Temporal trends of concentrations of per- and polyfluoroalkyl substances among adults with overweight and obesity in the United States: Results from the Diabetes Prevention Program and NHANES.

BACKGROUND: Understanding the temporal trends and change of concentrations of per- and polyfluoroalkyl substances (PFAS) is important to evaluate the health impact of PFAS at both the individual- and population-level, however, limited information is available for pre-diabetic adults in the U.S. OBJECTIVES: Determine trends and rate of change of plasma PFAS concentrations in overweight or obese U.S. adults and evaluate variation by sex, race/ethnicity, and age. METHODS: We described temporal trends of plasma PFAS concentrations using samples collected in 1996-1998, 1999-2001, and 2011-2012 from 957 pre-diabetic adults enrolled in the Diabetes Prevention Program (DPP) trial and Outcomes Study (DPPOS) and compared to serum concentrations from the National Health and Nutrition Examination Survey (NHANES 1999-2000, 2003-2016, adults with BMI ≥ 24 kg/m2). We examined associations between participants' characteristics and PFAS concentrations and estimated the rate of change using repeated measures in DPP/DPPOS assuming a first-order elimination model. RESULTS: Longitudinal measures of PFAS concentrations in DPP/DPPOS individuals were comparable to NHANES cross-sectional populational means. Plasma concentrations of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid, perfluorohexanesulfonic acid (PFHxS), N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA), and N-methylperfluorooctane sulfonamido acetic acid (MeFOSAA) started to decline after the year 2000 and concentrations of perfluorononanoic acid (PFNA) increased after 2000 and, for NHANES, decreased after 2012. We consistently observed higher PFOS, PFHxS and PFNA among male, compared to female, and higher PFOS and PFNA among Black, compared to white, participants. The estimated time for concentrations to decrease by half ranged from 3.39 years for EtFOSAA to 17.56 years for PFHxS. DISCUSSION: We observed a downward temporal trend in plasma PFOS concentrations that was consistent with the timing for U.S. manufacturers' phaseout. Male and Black participants consistently showed higher PFOS and PFNA than female and white participants, likely due to differences in exposure patterns, metabolism or elimination kinetics.

Type I error control for cluster randomized trials under varying small sample structures.

BACKGROUND: Linear mixed models (LMM) are a common approach to analyzing data from cluster randomized trials (CRTs). Inference on parameters can be performed via Wald tests or likelihood ratio tests (LRT), but both approaches may give incorrect Type I error rates in common finite sample settings. The impact of different combinations of cluster size, number of clusters, intraclass correlation coefficient (ICC), and analysis approach on Type I error rates has not been well studied. Reviews of published CRTs find that small sample sizes are not uncommon, so the performance of different inferential approaches in these settings can guide data analysts to the best choices. METHODS: Using a random-intercept LMM stucture, we use simulations to study Type I error rates with the LRT and Wald test with different degrees of freedom (DF) choices across different combinations of cluster size, number of clusters, and ICC. RESULTS: Our simulations show that the LRT can be anti-conservative when the ICC is large and the number of clusters is small, with the effect most pronouced when the cluster size is relatively large. Wald tests with the between-within DF method or the Satterthwaite DF approximation maintain Type I error control at the stated level, though they are conservative when the number of clusters, the cluster size, and the ICC are small. CONCLUSIONS: Depending on the structure of the CRT, analysts should choose a hypothesis testing approach that will maintain the appropriate Type I error rate for their data. Wald tests with the Satterthwaite DF approximation work well in many circumstances, but in other cases the LRT may have Type I error rates closer to the nominal level.

Using a Microsimulation of Energy Balance to Explore the Influence of Prenatal Sugar-Sweetened Beverage Intake on Child BMI.

OBJECTIVE: Experiments with animals suggest that high sugar consumption during pregnancy may predispose offspring to obesity, but few human studies have examined this relationship. This study explored the association between the consumption of sugar-sweetened beverages (SSBs) during pregnancy and caloric intake through childhood. METHODS: Using cohort data on child weight, height, and physical activity levels, a lab-validated microsimulation model of energy balance was employed to infer the caloric intake of children through age 11 years. Random effects models were then employed to explore the relationships between prenatal maternal consumption and inferred caloric intake during childhood. RESULTS: An additional daily serving of SSBs during the second trimester of pregnancy was associated with an increase in child consumption of 13 kcal/d (95% CI: 1.2-26.8). Age-stratified models adjusting for maternal and child covariates suggested that this association was strongest for children aged 2.5 to 5.5 years. The consumption of SSBs during the first trimester was not found to have a consistently positive relationship to caloric intake. CONCLUSIONS: These findings suggest that SSB consumption during the second trimester of pregnancy is associated with child energy intake and may influence anthropometry in early childhood, which is consistent with and suggestive of the presence of biological causal pathways alongside likely simultaneous contributions of social and environmental influences.

Per- and polyfluoroalkyl substances and calcifications of the coronary and aortic arteries in adults with prediabetes: Results from the diabetes prevention program outcomes study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are endocrine disrupting chemicals that have been associated with cardiovascular risk factors including elevated body weight and hypercholesterolemia. Therefore, PFAS may contribute to the development of atherosclerosis and cardiovascular disease (CVD). However, no previous study has evaluated associations between PFAS exposure and arterial calcification. METHODS AND RESULTS: This study used data from 666 prediabetic adults enrolled in the Diabetes Prevention Program trial who had six PFAS quantified in plasma at baseline and two years after randomization, as well as measurements of coronary artery calcium (CAC) and ascending (AsAC) and descending (DAC) thoracic aortic calcification 13-14 years after baseline. We performed multinomial regression to test associations between PFAS and CAC categorized according to Agatston score [low (<10), moderate (11-400) and severe (>400)]. We used logistic regression to assess associations between PFAS and presence of AsAC and DAC. We adjusted models for baseline sex, age, BMI, race/ethnicity, cigarette smoking, education, treatment assignment (placebo or lifestyle intervention), and statin use. PFAS concentrations were similar to national means; 53.9% of participants had CAC > 11, 7.7% had AsAC, and 42.6% had DAC. Each doubling of the mean sum of plasma concentrations of linear and branched isomers of perfluorooctane sulfonic acid (PFOS) was associated with 1.49-fold greater odds (95% CI: 1.01, 2.21) of severe versus low CAC. This association was driven mainly by the linear (n-PFOS) isomer [1.54 (95% CI: 1.05, 2.25) greater odds of severe versus low CAC]. Each doubling of mean plasma N-ethyl-perfluorooctane sulfonamido acetic acid concentration was associated with greater odds of CAC in a dose-dependent manner [OR = 1.26 (95% CI:1.08, 1.47) for moderate CAC and OR = 1.37 (95% CI:1.07, 1.74) for severe CAC, compared to low CAC)]. Mean plasma PFOS and n-PFOS were also associated with greater odds of AsAC [OR = 1.67 (95% CI:1.10, 2.54) and OR = 1.70 (95% CI:1.13, 2.56), respectively], but not DAC. Other PFAS were not associated with outcomes. CONCLUSIONS: Prediabetic adults with higher plasma concentrations of select PFAS had higher risk of coronary and thoracic aorta calcification. PFAS exposure may be a risk factor for adverse cardiovascular health among high-risk populations.

Per- and polyfluoroalkyl substances and kidney function: Follow-up results from the Diabetes Prevention Program trial.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitously detected in populations worldwide and may hinder kidney function. The objective of the study was to determine longitudinal associations of plasma PFAS concentrations with estimated glomerular filtration rate (eGFR) and evaluate whether a lifestyle intervention modify the associations. We studied 875 participants initially randomized to the lifestyle or placebo arms in the Diabetes Prevention Program (DPP, 1996-2002) trial and Outcomes Study (DPPOS, 2002-2014). We ran generalized linear mixed models accounting a priori covariates to evaluate the associations between baseline PFAS concentrations and repeated measures of eGFR, separately, for six PFAS (PFOS, PFOA, PFHxS, EtFOSAA, MeFOSAA, PFNA); then used quantile-based g-computation to evaluate the effects of the six PFAS chemicals as a mixture. The cohort was 64.9% female; 73.4% 40-64 years-old; 29.4% with hypertension; 50.5% randomized to lifestyle intervention and 49.5% to placebo and had similar plasma PFAS concentrations as the general U.S. population in 1999-2000. Most participants had normal kidney function (eGFR > 90 mL/min/1.73 m2) over the approximately 14 years of follow-up. We found that plasma PFAS concentrations during DPP were inversely associated with eGFR during DPPOS follow-up. Each quartile increase in baseline plasma concentration of the 6 PFAS as a mixture was associated with 2.26 mL/min/1.73 m2 lower eGFR (95% CI: -4.12, -0.39) at DPPOS Year 5, approximately 9 years since DPP randomization and PFAS measurements. The lifestyle intervention did not modify associations, but inverse associations were stronger among participants with hypertension at baseline. Among prediabetic adults, we found inverse associations between baseline plasma PFAS concentrations and measures of eGFR throughout 14 years of follow-up. The lifestyle intervention of diet, exercise and behavioral changes did not modify the associations, but persons with hypertension may have heightened susceptibility.

Per- and polyfluoroalkyl substances and blood pressure in pre-diabetic adults-cross-sectional and longitudinal analyses of the diabetes prevention program outcomes study.

The relationship of plasma concentration of per- and polyfluoroalkyl substances (PFAS) with blood pressure (BP) is uncertain. This study examined cross-sectional and prospective associations of PFAS with BP and hypertension. We quantified plasma PFAS concentrations from 957 participants enrolled in the lifestyle and placebo arms of the Diabetes Prevention Program (DPP), a randomized controlled trial with approximately 15 years of follow-up. We used multivariable linear and logistic regressions to test cross-sectional associations of six PFAS, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA), N-methyl-perfluorooctane sulfonamido acetic acid (MeFOSAA), and perfluorononanoic acid (PFNA), with BP and hypertension prevalence, respectively, at baseline. We used generalized linear mixed models to estimate longitudinal associations between baseline PFAS and the rate of BP changes, and Cox-Proportional hazard models to estimate risk of developing hypertension relative to baseline PFAS. Models were adjusted for baseline age, sex, race/ethnicity, treatment arm, educational attainment, income, marital status, smoking habit, alcohol drinking, and diet. We tested for effect modification by the treatment arm and sex, and accounted for multiple comparisons using the False-Discovery Rate (FDR). PFAS concentrations and hypertension prevalence within the study population (65.3% female, 57.7% White, 65.3% aged 40-59 years) were comparable to the general U.S. population. Cross-sectionally, we found small but statistically significant associations of baseline plasma concentrations of PFOA with systolic BP (ß per doubling: 1.49 mmHg, 95% CI: 0.29, 2.70); and MeFOSAA with hypertension (RR = 1.09 per doubling, 95% CI: 1.01, 1.19). Estimates were not statistically significant after FDR adjustment. Longitudinally, we observed null associations in the placebo arm, but some inverse associations of baseline PFOS and MeFOSAA with systolic BP in the lifestyle arm, perhaps due to regression toward the mean. Baseline PFAS concentrations also were not prospectively associated with hypertension risk. Overall, there were modest and mostly null associations of plasma PFAS concentrations with BP and hypertension.

Dietary characteristics associated with plasma concentrations of per- and polyfluoroalkyl substances among adults with pre-diabetes: Cross-sectional results from the Diabetes Prevention Program Trial.

Diet is assumed to be the main source of exposure to per- and polyfluoroalkyl substances (PFAS) in non-occupationally exposed populations, but studies on the diet-PFAS relationship in the United States are scarce. We extracted multiple dietary variables, including daily intakes of food group, diet scores, and dietary patterns, from self-reported dietary data collected at baseline (1996-1999) from adults with pre-diabetes enrolled in the Diabetes Prevention Program, and used linear regression models to evaluate relationships of each dietary variable with plasma concentrations of six PFAS (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid (EtFOSAA), 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA), perfluorononanoic acid (PFNA) adjusting for covariates. Participants (N = 941, 65% female, 58% Caucasian, 68% married, 75% with higher education, 95% nonsmoker) had similar PFAS concentrations compared to the general U.S. population during 1999-2000. Using a single food group approach, fried fish, other fish/shellfish, meat and poultry had positive associations with most PFAS plasma concentrations. The strongest effect estimate detected was between fried fish and PFNA [13.6% (95% CI: 7.7, 19.9) increase in median concentration per SD increase]. Low-carbohydrate and high protein diet score had positive association with plasma PFHxS. Some food groups, mostly vegetables and fruits, and the Dietary Approaches to Stop Hypertension diet score had inverse associations with PFOS and MeFOSAA. A vegetable diet pattern was associated with lower plasma concentrations of MeFOSAA, while high-fat meat and low-fiber and high-fat grains diet patterns were associated with higher plasma concentrations of PFOS, PFHxS, MeFOSAA and PFNA. We summarized four major dietary characteristics associated with variations in PFAS plasma concentrations in this population. Specifically, consuming more meat/fish/shellfish (especially fried fish, and excluding Omega3-rich fish), low-fiber and high-fat bread/cereal/rice/pasta, and coffee/tea was associated with higher plasma concentrations while dietary patterns of vegetables, fruits and Omega-3 rich fish were associated with lower plasma concentrations of some PFAS.

Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Incident Diabetes and Microvascular Disease.

OBJECTIVE: Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are suspected endocrine disruptors widely detected across populations. We examine the extent to which PFASs are associated with diabetes incidence and microvascular disease. Secondarily, we tested whether a lifestyle intervention modifies associations and decreases concentrations. RESEARCH DESIGN AND METHODS: We analyzed data from a prospective cohort of 957 participants from the Diabetes Prevention Program (DPP) trial and Diabetes Prevention Program Outcomes Study (DPPOS). At baseline, participants were randomized to an intensive lifestyle intervention of diet, physical activity, and behavior modification or a placebo medication. We quantified plasma concentrations of six PFASs at baseline and 2 years after randomization. Participants were monitored for ∼15 years, repeatedly tested for diabetes, and evaluated for microvascular disease at the end of the follow-up. RESULTS: A doubling in baseline branched perfluorooctanoic acid concentration was associated with a 14% increase in diabetes risk for the placebo (hazard ratio [HR] 1.14, 95% CI 1.04, 1.25) but not in the lifestyle intervention group (HR 1.01, 95% CI 0.92, 1.11, P interaction = 0.11). Mean change in plasma baseline branched perfluorooctanoic acid concentration was greater for the placebo (0.96 ng/mL; 95% CI 0.71, 1.22) compared with the lifestyle intervention group (0.31 ng/mL; 95% CI 0.14, 0.48) 2 years after randomization. Each doubling in N-ethyl-perfluorooctane sulfonamido acetic acid was associated with 17% greater odds of prevalent microvascular disease (OR 1.17, 95% CI 1.05, 1.31), and a similar association was observed for perfluorodimethylhexane sulfonic acid (OR 1.18, 95% CI 1.04, 1.35), regardless of treatment. CONCLUSIONS: Some plasma PFASs were associated with diabetes and microvascular disease. Our results suggest that exercise and diet may attenuate the diabetogenic association of PFASs.

A 2017 US Reference for Singleton Birth Weight Percentiles Using Obstetric Estimates of Gestation.

OBJECTIVE: To provide an updated birth weight-for-gestational age (BW-for-GA) reference in the United States by using the most recent, nationally representative birth data with obstetric estimates of gestational age (GA). METHODS: We abstracted 3 285 552 singleton births between 22 and 42 weeks' gestation with nonmissing race and/or ethnicity, infant sex, parity, birth weight, and obstetric estimate of GA from the 2017 US natality files. We used 2 techniques (nonlinear, resistant smoothing [4253H] and lambda-mu-sigma) to derive smoothed BW-for-GA curves and compared resulting BW-for-GA cut-points at the third, 10th, 90th, and 97th percentiles with US references from 1999 to 2009. RESULTS: The smoothed BW-for-GA curves from both techniques overlapped considerably with each other, with strong agreements seen between the 2 techniques (>99% agreement; κ-statistic >0.9) for BW-for-GA cut-points at the third, 10th, 90th, and 97th percentiles across all GAs. Cut-points from 2017 using the lambda-mu-sigma method captured 9.8% to 10.2% of births <10th and >90th percentiles and 2.6% to 3.3% of births below the third and above the 97th percentile across all GAs. However, cut-points from US references in 1999 and 2009 (when GA was based on last menstrual period) captured a much larger range of proportions of 2017 births at these thresholds, especially among preterm and postterm GA categories. CONCLUSIONS: We have provided an updated BW-for-GA reference in the United States using the most recent births with obstetric estimates of GA and information to calculate continuous measures of birth size that are sex or parity specific.

Per- and polyfluoroalkyl substances and blood lipid levels in pre-diabetic adults-longitudinal analysis of the diabetes prevention program outcomes study.

Exposure to per- and polyfluoroalkyl substances (PFASs) may interfere with lipid regulation. However, most previous studies were cross-sectional with the risk of reverse causation, suggesting a need for long-term prospective studies. We examined the relationship of baseline plasma PFAS concentrations with repeated measures of blood lipids. We included 888 prediabetic adults from the Diabetes Prevention Program (DPP) and DPP Outcomes Study, who had measurements of 6 plasma PFAS concentrations at baseline (1996-1999) and repeated measures of blood lipids over 15 years of follow-up, and were initially randomized to placebo or a lifestyle intervention. We used linear regression to examine cross-sectional associations of PFAS concentrations and lipid levels at baseline, and evaluated prospective risks of hypercholesterolemia and hypertriglyceridemia using Cox proportional hazard models, and tested for effect modification by study arm. Participants (65.9% female, 57.0% White, 65.9% aged 40-59 years) had comparable PFAS concentrations [e.g., median (IQR) perfluorooctanoic acid (PFOA) 4.9 ng/mL (3.2)] with the general U.S. population in 1999-2000. We observed higher total cholesterol at baseline per doubling of PFOA (ß: 6.1 mg/dL, 95% CI: 3.1, 9.04), perfluorohexane sulfonic acid (PFHxS, ß: 2.2 mg/dL, 95% CI: 0.2, 4.3), and perfluorononanoic acid (PFNA, ß: 2.9 mg/dL, 95% CI: 0.7, 5.0). Prospectively, baseline concentrations of several PFASs, including PFOA, PFOS, PFHxS and PFNA, predicted higher risks of incident hypercholesterolemia and hypertriglyceridemia, but only in the placebo group and not the lifestyle intervention group. For example, participants in the placebo group with PFOA concentration > median (4.9 ng/mL) were almost twice as likely (HR: 1.90, 95% CI: 1.25, 2.88) to develop hypertriglyceridemia compared to those ≤median. Findings suggest adverse effects of some PFASs on lipid profiles in prediabetic adults. However, the detrimental effect was attenuated with a lifestyle intervention.

Patterns of body mass index milestones in early life and cardiometabolic risk in early adolescence.

BACKGROUND: Few studies have examined the independent and combined relationships of body mass index (BMI) peak and rebound with adiposity, insulin resistance and metabolic risk later in life. We used data from Project Viva, a well-characterized birth cohort from Boston with repeated measures of BMI, to help fill this gap. METHODS: Among 1681 children with BMI data from birth to mid childhood, we fitted individual BMI trajectories using mixed-effects models with natural cubic splines and estimated age, and magnitude of BMI, at peak (in infancy) and rebound (in early childhood). We obtained cardiometabolic measures of the children in early adolescence (median 12.9 years) and analysed their associations with the BMI parameters. RESULTS: After adjusting for potential confounders, age and magnitude at infancy BMI peak were associated with greater adolescent adiposity, and earlier adiposity rebound was strongly associated with greater adiposity, insulin resistance and metabolic risk score independently of BMI peak. Children with a normal timing of BMI peak plus early rebound had an adverse cardiometabolic profile, characterized by higher fat mass index {ß 2.2 kg/m2 [95% confidence interval (CI) 1.6, 2.9]}, trunk fat mass index [1.1 kg/m2 (0.8, 1.5)], insulin resistance [0.2 units (0.04, 0.4)] and metabolic risk score [0.4 units (0.2, 0.5)] compared with children with a normal BMI peak and a normal rebound pattern. Children without a BMI peak (no decline in BMI after the rise in infancy) also had adverse adolescent metabolic profiles. CONCLUSIONS: Early age at BMI rebound is a strong risk factor for cardiometabolic risk, independent of BMI peak. Children with a normal peak-early rebound pattern, or without any BMI decline following infancy, are at greatest risk of adverse cardiometabolic profile in adolescence. Routine monitoring of BMI may help to identify children who are at greatest risk of developing an adverse cardiometabolic profile in later life and who may be targeted for preventive interventions.

Association of Perfluoroalkyl and Polyfluoroalkyl Substances With Adiposity.

Importance: Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are ubiquitous synthetic chemicals that are suspected endocrine disruptors. Objectives: To determine the extent to which PFASs are associated with increases in weight and body size and evaluate whether a lifestyle intervention modifies this association. Design, Setting, and Participants: This prospective cohort study included 957 individuals who participated in the Diabetes Prevention Program trial, conducted from July 1996 to May 2001, and the Diabetes Prevention Program Outcomes Study, conducted from September 2002 to January 2014. Statistical analysis was conducted from September 1, 2017, to May 25, 2018. Interventions and Exposures: The initial lifestyle intervention consisted of training in diet, physical activity, and behavior modification, with the major goals of achieving 7% weight loss with subsequent maintenance and a minimum of 150 minutes per week of physical activity. Participants randomized to placebo received standard information about diet and exercise. A total of 6 plasma PFASs were quantified at baseline and 2 years after randomization, means were calculated from baseline and year 2 concentrations, and means were summed to assess total PFAS burden. Main Outcomes and Measures: Weight, waist circumference, and hip girth were measured at baseline and at scheduled visits. Results: Of the 957 participants, 625 (65.3%) were women and 731 participants (76.4%) were between 40 and 64 years of age; 481 participants were randomized to the lifestyle intervention and 476 participants were randomized to the placebo arm. The PFAS concentrations were not different by treatment arm and were similar to concentrations reported for the US population in 1999-2000. The association of PFAS and weight change differed by treatment. Each doubling in total PFAS concentration was associated with an increase of 1.80 kg (95% CI, 0.43-3.17 kg; P = .01) from baseline to 9 years after randomization for the placebo group but not the lifestyle intervention group (-0.59 kg; 95% CI, -1.80 to 0.62 kg; P = .34). Similarly, each doubling in PFAS was associated with a 1.03-cm increase in hip girth in the Diabetes Prevention Program trial for the placebo group (95% CI, 0.18-1.88 cm; P = .02) but not the lifestyle intervention group (-0.09 cm; 95% CI, -0.82 to 0.63 cm; P = .80). No associations were observed for changes in mean waist circumference. Conclusions and Relevance: Among adults at high risk for diabetes, higher plasma PFAS concentration was associated with increases in weight and hip girth over time, but a lifestyle intervention attenuated these associations. Diet and exercise may mitigate the obesogenic effects of environmental chemicals. Trial Registration: ClinicalTrials.gov Identifier: NCT00004992 and NCT00038727.

Plasma Concentrations of Per- and Polyfluoroalkyl Substances at Baseline and Associations with Glycemic Indicators and Diabetes Incidence among High-Risk Adults in the Diabetes Prevention Program Trial.

BACKGROUND: Several per- and polyfluoroalkyl substances (PFAS) are ubiquitous anthropogenic pollutants almost universally detected in humans. Experimental evidence indicates that PFAS alter glucose metabolism and insulin secretion. However, epidemiological studies have yielded inconsistent results. OBJECTIVE: We sought to examine associations between plasma PFAS concentrations, glycemic indicators, and diabetes incidence among high-risk adults. METHODS: Within the Diabetes Prevention Program (DPP), a trial for the prevention of type 2 diabetes among high-risk individuals, we quantified baseline plasma concentrations of nine PFAS among 957 participants randomized to a lifestyle intervention or placebo. We evaluated adjusted associations for plasma PFAS concentrations with diabetes incidence and key glycemic indicators measured at baseline and annually over up to 4.6 y. RESULTS: Plasma PFAS concentrations were similar to those reported in the U.S. population in 1999-2000. At baseline, in cross-sectional analysis, a doubling in plasma perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) concentrations was associated with higher homeostatic model assessment of insulin resistance (HOMA-IR) [ßPFOS=0.39; 95% confidence interval (CI): 0.13, 0.66; ßPFOA=0.64; 95% CI: 0.34, 0.94], ß-cell function (HOMA-ß) (ßPFOS=9.62; 95% CI: 1.55, 17.70; ßPFOA=15.93; 95% CI: 6.78, 25.08), fasting proinsulin (ßPFOS=1.37 pM; 95% CI: 0.50, 2.25; ßPFOA=1.71 pM; 95% CI: 0.72, 2.71), and glycated hemoglobin (HbA1c) (ßPFOS=0.03%; 95% CI: 0.002, 0.07; ßPFOA=0.04%; 95% CI: 0.001, 0.07). There was no strong evidence of associations between plasma PFAS concentrations and diabetes incidence or prospective changes in glycemic indicators during the follow-up period. CONCLUSIONS: At baseline, several PFAS were cross-sectionally associated with small differences in markers of insulin secretion and ß-cell function. However, there was limited evidence suggesting that PFAS concentrations are associated with diabetes incidence or changes in glycemic indicators during the follow-up period. https://doi.org/10.1289/EHP1612.

Two-year follow-up of a primary care-based intervention to prevent and manage childhood obesity: the High Five for Kids study.

BACKGROUND: The obesity epidemic has spared no age group, even young infants. Most childhood obesity is incident by the age of 5 years, making prevention in preschool years a priority. OBJECTIVE: To examine 2-year changes in age- and sex-specific BMI z-scores and obesity-related behaviours among 441 of the 475 originally recruited participants in High Five for Kids, a cluster randomized controlled trial in 10 paediatric practices. METHODS: The intervention included a more intensive 1-year intervention period (four in-person visits and two phone calls) followed by a less intensive 1-year maintenance period (two in-person visits) among children who were overweight or obese and age 2-6 years at enrolment. The five intervention practices restructured care to manage these children including motivational interviewing and educational modules targeting television viewing and intakes of fast food and sugar-sweetened beverages. RESULTS: After 2 years, compared with usual care, intervention participants had similar changes in BMI z-scores (-0.04 units; 95% CI -0.14, 0.06), television viewing (-0.20 h/d; -0.49 to 0.09) and intakes of fast food (-0.09 servings/week; -0.34 to 0.17) and sugar-sweetened beverages (-0.26 servings/day; -0.67 to 0.14). CONCLUSION: High Five for Kids, a primarily clinical-based intervention, did not affect BMI z-scores or obesity-related behaviours after 2 years.

Maternal protein intake during pregnancy and linear growth in the offspring.

BACKGROUND: Observational and experimental evidence demonstrates that protein intake in infancy programs linear growth. To our knowledge, few studies have examined prenatal maternal protein intake. OBJECTIVE: Our objective was to examine associations of maternal protein intake during pregnancy with offspring linear growth. DESIGN: We analyzed data from 1961 mother-child pairs in Project Viva. We assessed first- and second-trimester diet with the use of food-frequency questionnaires and analyzed protein intake as grams per kilogram prepregnancy weight per day. We used research measures of offspring length at birth and in infancy (∼6 mo), early childhood (∼3 y), and midchildhood (∼7 y), as well as clinical growth measures obtained from after birth through midchildhood. We calculated sex-specific birth length z scores for gestational age with the use of international reference data. We used mixed models with repeated length measures to predict individual length gain velocities for birth to <6 mo and 6 mo to 7 y of age, then used these velocities as outcomes in adjusted linear regression models with maternal protein intake as the main predictor. RESULTS: Mean (range) second-trimester protein intake was 1.4 g · kg-1 · d-1 (0.3-3.1 g · kg-1 · d-1). After adjusting for maternal sociodemographics, gestational weight gain, maternal and paternal height, and (for postdelivery outcomes) child sex, gestational age, and breastfeeding duration, each 1-SD (0.36 g · kg-1 · d-1) increment in second-trimester protein intake corresponded to a -0.10 (95% CI: -0.18, -0.03) change in birth length z score, a -0.03 cm/mo (95% CI: -0.05, -0.01 cm/mo) change in slope of length growth from birth to <6mo, and a -0.09 cm/y (95% CI: -0.14, -0.05 cm/y) change in slope of length growth from 6 mo to midchildhood. Results were similar for first-trimester intake. CONCLUSIONS: In a population with relatively high protein intake during pregnancy, higher protein intake was associated with shorter offspring birth length and slower linear growth into midchildhood. Results suggest that higher protein intake during pregnancy does not increase fetal and child growth and may even reduce early length growth. Project Viva was registered at clinicaltrials.gov as NCT02820402.

The Linked CENTURY Study: linking three decades of clinical and public health data to examine disparities in childhood obesity.

BACKGROUND: Despite the need to identify the causes of disparities in childhood obesity, the existing epidemiologic studies of early life risk factors have several limitations. We report on the construction of the Linked CENTURY database, incorporating CENTURY (Collecting Electronic Nutrition Trajectory Data Using Records of Youth) Study data with birth certificates; and discuss the potential implications of combining clinical and public health data sources in examining the etiology of disparities in childhood obesity. METHODS: We linked the existing CENTURY Study, a database of 269,959 singleton children from birth to age 18 years with measured heights and weights, with each child's Massachusetts birth certificate, which captures information on their mothers' pregnancy history and detailed socio-demographic information of both mothers and fathers. RESULTS: Overall, 74.2 % were matched, resulting in 200,343 children in the Linked CENTURY Study with 1,580,597 well child visits. Among this cohort, 94.0 % (188,334) of children have some father information available on the birth certificate and 60.9 % (121,917) of children have at least one other sibling in the dataset. Using maternal race/ethnicity from the birth certificate as an indicator of children's race/ethnicity, 75.7 % of children were white, 11.6 % black, 4.6 % Hispanic, and 5.7 % Asian. Based on socio-demographic information from the birth certificate, 20.0 % of mothers were non-US born, 5.9 % smoked during pregnancy, 76.3 % initiated breastfeeding, and 11.0 % of mothers had their delivery paid for by public health insurance. Using clinical data from the CENTURY Study, 22.7 % of children had a weight-for-length ≥ 95(th) percentile between 1 and 24 months and 12.0 % of children had a body mass index ≥ 95(th) percentile at ages 5 and 17 years. CONCLUSIONS: By linking routinely-collected data sources, it is possible to address research questions that could not be answered with either source alone. Linkage between a clinical database and each child's birth certificate has created a unique dataset with nearly complete racial/ethnic and socio-demographic information from both parents, which has the potential to examine the etiology of racial/ethnic and socioeconomic disparities in childhood obesity.

Secular trends in family dinner frequency among adolescents.

BACKGROUND: Eating meals, particularly dinner, with family members has been found to be associated with improved dietary intake, lower prevalence of disordered eating behaviors, lower levels of substance abuse, and improved academic outcomes among adolescents. Limited research has examined how the frequency of family meals has changed over time. The objective of this study was to examine secular trends in family dinner frequency over a 12-year period using a large, nation-wide sample of adolescents. METHODS: Using data from two cohorts of the Growing up Today study (GUTS; n = 18,075 observations for 14,79,714 and 15 year olds), we compared family dinner frequency among 14-15-year-olds in 1996 (GUTS1) through 2008 (GUTS2) and rate of change in family dinner frequency from 1996 to 1998 (GUTS1) and 2004-2008 (GUTS2). We fit logistic models using generalized estimating equations with independence working correlation and empirical variance to account for correlation within individual and between siblings. RESULTS: From 1996 to 2008, the number of family dinners per week among males decreased from 5.3 to 4.6 (p = 0.04) and among females from 5.0 to 4.4 (p = 0.03). We found that the rate of decline in frequency of family meals was consistent in GUTS1 (1996-1998) and GUTS2 (2004-2008) among both males and females. CONCLUSIONS: From 1996 to 2008, frequency of family dinners decreased among adolescents. Future research should explore reasons for this decline as well as strategies to increase family meals among adolescents.

The Association between High-Deductible Health Plan Transition and Contraception and Birth Rates.

OBJECTIVE: To evaluate the association between employer-mandated enrollment into high-deductible health plans (HDHPs) and contraception and birth rates among reproductive-age women. DATA SOURCES/STUDY SETTING: Using data from 2002 to 2008, we examined 1,559 women continuously enrolled in a Massachusetts health plan for 1 year before and after an employer-mandated switch from an HMO to a HDHP, compared with 2,793 matched women contemporaneously enrolled in an HMO. STUDY DESIGN: We used an individual-level interrupted time series with comparison series design to examine level and trend changes in clinician-provided contraceptives and a differences-in-differences design to assess annual birth rates. DATA COLLECTION/EXTRACTION METHODS: Employer, plan, and member characteristics were obtained from enrollment files. Contraception and childbirth information were extracted from pharmacy and medical claims. PRINCIPAL FINDINGS: Monthly contraception rates were 19.0-24.0 percent at baseline. Level and trend changes did not differ between groups (p = .92 and p = .36, respectively). Annual birth rates declined from 57.1/1,000 to 32.7/1,000 among HDHP members and from 61.9/1,000 to 56.2/1,000 among HMO controls, a 40 percent relative reduction in odds of childbirth (odds ratio = 0.60; p = .02). CONCLUSIONS: Women who switched to HDHPs experienced a lower birth rate, which might reflect strategies to avoid childbirth-related out-of-pocket costs under HDHPs.

Infant Breastfeeding Duration and Mid-Childhood Executive Function, Behavior, and Social-Emotional Development.

OBJECTIVE: The authors aim was to examine associations of breastfeeding duration and exclusivity in infancy with executive function, behavior, and social-emotional development in mid-childhood. METHODS: The authors studied 1037 participants in Project Viva, a prebirth cohort that enrolled pregnant mothers from 1999 to 2002 and followed children for 7 to 10 years. Main exposures were: (1) duration of any breastfeeding in the first 12 months and (2) duration of exclusive breastfeeding in the first 6 months. Main outcomes were child executive function, behavior, and social-emotional development, assessed by (1) the Behavior Rating Inventory of Executive Function (BRIEF) and (2) the Strengths and Difficulties Questionnaire (SDQ), completed independently by parents and teachers. Higher scores indicate greater problems. RESULTS: In linear regression models adjusted for sociodemographics, maternal intelligence, home environment, early child care, and maternal depression, longer breastfeeding duration was not associated with substantially better executive function, behavior, or social-emotional development. For example, for each additional month of any breastfeeding, the BRIEF Global Executive Composite score (parent) was 0.10 points higher (95% confidence interval, -0.01 to 0.22) and the SDQ total difficulties score was 0.06 points higher (-0.01, 0.12). Breastfeeding duration was also not associated with BRIEF or SDQ subscales, nor was exclusive breastfeeding duration associated with any of the outcomes analyzed. CONCLUSION: Despite beneficial effects on general intelligence, longer duration of any breastfeeding or of exclusive breastfeeding was not associated with better executive function, behavior, or social-emotional development in mid-childhood.