Faculty Bibliography

Maternal immune activity during pregnancy has been associated with risk for psychiatric disorders in offspring, but less is known about its implications for children's emotional and behavioral development. This study examined whether concentrations of five cytokines assayed from prenatal serum were associated with socioeconomic status (SES) and racial disparities in their offspring's self-regulation abilities. Participants included 1,628 women in the Collaborative Perinatal Project (CPP). Seven behavioral items conceptually related to self-regulation were rated by CPP psychologists when children were 4 years old. Concentrations of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and IL-10 were assessed. Covariates included child sex and mother's age, psychiatric disorders, and medical conditions during pregnancy. There were significant SES differences in child self-regulation, with higher SES children scoring higher on self-regulation (β = .18, 95% CI [.11, .25]), but no racial differences. The concentration of IL-8 in maternal serum was associated with higher child self-regulation, β = .09, 95% CI [.02, .16]. In mediation analyses, variation in maternal IL-8 contributed to the association between family SES and child self-regulation (β = .02, 95% CI [.003, .030]), explaining about one-tenth of the SES disparities. This study suggests pregnancy as an early sensitive period and maternal immune activity as an important context for child development.

BACKGROUND:Low-income racially and ethnically diverse children are at higher risk for obesity compared with their counterparts; yet, few studies have assessed their diet quality. OBJECTIVE:The aim of the study was to evaluate the diet quality of a racially and ethnically diverse cohort of 2-year-olds using the Healthy Eating Index (HEI)-2010. METHODS:We used 24-hour dietary recall data from caregivers of toddlers (24-34 months) at 4 pediatric resident clinics that participated in the Greenlight Study to calculate compliance with the Dietary Guidelines for Americans (DGA) using total HEI score (range 0-100) and 12 component scores. RESULTS:Participants (n = 231) were mostly Hispanic (57%) or non-Hispanic black (27%) and from low-income families. Mean HEI-2010 score was 62.8 (standard deviation [SD] 10.5). Though not significant, Hispanics had the highest HEI score. Toddlers of caregivers without obesity, older than 35 years and born outside the United States had higher HEI scores. Most had high HEI component scores for dairy, fruit, and protein foods, but few achieved maximum scores, particularly for whole grains (13%), vegetables (10%), and fatty acid ratio (7%). CONCLUSIONS:Despite scores reflective of DGA recommendations for fruit, dairy and protein foods, toddlers in this diverse sample had low quality diets as measured by the HEI, driven largely by low component scores for whole grains, vegetables, and ratio of unsaturated to saturated fatty acids.

BACKGROUND AND PURPOSE:Data on the significance of combined white matter hyperintensities (WMH)/lacunar brain infarcts, and their progression over time for the prediction of stroke are scarce. We studied associations between the progression in combined measures of microvascular brain disease and risk of stroke in the ARIC study (Atherosclerosis Risk in Communities). METHODS:Prospective analysis of 907 stroke-free ARIC participants who underwent a brain magnetic resonance imaging (MRI) in 1993 to 1995, a second brain MRI in 2004 to 2006, and were subsequently followed for stroke incidence through December 31, 2017 (median [25%-75%] follow-up 12.6 [8.9-13.4] years). A combined measure of microvascular brain disease was defined at each visit and categorized by progression from first to second brain MRI as no progression; mild progression (increase of ≥1 unit in WMH grade or new lacune), and moderate progression (increase of ≥1 unit in WMH grade and new lacune). All definite/probable ischemic or hemorrhagic incident strokes occurring after this second MRI, and through 2017, were included. Associations between microvascular brain disease, progression in the combined measures, and stroke incidence were studied with Cox proportional hazard models, adjusting for age, sex, race, education level, time from first to second MRI, body mass index, smoking, hypertension, diabetes mellitus, and coronary heart disease. RESULTS:At the second brain MRI (mean age 72), the distribution of the combined measure was 37% WMH grade <2 and no lacune; 57% WMH grade ≥2 or lacune; and 6% WMH grade ≥2 and lacune. No progression in the combined measures was observed in 38% of participants, 57% showed mild progression and 5% showed moderate progression. Sixty-four incident strokes occurred during the follow-up period. Compared with no change in the combined measure, moderate progression of microvascular brain disease was significantly associated with higher risk of stroke (adjusted hazard ratio, 3.00 [95% CI, 1.30-6.94]). CONCLUSIONS:Progression of microvascular brain disease, manifesting as both new lacunes and increase in WMHs grade, is related to substantial increase in long-term risk of stroke.

Availability of medicines for treatment of cardiovascular disease (CVD) is low in low-income and middle-income countries (LMIC). Supply chain models to improve the availability of quality CVD medicines in LMIC communities are urgently required. Our team established contextualised revolving fund pharmacies (RFPs) in rural western Kenya, whereby an initial stock of essential medicines was obtained through donations or purchase and then sold at a small mark-up price sufficient to replenish drug stock and ensure sustainability. In response to different contexts and levels of the public health system in Kenya (eg, primary versus tertiary), we developed and implemented three contextualised models of RFPs over the past decade, creating a network of 72 RFPs across western Kenya, that supplied 22 categories of CVD medicines and increased availability of essential CVD medications from <30% to 90% or higher. In one representative year, we were able to successfully supply 5 793 981 units of CVD and diabetes medicines to patients in western Kenya. The estimated programme running cost was US$6.5-25 per patient, serving as a useful benchmark for public governments to invest in medication supply chain systems in LMICs going forward. One important lesson that we have learnt from implementing three different RFP models over the past 10 years has been that each model has its own advantages and disadvantages, and we must continue to stay nimble and modify as needed to determine the optimal supply chain model while ensuring consistent access to essential CVD medications for patients living in these settings.

OBJECTIVE:The use of financial incentives to promote physical activity (PA) has grown in popularity due in part to technological advances that make it easier to track and reward PA. The purpose of this study was to update the evidence on the effects of incentives on PA in adults. DATA SOURCES/METHODS:Medline, PubMed, Embase, PsychINFO, CCTR, CINAHL and COCH. ELIGIBILITY CRITERIA/UNASSIGNED:Randomised controlled trials (RCT) published between 2012 and May 2018 examining the impact of incentives on PA. DESIGN/METHODS:A simple count of studies with positive and null effects ('vote counting') was conducted. Random-effects meta-analyses were also undertaken for studies reporting steps per day for intervention and post-intervention periods. RESULTS:23 studies involving 6074 participants were included (64.42% female, mean age = 41.20 years). 20 out of 22 studies reported positive intervention effects and four out of 18 reported post-intervention (after incentives withdrawn) benefits. Among the 12 of 23 studies included in the meta-analysis, incentives were associated with increased mean daily step counts during the intervention period (pooled mean difference (MD), 607.1; 95% CI: 422.1 to 792.1). Among the nine of 12 studies with post-intervention daily step count data incentives were associated with increased mean daily step counts (pooled MD, 513.8; 95% CI:312.7 to 714.9). CONCLUSION/CONCLUSIONS:after incentives were removed, though post-intervention 'vote counting' and pooled results did not align. Nonetheless, and contrary to what has been previously reported, these findings suggest a short-term incentive 'dose' may promote sustained PA.

BACKGROUND:Youth with type 1 diabetes (T1D) are encouraged to participate in physical activity (PA). Studies have identified fear of hypoglycemia (FOH) as a barrier to participating in PA. OBJECTIVES/OBJECTIVE:To examine (a) PA patterns in youth with T1D by age group and (b) the relationship between both parental and youth FOH and youth PA. METHODS:A cross-sectional analysis from the SEARCH cohort study visit of youth ages 10 to 17 years with T1D (n = 1129) was conducted. Linear regression models estimated the association between self-reported number of days of vigorous PA (VPA) and moderate PA (MPA) and both youth- and parent-reported FOH. Multivariable models were adjusted for age, sex, race, duration of T1D, HbA1c, use of continuous glucose monitoring (CGM), recent severe hypoglycemia, primary insulin regimen, and BMI. RESULTS:Participants were 52% female, had mean (sd) age 14.4 (4.2) years, diabetes duration 7.5 years (1.8), HbA1c 9.2% (1.7). Older youth were less likely to engage in VPA (P < .01), or sports teams (P < .01), but more likely to engage in MPA (P < .01). Higher youth FOH (behavior subscale) was associated with increased levels of VPA (β (se) 0.30 (0.11), P = .01) but not significantly associated with MPA (P = .06). There was no statistically significant association between parental FOH and youth PA. CONCLUSIONS:In SEARCH participants with T1D, VPA, and team sports participation declined with age, while MPA increased. We observed that higher scores on the youth FOH behavioral subscale were associated with increased VPA levels, suggesting that FOH may be less of a barrier to PA than previously thought.

While the incidence of geriatric trauma continues to increase, outcomes following severe blunt liver injury (BLI) are unknown. We sought to investigate independent predictors of mortality among elderly trauma patients with severe BLI. A retrospective study of the NTDB (2014-15) identified patients with isolated, high-grade BLI. Patients were stratified into two groups, non-elderly (<65 years) and elderly (≥65 years), and then two management groups: operative within 24 h of admission and non-operative. Demographics and outcomes were compared. Multivariable logistic regression was used to estimate association with mortality. A total of 1133 patients met our inclusion criteria. 107 patients required surgery and 1011 patients were managed non-operatively. Age was independently associated with mortality (AOR 1.04, p < .001). For patients <65 years, need for operative intervention was associated with a 55 times greater likelihood of death (AOR 55.1, p < .001). In patients ≥65 years, operative intervention was associated with a 122 times greater likelihood of death (AOR 122.09, p = .005). Age is independently associated with mortality in patients with high grade BLI.

OBJECTIVES/OBJECTIVE:The Nigerian Urban Reproductive Health Initiative (NURHI) was implemented in six urban sites in Nigeria from 2009 to early 2015. Under a second phase (NURHI-2), activities ceased operations in four of the original six sites in 2015 (Ilorin, Abuja, Benin City and Zaria), and continued in two sites (Kaduna and Ibadan). This paper examines the sustainability of facility-based intervention activities implemented under NURHI-1 in Ilorin and Kaduna. METHODS:A qualitative study that used in-depth interviews was conducted with 31 service providers purposively selected from 10 of the NURHI-1 intervention facilities in Ilorin and six in Kaduna. Interviews were digitally recorded and transcripts uploaded into ATLAS.ti for analysis. Structured observations to document renovations implemented during the NURHI-1 interventions were also conducted in the health facilities. RESULTS:Family planning (FP) awareness creation within the facilities and integration of FP into existing maternal and child health and HIV services, were sustained in both cities. The majority of the equipment supplied as part of the NURHI 72-hour clinic makeover were still functional in both cities. Respondents in both cities reported that FP awareness and demand were sustained. On the whole, challenges with sustaining activities were reported more among respondents in Ilorin than Kaduna. In Ilorin, NURHI outreach activities and trainings, had discontinued while in Kaduna, they were no longer being implemented to the same degree as occurred during NURHI-1. Inadequate funds was a major reason for discontinued activities in both cities while integration of FP into existing services enhanced sustainability. CONCLUSIONS:Many activities were not sustained in Ilorin compared with Kaduna although FP awareness and demand remained high in both cities. Integration of FP into existing services promoted sustainability in Ilorin and Kaduna. A gradual closeout of donor projects with concomitant input from government and indigenous institutions could be useful in sustaining donor activities.

Elevated blood pressure in childhood is an important risk factor for hypertension in adulthood. Environmental exposures have been associated with elevated blood pressure over the life course and exposure to mercury (Hg) has been linked to cardiovascular effects in adults. As subclinical vascular changes begin early in life, Hg may play a role in altered blood pressure in children. However, the evidence linking early life Hg exposure to altered blood pressure in childhood has been largely inconsistent. In the ongoing New Hampshire Birth Cohort Study, we investigated prenatal and childhood Hg exposure at multiple time points and associations with blood pressure measurements in 395 young children (mean age 5.5 years, SD 0.4). Hg exposure was measured in children's toenail clippings at age 3 and in urine at age 5-6 years, as well as in maternal toenail samples collected at ∼28 weeks gestation and 6 weeks postpartum, the latter two samples reflecting early prenatal and mid-gestation exposures, respectively. Five measurements of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were averaged for each child using a standardized technique. In covariate-adjusted linear regression analyses, we observed that a 0.1 μg/g increase in child toenail Hg at age 3 or a 0.1 μg/L urine Hg at age 5-6 were individually associated with greater DBP (toenail β: 0.53 mmHg; 95% CI: -0.02, 1.07; urine β: 0.48 mmHg; 95% CI: 0.10, 0.86) and MAP (toenail β: 0.67 mmHg; 95% CI: 0.002, 1.33; urine β: 0.55 mmHg; 95% CI: 0.10, 1.01). Neither early prenatal nor mid-gestation Hg exposure, as measured by maternal toenails, were related to any changes to child BP. Simultaneous inclusion of both child urine Hg and child toenail Hg in models suggested a potentially stronger relationship of urine Hg at age 5-6 with DBP and MAP, as compared to toenail Hg at age 3. Our findings suggest that Hg exposure during childhood is associated with alterations in BP. Childhood may be an important window of opportunity to reduce the impacts of Hg exposure on children's blood pressure, and in turn, long-term health.

BACKGROUND:Fetal growth is predictive of health later in life. Both toxic and essential metals influence fetal growth, but most studies have focused on these elements individually and used birth weight as an indicator of fetal growth. The objective of the current study was to investigate the impact of a mixture of metals on fetal size in mid-pregnancy in a predominately lower income Hispanic pregnancy cohort in Los Angeles. METHODS:For our primary analysis, we focused on six elements that have previously been associated individually with fetal size, including arsenic (As), barium (Ba), cadmium (Cd), mercury (Hg), molybdenum (Mo), and tin (Sn), measured in maternal urine samples collected in early pregnancy (median: 12.4 weeks gestation). In an exploratory analysis, we additionally included cobalt (Co), nickel (Ni), antimony (Sb), and thallium (Tl). Using covariate-adjusted Bayesian Kernel Machine Regression (BKMR) as our main mixture modeling approach, we examined the impact of these metals on fetal biometry measures obtained between 18 and 22 weeks gestation, with a focus on estimated fetal weight (EFW). RESULTS: = 0.03). In an exploratory analysis accounting for a larger mixture of metals, Mo and Ba consistently contributed most to associations with EFW. An inverse association was also identified between Sb and EFW. CONCLUSIONS:Our results suggest that Mo may promote fetal growth, while Ba and Sb may reduce fetal growth, in this population.