidence interval] 1.32 [1.22-1.43]). Residential instability and economic dependency were not associated with scheduling. No deprivation domain was associated with time to the first attended appointment, cancellations, or no-shows. Conclusions and Relevance: In this cohort, area-level deprivation was associated with whether patients were scheduled for an appointment but not with wait time or missed visits after scheduling. These findings suggest that equity interventions should focus on completion of referral and scheduling processes.

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Maternal and Neonatal Predictors of Severe Adverse Outcomes among Low-Birth-Weight Neonates in Kericho County, Kenya

Mukthar, V. K.; Cheptoo, J.; Shisanya, M. S.

2026-07-16 nursing 10.64898/2026.07.13.26357928 medRxiv
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Background. Low-birth-weight (LBW) neonates carry a disproportionate share of newborn morbidity and mortality in sub-Saharan Africa. Distinguishing which maternal and neonatal characteristics mark the highest risk supports bedside risk stratification in resource-limited newborn units. This study examined maternal and neonatal predictors of severe adverse outcomes among LBW neonates admitted to a county referral hospital in Kenya. Methods. A facility-based cross-sectional analysis was conducted on 169 LBW neonate-mother pairs admitted to the newborn unit at Kericho County Referral Hospital. The outcome was a severe adverse outcome, defined as a composite of respiratory distress, sepsis, hypothermia, hypoglycaemia, prolonged admission (>= 7 days), or neonatal death. Maternal and neonatal factors were screened using chi-square, Fisher's exact, and independent-samples t tests, with crude odds ratios (ORs) and 95% confidence intervals (CIs). A restricted multivariable logistic regression, limited to maternal and neonatal predictors, produced adjusted odds ratios (AORs). Results. Severe adverse outcomes occurred in 136 of 169 neonates (80.5%). At the bivariate level, pregnancy-induced hypertension (PIH; OR = 6.69, 95% CI 1.53-29.27, p = 0.004) and preterm birth (OR = 3.79, 95% CI 1.50-9.56, p = 0.003) were associated with higher odds of a severe outcome, and severe outcomes clustered at lower birth weight and gestational age and higher neonatal risk-factor counts (all p < 0.001). In the restricted adjusted model, PIH (AOR = 7.66, 95% CI 1.56-37.55, p = 0.012) and birth weight (AOR = 0.997 per gram, p = 0.002) retained independent significance. Conclusion. Neonatal biological vulnerability-particularly lower birth weight-together with maternal pregnancy-induced hypertension were the predictors most strongly and independently associated with severe adverse outcomes. Risk stratification of LBW neonates should prioritise the smallest infants and those born to mothers with hypertensive disease. Keywords: low birth weight; neonatal outcomes; pregnancy-induced hypertension; preterm birth; risk stratification; Kenya

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Does genetic liability for autism influence alcohol use?

Page, S.; Easey, K.; Sedgewick, F.; Rai, D.; Stergiakouli, E.

2026-08-31 epidemiology 10.64898/2026.08.26.26360336 medRxiv
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A body of research suggests that autistic individuals are less likely to drink alcohol than neurotypicals. However, emerging studies support a link between autism and alcohol use. This complex relationship is also reflected in studies that have examined the genetic overlap between the two traits. However, it is unclear whether there is a direct causal relationship between them. To explore this, we applied a combination of polygenic score and Mendelian randomisation analyses using publicly available genome-wide summary statistics and phenotypic measures of autism and alcohol consumption from UK Biobank. LD score regression analyses did not provide evidence of a genetic correlation between genetic liability for autism and drinks consumed per week (rg=-0.08; CI95%=-0.19, 0.03). Further, findings from polygenic score analyses did not support an association between genetic liability for autism and overall monthly alcohol intake. Univariable Mendelian randomisation analyses showed little evidence for a total effect of autism, attention deficit hyperactivity disorder (ADHD) or depression on overall monthly alcohol consumption. Multivariable Mendelian randomisation analyses also showed little evidence of a direct effect of autism on drinks per week when controlling for ADHD and depression. It is plausible that genetic liability for autism does not directly increase the amount of alcohol consumed but instead operates via commonly co-occurring difficulties in the autistic community. However, our findings may be due to methodological shortcomings, including weak instruments biasing effects towards to the null. Consequently, results should be interpreted with caution and further research conducted to address these issues.

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Genetic nurture and direct genetic transmission effects on body mass index across age

Trindade Pons, V.; Gillespie, N.; Smit, R. A. J.; Arias, J. D.; Yin, X.; Berndt, S. I.; Oldehinkel, A. J.; van Loo, H.

2026-09-02 public and global health 10.64898/2026.08.31.26361795 medRxiv
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Obesity is a growing public health challenge, with body mass index (BMI) influenced by both genetic and environmental factors. While the role of direct genetic transmission is well established, evidence for genetic nurture effects, in which parental genotypes impact offspring through the environment, has remained mixed. This study investigates direct genetic transmission and genetic nurture effects on BMI across ages, using parent-offspring trios and pairs from the Dutch Lifelines cohort study (N = 18,897 offspring, aged 8 to 67 years). We leveraged the latest multi-ancestry BMI polygenic score (PGS) to construct transmitted (PGS-T) and non-transmitted (PGS-NT) polygenic scores, where PGS-NT consists of parental alleles not passed on to offspring and serves as a proxy for genetic nurture. Linear mixed models showed a large effect of PGS-T on offspring BMI (Beta = 0.416, p < 0.001), corresponding to a 1.85 kg/m2 increase per SD increase in PGS-T. PGS-NT had a small but significant effect (Beta = 0.026, p = 0.013), consistent with a genetic nurture effect accounting for approximately 6.6% of the effect of direct transmission. Parent-of-origin analyses showed that maternal PGS-NT effects were larger than paternal effects. PGS-T interactions with age indicated that direct transmission effects increased in childhood and stabilized in adulthood, while PGS-NT effects remained stable across age. Our findings suggest that direct genetic transmission is the dominant influence on BMI, while results are consistent with small genetic nurture effects that are driven by the maternal side.

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Identifying adverse experiences in childhood in the Born in Bradford Birth Cohort children

Lam, N.; Wadman, R.; Watmuff, A.; Gilbody, S.

2026-08-21 epidemiology 10.64898/2026.08.18.26360723 medRxiv
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Adverse experiences in childhood (AEs) typically refer to undesirable events, including child maltreatment and household challenges. Various survey measures and linked routine data in the Born in Bradford Birth Cohort (BiB) datasets can provide a contemporary understanding of the distribution of AEs in the population and the factors related to their occurrence. This study aimed to identify relevant survey data on AEs collected from BiB families and to summarise the prevalence of AEs from birth to early adolescence (ages 12-15) among BiB children. We included BiB children who participated in the follow-ups - Growing Up (GUp, n=5253) and Age of Wonder (AoW, n=2662). Four AEs were identified - parental mental illness, parental substance use, children not living with both parents in the same home, and being bullied by peers. The survey data included 1) health, substance use, living arrangements, and children's bullying experience reported by parent(s) at baseline (2007-2011, around birth) and/or GUp (2017-2022, during mid-childhood), and 2) bullying experience and living arrangements self-reported by children at AoW (2022-2024, during early adolescence). Additionally, we included parents' primary care records regarding any mental illness or substance use. Overall, 3371 (64.2%) children experienced at least one of the four AEs between birth and early adolescence. The most common AE was parental mental illness, whereas parental substance use was the least common. Children across all sociodemographic groups experienced AEs. Asian children, or those whose mothers were not materially deprived, appeared less likely to experience AEs. Conversely, children of White or Mixed ethnicities, or whose mothers were materially deprived, were more likely to experience AEs. Consistent with similar studies, our findings show that AEs are widespread but disproportionately affect certain sociodemographic subgroups among BiB children. These disparities can be reduced by early-years policies that provide practical family support, guided by continuously collected AE data.

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Knowledge and Associated Factors Influencing Oral Care Provision Among ICU Nurses Caring for Mechanically Ventilated Patients at Tenwek Hospital, Kenya

Mukthar, V. K.; Tuei, S.; Towett, P.

2026-07-16 nursing 10.64898/2026.07.13.26357953 medRxiv
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Background: Oral care is a critical nursing intervention for mechanically ventilated patients in intensive care units because it reduces oral microbial colonization and contributes to the prevention of ventilator-associated pneumonia, a major cause of morbidity, prolonged hospitalization, and increased healthcare costs among critically ill patients. Despite the availability of evidence-based guidelines, gaps in nurses knowledge and inconsistent implementation of oral care practices remain challenges, particularly in low- and middle-income settings. Objective: This study aimed to assess the level of knowledge among intensive care unit nurses regarding oral care for mechanically ventilated patients at Tenwek Hospital, Kenya, determine factors influencing knowledge, and examine the relationship between nurses knowledge and selected demographic and professional characteristics. Methods: An analytical cross-sectional study design was employed. The study was conducted among intensive care unit nurses at Tenwek Hospital. A sample of 38 nurses was selected from a target population of 60 intensive care unit nurses using simple random sampling. Data were collected using a structured self-administered questionnaire assessing socio-demographic characteristics, knowledge of evidence-based oral care practices, awareness of guidelines, and factors influencing knowledge. Data were analyzed using descriptive statistics, chi-square tests, Pearson correlation, and logistic regression, with statistical significance set at probability value less than 0.05. Results: Thirty-five nurses participated, yielding a response rate of 92.1 percent. The findings demonstrated generally high knowledge levels regarding oral care practices for mechanically ventilated patients. Most nurses correctly identified recommended oral care frequency (88.6 percent), oral assessment before care (91.4 percent), suctioning before and after oral care (94.3 percent), and the role of oral care in preventing ventilator-associated pneumonia (97.1 percent). However, knowledge gaps were identified in areas such as toothbrushing practices and documentation of oral care procedures. Training, continuing professional education, availability of guidelines, workload, resources, supervision, and teamwork were identified as important factors influencing knowledge. The findings revealed that professional qualification (probability value equal to 0.02), intensive care unit experience (probability value equal to 0.030) and formal oral care training (probability value equal to 0.021) were significantly associated with nurses knowledge of oral care practices. Conclusion: Intensive care unit nurses at Tenwek Hospital demonstrated adequate knowledge of evidence-based oral care practices for mechanically ventilated patients. However, targeted educational interventions are required to address identified gaps and strengthen standardized oral care delivery. Continuous professional development, consistent use of guidelines, supportive supervision, and adequate resource provision are recommended to enhance patient safety and reduce preventable intensive care unit complications such as ventilator-associated pneumonia. Keywords: Intensive care unit nurses; Oral care; Mechanically ventilated patients; Ventilator-associated pneumonia; Nursing knowledge; Evidence-based practice

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Genetic and Behavioral Variation Underlying an Integrated Temporal Phenotype in an Admixed South American Population

Marchesano, M.; Spangenberg, L.; Casaravilla, C.; Castillo Stratta, J.; Silva, A.; Tassino, B.

2026-08-24 genetics 10.64898/2026.08.18.745563 medRxiv
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Chronotype is a complex trait reflecting individual differences in the temporal organization of rest and activity, with important health implications. The Uruguayan population, characterized by a tri-hybrid origin (African, European, and Indigenous), exhibits a bias toward eveningness. The genetic variation in clock genes underlying chronotype in this population remains unexplored. To address this gap, we analyze healthy young adults from the extremes of the chronotype distribution (early, n = 37; late, n = 38; 63% female; 23.1 {+/-} 3.4 years), integrating self-reported measures, actigraphy, and low-pass whole-genome sequencing. Global ancestry is predominantly European, with Indigenous and African components, and does not differ between chronotypes. Variant density is highest in PER2. T-allele carriers of a PER2 variant previously associated with late chronotypes (rs35333999) differ from non-carriers in activity acrophase. Multidimensional scaling of variants across 19 canonical clock genes reveal differential representation of early and late chronotypes across genetic clusters. When examined by functional groups, the signal is restricted to genes involved in degradation of the circadian clock's repressor arm, with BTRC, a mediator of PER2 degradation, showing the same pattern when assessed individually. We derive a joint behavioral component capturing the variation in food intake, moderate-to-vigorous physical activity, light exposure, and sleep timing, which correlates with dim-light melatonin onset (DLMO), the gold-standard marker of circadian phase, and show differences among genetic clusters. Our integrative multilevel approach suggests a complex interplay between behavioral and genetic factors shaping chronotype in this cohort, highlighting the PER2BTRC axis as a candidate mechanism for future investigations.

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Childhood Bullying as a Cumulative Health Risk: A Dose-Response Analysis of Peer Victimization and Adult Mental and Behavioral Health Outcomes in Saudi Arabia

Bin Hamdan, D. A.

2026-08-19 epidemiology 10.64898/2026.08.17.26360648 medRxiv
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Childhood peer victimization is increasingly recognized as an adverse childhood experience (ACE) with long-term consequences for population health. Most existing research treats bullying as a binary exposure, obscuring the dose-response mechanisms through which cumulative victimization generates escalating health risks. This methodological gap is particularly consequential for prevention, and evidence from the Gulf Cooperation Council (GCC) region remains systematically sparse. This study conducts a national dose-response analysis of childhood bullying and adult health outcomes in Saudi Arabia using the WHO Adverse Childhood Experiences International Questionnaire (ACE-IQ), administered to a nationally representative sample of 10,156 adults by the King Abdullah International Medical Research Center (KAIMRC) and the National Family Safety Program (NFSP), Ministry of National Guard Health Affairs (2013). We conducted a cross-sectional secondary analysis examining associations between bullying frequency and five adult health outcomes: physician-diagnosed anxiety disorder, suicidal ideation, sleep disturbance, tobacco smoking, and substance use. The analytical sample comprised 4,632 adults reporting any childhood peer victimization. Binary logistic regression models adjusted for socioeconomic status, gender, age cohort, parental supervision, and family structure were estimated separately for each outcome. Three pre-specified hypotheses were tested: (H1) any bullying exposure is associated with higher odds of adverse adult health outcomes; (H2) increasing frequency follows a dose-response gradient; and (H3) associations are amplified among socioeconomically disadvantaged respondents and attenuated among those reporting higher parental attention. A consistent dose-response gradient was observed. Frequent victims showed substantially higher adjusted odds of tobacco smoking (OR = 6.55, 95% CI 5.81-7.32) and substance use (OR = 2.71, 95% CI 2.26-3.31) compared to those never bullied. Internalizing outcomes showed significant gradients for anxiety disorder (OR = 0.37, 95% CI 0.16-0.86) and sleep disturbance (OR = 0.39, 95% CI 0.20-0.76). Religion-targeted verbal victimization was the strongest independent predictor of suicidal ideation (OR = 3.01, 95% CI 1.83-4.97) and substance use (OR = 3.24, 95% CI 1.92-5.46), independent of bullying frequency. Bullying-health associations were significantly amplified among socioeconomically disadvantaged respondents, consistent with fundamental cause theory. Parental supervision was protective against substance use (OR = 0.45, 95% CI 0.30-0.67) but showed a paradoxical positive association with suicidal ideation, interpreted as a reactive parenting effect in the cross-sectional design. These findings establish childhood bullying as a cumulative, graded public health risk whose consequences are amplified by structural disadvantage. Prevention strategies must extend beyond school-level programs to address structural inequalities and integrate family-based and community-level protective factors. This study contributes population-level ACE evidence from the underrepresented GCC region and provides a foundation for integrating bullying prevention into Saudi Arabia's Vision 2030 national health agenda.