Faculty Bibliography

BACKGROUND:Maternal antenatal depression experienced around conception or during pregnancy may adversely affect child development. This study explores three potential mechanisms of the effects of antenatal depression on children's developmental delays at 2-3 years: gestational age of the child, continued depressive symptoms postnatally, and interrupted breastfeeding practices. METHODS:Mothers (N = 2888) of 3450 children, including 2303 singletons and 1147 multiples from the Upstate KIDS cohort provided data. Linked hospital discharge data was combined with mothers' reports to identify women with moderate to severe antenatal depression. Gestational age was extracted from birth certificates. Mothers completed a depression screener at 4 months postpartum, reported about their breastfeeding practices from 4 to 12 months postpartum, and completed a developmental delay screener when children were 24, 30, and 36 months. RESULTS:In unadjusted path analysis models, mothers with antenatal depression had more postnatal depressive symptoms and breastfed fewer months, which translated into children being more likely to have developmental delays. Gestational age was not a mediator. Effects were similar across girls and boys and singletons and twins, and largely held when adjusting for covariates. LIMITATIONS/CONCLUSIONS:Main limitations were the relatively advantaged sample and reliance on maternal report. CONCLUSIONS:Maternal antenatal depression may impact child development through continued depressive symptoms in the postpartum period and through reduced breastfeeding duration suggesting additional targets for intervention.

Knowledge on the role in cancer etiology of environmental exposures as pesticides is a pre-requisite for primary prevention. We review 62 epidemiological studies on exposure to pesticides and cancer risk in humans published from 2017 to 2021, with emphasis on new findings, methodological approaches, and gaps in the existing literature. While much of the recent evidence suggests causal relationships between pesticide exposure and cancer, the strongest evidence exists for acute myeloid leukemia (AML) and colorectal cancer (CRC), diseases in which the observed associations were consistent across several studies, including high quality prospective studies and those using biomarkers for exposure assessment, with some observing dose-response relationships. Though high-quality studies have been published since the IARC monograph on organophosphate insecticides in 2017, there are still gaps in the literature on carcinogenic evidence in humans for a large number of pesticides. To further knowledge, we suggest leveraging new techniques and methods to increase sensitivity and precision of exposure assessment, incorporate multi-omics data, and investigate more thoroughly exposure to chemical mixtures. There is also a strong need for better and larger population-based cohort studies that include younger and non-occupationally exposed individuals, particularly during developmental periods of susceptibility. Though the existing evidence has limitations, as always in science, there is sufficient evidence to implement policies and regulatory action that limit pesticide exposure in humans and, hence, further prevent a significant burden of cancers.

Background: Healthy lifestyle behaviors that can prevent adverse health outcomes, including obesity, are formed in early childhood. This study describes feeding, television, and sleep behaviors among one-year-old infants and examines differences by sociodemographic factors. Methods: Caregivers of one-year-olds presenting for well care at two clinics, control sites for the Greenlight Study, were queried about feeding, television time, and sleep. Adjusted associations between sociodemographic factors and behaviors were performed by modified Poisson (binary), multinomial logistic (multi-category), or linear (continuous) regression models. Results: Of 235 one-year-olds enrolled, 81% had Medicaid, and 45% were Hispanic, 36% non-Hispanic Black, 19% non-Hispanic White. Common behaviors included 20% exclusive bottle use, 32% put to bed with bottle, mean daily juice intake of 4.1 ± 4.6 ounces, and active television time 45 ± 73 min. In adjusted analyses compared to Hispanic caregivers, non-Hispanic Black caregivers were less likely to report exclusive bottle use (odds ratio: 0.11, 95% confidence interval [CI] 0.03"“0.39), reported 2.4 ounces more juice (95% CI 1.0"“3.9), 124 min more passive television time (95% CI 60"“188), and 37 min more active television time (95% CI 10"“64). Increased caregiver education and higher income were associated with 0.4 (95% CI 0.13"“0.66) and 0.3 (95% CI 0.06"“0.55) more servings of fruits and vegetables per day, respectively. Conclusion: In a diverse sample of one-year-olds, caregivers reported few protective behaviors that reduce the risk for adverse health outcomes including obesity. Differences in behavior by race/ethnicity, income, and education can inform future interventions and policies. Future interventions should strive to create culturally effective messaging to address common adverse health behaviors.

IMPORTANCE:Head injury is associated with significant short-term morbidity and mortality. Research regarding the implications of head injury for long-term survival in community-dwelling adults remains limited. OBJECTIVE:To evaluate the association of head injury with long-term all-cause mortality risk among community-dwelling adults, with consideration of head injury frequency and severity. DESIGN, SETTING, AND PARTICIPANTS:This cohort study included participants with and without head injury in the Atherosclerosis Risk in Communities (ARIC) study, an ongoing prospective cohort study with follow-up from 1987 through 2019 in 4 US communities in Minnesota, Maryland, North Carolina, and Mississippi. Of 15 792 ARIC participants initially enrolled, 1957 were ineligible due to self-reported head injury at baseline; 103 participants not of Black or White race and Black participants at the Minnesota and Maryland field centers were excluded due to race-site aliasing; and an additional 695 participants with missing head injury date or covariate data were excluded, resulting in 13 037 eligible participants. EXPOSURES:Head injury frequency and severity, as defined via self-report in response to interview questions and via hospital-based International Classification of Diseases diagnostic codes (with head injury severity defined in the subset of head injury cases identified using these codes). Head injury was analyzed as a time-varying exposure. MAIN OUTCOMES AND MEASURES:All-cause mortality was ascertained via linkage to the National Death Index. Data were analyzed between August 5, 2021, and October 23, 2022. RESULTS:More than one-half of participants were female (57.7%; 42.3% men), 27.9% were Black (72.1% White), and the median age at baseline was 54 years (IQR, 49-59 years). Median follow-up time was 27.0 years (IQR, 17.6-30.5 years). Head injuries occurred among 2402 participants (18.4%), most of which were classified as mild. The hazard ratio (HR) for all-cause mortality among individuals with head injury was 1.99 (95% CI, 1.88-2.11) compared with those with no head injury, with evidence of a dose-dependent association with head injury frequency (1 head injury: HR, 1.66 [95% CI, 1.56-1.77]; 2 or more head injuries: HR, 2.11 [95% CI, 1.89-2.37]) and severity (mild: HR, 2.16 [95% CI, 2.01-2.31]; moderate, severe, or penetrating: HR, 2.87 [95% CI, 2.55-3.22]). Estimates were similar by sex and race, with attenuated associations among individuals aged 54 years or older at baseline. CONCLUSIONS AND RELEVANCE:In this community-based cohort with more than 3 decades of longitudinal follow-up, head injury was associated with decreased long-term survival time in a dose-dependent manner, underscoring the importance of measures aimed at prevention and clinical interventions to reduce morbidity and mortality due to head injury.

IMPORTANCE:Despite recent growth in online redemption of Supplemental Nutrition Assistance Program (SNAP) benefits, no previous work has tested the impact of economic and behavioral economic strategies on food purchasing behaviors in an online grocery retail setting among adults with low income. OBJECTIVE:To examine the extent to which financial incentives and default shopping cart options influence fruit and vegetable purchases. DESIGN, SETTING, AND PARTICIPANTS:This randomized clinical trial used an experimental online grocery store for adults who currently or have ever received SNAP benefits. From October 7 to December 2, 2021, participants were instructed to shop for a week's worth of groceries for their household, with a budget tailored to household size; no payment was taken. INTERVENTIONS:Random assignment to 1 of 4 conditions: no intervention, 50% discount on eligible fruits and vegetables, prefilled shopping carts with tailored fruit and vegetable items (ie, default options), or a combination of the discount and default options. MAIN OUTCOMES AND MEASURES:The primary outcome was the percentage of nondiscounted dollars spent on eligible fruit and vegetables per basket. RESULTS:Of 2744 participants, mean (SD) age was 46.7 (16.0) years, and 1447 (52.7%) identified as women. A total of 1842 participants (67.1%) reported currently receiving SNAP benefits and 1492 (54.4%) reported shopping online for groceries in the previous 12 months. Participants spent a mean (SD) 20.5% (23.5%) of total dollars on eligible fruits and vegetables. Compared with no intervention, those in the discount condition spent 4.7% (98.3% CI, 1.7%-7.7%) of more total dollars on eligible fruits and vegetables; those in the default condition, 7.8% (98.3% CI, 4.8%-10.7%) more; and those in the combination condition, 13.0% (98.3% CI, 10.0%-16.0%) more (P < .001 for all). There was no difference between the discount and the default conditions (P = .06), but the effect in the combination condition was significantly larger than both discount and default conditions (P < .001). Default shopping cart items were purchased by 679 participants (93.4%) in the default condition and 655 (95.5%) in the combination condition, whereas 297 (45.8%) in the control and 361 (52.9%) in the discount conditions purchased those items (P < .001). No variation was observed by age, sex, or race and ethnicity, and results were similar when those who reported never shopping online for groceries were excluded. CONCLUSIONS AND RELEVANCE:In this randomized clinical trial, financial incentives for fruits and vegetables and default options, especially in combination, led to meaningful increases in online fruit and vegetable purchases among adults with low income. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT04766034.

Child adversity is often associated with poor quality of life in pediatric gastrointestinal disorders, including non-allergic food reactions (food intolerances), which may be improved using mind-body interventions. We conducted an observational study to (1) describe child adversity (stressors) and resilience factors in children with food intolerances, and (2) explore the association between stressors and self-reported use of integrative modalities. A retrospective chart review of children ≥4-years-old presenting to a pediatric food intolerances clinic from 2017 to 2020 was performed (n = 130). Use of integrative medicine at intake, demographic, illness, and social history data were collected. Qualitative analysis identified exposure to stressors and resilience strategies. Correlation was assessed using a chi-square test. Management of the medical condition was the most common stressor, indicating impact on quality of life. Resilience strategies included themes of self-coping and social support. Individuals with one or more stressors were more likely to be using an integrative modality (most commonly, mind-body interventions) prior to their visit (X² = 8.1, p = 0.004). Our hypothesis-generating study suggests that screening for child adversity and integrative medicine use may be used to better address quality of life and personalized approaches to treat pediatric food intolerances.

SIGNIFICANCE STATEMENT:Low muscle mass is related to frailty and increased mortality in older adults. However, muscle mass is not easily assessed in routine clinical practice. This paper describes a novel creatinine muscle index (CMI) on the basis of serum creatinine and cystatin C. CMI was moderately associated with frailty among older adults. A significantly higher proportion of individuals with weak grip strength were in the lowest tertile of CMI. The index was also associated with mortality. These results are consistent with the hypothesis that creatinine filtration may be an index of muscle mass, which may have utility in clinical practice. BACKGROUND:Low muscle mass is related to frailty and increased mortality in older adults. However, muscle mass is not easily assessed in routine clinical practice. METHODS:This study describes a novel creatinine muscle index (CMI) on the basis of serum creatinine and cystatin C in a community-based sample of older adults from the Atherosclerosis Risk in Communities Study. Analyses included 4639 participants who attended visit 5 (2011-2013) and 12,786 participants who attended visit 2 (1990-1992). CMI was defined as creatinine filtration (the product of serum creatinine times eGFR on the basis of cystatin C) and was analyzed in sex-specific tertiles. Cross-sectional associations of CMI with a frailty trichotomy, defined by the number (robust [0]/prefrail [1-2]/frail [3-5]) of five frailty components (weight loss, slowness, exhaustion, weakness, and low physical activity), were studied using polychotomous logistic regression and binary logistic regression with each frailty component. Cox regression was used to estimate associations of CMI at visit 5 and visit 2 with mortality. Models were adjusted for demographics, clinical variables, and comorbid conditions. RESULTS:CMI (tertile 1 versus 3) was moderately associated with frailty (visit 5: adjusted odds ratio 4.23 [95% confidence interval (CI), 2.02 to 8.87] in men and 2.34 [95% CI, 1.41 to 3.89] in women) and with mortality (visit 5: adjusted hazard ratio 1.45 [95% CI, 1.08 to 1.94] in men and 1.55 [95% CI, 1.13 to 2.12] in women; similar results were seen at visit 2). CONCLUSION:Lower CMI was associated with frailty and increased mortality, two clinical outcomes known to be associated with decreased muscle mass. Creatinine filtration may be an index of muscle mass and have utility in clinical practice, particularly at low levels.

SIGNIFICANCE STATEMENT:The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict 2- and 5-year risk of kidney failure in populations with eGFR <60 ml/min per 1.73 m 2 . However, the CKD-EPI 2021 creatinine equation for eGFR is now recommended for use but has not been fully tested in the context of KFRE. In 59 cohorts comprising 312,424 patients with CKD, the authors assessed the predictive performance and calibration associated with the use of the CKD-EPI 2021 equation and whether additional variables and accounting for the competing risk of death improves the KFRE's performance. The KFRE generally performed well using the CKD-EPI 2021 eGFR in populations with eGFR <45 ml/min per 1.73 m 2 and was not improved by adding the 2-year prior eGFR slope and cardiovascular comorbidities. BACKGROUND:The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict kidney failure risk in people with GFR <60 ml/min per 1.73 m 2 . METHODS:Using 59 cohorts with 312,424 patients with CKD, we tested several modifications to the KFRE for their potential to improve the KFRE: using the CKD-EPI 2021 creatinine equation for eGFR, substituting 1-year average ACR for single-measure ACR and 1-year average eGFR in participants with high eGFR variability, and adding 2-year prior eGFR slope and cardiovascular comorbidities. We also assessed calibration of the KFRE in subgroups of eGFR and age before and after accounting for the competing risk of death. RESULTS:The KFRE remained accurate and well calibrated overall using the CKD-EPI 2021 eGFR equation. The other modifications did not improve KFRE performance. In subgroups of eGFR 45-59 ml/min per 1.73 m 2 and in older adults using the 5-year time horizon, the KFRE demonstrated systematic underprediction and overprediction, respectively. We developed and tested a new model with a spline term in eGFR and incorporating the competing risk of mortality, resulting in more accurate calibration in those specific subgroups but not overall. CONCLUSIONS:The original KFRE is generally accurate for eGFR <45 ml/min per 1.73 m 2 when using the CKD-EPI 2021 equation. Incorporating competing risk methodology and splines for eGFR may improve calibration in low-risk settings with longer time horizons. Including historical averages, eGFR slopes, or a competing risk design did not meaningfully alter KFRE performance in most circumstances.