Faculty Bibliography

Fetal iron status has long-lasting effects on neurodevelopmental outcomes and risk of psychopathology. Although prenatal exposure to maternal psychological stress has been linked to offspring peripheral iron status at birth, it is unknown whether maternal prenatal stress is related to fetal brain iron during gestation. We utilized 86 multi-echo functional magnetic resonance imaging (fMRI) scans from 52 fetuses (23 females; gestational age [GA] 24-38 weeks) to estimate R2* relaxometry as a proxy for fetal brain iron levels. Our results showed that greater maternal anxiety symptoms were associated with higher estimated fetal iron levels in the left cerebellar vermis after controlling for fetal sex and GA. Our finding suggests that fetal brain iron levels may be sensitive to exposure to maternal stress in utero. In a subset of participants with available infant outcome data (n = 31), no significant associations were found between fetal brain iron levels and later cognitive, language, and motor development during infancy. Overall, this study presents the first evidence of associations between maternal prenatal stress and fetal brain iron, which lays the groundwork for future investigations of biological embedding of prenatal maternal stress on the fetal brain and later neurodevelopment through prenatal iron accumulation as a potential mechanism.

[This corrects the article DOI: 10.1016/j.lana.2024.100895.].

RATIONALE & OBJECTIVE/OBJECTIVE:Arterial stiffness is associated with prevalent chronic kidney disease (CKD). Whether arterial stiffness is prospectively associated with incident CKD is inconclusive. STUDY DESIGN/METHODS:Longitudinal cohort study. SETTING & PARTICIPANTS/METHODS:Using data from the Atherosclerosis Risk in Communities (ARIC) Study, the primary analysis included 3,161 participants without prevalent CKD at visit 5; a secondary analysis studied 4,341 participants with any estimated glomerular filtration rate (eGFR) record across visits 5 to 7. EXPOSURE/METHODS:Carotid-femoral pulse wave velocity (cfPWV), heart-femoral PWV (hfPWV), heart-ankle PWV (haPWV), brachial-ankle PWV (baPWV), heart-carotid PWV (hcPWV), and femoral-ankle PWV (faPWV). OUTCOMES/RESULTS:accompanied by >25% decline eGFR or CKD hospitalization. Secondary analysis - eGFR slope. ANALYTICAL APPROACH/METHODS:Primary analysis - Cox regression models to calculate hazard ratio (HR). Secondary analysis - multilevel mixed effects models to estimate the eGFR slope across visits. RESULTS:/year [95% CI, -0.56 to -0.33] in Q4 versus -0.37 [95% CI, -0.48 to -0.26] in Q1). All p-value <0.05. faPWV was not associated with incident CKD or eGFR slope. LIMITATIONS/CONCLUSIONS:Residual confounding. CONCLUSIONS:Greater arterial stiffness, especially higher cfPWV, hfPWV, and haPWV, was prospectively associated with a higher risk of incident CKD and faster decline in eGFR among community-dwelling older adults, supporting a pathophysiological contribution of arterial stiffness to the development of CKD.

INTRODUCTION/BACKGROUND:In 2016, California legalized cannabis for adult recreational use; after recreational sales began in 2018, it became the largest retail market worldwide. This study profiled specific risks and prevention opportunities across age groups and examined changes in medically significant child cannabis exposures before and after legalization. METHODS:Researchers conducted analyses, including interrupted time-series, to examine 1695 California Poison Control System (CPCS) reports of cannabis exposure in children 0-17 years of age, from 2010-2020. Analyses were confined to moderate and severe exposures, identified by CPCS toxicologists as requiring medical attention. RESULTS:Monthly rates of moderate/severe cannabis exposure per million children increased following legalization (β=0.06, CI [0.05, 0.08]), especially in children under 5. Fourteen percent required critical care admission. Exposures were primarily unintentional in younger children (87.7-99.2%) and intentional in adolescents (85.5%). Across all ages, most exposures occurred in the home (94.0%) and involved edible products (83.5%). An analysis of packaging on edible brands frequently cited in health records found that most could be easily mistaken for popular candies and snack foods. CONCLUSIONS:Following cannabis legalization in California, reports of child cannabis exposures requiring medical attention increased significantly. Most reported cannabis exposures occurred in the home through the ingestion of edible products, often packaged to look like popular candy and snack food brands. To prevent these harms, cannabis legalization should be accompanied by robust marketing and packaging regulations (e.g., plain labels, larger warning labels). Secondary prevention should focus on educating parents and caregivers on safe cannabis storage in the home.

In the original publication [...].

BACKGROUND:Evidence suggests prenatal phthalate exposure adversely affects children's behavior. However, epidemiological studies on alternative plasticizers remain scarce. This study investigated associations of gestational exposure to phthalates and alternative plasticizers with internalizing and externalizing behaviors in children aged 1.5-5 years. METHODS:The study included 2617 mother-child dyads from 13 Environmental influences on Child Health Outcomes (ECHO) cohorts. Maternal urine samples, primarily collected mid- to late-pregnancy, were analyzed for 27 phthalate metabolites and 6 alternative plasticizer metabolites. Based on detection frequency, metabolite concentrations were modeled either continuously or categorically (Group 1: non-detectable, 2: lower detectable, 3: higher detectable). Covariate-adjusted associations between individual metabolite concentrations and internalizing and externalizing T-scores on the Child Behavior Checklist for Ages 1½-5 were estimated using linear mixed-effects models. Effect modification by child sex was also examined. RESULTS:for MHxP Group 3 = 1.23, 95% CI: 0.35, 2.12). We observed no robust associations between phthalate metabolites and internalizing T-scores, nor between cyclohexane-1,2-dicarboxylic acid mono carboxyisooctyl ester (DINCH) metabolites and any behavioral outcomes. Child sex modified associations between several metabolites and externalizing T-scores, although the direction of effect varied by metabolite. CONCLUSION/CONCLUSIONS:This large-scale study suggests that prenatal exposure to several phthalates, but not to the alternative plasticizer DINCH, may be associated with a small-to-modest increase in externalizing behaviors in young children.

BACKGROUND:Prenatal exposure to organophosphate esters (OPEs) has been linked to neurotoxic effects in children; however, epidemiological evidence remains inconclusive. We investigated associations of prenatal OPE exposure with child behaviors. METHODS:We analyzed data of 2948 mother-child dyads from 12 prospective cohorts of the Environmental influences on Child Health Outcomes (ECHO) Cohort. Nine OPE biomarkers quantified in prenatal maternal urine were modeled based on detection frequency. Child behaviors were assessed using the Child Behavior Checklist for Ages 1½-5. We used linear mixed effects models to examine associations between each OPE biomarker and composite T-scores. We evaluated child sex and social vulnerability as potential effect modifiers. RESULTS: = -0.89, 95% CI: -1.74, -0.04). Associations between high BCPP exposure and higher externalizing and total problem T-scores were stronger among children from highly vulnerable neighborhoods compared to those from less vulnerable neighborhoods (p-interaction < 0.1). Child sex modified associations for bis(1,3-dichloro-2-propyl) phosphate and high BCPP exposure, with males exhibiting greater adverse behaviors for all associations. DISCUSSION/CONCLUSIONS:Gestational exposure to several OPEs may be adversely associated with early behavioral development.