The Birth and Beyond (BABY) study: protocol for a birth cohort study investigating the social and environmental determinants of pregnancy-related outcomes in Black American families.

INTRODUCTION: In the USA, Black birthing people and infants experience disproportionately worse pregnancy-related health outcomes. The causes for these disparities are unknown, but evidence suggests that they are likely socially and environmentally based. Efforts to identify the determinants of these racial disparities are urgently needed to elucidate the highest priority targets for intervention. The Birth and Beyond (BABY) study evaluates how micro-level (eg, interpersonal and family) and macro-level (eg, neighbourhood and environmental) risk and resiliency factors transact to shape birth person-infant health, and underlying psychobiological mechanisms. METHODS AND ANALYSIS: The BABY study will follow 350 Black families (birthing parents, non-birthing parents and infants) from pregnancy through the first postpartum year, with research visits during pregnancy and at infant ages 6 and 12 months. Research visits comprise a combination of interview about a range of recent and life course stress and resiliency exposures and supports, psychophysiological (sympathetic, parasympathetic and adrenocortical) assessment and behavioural observations of parent-infant coregulatory behaviours. Spatial analyses are completed by mapping parent current and past residential addresses onto archival public data (eg, about neighbourhood quality and racial segregation). Finally, EMRs are abstracted for information about birthing parent relevant medical history, pregnancy conditions and infant birth outcomes. Analyses will evaluate the risk and resiliency mechanisms that contribute to pregnancy and birth-related outcomes for Black birthing people and their infants, and the protective role of individual, familial, cultural, and community supports. ETHICS AND DISSEMINATION: The BABY study has been approved by the Institutional Review Board at Albany Medical Centre. The study team consulted with local organisations and groups comprised of stakeholders and community leaders and continues to do so throughout the study. Research results will be disseminated with the scientific and local community as appropriate.

Remnant cholesterol, iron status and diabetes mellitus: a dose-response relationship and mediation analysis.

BACKGROUND: Remnant cholesterol (RC) is recognized as a risk factor for diabetes mellitus (DM). Although iron status has been shown to be associated with cholesterol metabolism and DM, the association between RC, iron status, and DM remains unclear. We examined the relationship between RC and iron status and investigated the role of iron status in the association between RC and DM. METHODS: A total of 7308 patients were enrolled from the China Health and Nutrition Survey. RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Iron status was assessed as serum ferritin (SF) and total body iron (TBI). DM was ascertained by self-reported physician diagnosis and/or antidiabetic drug use and/or fasting plasma glucose ≥ 126 mg/dL and/or glycated haemoglobin ≥ 6.5%. General linear models were used to evaluate the relationships between RC and iron status. Restricted cubic splines were used to assess the association between RC and DM. Mediation analysis was used to clarified the mediating role of iron status in the association between the RC and DM. RESULTS: The average age of the participants was 50.6 (standard deviation = 15.1) years. Higher RC was significantly associated with increased SF (ß = 73.14, SE = 3.75, 95% confidence interval [CI] 65.79-80.49) and TBI (ß = 1.61, SE = 0.08, 95% CI 1.44-1.78). J-shape relationships were found in the association between RC levels with DM, as well as iron status with DM. Significant indirect effects of SF and TBI in the association between RC and DM were found, with the index mediated at 9.58% and 6.37%, respectively. CONCLUSIONS: RC has a dose-response relationship with iron status. The association between RC and DM was mediated in part by iron status. Future studies are needed to confirm these findings and further clarify the underlying mechanism.

Complementing the United States Household Food Security Survey Module with Items Reflecting Social Unacceptability.

BACKGROUND: Social unacceptability of food access is part of the lived experience of food insecurity but is not assessed as part of the United States Household Food Security Survey Module (HFSSM). OBJECTIVES: The objectives were as follows: 1) to determine the psychometric properties of 2 additional items on social unacceptability in relation to the HFSSM items and 2) to test whether these 2 items provided added predictive accuracy to that of the HFSSM items for mental health outcomes. METHODS: Cross-sectional data used were from the Intersection of Material-Need Insecurities and HIV and Cardiovascular Health substudy of the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study. Data on the 10-item HFSSM and 2 new items reflecting social unacceptability were collected between Fall 2020 and Fall 2021 from 1342 participants from 10 United States cities. The 2 social unacceptability items were examined psychometrically in relation to the HFSSM-10 items using models from item response theory. Linear and logistic regression was used to examine prediction of mental health measured by the 20-item Center for Epidemiologic Studies Depression scale and the 10-item Perceived Stress Scale. RESULTS: The social unacceptability items were affirmed throughout the range of severity of food insecurity but with increasing frequency at higher severity of food insecurity. From item response theory models, the subconstructs reflected in the HFSSM-10 and the subconstruct of social unacceptability were distinct, not falling into one dimension. Regression models confirmed that social unacceptability was distinct from the subconstructs reflected in the HFSSM-10. The social unacceptability items as a separate scale explained more (∼1%) variation in mental health than when combined with the HFSSM-10 items in a single scale, and the social unacceptability subconstruct explained more (∼1%) variation in mental health not explained by the HFSSM-10. CONCLUSIONS: Two social unacceptability items used as a separate scale along with the HFSSM-10 predicted mental health more accurately than did the HFSSM-10 alone.

The menopause-related gut microbiome: associations with metabolomics, inflammatory protein markers, and cardiometabolic health in women with HIV.

OBJECTIVE: This study aimed to identify menopause-related gut microbial features, as well as their related metabolites and inflammatory protein markers, and link with cardiometabolic risk factors in women with and without HIV. METHODS: In the Women's Interagency HIV Study, we performed shotgun metagenomic sequencing on 696 stool samples from 446 participants (67% women with HIV), and quantified plasma metabolomics and serum proteomics in a subset (~86%). We examined the associations of menopause (postmenopausal vs premenopausal) with gut microbial features in a cross-sectional repeated-measures design and further evaluated those features in relation to metabolites, proteins, and cardiometabolic risk factors. RESULTS: Different overall gut microbial composition was observed by menopausal status in women with HIV only. We identified a range of gut microbial features that differed between postmenopausal and premenopausal women with HIV (but none in women without HIV), including abundance of 32 species and functional potentials involving 24 enzymatic reactions and lower ß-glucuronidase bacterial gene ortholog. Specifically, highly abundant species Faecalibacterium prausnitzii , Bacteroides species CAG:98 , and Bifidobacterium adolescentis were depleted in postmenopausal versus premenopausal women with HIV. Menopause-depleted species (mainly Clostridia ) in women with HIV were positively associated with several glycerophospholipids, while negatively associated with imidazolepropionic acid and fibroblast growth factor 21. Mediation analysis suggested that menopause may decrease plasma phosphatidylcholine plasmalogen C36:1 and C36:2 levels via reducing abundance of species F. prausnitzii and Acetanaerobacterium elongatum in women with HIV. Furthermore, waist-to-hip ratio was associated with menopause-related microbes, metabolites, and fibroblast growth factor 21 in women with HIV. CONCLUSIONS: Menopause was associated with a differential gut microbiome in women with HIV, related to metabolite and protein profiles that potentially contribute to elevated cardiometabolic risk.

Sex Hormones, the Stool Microbiome, and Subclinical Atherosclerosis in Women With and Without HIV.

CONTEXT: Cardioprotective roles of endogenous estrogens may be particularly important in women with HIV, who have reduced estrogen exposure and elevated cardiovascular disease risk. The gut microbiome metabolically interacts with sex hormones, but little is known regarding possible impact on cardiovascular risk. OBJECTIVE: To analyze potential interplay of sex hormones and gut microbiome in cardiovascular risk. METHODS: Among 197 postmenopausal women in the Women's Interagency HIV Study, we measured 15 sex hormones in serum and assessed the gut microbiome in stool. Presence of carotid artery plaque was determined (B-mode ultrasound) in a subset (n = 134). We examined associations of (i) sex hormones and stool microbiome, (ii) sex hormones and plaque, and (iii) sex hormone-related stool microbiota and plaque, adjusting for potential confounders. RESULTS: Participant median age was 58 years and the majority were living with HIV (81%). Sex hormones (estrogens, androgens, and adrenal precursors) were associated with stool microbiome diversity and specific species, similarly in women with and without HIV. Estrogens were associated with higher diversity, higher abundance of species from Alistipes, Collinsella, Erysipelotrichia, and Clostridia, and higher abundance of microbial ß-glucuronidase and aryl-sulfatase orthologs, which are involved in hormone metabolism. Several hormones were associated with lower odds of carotid artery plaque, including dihydrotestosterone, 3α-diol-17G, estradiol, and estrone. Exploratory mediation analysis suggested that estrone-related species, particularly from Collinsella, may mediate the protective association of estrone with plaque. CONCLUSION: Serum sex hormones are significant predictors of stool microbiome diversity and composition. The gut microbiome may play a role in estrogen-related cardiovascular protection.

Life course history of physical and sexual abuse is associated with cardiovascular disease risk among women living with and without HIV.

OBJECTIVE: Sexual and physical abuse predict cardiovascular disease (CVD) among women in the general population. Women living with HIV (WLWH) report more abuse and have higher CVD risk compared with other women, yet associations between abuse history and CVD have not been considered among WLWH. This study fills this gap, and describes possible pathways linking abuse to CVD risk among WLWH and women living without HIV (WLWOH). METHODS: Using 25 years of data from the Women's Interagency HIV Study (WIHS; n  = 2734; WLWH n  = 1963; WLWOH n  = 771), we used longitudinal generalized estimating equations (GEE) to test associations between sexual and physical abuse with CVD risk. Framingham (FRS-H) and the American College of Cardiology/American Heart Association-Pooled Cohort Equation (ACC/AHA-PCE) scores were examined. Analyses were stratified by HIV-serostatus. RESULTS: Among WLWH, childhood sexual abuse was associated with higher CVD risk ( ßFRS-H  = 1.25, SE = 1.08, P  = 0.005; ßACC/AHA-PCE  = 1.14, SE = 1.07, P  = 0.04) compared with no abuse. Adulthood sexual abuse was associated with higher CVD risk for WLWH ( ßFRS-H  = 1.39, SE = 1.08, P  < 0.0001) and WLWOH ( ßFRS-H  = 1.58, SE = 1.14, P  = 0.0006). Childhood physical abuse was not associated with CVD risk for either group. Adulthood physical abuse was associated with CVD risk for WLWH ( ßFRS-H  = 1.44, SE = 1.07; P  < 0.0001, ßACC/AHA-PCE  = 1.18, SE = 1.06, P  = 0.002) and WLWOH ( ßFRS-H  = 1.68, SE = 1.12, P  < 0.0001; ßACC/AHA-PCE  = 1.24, SE = 1.11, P  = 0.03). Several pathway factors were significant, including depression, smoking, and hepatitis C infection. CONCLUSION: Life course abuse may increase CVD risk among WLWH and women at high risk of acquiring HIV. Some comorbidities help explain the associations. Assessing abuse experiences in clinical encounters may help contextualize cardiovascular risk among this vulnerable population and inform intervention.

Midlife body mass index, central adiposity and neuropsychological performance over 10 years in women living with and without HIV.

Background and objective: Observations of overweight and obesity in association with neuropsychological performance (NP) vary over the adult life course depending on baseline levels, biological sex, age, race, temporality of measurements, and other factors. Therefore, similar published analyses across cohorts are inconsistent. In our sample of women living with HIV (WLWH) and women without HIV (WWOH), we conducted comparable analyses as those published in men with and without HIV. We examined cross-sectional and longitudinal associations between body mass index (BMI) and waist circumference (WC) and NP. Methods: Four hundred thirty two 432 virologically-suppressed WLWH and 367 WWOH, ≥40 years in the Women's Interagency HIV Study (WIHS) with anthropometry and NP assessments every two years from 2009-2019 were included in the study. Demographically-adjusted T-scores were calculated for six NP domains: learning, memory, executive function, processing speed, attention and working memory, and motor function. Multivariable linear regression models stratified by HIV status were used to examine cross-sectional associations of BMI and WC by NP domain; repeated measures analyses assessed baseline BMI and WC in association with longitudinal change in NP. Covariates included sociodemographic, behavioral, and HIV-related characteristics. Results: At baseline among all women, the median age was 45 years, 65% were Non-Latinx Black women, and 45% were obese women. Obese WLWH (BMI≥30.0 kg/m2) had poorer executive function (ß=-2.27, 95%CI [-4.46, -0.07]) versus WLWH with healthy BMI (18.5-24.9 kg/m2). Longitudinally over ~8 years, obese versus overweight WWOH improved on memory (ß=2.19, 95%CI [0.13, 4.26]), however overweight versus healthy WWOH experienced declining memory (ß= -2.67, 95%CI [-5.40, -0.07]). Increasing WC was associated with declining executive, processing speed, and motor function (p's<0.05); an at-risk WC was associated with improved memory (ß=1.81, 95%CI [0.19, 3.44]) among WWOH. Among WLWH, increasing BMI was associated with improved learning (ß=0.07, 95%CI [0.00, 0.15]. Conclusion: Our cross-sectional and longitudinal analyses evaluating the associations of BMI and WC and NP were mixed compared to previous reports. This illustrates the importance of sociodemographic characteristics, baseline levels of exposures and outcomes, HIV status, temporality of measurements, and other factors when evaluating aging HIV epidemiology study results.

Maternal-infant interaction quality is associated with child NR3C1 CpG site methylation at 7 years of age.

OBJECTIVE: Infancy is both a critical window for hypothalamic-pituitary-adrenal (HPA) axis development, and a sensitive period for social-emotional influences. We hypothesized that the social-emotional quality of maternal-infant interactions are associated with methylation of HPA-axis gene NR3C1 later in childhood. METHODS: Using a subsample of 114 mother-infant pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC), linear regression models were created to predict variance in methylation of seven selected CpG sites from NR3C1 in whole blood at age 7 years, including the main predictor variable of the first principal component score of observed maternal-infant interaction quality (derived from the Thorpe Interaction Measure at 12 months of age) and covariates of cell-type proportion, maternal financial difficulties and marital status at 8 months postnatal, child birthweight, and sex. RESULTS: CpG site cg27122725 methylation was negatively associated with warmer, more positive maternal interaction with her infant (ß = 0.19, p = .02, q = 0.13). In sensitivity analyses, the second highest quartile of maternal behavior (neutral, hesitant behavior) was positively associated with cg12466613 methylation. The other five CpG sites were not significantly associated with maternal-infant interaction quality. CONCLUSIONS: Narrow individual variation of maternal interaction with her infant is associated with childhood methylation of two CpG sites on NR3C1 that may be particularly sensitive to environmental influences. Infancy may be a sensitive period for even small influences from the social-emotional environment on the epigenetic determinants of HPA-axis function.

Stressors and Impact of the COVID-19 Pandemic on Vulnerable Hispanic Caregivers and Children.

Psychological sequelae are important elements of the burden of disease among caregivers. Recognition of the impact of adversity and stress biomarkers is important to prevent mental health problems that affect rearing practices and child well-being. This cross-sectional study explored social determinants of health (SDoH)-mediated stressors during COVID-19 and risks for mental health problems among caregivers of children with prenatal Zika virus exposure. Twenty-five Hispanic caregivers completed surveys assessing SDoH vulnerabilities, COVID-exposures and impact, post-traumatic stress disorder (PTSD) symptomatology, and provided a hair sample for cortisol concentration (HCC). Most caregivers had low education, household income < $15,000/year, and were unemployed. Stressors included disrupted child education and specialized services, and food insecurity. While most reported PTSD symptomatology, multivariate linear regression models adjusted for the caregiver's age, education, and the child's sex, revealed that caregivers with high symptomatology had significantly lower HCC than those with low symptomatology and those with food insecurity had significantly higher HCC than participants without food insecurity. The impact of COVID-19 on daily life was characterized on average between worse and better, suggesting variability in susceptibility and coping mechanisms, with the most resilient identifying community support and spirituality resources. SDoH-mediators provide opportunities to prevent adverse mental health outcomes for caregivers and their children.

Social Determinants, Cardiovascular Disease, and Health Care Cost: A Nationwide Study in the United States Using Machine Learning.

Background Existing studies on cardiovascular diseases (CVDs) often focus on individual-level behavioral risk factors, but research examining social determinants is limited. This study applies a novel machine learning approach to identify the key predictors of county-level care costs and prevalence of CVDs (including atrial fibrillation, acute myocardial infarction, congestive heart failure, and ischemic heart disease). Methods and Results We applied the extreme gradient boosting machine learning approach to a total of 3137 counties. Data are from the Interactive Atlas of Heart Disease and Stroke and a variety of national data sets. We found that although demographic composition (eg, percentages of Black people and older adults) and risk factors (eg, smoking and physical inactivity) are among the most important predictors for inpatient care costs and CVD prevalence, contextual factors such as social vulnerability and racial and ethnic segregation are particularly important for the total and outpatient care costs. Poverty and income inequality are the major contributors to the total care costs for counties that are in nonmetro areas or have high segregation or social vulnerability levels. Racial and ethnic segregation is particularly important in shaping the total care costs for counties with low poverty rates or social vulnerability level. Demographic composition, education, and social vulnerability are consistently important across different scenarios. Conclusions The findings highlight the differences in predictors for different types of CVD cost outcomes and the importance of social determinants. Interventions directed toward areas that have been economically and socially marginalized may aid in reducing the impact of CVDs.

Childhood violence exposure and externalizing behaviors: A systematic review of the role of physiological biomarkers.

Childhood exposure to violence has been consistently linked to externalizing behaviors like delinquency and aggression. Growing evidence indicates that physiological biomarkers from the parasympathetic and sympathetic nervous systems (PNS and SNS) and hypothalamic-pituitary-adrenal (HPA) axis may moderate or mediate the relation between childhood violence exposure and externalizing behaviors. We conducted a systematic review to synthesize recent findings on physiological biomarkers as mediators and/or moderators of this association across the life course, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our search yielded 3878 articles, of which 44 met inclusion criteria (describing a total of 46 independent studies). We found consistent evidence for blunted HPA-axis reactivity as a mediator of the relation between childhood violence exposure and subsequent externalizing behaviors, and for non-reciprocal PNS/SNS activation as moderators exacerbating this relation. However, the results of the majority of included studies that demonstrated significant moderating effects of physiological biomarkers varied by participant sex, type of childhood violence exposure, and type of stimuli used to induce physiological reactivity. The observed mixed findings are consistent with some theories that emphasize that both high and low stress reactivity can be adaptive depending on one's early environment. These findings highlight the need for systematic explorations of heterogeneity, theory-driven research questions, and longitudinal studies that span multiple developmental periods and multiple biological systems. Clinical implications include the need to assess physiological biomarkers in treatment and intervention studies and the potential to target interventions based on both autonomic functioning and environmental contexts.

Developmental Origins of Pregnancy-Related Morbidity and Mortality in Black U.S. Women.

In the US, Black women are at disproportionate risk for pregnancy-related morbidity and mortality (PRMM). Disparities in PRMM have been tied to elevated rates of obstetric cardiometabolic complications for Black women. Research seeking to elucidate the determinants of Black PRMM to date have focused predominantly on risk factors occurring during pregnancy (e.g., health risk behaviors, quantity and quality of prenatal care, provider behaviors, and attitudes). Meanwhile, other research investigating the developmental origins of health and disease (DOHaD) model indicates that the origins of adult cardiometabolic health can be traced back to stress exposures occurring during the intrauterine and early life periods. Despite the relevancy of this work to Black PRMM, the DOHaD model has never been applied to investigate the determinants of Black PRMM. We argue that the DOHaD model represents a compelling theoretical framework from which to conceptualize factors that drive racial disparities PRMM. Research and intervention working from a developmental origins orientation may help address this urgent public health crisis of Black PRMM.

Maternal depression and adverse neighbourhood conditions during pregnancy are associated with gestational epigenetic age deceleration.

Gestational epigenetic age (GEA) acceleration and deceleration can indicate developmental risk and may help elucidate how prenatal exposures lead to offspring outcomes. Depression and neighbourhood conditions during pregnancy are well-established determinants of birth and child outcomes. Emerging research suggests that maternal depression may contribute to GEA deceleration. It is unknown whether prenatal neighbourhood adversity would likewise influence GEA deceleration. This study examined whether maternal depression and neighbourhood conditions independently or jointly contributed to GEA deceleration, and which social and environmental neighbourhood conditions were associated with GEA. Participants were from the Albany Infant and Mother Study (n = 204), a prospective non-probability sampled cohort of higher risk racial/ethnic diverse mother/infant dyads. GEA was estimated from cord blood. Depressive symptoms and census-tract level neighbourhood conditions were assessed during pregnancy. Maternal depression (ß = -0.03, SE = 0.01, p = 0.008) and neighbourhood adversity (ß = -0.32, SE = 0.14, p = 0.02) were independently associated with GEA deceleration, controlling for all covariates including antidepressant use and cell type proportions. Neighbourhood adversity did not modify the association of maternal depression and GEA (ß = 0.003, SE = 0.03, p = 0.92). igher levels of neighbourhood poverty, public assistance, and lack of healthy food access were each associated with GEA deceleration; higher elementary school test scores (an indicator of community tax base) were associated with GEA acceleration (all p < 0.001). The results of this study indicated that maternal depression and neighbourhood conditions were independently and cumulatively associated GEA in this diverse population.

Early Childhood Neurodevelopmental Outcomes in Children with Prenatal Zika Virus Exposure: A Cohort Study in Puerto Rico.

OBJECTIVE: To describe anthropometric, sensory, and neurodevelopmental outcomes of children who were Zika virus-exposed from birth to 36 months. STUDY DESIGN: The study cohort included 114 children born to mothers with confirmed and probable Zika virus pregnancy infection in 2016-2017. Children attending study visits from May 2017 through February 2020 underwent physical/neurologic, sensory examinations, and neurodevelopmental assessments with the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and Ages and Stages Questionnaires, Third Edition (ASQ-3). RESULTS: Three of the 114 children (2.6%) had microcephaly (z-score for head circumference ≤-2) at birth, 19 of 35 (54.3%) had posterior eye abnormalities in retinal images, and 11 of 109 (10.1%) had nonspecific findings on brain ultrasound. Three of 107 children (2.8%) failed hearing screening at birth. Of those children with follow-up data, 17 of 97 (17.5%) failed age-appropriate vision screening. The BSID-III identified developmental delay in at least 1 domain in at least one-third of children, with higher prevalence in the language domain. ASQ-3 screen positive delay peaked at around 24 or 36 months, with some domains showing a decrease at older ages. Correlations among BSID-III and ASQ-3 scores were observed, representing professional and parental perspectives at 24 and 36 months (r = 0.32-0.78; P < .05). CONCLUSIONS: The presence of neurodevelopmental sequelae in early childhood suggests that identification of long-term impairment remains critical to attaining optimal child development. Long-term follow-up highlights vulnerability in the language domain, which likely could be influenced by early intervention, promoting cognitive development and school readiness in exposed children.

Childhood Adversity Trajectories and Violent Behaviors in Adolescence and Early Adulthood.

Violence and other antisocial behaviors, including fighting and weapon carrying, are highly prevalent among adolescents but usually decrease in young adulthood. Childhood adversities, including exposure to abuse, intimate partner violence, and household substance use and mental health problems, have been linked to violent behaviors in adolescence and adulthood. However, few studies of childhood adversity as determinants of persistent violent behavior among community-based samples have been conducted. Furthermore, the effects of adversity timing and duration on subsequent violent behaviors are unclear. We examined the association between five childhood adversity trajectories (representing stable-low, stable-mild, decreasing, increasing, and stable-high adversity from birth through age 11.5 years) and physical fighting and weapon carrying at ages 13-20 years among a sample of young adults followed continuously since birth from the Avon Longitudinal Study of Parents and Children (n = 9,665). The prevalence of violent behaviors declined sharply as participants aged (e.g., whereas 42.8% reported engaging in physical fighting in the past year at ages 13-15 years, this dropped to 10.4% at ages 17-20 years). Childhood adversity trajectories exhibited a strong dose-response relation with physical fighting and weapon carrying, with particularly pronounced relations for violent behaviors persisting across both adolescence and early adulthood (e.g., for physical fighting at both ages 13-15 years and 17-20 years compared to no fighting at either period, adjusted odds ratio [aOR] = 1.62, 95% confidence interval [CI] = 1.31-2.00 for stable-mild; aOR = 2.33, 95% CI = 1.64-3.33 for decreasing; aOR = 3.18, 95% CI = 2.20-4.60 for increasing; and aOR = 3.73, 95% CI = 2.13-6.52 for stable-high adversity, compared to stable-low adversity). This work highlights the substantial implications of exposure to childhood adversity for youth violence prevention.

Abdominal volume index trajectories and risk of diabetes mellitus: Results from the China Health and Nutrition Survey.

AIMS/INTRODUCTION: Abdominal obesity is a risk factor for developing diabetes mellitus, but trajectories of abdominal obesity over time and incident diabetes mellitus have not been considered. We derived trajectories of abdominal volume index (AVI) over 16 years of follow up, and examined the associations between AVI trajectories and risk of diabetes mellitus. MATERIALS AND METHODS: Data were used from the China Health and Nutrition Survey, and 5,267 participants were enrolled to fit the trajectory of AVI by using latent class growth models. Multivariate logistic regression models explored the relationship between different AVI trajectories and risk of diabetes mellitus. In addition, we examined the slope of the AVI trajectories in relation to age to identify appropriate life course intervention opportunities for the prevention of diabetes mellitus. RESULTS: Three trajectories were derived reflecting graded categories in the speed and slope of increase in AVI over time: slow, intermediate and fast increase group, respectively. After multivariate adjustment, the odds ratios for diabetes mellitus among those in the intermediate and fast increase groups were 1.81 (95% confidence interval 1.37-2.38, P < 0.001) and 2.80 (95% confidence interval 1.85-4.24, P < 0.001) respectively, relative to the slow increase group. The distribution of AVI slope in the slow increase group showed an inverted "U" shape, whereas the fast increase group presented a "U" shape. CONCLUSIONS: AVI trajectory is associated with an increased risk of diabetes mellitus. These results provide new insights on the relationship between abdominal adiposity and diabetes mellitus, which in turn can help improve clinical and public health intervention for diabetes mellitus prevention.

Cardiovascular risk score associations with frailty in men and women with or at risk for HIV.

OBJECTIVE: To understand the relationship between cardiovascular disease (CVD) risk and frailty among men (MWH) and women living with HIV (WWH), or at risk for HIV. DESIGN: We considered 10-year coronary heart disease and atherosclerotic CVD risk by Framingham risk score (FRS, 2001 National Cholesterol Education Program Adult Treatment Program III) and Pooled Cohort Equations (PCE, 2013 American College of Cardiology/American Heart Association) in relation to the Fried Frailty Phenotype (FFP) in the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS). METHODS: FFP was ascertained in MACS from 2004 to 2019 and in WIHS from 2005 to 2006 and 2011-2019. FFP score at least three of five components defined frailty. Repeated measures logistic regression (both cohorts) and Cox proportional hazards regression (MACS) were performed, controlled for education, income, cholesterol medication and hepatitis C virus serostatus, and among MWH and WWH, CD4+ cell count/µl, antiretroviral therapy, and HIV viral load. RESULTS: There were 5554 participants (1265 HIV seronegative/1396 MWH; 768 seronegative/1924 WWH) included. Among men, high-risk FRS was associated with increased risk of incident frailty among seronegative [adjusted hazard ratio (aHR)) = 2.12, 95% confidence interval (CI):1.22-3.69] and MWH (aHR = 2.19, 95% CI: 1.33-3.61). Similar associations were seen with high-risk PCE and incident frailty among SN (aHR = 1.88, 95% CI: 1.48-2.39) and MWH (aHR = 1.59, 95% CI: 1.26-2.00). Among women, high-risk PCE was associated with frailty in SN [adjusted odds ratio (aOR) = 1.43, 95% CI: 1.02-2.00] and WWH (aOR = 1.36, 95% CI: 1.08-1.71); however, high-risk FRS was not (seronegative: aOR = 1.03, 95% CI: 0.30-3.49; WWH: aOR = 0.86, 95% CI: 0.23-3.20). CONCLUSION: Higher CVD risk was associated with increased frailty regardless of HIV serostatus among men and women. These findings may inform clinical practices of screening for frailty.

Prenatal Lead and Depression Exposures Jointly Influence Birth Outcomes and NR3C1 DNA Methylation.

Many gestational exposures influence birth outcomes, yet the joint contribution of toxicant and psychosocial factors is understudied. Moreover, associated gestational epigenetic mechanisms are unknown. Lead (Pb) and depression independently influence birth outcomes and offspring NR3C1 (glucocorticoid receptor) DNA methylation. We hypothesized that gestational Pb and depression would jointly influence birth outcomes and NR3C1 methylation. Pregnancy exposure information, DNA methylation, and birth outcome data were collected prospectively from n = 272 mother-infant pairs. Factor analysis was used to reduce the dimensionality of NR3C1. Multivariable linear regressions tested for interaction effects between gestational Pb and depression exposures with birth outcomes and NR3C1. Interaction effects indicated that higher levels of Pb and depression jointly contributed to earlier gestations, smaller infant size at birth, and asymmetric fetal growth. Pb and depression were also jointly associated with the two primary factor scores explaining the most variability in NR3C1 methylation; NR3C1 scores were associated with some infant outcomes, including gestational age and asymmetric fetal growth. Pb and depression can cumulatively influence birth outcomes and epigenetic mechanisms, which may lay the foundation for later health risk. As toxicants and social adversities commonly co-occur, research should consider the life course consequences of these interconnected exposures.

Prenatal Exposure to Favorable Social and Environmental Neighborhood Conditions Is Associated with Healthy Pregnancy and Infant Outcomes.

Neighborhood and individual level risks commonly co-occur for pregnant women and may cumulatively contribute to birth outcomes. Moreover, the relationship between favorable social and environmental neighborhood conditions and perinatal outcomes has been understudied. This study considered the accumulated impact of prenatal exposure to positive neighborhood social, environmental, and educational conditions in relation to maternal health during pregnancy and birth size outcomes. In a prospective study of a multi-ethnic and socioeconomically diverse cohort (n = 239) of pregnant women and their infants, neighborhoods were characterized by the Child Opportunity Index (COI), a census-tract composite indicator representing favorable social, environmental, and educational community conditions. Adjusted generalized estimating equations showed that favorable neighborhood conditions promoted the growth of longer and heavier infant bodies, and reduced the risk of intrauterine growth restriction. The associations were stronger for female versus male infants, though not significantly different. Moreover, COI was associated with better maternal mental health and diet during pregnancy; diet significantly mediated the association between COI and birth size outcomes. This study underscores the importance of considering the accumulated benefit of neighborhood assets for maternal and infant health. Interventions that capitalizes on the full range of contextual assets in which mothers live may promote pregnancy health and fetal growth.