Publications

BACKGROUND: Trial recruitment is a major determinant of study success, and participants' non-arrival at study visits represents a significant barrier to study completion. Little is known about the participant and study process characteristics associated with visit non-arrival.

OBJECTIVE: To investigate factors associated with non-arrival at initial in-person screening visits in two ongoing randomized controlled trials.

METHODS: The Groceries for Black Residents of Boston to Stop Hypertension trials (GoFresh and GoFreshRx) studied whether home-delivered, DASH-patterned groceries can reduce blood pressure among Black adults living in urban food priority areas. In this analysis, we examined sociodemographic and study-related factors associated with participant non-arrival at their initial study visit (defined as rescheduling or not showing up at all). Associations were determined using logistic regression with adjustment for age, estimated gender, and hypertension treatment status.

RESULTS: Among 2224 participants (mean age = 44.0 years, 72.5 % women), the non-arrival rate at screening visit 1 was 29.5 %. Older participants were more likely to arrive, while those with larger families and a longer duration between initial contact and visit were less likely to arrive. Participant's method of contacting the study, visit time, and season of visit were not associated with visit non-arrival.

CONCLUSION: In this large trial recruitment drive, older age, larger family size, and a longer time between initial contact and scheduled visit were associated with non-arrival at initial study visits. These factors represent potential targets for future interventions that either accommodate patient factors or intervene upon study process barriers to achieve timely recruitment goals.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) disproportionately affects Black adults and those with lower socioeconomic status in the United States. The aim of this study was to examine the associations between socioeconomic status and CKD, albuminuria/stage 1-2 CKD, and stage 3-5 CKD, and to assess differences between Black and White adults.

STUDY DESIGN: We used data from the 2017-2020 National Health and Nutrition Examination Survey. CKD was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2 based on the race-free CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation (stage 3-5 CKD) and/or a urinary albumin-creatinine ratio of >30 mg/g (albuminuria/stage 1-2 CKD).

SETTING & PARTICIPANTS: Respondents to the 2017-2020 National Health and Nutrition Examination Survey with Black or White race.

EXPOSURE: Measures of socioeconomic status (income to poverty ratio, insurance status, education, employment status, and health care access).

ANALYTICAL APPROACH: We examined the relationship between measures of socioeconomic status and CKD, albuminuria/stage 1-2 CKD, and stage 3-5 CKD using survey-weighted Poisson regressions controlling for age, sex, and medical comorbid conditions.

RESULTS: The weighted sample (N = 182,622,525) was 52.2% women and 15.5% Black, with a mean age of 49.1 years. The prevalence of CKD was 15.6% in the overall sample, 20.9% among Black adults, and 14.7% among White adults. Higher income, higher education levels, and having health insurance were associated with a lower prevalence of CKD in the overall sample and among White adults, but not among Black adults. This pattern was consistent for those with albuminuria/stage 1-2 CKD, but not for those with stage 3-5 CKD.

LIMITATIONS: This study is limited by its cross-sectional design. In addition, data were based on single measurements and thus may be less precise in estimating the prevalence of chronic disease.

CONCLUSIONS: Higher socioeconomic status was inversely associated with albuminuria/stage 1-2 CKD and CKD among White but not Black adults. Future work should investigate the mechanisms by which albuminuria/stage 1-2 CKD remains independent of socioeconomic status among Black adults.

BACKGROUND: Prenatal per- and polyfluoroalkyl substance (PFAS) exposures may influence offspring blood pressure (BP), but long-term studies in diverse populations remain limited.

METHODS: Participants were from the Boston Birth Cohort. We measured PFAS in maternal plasma collected 24 to 72 hours after delivery and extracted children's BP from medical records. We calculated age-, sex-, and height-specific BP percentiles and defined elevated BP as systolic/diastolic BP ≥90th percentile (ages 3 to <13 years) or ≥120/80 mm Hg (ages 13 to <18 years). We used adjusted mixed-effects linear and modified Poisson models to examine associations of PFAS with BP percentiles and elevated BP. We used linear spline mixed-effects models to predict BP trajectories at ages 3 to 18 years by PFAS levels.

RESULTS: We included 13 404 BP measurements from 1094 children (median follow-up: 12 years [interquartile range, 9-15 years]; 61% Black and 22% Hispanic). Overall, higher perfluorodecanoic acid (PFDeA), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUnA) were associated with higher systolic BP percentile. The associations differed by child life stage, sex, race and ethnicity. For example, associations of PFDeA with systolic BP percentile were stronger in older (β3-5y=0.40; β6-12y=1.06; β13-18y=2.55), male (βmale=1.51; βfemale=0.52), and Black (βBlack=1.75; βHispanic=0.45) children. In male children, each doubling of perfluoroheptanesulfonic acid (PFHpS) was associated with a 9% higher risk of elevated BP at ages 6 to 12 years and a 17% higher risk at 13 to 18 years, with no increased risk at 3 to 5 years. PFHpS was associated with a dose-dependent divergence in BP trajectories beginning at age 13 years.

CONCLUSIONS: Prenatal exposures to certain PFAS were associated with offspring BP, with stronger associations in adolescents, male children, and Black children. Prenatal PFAS exposures may have intergenerational, long-term, and latent hypertensive effects.

BACKGROUND: Orthostatic hypertension is an emerging risk factor for adverse events. Recent consensus statements combine an increase in blood pressure upon standing with standing hypertension, but whether these 2 components have similar risk associations with cardiovascular disease (CVD) is unknown.

METHODS: The ARIC study (Atherosclerosis Risk in Communities) measured supine and standing blood pressure during visit 1 (1987-1989). We defined systolic orthostatic increase (a rise in systolic blood pressure [SBP] ≥20 mm Hg, standing minus supine blood pressure) and elevated standing SBP (standing SBP ≥140 mm Hg) to examine the new consensus statement definition (rise in SBP ≥20 mm Hg and standing SBP ≥140 mm Hg). We used Cox regression to examine associations with incident coronary heart disease, heart failure, stroke, fatal coronary heart disease, and all-cause mortality.

RESULTS: Of 11 369 participants (56% female; 25% Black adults; mean age, 54 years) without CVD at baseline, 1.8% had systolic orthostatic increases, 20.1% had standing SBP ≥140 mm Hg, and 1.3% had systolic orthostatic increases with standing SBP ≥140 mm Hg. During up to 30 years of follow-up, orthostatic increases were not significantly associated with any of the adverse outcomes of interest, while standing SBP ≥140 mm Hg was significantly associated with all end points. In joint models comparing systolic orthostatic increases and standing SBP ≥140 mm Hg, standing SBP ≥140 mm Hg was significantly associated with a higher risk of CVD, and associations differed significantly from systolic orthostatic increases.

CONCLUSIONS: Unlike systolic orthostatic increases, standing SBP ≥140 mm Hg was strongly associated with CVD outcomes and death. These differences in CVD risk raise important concerns about combining systolic orthostatic increases and standing SBP ≥140 mm Hg in a consensus definition for orthostatic hypertension.

OBJECTIVE: There is a secular trend towards earlier age of menarche in the US and globally. Earlier age at menarche (AAM) has been associated with metabolic disorders that increase risk for preterm delivery (PTD), yet no studies in the US have investigated whether AAM influences risk of PTD. This study tested the hypothesis that AAM is associated with PTD.

DESIGN: A case-control study.

SETTING: The Boston Medical Center (BMC) in Boston, Massachusetts.

POPULATION OR SAMPLE: 8264 mother-newborn dyads enrolled at birth at BMC between 1998 and 2019, of which 2242 mothers had PTD (cases) and 6022 did not have PTD (controls).

METHODS: Multivariable-adjusted logistic regression models and restricted cubic splines were used to examine the association between AAM and risk of PTD. The combined impact of AAM and age at delivery on the risk of PTD was also examined.

MAIN OUTCOME MEASURES: Preterm delivery and gestational age (GA) was defined by maternal last menstrual period and early ultrasound documented in medical records.

RESULTS: Maternal age at delivery was 28.1 ± 6.5 years and AAM was 12.85 ± 1.86 years. Multivariable-adjusted cubic spline suggested an inverse dose-response association of AAM with odds of PTD and, consistently, a positive association with GA. A 1-year earlier AAM was associated with 5% (95% CI 2%-8%) higher odds of PTD, after adjustment for maternal year of birth, parity, maternal place of birth, education, smoking status and Mediterranean-style diet score. The association between AAM and PTD was stronger among older mothers whose age at delivery was ≥35 years.

CONCLUSIONS: Earlier AAM is associated with higher odds for PTD, and this association is stronger among women at advanced reproductive age.

INTRODUCTION: Metabolite signatures for blood pressure (BP) may reveal biomarkers, elucidate pathogenesis, and provide prevention targets for high BP. Knowledge regarding metabolites associated with BP in adolescence remains limited.

OBJECTIVES: Investigate the associations between metabolites and adolescent BP, both cross-sectionally (in early and late adolescence) and prospectively (from early to late adolescence).

METHODS: Participants are from the Project Viva prospective cohort. During the early (median: 12.8 years; N = 556) and late (median: 17.4 years; N = 501) adolescence visits, we conducted untargeted plasma metabolomic profiling and measured systolic (SBP) and diastolic BP (DBP). We used linear regression to identify metabolites cross-sectionally associated with BP at each time point, and to assess prospective associations of changes in metabolite levels from early to late adolescence with late adolescence BP. We used Weighted Gene Correlation Network Analysis and Spearman's partial correlation to identify metabolite clusters associated with BP at each time point.

RESULTS: In the linear models, higher androgenic steroid levels were consistently associated with higher SBP and DBP in early and late adolescence. A cluster of 59 metabolites, mainly composed of androgenic steroids, correlated with higher SBP and DBP in early adolescence. A cluster primarily composed of fatty acid lipids was marginally associated with higher SBP in females in late adolescence. Multiple metabolites, including those in the creatine and purine metabolism sub-pathways, were associated with higher SBP and DBP both cross-sectionally and prospectively.

CONCLUSION: Our results shed light on the potential metabolic processes and pathophysiology underlying high BP in adolescents.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) such as preeclampsia and gestational hypertension are major contributors to maternal and child morbidity and mortality. Previous studies have reported associations with selected metals and vitamins but are limited in sample size and non-prospective study designs. We evaluated prospective associations of metal mixtures with HDP and tested interactions by vitamins.

STUDY DESIGN: We measured first trimester (median = 10.1 weeks) concentrations of essential (copper, magnesium, manganese, selenium, zinc) and nonessential (arsenic, barium, cadmium, cesium, mercury, lead) metals in red blood cells (n = 1,386) and vitamins (B12 and folate) in plasma (n = 924) in Project Viva, a pre-birth US cohort. We collected diagnosis of HDP by reviewing medical records. We used multinomial logistic regression and Bayesian Kernel Machine Regression to estimate individual and joint associations of metals with HDP and interactions by vitamins, after adjusting for key covariates.

RESULTS: The majority of participants were non-Hispanic white (72.5 %), never smokers (68.5 %) with a mean (SD) age of 32.3 (4.6) years. Fifty-two (3.8 %) developed preeclampsia and 94 (6.8 %) gestational hypertension. A doubling in first trimester erythrocyte copper was associated with 78 % lower odds of preeclampsia (OR=0.22, 95 % confidence interval: 0.08, 0.60). We also observed significant associations between higher erythrocyte total arsenic and lower odds of preeclampsia (OR=0.80, 95 % CI: 0.66, 0.97) and higher vitamin B12 and increased odds of gestational hypertension (OR=1.79, 95 % CI: 1.09, 2.96), but associations were attenuated after adjustment for dietary factors. Lower levels of the overall metal mixture and essential metal mixture were associated with higher odds of preeclampsia. We found no evidence of interactions by prenatal vitamins or between metals.

CONCLUSION: Lower levels of a first-trimester essential metal mixture were associated with an increased risk of preeclampsia, primarily driven by copper. No associations were observed between other metals and HDP after adjustment for confounders and diet.

INTRODUCTION: Hair cortisol concentration (HCC) is a biomarker of long-term stress. Higher HCC is associated with higher adiposity in adults; however, associations are not well characterized in adolescents.

OBJECTIVE: To examine cross-sectional associations of HCC with adiposity in late adolescence.

METHODS: Amongst 336 non-Hispanic White participants (48.5% female, mean 17.7 years) in Project Viva, we used multivariable linear regression models, overall and sex-stratified, to estimate associations of HCC with body mass index (BMI), bioelectric impedance (BIA) percent body fat, waist circumference (WC) and dual X-ray absorptiometry-measured percent and total fat or trunk fat mass. We adjusted models for age and known predictors of adiposity.

RESULTS: Median (interquartile range) HCC was 2.1 pm/mg (1.0-4.5) and mean (SD) BMI was 23.1 kg/m2 (3.9), BIA %body fat 20.2% (9.9) and WC 80.6 cm (10.9). In adjusted models, higher HCC (per doubling) was associated with higher BMI (β = 0.19 kg/m2; 95%CI 0.00, 0.37) and BIA percent body fat (β = 0.41%; 95%CI 0.04, 0.77). We observed no evidence of effect modification by sex.

CONCLUSIONS: Higher HCC was associated with greater adiposity in late adolescence. Further research is needed to disentangle the relationship between HCC and adolescent adiposity, including the temporal direction of the relationship and sex-specific associations.

BACKGROUND: Prenatal per- and polyfluoroalkyl substance (PFAS) exposures are associated with adverse offspring health outcomes, yet the underlying pathological mechanisms are unclear. Cord blood metabolomics can identify potentially important pathways associated with prenatal PFAS exposures, providing mechanistic insights that may help explain PFAS' long-term health effects.

METHODS: The study included 590 mother-infant dyads from the Boston Birth Cohort. We measured PFAS in maternal plasma samples collected 24-72 h after delivery and metabolites in cord plasma samples. We used metabolome-wide association studies and pathway enrichment analyses to identify metabolites and pathways associated with individual PFAS, and quantile-based g-computation models to examine associations of metabolites with the PFAS mixture. We used False Discovery Rate to account for multiple comparisons.

RESULTS: We found that 331 metabolites and 18 pathways were associated with ≥ 1 PFAS, and 38 metabolites were associated with the PFAS mixture, predominantly amino acids and lipids. Amino acids such as alanine and lysine and their pathways, crucial to energy generation, biosynthesis, and bone health, were associated with PFAS and may explain PFAS' effects on fetal growth restriction. Carnitines and carnitine shuttle pathway, associated with 7 PFAS and the PFAS mixture, are involved in mitochondrial fatty acid β-oxidation, which may predispose higher risks of fetal and child growth restriction and cardiovascular diseases. Lipids, such as glycerophospholipids and their related pathway, can contribute to insulin resistance and diabetes by modulating transporters on cell membranes, participating in β-cell signaling pathways, and inducing oxidative damage. Neurotransmission-related metabolites and pathways associated with PFAS, including cofactors, precursors, and neurotransmitters, may explain the PFAS' effects on child neurodevelopment. We observed stronger associations between prenatal PFAS exposures and metabolites in males.

CONCLUSIONS: This prospective birth cohort study contributes to the limited literature on potential metabolomic perturbations for prenatal PFAS exposures. Future studies are needed to replicate our findings and link prenatal PFAS associated metabolomic perturbations to long-term child health outcomes.

IMPORTANCE: Limited access to healthy foods, resulting from residence in neighborhoods with low food access, is a public health concern. The contribution of this exposure in early life to child obesity remains uncertain.

OBJECTIVE: To examine associations of neighborhood food access during pregnancy or early childhood with child body mass index (BMI) and obesity risk.

DESIGN, SETTING, AND PARTICIPANTS: Data from cohorts participating in the US nationwide Environmental Influences on Child Health Outcomes consortium between January 1, 1994, and March 31, 2023, were used. Participant inclusion required a geocoded residential address in pregnancy (mean 32.4 gestational weeks) or early childhood (mean 4.3 years) and information on child BMI.

EXPOSURES: Residence in low-income, low-food access neighborhoods, defined as low-income neighborhoods where the nearest supermarket is more than 0.5 miles for urban areas or more than 10 miles for rural areas.

MAIN OUTCOMES AND MEASURES: BMI z score, obesity (age- and sex-specific BMI ≥95th percentile), and severe obesity (age- and sex-specific BMI ≥120% of the 95th percentile) from age 0 to 15 years.

RESULTS: Of 28 359 children (55 cohorts; 14 657 [51.7%] male and 13 702 [48.3%] female; 590 [2.2%] American Indian, Alaska Native, Native Hawaiian, or Other Pacific Islander; 1430 [5.4%] Asian; 4034 [15.3%] Black; 17 730 [67.2%] White; and 2592 [9.8%] other [unspecified] or more than 1 race; 5754 [20.9%] Hispanic and 21 838 [79.1%] non-Hispanic) with neighborhood food access data, 23.2% resided in low-income, low-food access neighborhoods in pregnancy and 24.4% in early childhood. After adjusting for individual sociodemographic characteristics, residence in low-income, low-food access (vs non-low-income, low-food access) neighborhoods in pregnancy was associated with higher BMI z scores at ages 5 years (β, 0.07; 95% CI, 0.03-0.11), 10 years (β, 0.11; 95% CI, 0.06-0.17), and 15 years (β, 0.16; 95% CI, 0.07-0.24); higher obesity risk at 5 years (risk ratio [RR], 1.37; 95% CI, 1.21-1.55), 10 years (RR, 1.71; 95% CI, 1.37-2.12), and 15 years (RR, 2.08; 95% CI, 1.53-2.83); and higher severe obesity risk at 5 years (RR, 1.21; 95% CI, 0.95-1.53), 10 years (RR, 1.54; 95% CI, 1.20-1.99), and 15 years (RR, 1.92; 95% CI, 1.32-2.80). Findings were similar for residence in low-income, low-food access neighborhoods in early childhood. These associations were robust to alternative definitions of low income and low food access and additional adjustment for prenatal characteristics associated with child obesity.

CONCLUSIONS: Residence in low-income, low-food access neighborhoods in early life was associated with higher subsequent child BMI and higher risk of obesity and severe obesity. We encourage future studies to examine whether investments in neighborhood resources to improve food access in early life would prevent child obesity.