Faculty Bibliography

BACKGROUND:Walkable neighborhoods are purported to impact a range of cardiometabolic outcomes through increased walking, but there is limited research that examines multiple cardiometabolic outcomes. Additionally, few Walk Score (a novel measure of neighborhood walkability) studies have been conducted in a European context. We evaluated associations between neighborhood Walk Score and selected cardiometabolic outcomes, including obesity, hypertension and heart rate, among adults in the Paris metropolitan area. METHODS AND RESULTS/RESULTS:We used data from the second wave of the RECORD Study on 5993 participants recruited in 2011-2014, aged 34-84 years, and residing in Paris (France). To this existing dataset, we added Walk Score values for participants' residential address. We used multilevel linear models for the continuous outcomes and modified Poisson models were used for our categorical outcomes to estimate associations between the neighborhood Walk Score (both as a continuous and categorical variable) (0-100 score) and body mass index (BMI) (weight/height2 in kg/m2), obesity (kg/m2), waist circumference (cm), systolic blood pressure (SBP) (mmHg), diastolic blood pressure (DBP) (mmHg), hypertension (mmHg), resting heart rate (RHR) (beats per minute), and neighborhood recreational walking (minutes per week). Most participants lived in Walker's Paradise (48.3%). In multivariate models (adjusted for individual variables, neighborhood variables, and risk factors for cardiometabolic outcomes), we found that neighborhood Walk Score was associated with decreased BMI (β: -0.010, 95% CI: -0.019 to -0.002 per unit increase), decreased waist circumference (β: -0.031, 95% CI: -0.054 to -0.008), increased neighborhood recreational walking (β: +0.73, 95% CI: +0.37 to +1.10), decreased SBP (β: -0.030, 95% CI: -0.063 to -0.0004), decreased DBP (β: -0.028, 95% CI: -0.047 to -0.008), and decreased resting heart rate (β: -0.026 95% CI: -0.046 to -0.005). CONCLUSIONS:In this large population-based study, we found that, even in a European context, living in a highly walkable neighborhood was associated with improved cardiometabolic health. Designing walkable neighborhoods may be a viable strategy in reducing cardiovascular disease prevalence at the population level.

BACKGROUND: Large amounts of various chemical contaminants, including perfluoroalkyl substances (PFASs), were released at the time of the World Trade Center (WTC) disaster. Thousands of children who lived and/or attended school near the disaster site were exposed to these substances but few studies have examined the possible consequences related to these exposures. OBJECTIVES: To examine the relationship of PFASs serum levels with cardiometabolic profile in children and adolescents enrolled in the World Trade Center Health Registry (WTCHR) and a matched comparison group. METHODS: We evaluated WTCHR enrollees who resided in New York City and were born between September 11, 1993 and September 10, 2001, and a matched comparison group consisting of individuals who were ineligible for WTCHR participation upon distance of their home, school or work from the WTC and lack of participation in rescue and recovery activities. Matching was based on date of birth, sex, race, ethnicity, and income. We assessed exposure to PFASs, as measured by serum levels and association with cardiometabolic profile as measured by arterial wall stiffness, body mass index, insulin resistance, fasting total cholesterol, HDL, LDL and triglycerides. RESULTS: A total of 402 participants completed the study and serum samples were analyzed from 308 participants, 123 in the WTCHR group and 185 in the comparison group. In multivariable regression analysis, after adjusting for relevant confounders, we observed a significant, positive association of perfluorooctanoic acid (PFOA) with triglycerides (beta coefficient=0.14, 95% CI: 0.02, 0.27, 15.1% change), total cholesterol (beta coefficient=0.09, 95% CI: 0.04, 0.14, 9.2% change), and LDL cholesterol (beta coefficient=0.11, 95% CI: 0.03, 0.19, 11.5% change). Perfluorohexanesulfonic acid levels were associated with decreased insulin resistance (beta coefficient=-0.09, 95% CI: -0.18, -0.003, -8.6% change); PFOA and perfluorononanoic acid were associated with increased brachial artery distensibility. CONCLUSIONS: This research adds to our knowledge of the physical health impacts in a large group of children exposed to the WTC disaster. Abnormal lipid levels in young adults might be an early marker of atherosclerosis and cardiovascular diseases and our findings highlight the importance of conducting longitudinal studies in this population.

BACKGROUND: Research of adults and school-aged children suggest a neurodevelopmental basis for psychiatric disorders. We examined whether infant neuromotor development predicted internalizing and externalizing problems in young children. METHODS: In Generation R, a population-based cohort in the Netherlands (2002-2006), trained research assistants evaluated the neuromotor development of 4006 infants aged 2 to 5 months by using an adapted version of Touwen's Neurodevelopmental Examination (tone, responses, and senses and other observations). We defined nonoptimal neuromotor development as scores in the highest tertile. Mothers and fathers rated their children's behavior at ages 1.5, 3, 6, and 10 years with the Child Behavior Checklist (n = 3474, response: 86.7%). The associations were tested with generalized linear mixed models. RESULTS: Overall, neuromotor development predicted internalizing scores, but no association was observed with externalizing scores. Nonoptimal muscle tone was associated with higher internalizing scores (mothers' report: beta = .07; 95% confidence interval [CI]: 0.01 to 0.13; fathers' report: beta = .09, 95% CI: 0.00 to 0.16). In particular, nonoptimal low muscle tone was associated with higher internalizing scores (mothers' report: beta = .11; 95% CI: 0.05 to 0.18; fathers' report: beta = .13; 95% CI: 0.04 to 0.22). We also observed an association between senses and other observations with internalizing scores. There was no relationship between high muscle tone or reflexes and internalizing scores. CONCLUSIONS: Common emotional problems in childhood have a neurodevelopmental basis in infancy. Neuromotor assessment in infancy may help identify vulnerability to early internalizing symptoms and offer the opportunity for targeted interventions.

Strong evidence now supports the notion that organophosphate pesticides damage the fetal brain and produce cognitive and behavioral dysfunction through multiple mechanisms, including thyroid disruption. A regulatory ban was proposed, but actions to end the use of one such pesticide, chlorpyrifos, in agriculture were recently stopped by the Environmental Protection Agency under false scientific pretenses. This manuscript describes the costs and consequences of this policy failure and notes how this case study is emblematic of a broader dismissal of scientific evidence and attacks on scientific norms. Scientists have a responsibility to rebut and decry these serious challenges to human health and scientific integrity.

Background: The relation between breastfeeding and early motor development is difficult to characterize because of the problems in existing studies such as incomplete control for confounding, retrospective assessment of infant feeding, and even the assessment of some motor skills too early.Objective: We sought to estimate associations between infant feeding and time to achieve major motor milestones in a US cohort.Design: The Upstate New York Infant Development Screening Program (Upstate KIDS Study) enrolled mothers who delivered live births in New York (2008-2010). Mothers of 4270 infants (boys: 51.7%) reported infant motor development at 4, 8, 12, 18, and 24 mo postpartum; information on infant feeding was reported at 4 mo. Accelerated failure time models were used to compare times to standing or walking across feeding categories while adjusting for parental characteristics, daycare, region, and infant plurality, sex, rapid weight gain, and baseline neurodevelopmental test results. Main models were stratified by preterm birth status.Results: The prevalence of exclusive breastfeeding in preterm infants was lower than in term infants at 4 mo postpartum (8% compared with 19%). After adjustment for confounders, term infants who were fed solids in addition to breast milk at 4 mo postpartum achieved both standing [acceleration factor (AF): 0.93; 95% CI: 0.87, 0.99] and walking (AF: 0.93; 95% CI: 0.88, 0.98) 7% faster than did infants who were exclusively breastfed, but these findings did not remain statistically significant after correction for multiple testing. We did not identify feeding-associated differences in motor milestone achievement in preterm infants.Conclusion: Our results suggest that differences in feeding likely do not translate into large changes in motor development. The Upstate KIDS Study was registered at clinicaltrials.gov as NCT03106493.

Adequate docosahexaenoic acid (DHA) is essential for the optimal growth and development of the fetus. Maternal DHA content fluctuates during pregnancy. The correlation of DHA content with dietary intake might be varied over the course of pregnancy. We aimed to compare the dietary DHA intake, estimated by a DHA-specific semiquantitative food frequency questionnaire (FFQ) against its blood content, among mid- and late-term pregnant women. A total of 804 Chinese pregnant women completed the tailored FFQ and provided fasting venous blood samples. Dietary DHA intake (mg/day) in the previous month was calculated from the FFQ using Chinese Food Composition Table. DHA concentrations (weight percent of total fatty acids) in plasma and erythrocytes were measured by capillary gas chromatography. Spearman correlation coefficients (r_s) between DHA intake and its relative concentrations were calculated. After adjustment for maternal age, pre-pregnancy body mass index, stage of pregnancy, parity, education level, ethnicity, and annual family income per capita, the correlation coefficients of DHA intake with its concentrations in plasma and erythrocytes were 0.35 and 0.33, respectively (p < 0.001). The correlations were relatively stronger among women in late pregnancy (r_s = 0.44 in plasma and 0.39 in erythrocytes) than those in mid-pregnancy (r_s = 0.25 and 0.26). The significant correlations were consistently observed in subgroups stratified by regions, except for erythrocytes in women living in a coastland area. Multiple regression analyses also indicated significant positive linear correlations between DHA intake and its plasma or erythrocytes concentrations (p < 0.001). In conclusion, dietary DHA intake, estimated by the FFQ, was positively correlated with its concentrations in plasma and erythrocytes in Chinese pregnant women, especially for women in late pregnancy, with the exception of the erythrocytes of those living in a coastland area.

Although the Child Behavior Checklist 1½-5's 12-item Diagnostic and Statistical Manual of Mental Disorders-Autism Spectrum Problems Scale (formerly called Pervasive Developmental Problems scale) has been used in several studies as an autism spectrum disorder screener, the base rate and stability of its items and its measurement model have not been previously studied. We therefore examined the structure, longitudinal invariance, and stability of the Child Behavior Checklist 1½-5's Diagnostic and Statistical Manual of Mental Disorders-Autism Spectrum Problems Scale in the diverse Generation R (Rotterdam) sample based on mothers' ratings at 18 months ( n = 4695), 3 years ( n = 4571), and 5 years ( n = 5752). Five items that seemed especially characteristic of autism spectrum disorder had low base rates at all three ages. The rank order of base rates for the 12 items was highly correlated over time ( Qs ⩾ 0.86), but the longitudinal stability of individual items was modest (phi coefficients = 0.15-0.34). Confirmatory factor analyses indicated that the autism spectrum disorder scale model manifested configural, metric, and scalar longitudinal invariance over the time period from 18 months to 5 years, with large factor loadings. Correlations over time for observed autism spectrum disorder scale scores (0.25-0.50) were generally lower than the correlations across time of the latent factors (0.45-0.68). Results indicated significant associations of the autism spectrum disorder scale with later autism spectrum disorder diagnoses.

BACKGROUND: Early-life exposure to bisphenol A (BPA) has been implicated to play a role in the development of obesity. OBJECTIVE: A systematic review with meta-analyses of experimental rodent studies was conducted to answer the following question: does early-life exposure to BPA affect the obesity-related outcomes body weight, fat (pad) weight, and circulating and tissue levels of triglycerides, free fatty acids (FFA), and leptin? METHODS: The methodology was prespecified in a rigorous protocol using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) approach. Using PubMed and EMBASE, we identified 61 articles that met the inclusion criteria. The risk of bias and the methodological quality of these articles were assessed using the SYRCLE Risk of Bias tool, and a confidence-rating methodology was used to score the quality of evidence. Meta-analyses were performed using random effect models and standardized mean differences (SMDs), or, where possible, mean differences (MDs) were calculated. RESULTS: Overall summary estimates indicated significant positive associations between BPA and fat weight [SMD=0.67 (95% CI: 0.53, 0.81)], triglycerides [SMD=0.97 (95% CI: 0.53, 1.40)], and FFA [SMD=0.86 (95% CI: 0.50, 1.22)], and a nonsignificant positive association with leptin levels [MD=0.37 (95% CI: -0.14, 0.87)] and a significant negative association with body weight were estimated [MD=-0.22 (95% CI: -0.37, -0.06)]. Subgroup analyses revealed stronger positive associations for most outcome measures in males and at doses below the current U.S. reference dose of 50mug/kg/d compared with doses above the reference dose. It should be noted that there was substantial heterogeneity across studies for all outcomes assessed and that there was insufficient information to assess risk of bias for most studies. CONCLUSIONS: Findings from our systematic review suggest that early-life exposure to BPA may increase adiposity and circulating lipid levels in rodents. https://doi.org/10.1289/EHP1233.

Using a population-based birth cohort in upstate New York (2008-2010), we examined the determinants of brain-derived neurotrophic factor (BDNF) measured in newborn dried blood spots (n = 2,637). We also examined the association between neonatal BDNF and children's development. The cohort was initially designed to examine the influence of infertility treatment on child development but found no impact. Mothers rated children's development in five domains repeatedly through age 3 years. Socioeconomic and maternal lifestyle determinants of BDNF were examined using multivariable linear regression models. Generalized linear mixed models estimated odds ratios for neonatal BDNF in relation to failing a developmental domain. Smoking and drinking in pregnancy, nulliparity, non-White ethnicity/race, and prepregnancy obesity were associated with lower neonatal BDNF. Neonatal BDNF was not associated with failure for developmental domains; however, there was an interaction between BDNF and preterm birth. In preterm infants, a higher BDNF was associated with lower odds of failing any developmental domains, after adjusting for confounders and infertility treatment. This result was particularly significant for failure in communication. Our findings suggest that BDNF levels in neonates may be impacted by maternal lifestyle characteristics. More specifically, lower neonatal BDNF might be an early marker of aberrant neurodevelopment in preterm infants.