Major Gaps in Understanding Dietary Supplement Use in Health and Disease.

Precise dietary assessment is critical for accurate exposure classification in nutritional research, typically aimed at understanding how diet relates to health. Dietary supplement (DS) use is widespread and represents a considerable source of nutrients. However, few studies have compared the best methods to measure DSs. Our literature review on the relative validity and reproducibility of DS instruments in the United States [e.g., product inventories, questionnaires, and 24-h dietary recalls (24HR)] identified five studies that examined validity (n = 5) and/or reproducibility (n = 4). No gold standard reference method exists for validating DS use; thus, each study's investigators chose the reference instrument used to measure validity. Self-administered questionnaires agreed well with 24HR and inventory methods when comparing the prevalence of commonly used DSs. The inventory method captured nutrient amounts more accurately than the other methods. Reproducibility (over 3 months to 2.4 years) of prevalence of use estimates on the questionnaires was acceptable for common DSs. Given the limited body of research on measurement error in DS assessment, only tentative conclusions on these DS instruments can be drawn at present. Further research is critical to advancing knowledge in DS assessment for research and monitoring purposes.

Development of a Population-Level Dichotomous Indicator of Minimum Dietary Diversity as a Proxy for Micronutrient Adequacy in Adolescents Aged 10-19 Y in the United States.

BACKGROUND: Diversity is a key component of diet quality and health, but no indicator exists for adolescents under the age of 15 y. OBJECTIVES: To establish a dichotomous indicator for population-level assessment of adolescent dietary diversity as a proxy for micronutrient adequacy. METHODS: We used the probability approach to construct mean probability of adequacy (MPA) of 11 micronutrients from 2 d of 24-h dietary recall data from NHANES, 2007-2018. For each micronutrient, probability of adequacy (PA) was calculated using the best linear unbiased predictor of usual intake. Adolescent dietary diversity score (ADDS) was derived with a maximum score of 10 food groups. Generalized linear mixed models were used to examine associations between ADDS and MPA. Receiver operating characteristic analysis was used to establish a cutoff for minimum dietary diversity for adolescents (MDD-A) using an energy-adjusted logistic model with ADDS predicting MPA > 0.6. RESULTS: PA was >80% for all nutrients except vitamin C (42.1%), folate (65.7%), and calcium (23.8%). Population MPA was 79.4%, and nearly 92% of adolescents had an MPA > 0.6. ADDS was positively associated with MPA, and energy was a significant confounder. The area under the curve was >0.8 on both days with sensitivity and specificity ranging from 0.71 to 0.80. The MDD-A cutoff was calculated as 5.12 and 5.10 food groups on days 1 and 2, respectively. CONCLUSIONS: In U.S. adolescents, the best cutoff for a dichotomous indicator of dietary diversity as a proxy for micronutrient adequacy is 6 food groups in a given day. Future research could validate MDD-A and its associated cutoff for use across country contexts.

Length of Overnight Fasting and 6-year Weight Change in the Cancer Prevention Study-3.

BACKGROUND: Longer overnight fasting (ONF) is a potential strategy for weight control. Although promising, the evidence from large population-based studies is limited. OBJECTIVES: To examine the association of self-reported ONF duration with 3- and 6-y weight change in the American Cancer Society's Cancer Prevention Study-3 prospective cohort. METHODS: United States adult Cancer Prevention Study-3 participants completed a 24-h validated meal and snack timing and frequency grid (weekday and weekend) in 2015, from which weighted ONF hours were calculated. Participants reported body weight in 2015, 2018, and 2021. Three- and 6-y weight change (kg, and % body weight) were assessed. RESULTS: Among 104,420 mostly female (78.5%) participants aged 52.7 ± 9.5 (standard deviation) y followed for 6 y, a 1-h increase in ONF length was associated with a small but statistically significant reduction in weight gain over 3- and 6-y periods [multivariable-adjusted mean difference in % body weight = -0.02, 95% confidence interval (CI): -0.05, -0.00, P = 0.03 and -0.04, 95% CI: -0.07, -0.01, P = 0.007, respectively]. The mean difference of 6-y % reduction in weight gain was slightly greater among individuals with overweight (-0.05, 95% CI: -0.10, 0.00, P = 0.05) and obesity (-0.06, 95% CI: -0.12, 0.01, P = 0.08) compared with those with healthy body mass index (-0.03, 95% CI:-0.07, 0.01, P = 0.13) or underweight (0.16, 95% CI: -0.04, 0.36, P = 0.13, Pinteraction < 0.0001). Stronger associations were observed among those ≤55 y than 56+ (Pinteraction = 0.01), and those with higher waist circumference (Pinteraction < 0.0001) but not by sex or earlier/later fasting period. CONCLUSIONS: Longer ONF was associated with slightly lower body weight in adult males and females over 6 y that was stronger among those with overweight or obesity, higher waist circumference, and those aged ≤55 y. The magnitude of weight change, although in the hypothesized direction, suggests that prolonged ONF may have modest impact on weight control over time.

Association of prenatal vitamin E levels with child asthma and wheeze.

BACKGROUND: We investigated the individual and interaction effects of maternal plasma 𝛂- and ϒ-tocopherol levels (vitamin E isomers) on child asthma and wheeze at age 8-9. METHODS: Mother-child dyads were enrolled between 2006 and 2011 into the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) prenatal cohort. Maternal second-trimester samples were analyzed for tocopherol and lipid concentrations. We assessed child asthma/wheeze using the International Study of Asthma and Allergies in Childhood (ISAAC) and other self-reported Ent wheeze. In multivariable logistic regression analyses, we assessed associations between vitamin E isomers and child asthma/wheeze outcomes (n = 847 mother-child dyads) and tested for prespecified interaction terms. RESULTS: Median cholesterol-corrected tocopherol levels (interquartile range (IQR)) were 5.0 (4.3-5.7) and 0.8 (0.7-0.9) (umol/mmol) for 𝛂- and ϒ-tocopherol, respectively. Associations between 𝛂-tocopherol and asthma outcome variables were inverse but not statistically significant. In contrast, for ϒ-tocopherol, associations were in the positive direction, but also nonsignificant. Interactions analysis between tocopherols did not reach statistical significance for any outcome. Among children of women with a history of asthma, the likelihood of ever asthma in the child appears to be decreasing with increasing maternal 𝛂-tocopherol levels, whereas this trend was not observed among those without a history of asthma (p-interaction = .05). CONCLUSION: We observed no associations for prenatal 𝛂- or ϒ-tocopherol concentrations with child asthma/wheeze. We detected some evidence of effect modification by maternal asthma history in associations between 𝛂-tocopherol and child asthma.

Alcohol consumption and prognosis and survival in breast cancer survivors: The Pathways Study.

BACKGROUND: The impact of alcohol consumption on breast cancer (BC) prognosis remains unclear. METHODS: The authors examined short-term alcohol intake in relation to recurrence and mortality in 3659 women who were diagnosed with stage I-IV BC from 2003 to 2013 in the Pathways Study. Alcohol drinking in the past 6 months was assessed at cohort entry (mean, 2 months postdiagnosis) and 6 months later using a food-frequency questionnaire. Study end points were recurrence and death from BC, cardiovascular disease, and all causes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models. RESULTS: Over an average follow-up of 11.2 years, 524 recurrences and 834 deaths (369 BC-specific and 314 cardiovascular disease-specific) occurred. Compared with nondrinkers (36.9%), drinkers were more likely younger, more educated, and current or past smokers. Overall, alcohol consumption was not associated with recurrence or mortality. However, women with higher body mass index (BMI ≥ 30 kg/m2 ) had lower risk of overall mortality with increasing alcohol consumption for occasional drinking (HR, 0.71; 95% CI, 0.54-0.94) and regular drinking (HR, 0.77; 95% CI, 0.56-1.08) around the time of diagnosis, along with 6 months later, in a dose-response manner (p < .05). Women with lower BMI (<30 kg/m2 ) were not at higher risk of mortality but were at possibly higher, yet nonsignificant, risk of recurrence for occasional drinking (HR, 1.29; 95% CI, 0.97-1.71) and regular drinking (HR, 1.19; 95% CI, 0.88-1.62). CONCLUSIONS: Alcohol drinking around the time of and up to 6 months after BC diagnosis was associated with lower risk of all-cause mortality in obese women. A possible higher risk of recurrence was observed in nonobese women.

Self-Reported Eating-Occasion Frequency and Timing are Reproducible and Relatively Valid in the American Cancer Society Cancer Prevention Study-3 Diet Assessment Substudy.

BACKGROUND: Accurate assessment of eating-occasion behaviors, such as timing, frequency, and consumption intervals, is important for evaluating associations with obesity and other chronic diseases. OBJECTIVES: The main objective of this study was to assess the relative validity of a 24-hour grid approach to assess eating-occasion timing and frequency in comparison to data derived from repeated 24-hour dietary recalls (DRs). A second objective was to assess the 1-year test-retest reproducibility of the 24-hour grid. METHODS: Between 2015 and 2016, 626 participants in the Cancer Prevention Study-3 (CPS-3) Diet Assessment Substudy (mean age, 52 years; age range, 31-70 years; 64% female; 64% non-Hispanic white, 22% non-Hispanic black, 14% Hispanic) completed 2 grids and up to 6 unannounced, telephone, interviewer-administered DRs over 1 year. Spearman correlations (ρ; 95% CIs) were calculated to assess reproducibility between the repeated eating-occasion grid-derived variables (e.g., numbers of snacks and meals per day, timing of eating occasions) and to assess relative validity by comparing the meal grid and DR-derived summary data separately for weekdays and weekend days. RESULTS: Reproducibility correlations for eating-occasion variables derived from the eating-occasion grids completed 1 year apart were ≥0.5 for the majority of variables analyzed for both weekdays and weekend days, including numbers of snacks and meals per day and timing of the first and last eating occasions of the day. Relative validity was highest among weekday variables and was ≥0.5 for the majority of variables, with correlations ranging from ρ values of 0.32 (number of meals per day) to 0.68 (hour of the first eating occasion). CONCLUSIONS: These findings suggest the eating-occasion grid used in CPS-3 has good reproducibility over 1 year and yields estimates comparable to those from a more detailed method of assessment of eating timing and frequency.

Prenatal Exposure to Mixtures of Persistent Endocrine-disrupting Chemicals and Birth Size in a Population-based Cohort of British Girls.

BACKGROUND: Previous studies of endocrine-disrupting chemicals have examined one of these chemicals at a time in association with an outcome; studying mixtures better approximates human experience. We investigated the association of prenatal exposure to mixtures of persistent endocrine disruptors (perfluoroalkyl and polyfluoroalkyl substances [PFAS], polychlorinated biphenyls [PCBs], and organochlorine pesticides) with birth size among female offspring in the Avon Longitudinal Study of Parents and Children (ALSPAC), based in the United Kingdom in 1991-1992. METHODS: We quantified concentrations of 52 endocrine-disrupting chemicals in maternal serum collected during pregnancy at median 15-week gestation. Birth weight, crown-to-heel length, and head circumference were measured at birth; ponderal index and small for gestational age were calculated from these. We used repeated holdout Weighted Quantile Sum (WQS) regression and Bayesian kernel machine regression to examine mixtures in 313 mothers. RESULTS: Using WQS regression, all mixtures (each chemical class separately and all three together) were inversely associated with birth weight. A one-unit increase in WQS index (a one-decile increase in chemical concentrations) for all three classes combined was associated with 55 g (ß = -55 g, 95% confidence interval [CI] = -89, -22 g) lower birth weight. Associations were weaker but still inverse using Bayesian kernel machine regression. Under both methods, PFAS were the most important contributors to the association with birth weight. We also observed inverse associations for crown-to-heel length. CONCLUSIONS: These results are consistent with the hypothesis that prenatal exposure to mixtures of persistent endocrine-disrupting chemicals affects birth size.

The Cancer Prevention Study-3 FFQ Is a Reliable and Valid Measure of Nutrient Intakes among Racial/Ethnic Subgroups, Compared with 24-Hour Recalls and Biomarkers.

BACKGROUND: Valid assessment of dietary intake in diverse populations is important for studies of chronic disease risk in the United States. OBJECTIVES: We evaluated the reproducibility and validity of a food frequency questionnaire (FFQ) modified for the American Cancer Society's Cancer Prevention Study-3 (CPS-3) prospective cohort, among a racially/ethnically diverse subgroup. METHODS: The Diet Assessment Substudy included 677 CPS-3 participants (64% women; 61% non-Hispanic white, 24% non-Hispanic black, 15% Hispanic), aged 31-70 y, who completed 2 FFQs 1 y apart (FFQ1, FFQ2), 4-6 telephone-administered 24-h dietary recalls (24HRs), and 2 fasting blood samples and 24-h urine collections ∼6 mo apart in the interim. Spearman rank correlation coefficients (ρ) were used to evaluate FFQ reproducibility and validity compared with 24HRs for 67 nutrient exposures. For 18 of these nutrients, we used the method of triads to calculate validity coefficients (VCs, ρ) from pairwise correlations of FFQ2, 24HRs, and biomarkers. Analyses were stratified by sex, race/ethnicity, education, and BMI. RESULTS: Mean (range) FFQ reproducibility correlations were ρ = 0.65 (0.50-0.91) for men and ρ = 0.63 (0.37-0.89) for women; mean (range) energy-adjusted, deattenuated correlations of FFQ2 with 24HRs were ρ = 0.60 (0.33-0.84) for men and ρ = 0.55 (0.21-0.79) for women. FFQ2 VCs (ρ) among men ranged from 0.42 for ß-cryptoxanthin to 0.91 for omega-3 (n-3) fatty acids and, among women, from 0.41 for sodium to 0.79 for total vitamin D. Mean FFQ reproducibility and validity were highest among whites (ρ = 0.68, ρ = 0.58, respectively) and slightly lower among blacks (ρ = 0.57, ρ = 0.49, respectively) and Hispanics (ρ = 0.59, 0.55, respectively). FFQ reproducibility and validity were slightly lower among those with less than a 4-y college degree, and those with a BMI ≥30 kg/m2. CONCLUSIONS: Reproducibility and validity of the CPS-3 FFQ were comparable with similar studies for most nutrients, among all subgroups. These findings support future dietary analyses in the contemporary CPS-3 cohort and other similar cohorts.

A novel evolutionary-concordance lifestyle score is inversely associated with all-cause, all-cancer, and all-cardiovascular disease mortality risk.

PURPOSE: Evolutionary discordance may contribute to the high burden of chronic disease-related mortality in modern industrialized nations. We aimed to investigate the associations of a 7-component, equal-weight, evolutionary-concordance lifestyle (ECL) score with all-cause and cause-specific mortality. METHODS: Baseline data were collected in 2003-2007 from 17,465 United States participants in the prospective REasons for Geographic and Racial Differences in Stroke (REGARDS) study. The ECL score's components were: a previously reported evolutionary-concordance diet score, alcohol intake, physical activity, sedentary behavior, waist circumference, smoking history, and social network size. Diet was assessed using a Block 98 food frequency questionnaire and anthropometrics by trained personnel; other information was self-reported. Higher scores indicated higher evolutionary concordance. We used multivariable Cox proportional hazards regression models to estimate ECL score-mortality associations. RESULTS: Over a median follow-up of 10.3 years, 3771 deaths occurred (1177 from cardiovascular disease [CVD], 1002 from cancer). The multivariable-adjusted hazard ratios (HR) (95% confidence intervals [CI]) for those in the highest relative to the lowest ECL score quintiles for all-cause, all-CVD, and all-cancer mortality were, respectively, 0.45 (0.40, 0.50), 0.47 (0.39, 0.58), and 0.42 (0.34, 0.52) (all P trend < 0.01). Removing smoking and diet from the ECL score attenuated the estimated ECL score-all-cause mortality association the most, yielding fifth quintile HRs (95% CIs) of 0.56 (0.50, 0.62) and 0.50 (0.46, 0.55), respectively. CONCLUSIONS: Our findings suggest that a more evolutionary-concordant lifestyle may be inversely associated with all-cause, all-CVD, and all-cancer mortality. Smoking and diet appeared to have the greatest impact on the ECL-mortality associations.

Plant food intake is associated with lower cadmium body burden in middle-aged adults.

PURPOSE: Dietary intake is a primary source of cadmium (Cd) exposure in the non-smoking population. Plant foods containing metal-binding plant compounds such as polyphenols, phytates, and phytochelatins may reduce Cd bioavailability and result in lower Cd body burden. In this study, we investigated the association between plant food intake and urinary creatinine-adjusted Cd (uCd), a well-established marker of Cd body burden. METHODS: Participants were from a cross-sectional sample of 1901 adults in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Dietary intake was assessed with a food frequency questionnaire. We created a 12-point plant food score (PFS) based on reported intake across seven categories (fruits, vegetables, legumes, nuts/seeds, whole grains, tea, and wine). Higher scores indicated higher consumption and diversity of plant food intake. Multivariable linear regression models were used to estimate the association between PFS and uCd. Due to the influence of age and smoking on Cd status, stratified analyses were conducted. RESULTS: Mean PFS was 5.4 (SD 2.2) and mean uCd was 0.53 µg/g creatinine (SD 0.39). In adjusted models, PFS was not associated with uCd (p > 0.05). In stratified analyses, PFS was inversely associated with uCd (p = 0.047) with a 1-point higher PFS associated with 0.018 µg/g lower uCd among middle-aged (45-59) adults. No significant association was observed between PFS and uCd in older (≥ 60) adults. The association of PFS and uCd did not differ by smoking status. CONCLUSION: Our findings suggest higher plant food intake is associated with lower Cd body burden in middle-aged but not older adults.

Adolescent physical activity, sedentary behavior and sleep in relation to body composition at age 18 years in urban South Africa, Birth-to-Twenty+ Cohort.

BACKGROUND: Adolescence is marked by a decline in physical activity, rapid physical growth and changes in body composition, which have been linked to body composition. Prospective data on these associations are rare, particularly in Africa. AIM: The aim of this study was to examine the association of longitudinal patterns across adolescent in physical activity, sedentary behavior and sleep, with anthropometry and body composition at age 18 years in urban South Africa. METHODS: We analyzed data from the Birth-to-Twenty Plus Cohort (Bt20+), a longitudinal study of children born in 1990 in Soweto-Johannesburg, South Africa. We used general linear models to investigate the association of adolescent (ages 12 to 18 years) longitudinal trends in physical activity, sedentary behavior and schoolnight sleep and overall physical activity patterns, with body mass index (BMI), waist circumference, fat mass index (FMI), lean mass index (LMI) and percent body fat at age 18 years. RESULTS: The final study sample included 1337 participants with anthropometric measurements (52% female) and 958 participants with body composition measurements (53% female). Males who were consistently more active and consistently walked to school over adolescence had lower waist circumference (B = - 2.0, 95% CI: - 3.9 to - 0.2), FMI (B = - 0.8, 95%: CI: - 1.2 to - 0.1) and percent body fat (B = -2.9, 95% CI: - 4.9 to - 0.9) at age 18 years than those who decreased activity and did not walk to school. Consistently-sedentary females had higher waist circumference than those whose sedentary behavior increased over adolescence (B = 5.4, 95% CI: 0.2 to 10.6). Males who reported sleeping 9 h or more per night on schoolnights had significantly lower BMI (B = -1.0, 95% CI: - 1.4 to- 0.5), and percent body fat (B = -1.5, 95%CI - 2.8 to - 0.1) than those who reported sleeping 8 h or less per night. CONCLUSION: Patterns of adolescent physical activity, sedentary behavior and sleep are related to young-adult body composition in urban South Africa. These modifiable behaviors may be paths for public health interventions to curb overweight and obesity in many low- or middle-income countries.

Prenatal polyunsaturated fatty acids and child asthma: Effect modification by maternal asthma and child sex.

BACKGROUND: Findings on prenatal polyunsaturated fatty acid (PUFA) intake and child wheeze and asthma have been inconsistent. OBJECTIVE: We sought to examine associations between prenatal PUFA status and child wheeze/asthma and modifying effects of maternal asthma/atopy, child sex, and maternal race. METHODS: Analyses included 1019 mother-child dyads with omega-3 (n-3) and omega-3 (n-6) PUFAs measured in second-trimester plasma; n-6/n-3 ratios were calculated. Child wheeze/asthma outcomes ascertained at age 4 to 6 years included ever physician-diagnosed asthma, current wheeze (symptoms past 12 months), current asthma (diagnosis and medication and/or symptoms past 12 months), and current diagnosed asthma. Each PUFA indicator and outcome was analyzed in separate models using modified Poisson regression with interaction terms. RESULTS: In quartile (Q) analyses, higher n-6 PUFAs were associated with increased risk of ever (risk ratio [RR] high vs low [RR Q4 vs Q1], 1.70; 95% CI, 1.07-2.71) and current (RR Q4 vs Q1, 1.70; 95% CI, 1.07-2.71) diagnosed asthma, whereas n-3 PUFAs were associated with lower risk (RR Q4 vs Q1, 0.59; 95% CI, 0.33-1.03) of current diagnosed asthma (Ptrend < .05 for all). Higher n-6 PUFAs were associated with a higher risk of all respiratory outcomes among children born to women with asthma (Pinteraction < .05 for all outcomes). A significant 3-way interaction between child sex, maternal asthma, and n-6/n-3 PUFA indicated that male children born to women with asthma and a higher ratio had the highest risk across wheeze/asthma outcomes (Pinteraction < .05). CONCLUSIONS: Associations between prenatal PUFA status and childhood wheeze/asthma were modified by maternal history of asthma and child sex.

The American Cancer Society Cancer Prevention Study-3 FFQ Has Reasonable Validity and Reproducibility for Food Groups and a Diet Quality Score.

BACKGROUND: FFQs are commonly used to assess dietary intake and it is important to evaluate their performance in the target population. OBJECTIVE: We evaluated the reproducibility and relative validity of the Cancer Prevention Study-3 (CPS-3) FFQ in estimating usual intake of 63 food groups and diet quality in accordance with the American Cancer Society dietary guidelines for cancer prevention. METHODS: A subset of participants from the CPS-3 (433 women, 244 men), 31-70 y of age, were included in a cross-sectional diet assessment substudy (2015-2016). Reproducibility was assessed by comparing estimates from repeat FFQs, approximately 1 y apart, using Spearman correlation coefficient (rs) and Pearson correlation coefficient (rp) correlations for food groups and diet quality, respectively. Validity was assessed similarly by comparing FFQ estimates with estimates from ≤6 interviewer-administered 24-h dietary recall (24HR). Analyses were stratified by sex and race/ethnicity. RESULTS: Reproducibility correlations for repeated FFQs were > 0.50 for 83-97% of food groups analyzed across strata of sex and race. Although participants tended to overreport plant foods (e.g., fruits and legumes) and underreport refined grains and sugar-sweetened beverages, the median energy-adjusted, deattenuated Spearman correlations comparing the second FFQ to the 24HR were 0.50 and 0.52 among men and women (range: 0.05-0.82), respectively, suggesting that ranking was preserved for most food groups. Validity was highest for coffee, alcohol, and total dairy, and lowest for pasta and regular-fat yogurt. Median validity across food groups varied by race/ethnicity and was highest among whites (rs = 0.54) followed by Hispanics (rs = 0.49) and African Americans (rs = 0.45). The diet quality score had good validity in all subgroups examined, but was higher among men (rp = 0.69) than women (rp = 0.61), and lower among whites (rp = 0.62) than Hispanics (rp = 0.64) or African Americans (rp = 0.73). CONCLUSIONS: This study indicates good reproducibility and validity of the CPS-3 FFQ for most major food groups and the diet quality score in all sex and race/ethnicity groups examined.

Development and Validation of Novel Dietary and Lifestyle Inflammation Scores.

BACKGROUND: Chronically higher inflammation, which may partly result from diet and lifestyle, is implicated in risk for multiple chronic diseases. The dietary inflammatory index (DII) and empirical dietary inflammatory pattern (EDIP), developed to characterize dietary contributions to systemic inflammation, have several limitations. There are no scores to characterize contributions of lifestyle to inflammation. OBJECTIVES: To reflect dietary/lifestyle contributions to inflammation, we developed novel, inflammation biomarker panel-weighted, dietary (DIS) and lifestyle (LIS) inflammation scores in a subset (n = 639) of the Reasons for Geographic and Racial Differences in Stroke Study (REGARDS) cohort. METHODS: We selected a priori 19 food groups and 4 lifestyle characteristics to comprise the DIS and LIS, respectively. We calculated the components' weights based on their strengths of association with an inflammation biomarker score [comprising high-sensitivity C-reactive protein (hsCRP), IL-6, IL-8, and IL-10] using multivariable linear regression. The sums of the weighted components constitute the scores, such that higher scores reflect, on balance, more proinflammatory exposures. We calculated the DIS, LIS, DII, and EDIP with cross-sectional data from the remaining REGARDS cohort (  n = 14,210 with hsCRP measurements) and 2 other study populations with hsCRP and/or an 8-component inflammation biomarker panel, and investigated their associations with circulating inflammation biomarker concentrations using multivariable logistic regression. RESULTS: In REGARDS, those in the highest relative to the lowest DIS, LIS, DII, and EDIP quintiles had statistically significant 1.66-, 4.29-, 1.56-, and 1.32-fold higher odds of a high hsCRP concentration (>3 mg/dL), respectively (all P-trend < 0.001). Those in the highest relative to the lowest joint DIS/LIS quintile had a statistically significant 7.26-fold higher odds of a high hsCRP concentration. Similar findings were noted in the other 2 validation populations. CONCLUSION: Our results support that dietary and lifestyle exposures collectively contribute substantially to systemic inflammation, and support the use of our novel DIS and LIS.

Association between in utero perfluoroalkyl substance exposure and anti-Müllerian hormone levels in adolescent females in a British cohort.

Evidence indicates that in utero environmental exposures could influence reproduction in female offspring. Perfluoroalkyl substances (PFAS) are synthetic, ubiquitous endocrine disrupting chemicals that can cross the placental barrier. Lower levels of anti-Müllerian hormone (AMH), a biomarker of ovarian reserve, are associated with reduced fertility. We investigated the association between in utero PFAS exposure and AMH levels in female adolescents using data from the Avon Longitudinal Study of Parents and Children, a British pregnancy cohort recruited between 1991 and 1992. Maternal serum samples were collected during pregnancy and analyzed for concentrations of commonly found PFAS-perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA). AMH levels were measured in serum of female offspring (mean age, 15.4 years) and log-transformed for analyses. We used a sample of 446 mother-daughter dyads for multivariable linear regression analyses, controlling for maternal age at delivery, pre-pregnancy body-mass index, and maternal education. Multiple imputation was utilized to impute missing values of AMH (61.2%) and covariates. Median PFAS concentrations (ng/mL) were as follows: PFOS 19.8 (IQR:15.1, 24.9), PFOA 3.7 (IQR: 2.8, 4.8), PFHxS 1.6 (IQR: 1.2, 2.2), PFNA 0.5 (IQR: 0.4, 0.7). The geometric mean AMH concentration was 3.9 ng/mL (95% CI: 3.8, 4.0). After controlling for confounders, mean differences in AMH per one ng/mL higher PFOA, PFOS, PFHxS, and PFNA were 3.6% (95% CI: 1.4%, 8.6%), 0.7% (95% CI: 0.2%, 1.5%), 0.9% (95% CI: 0.4%, 2.2%), and 12.0% (95% CI: 42.8%, 66.8%) respectively. These findings suggest there is no association between in utero PFAS exposure and AMH levels in female adolescents.

Dietary quality, as measured by the Alternative Healthy Eating Index for Pregnancy (AHEI-P), in couples planning their first pregnancy.

OBJECTIVE: Dietary quality (DQ), as assessed by the Alternative Healthy Eating Index for Pregnancy (AHEI-P), and conception and pregnancy outcomes were evaluated. DESIGN: In this prospective cohort study on couples planning their first pregnancy. Cox proportional hazards regression assessed the relationship between AHEI-P score and clinical pregnancy, live birth and pregnancy loss. SETTING: Participants were recruited from the Northeast region of the USA.Participants: Healthy, nulliparous couples (females, n 132; males, n 131; one male did not enrol). RESULTS: There were eighty clinical pregnancies, of which sixty-nine resulted in live births and eleven were pregnancy losses. Mean (sd) female AHEI-P was 71·0 (13·7). Of those who achieved pregnancy, those in the highest tertile of AHEI-P had the greatest proportion of clinical pregnancies; however, this association was not statistically significant (P = 0·41). When the time it took to conceive was considered, females with the highest AHEI-P scores were 20 % and 14 % more likely to achieve clinical pregnancy (model 1: hazard ratio (HR) = 1·20; 95 % CI 0·66, 2·17) and live birth (model 1: HR = 1·14; 95 % CI 0·59, 2·20), respectively. Likelihood of achieving clinical pregnancy and live birth increased when the fully adjusted model, including male AHEI-P score, was examined (clinical pregnancy model 4: HR = 1·55; 95 % CI 0·71, 3·39; live birth model 4: HR = 1·36; 95 % CI 0·59, 3·13). CONCLUSIONS: The present study is the first to examine AHEI-P score and achievement of clinical pregnancy. DQ was not significantly related to pregnancy outcomes, even after adjustments for covariates.

Longitudinal patterns of physical activity, sedentary behavior and sleep in urban South African adolescents, Birth-To-Twenty Plus cohort.

BACKGROUND: Adolescence is a critical phase of human development that lays the foundation for health in later life. Of the 1.8 billion adolescents in the world, roughly 90% live in low and middle-income countries. Yet most longitudinal studies of adolescent physical activity, sedentary behavior, and sleep come from high-income countries. There is a need for a better understanding of these behaviors to inform obesity and chronic disease prevention strategies. AIMS: The aim of this study is to identify longitudinal patterns and associations between physical activity, sedentary behavior and sleep in urban South African adolescents. METHODS: We analyzed data from the Birth-to-Twenty Plus Cohort (Bt20+), a longitudinal study of children in Soweto, Johannesburg, South Africa. Behaviors were self-reported annually between ages 12 and 17 y. We used Latent Class Growth Analysis to group participants into classes based on common longitudinal trajectories of time spent in informal physical activity, organized sports, walking to and from school, sedentary behavior, and school-night and weekend sleep, respectively. We performed group-based multi-trajectory modeling to identify latent clusters of individuals who followed similar trajectories of informal physical activity, organized sports and walking to and from school, and who followed similar trajectories of these three domains together with sedentary behavior and sleep. RESULTS: The large majority of males (82%) and all females failed to meet the World Health Organization (WHO) physical activity recommendation for adolescents of 60 min of moderate-vigorous intensity physical activity per day. The physical activity domains clustered together in three multi-trajectory groups that define individuals' overall physical activity pattern. While two patterns indicated decreases in physical activity throughout adolescence, one pattern, including 29% of the sample in males and 17% of the sample in females, indicated higher levels of activity throughout adolescence. Sedentary behavior and sleep trajectories did not cluster together with the physical activity domains. CONCLUSION: Most adolescents in this South African population did not meet WHO recommendations for physical activity. In this population, trajectories of sedentary behavior and sleep were independent of physical activity.

Association Between Maternal 2nd Trimester Plasma Folate Levels and Infant Bronchiolitis.

Objectives Viral bronchiolitis is the most common cause of infant hospitalization. Folic acid supplementation is important during the periconceptional period to prevent neural tube defects. An area of investigation is whether higher prenatal folate is a risk factor for childhood respiratory illnesses. We investigated the association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Methods We conducted a retrospective cohort analysis in a subset of mother-infant dyads (n = 676) enrolled in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study and Tennessee Medicaid. Maternal folate status was determined using 2nd trimester (16-28 weeks) plasma samples. Bronchiolitis diagnosis in the first year of life was ascertained using International Classification of Diagnosis-9 codes from Medicaid administrative data. We used multivariable logistic regression to assess the adjusted association of prenatal folate levels and infant bronchiolitis outcome. Results Half of the women in this lower-income and predominately African-American (84%) study population had high levels of folate (median 2nd trimester level 19.2 ng/mL) and 21% of infants had at least one bronchiolitis healthcare visit. A relationship initially positive then reversing between maternal plasma folate and infant bronchiolitis was observed that did not reach statistical significance (poverall = .112, pnonlinear effect = .088). Additional adjustment for dietary methyl donor intake did not significantly alter the association. Conclusions for Practice Results did not confirm a statistically significant association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Further work is needed to investigate the role of folate, particularly higher levels, in association with early childhood respiratory illnesses.

Diet Quality of Pregnant American Indian Women in the Northern Plains.

INTRODUCTION: We examined diet quality and intake of pregnancy-specific micronutrients among pregnant American Indian women in the Northern Plains. METHODS: We conducted an analysis of nutrition data from the Prenatal Alcohol and SIDS and Stillbirth (PASS) Network Safe Passage Study and the PASS Diet Screener study (N = 170). Diet intake, including dietary supplementation, was assessed by using three 24-hour recalls conducted on randomly selected, nonconsecutive days. Diet intake data were averaged across the participant's recalls and scored for 2 dietary indices: the Healthy Eating Index 2010 (HEI-2010) and the Alternate Healthy Eating Index for Pregnancy (AHEI-P). We also assessed nutrient adequacy with Dietary Reference Intakes for pregnancy. RESULTS: On average, participants were aged 26.9 (standard deviation [SD], 5.5) years with a pre-pregnancy body mass index of 29.8 (SD, 7.5) kg/m2. Mean AHEI-P and HEI-2010 scores (52.0 [SD, 9.0] and 49.2 [SD, 11.1], respectively) indicated inadequate adherence to dietary recommendations. Micronutrient intake for vitamins D and K, choline, calcium, and potassium were lower than recommended, and sodium intake was higher than recommended. CONCLUSION: Our findings that pregnant American Indian women are not adhering to dietary recommendations is consistent with studies in other US populations. Identifying opportunities to partner with American Indian communities is necessary to ensure effective and sustainable interventions to promote access to and consumption of foods and beverages that support the adherence to recommended dietary guidelines during pregnancy.

Ancestry-Adjusted Vitamin D Metabolite Concentrations in Association With Cytochrome P450 3A Polymorphisms.

We investigated the association between genetic polymorphisms in cytochrome P450 (CYP2R1, CYP24A1, and the CYP3A family) with nonsummer plasma concentrations of vitamin D metabolites (25-hydroxyvitamin D3 (25(OH)D3) and proportion 24,25-dihydroxyvitamin D3 (24,25(OH)2D3)) among healthy individuals of sub-Saharan African and European ancestry, matched on age (within 5 years; n = 188 in each ancestral group), in central suburban Pennsylvania (2006-2009). Vitamin D metabolites were measured using high-performance liquid chromatography with tandem mass spectrometry. Paired multiple regression and adjusted least-squares mean analyses were used to test for associations between genotype and log-transformed metabolite concentrations, adjusted for age, sex, proportion of West-African genetic ancestry, body mass index, oral contraceptive (OC) use, tanning bed use, vitamin D intake, days from summer solstice, time of day of blood draw, and isoforms of the vitamin D receptor (VDR) and vitamin D binding protein. Polymorphisms in CYP2R1, CYP3A43, vitamin D binding protein, and genetic ancestry proportion remained associated with plasma 25(OH)D3 after adjustment. Only CYP3A43 and VDR polymorphisms were associated with proportion 24,25(OH)2D3. Magnitudes of association with 25(OH)D3 were similar for CYP3A43, tanning bed use, and OC use. Significant least-squares mean interactions (CYP2R1/OC use (P = 0.030) and CYP3A43/VDR (P = 0.013)) were identified. A CYP3A43 genotype, previously implicated in cancer, is strongly associated with biomarkers of vitamin D metabolism. Interactive associations should be further investigated.