Gestational exposure to organochlorine compounds and metals and infant birth weight: effect modification by maternal hardships.

BACKGROUND: Gestational exposure to toxic environmental chemicals and maternal social hardships are individually associated with impaired fetal growth, but it is unclear whether the effects of environmental chemical exposure on infant birth weight are modified by maternal hardships. METHODS: We used data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pan-Canadian cohort of 1982 pregnant females enrolled between 2008 and 2011. We quantified eleven environmental chemical concentrations from two chemical classes - six organochlorine compounds (OCs) and five metals - that were detected in ≥ 70% of blood samples collected during the first trimester. We examined fetal growth using birth weight adjusted for gestational age and assessed nine maternal hardships by questionnaire. Each maternal hardship variable was dichotomized to indicate whether the females experienced the hardship. In our analysis, we used elastic net to select the environmental chemicals, maternal hardships, and 2-way interactions between maternal hardships and environmental chemicals that were most predictive of birth weight. Next, we obtained effect estimates using multiple linear regression, and plotted the relationships by hardship status for visual interpretation. RESULTS: Elastic net selected trans-nonachlor, lead, low educational status, racially minoritized background, and low supplemental folic acid intake. All were inversely associated with birth weight. Elastic net also selected interaction terms. Among those with increasing environmental chemical exposures and reported hardships, we observed stronger negative associations and a few positive associations. For example, every two-fold increase in lead concentrations was more strongly associated with reduced infant birth weight among participants with low educational status (ß = -100 g (g); 95% confidence interval (CI): -215, 16), than those with higher educational status (ß = -34 g; 95% CI: -63, -3). In contrast, every two-fold increase in mercury concentrations was associated with slightly higher birth weight among participants with low educational status (ß = 23 g; 95% CI: -25, 71) compared to those with higher educational status (ß = -9 g; 95% CI: -24, 6). CONCLUSIONS: Our findings suggest that maternal hardships can modify the associations of gestational exposure to some OCs and metals with infant birth weight.

Folate and synthetic folic acid content in Canadian fortified foods two decades after mandatory fortification.

In 1998, Health Canada mandated folic acid fortification of white flour and enriched grain products to prevent neural tube defects. At the time, neither the Canadian Nutrient File (CNF) nor product labels reflected the actual folate content of foods. We aimed to assess if 20 years post-fortification, the CNF values for total folate and synthetic folic acid accurately reflect amounts determined by direct analysis. Using the 2001 Food Expenditure Survey and ACNielsen Company data, we identified 10-15 of the most purchased fortified foods across seven food categories in Canada. Total folate concentrations were determined by tri-enzyme digestion and microbial assay. Folic acid concentrations were determined using liquid chromatography-tandem mass spectrometry. Except for "cooked pastas", mean total folate content of foods (n = 89) were significantly higher than CNF values across categories (p < 0.05), reflecting 167% ± 54% of CNF values. Similarly, mean folic acid content of foods was higher than CNF values for all categories except "cooked pastas" (p < 0.05), with a mean of 188% ± 94% of CNF values; the latter CNF values included uncooked pasta. In sum, 20 years post-fortification, and 10 years since the last direct measurement, CNF and product label values still underestimate actual total folate and the folic acid content of foods. These findings emphasize that dietary estimates established using the CNF may significantly underestimate actual intakes and thus caution should be exercised when interpreting estimates of nutritional adequacy based on these values.

Proportions of trans fatty acids in erythrocytes of Canadian adults before the prohibition of partially hydrogenated oils in foods: results from the Canadian Health Measures Survey 2012-2015.

BACKGROUND: The partially hydrogenated oil (PHO) prohibition came into effect in Canada in September 2018 to reduce the intakes of total trans fatty acids (t-TFAs) and industrially produced TFAs (i-TFAs). OBJECTIVES: We aimed to estimate the red blood cell (RBC) proportions of t-TFA (primary objective) and total 18:1 TFA (secondary objective) of adults in Canada before the PHO prohibition and to identify the population subgroups at risk of higher TFA intakes. METHODS: We pooled data from 4025 adult participants of the cross-sectional Canadian Health Measures Survey cycles 3 and 4 (2012-2015). We estimated mean proportions, relative to total fatty acids (FAs), of RBC t-TFA and 18:1 TFA and their associations with sociodemographic, health, and lifestyle characteristics using multiple linear regression models. RESULTS: The nonadjusted mean RBC proportions of t-TFA and total 18:1 TFA were 0.59% (95% CI: 0.54, 0.63) and 0.27% (95% CI: 0.25, 0.29), respectively. In the adjusted models, the same participant characteristics were associated with t-TFA and 18:1 TFA but differences were generally smaller for 18:1 TFA than for t-TFA. Race, BMI, and alcohol intake were independently associated with RBC t-TFA and 18:1 TFA. Asian and Black participants had lower RBC t-TFA (-0.05% and -0.10% of total FA, respectively) than White participants. Obesity and high risk alcohol drinking were associated with slightly lower (≤0.06%) t-TFA proportions than lower adiposity and alcohol intake concentrations, respectively. CONCLUSIONS: Pre-PHO prohibition in food in Canada, t-TFA proportions were relatively low compared with a proposed threshold of 1% of total RBC FAs, over which cardiovascular disease risk may be higher. Previous voluntary initiatives to reduce i-TFA in the food supply may explain these relatively low RBC t-TFA concentrations. Some population subgroups had higher baseline RBC TFA than other subgroups, but the physiological implications of these small differences, at relatively low baseline RBC TFA proportions, remain to be determined.

Risk of bias in cross-sectional studies: Protocol for a scoping review of concepts and tools.

Cross-sectional studies are commonly used to study human health and disease, but are especially susceptible to bias. This scoping review aims to identify and describe available tools to assess the risk of bias (RoB) in cross-sectional studies and to compile the key bias concepts relevant to cross-sectional studies into an item bank. Using the JBI scoping review methodology, the strategy to locate relevant RoB concepts and tools is a combination of database searches, prospective review of PROSPERO registry records; and consultation with knowledge users and content experts. English language records will be included if they describe tools, checklists, or instruments which describe or permit assessment of RoB for cross-sectional studies. Systematic reviews will be included if they consider eligible RoB tools or use RoB tools for RoB of cross-sectional studies. All records will be independently screened, selected, and extracted by one researcher and checked by a second. An analytic framework will be used to structure the extraction of data. Results for the scoping review are pending. Results from this scoping review will be used to inform future selection of RoB tools and to consider whether development of a new RoB tool for cross-sectional studies is needed.

A scoping review shows that no single existing risk of bias assessment tool considers all sources of bias for cross-sectional studies.

OBJECTIVES: Different tools to assess the potential risk of bias (RoB) for cross-sectional studies have been developed, but it is unclear whether all pertinent bias concepts are addressed. We aimed to identify RoB concepts applicable to cross-sectional research validity and to explore coverage for each in existing appraisal tools. STUDY DESIGN AND SETTING: This scoping review followed the Joanna Briggs Institute methodology. We included records of any study design describing or reporting methods, concepts or tools used to consider RoB in health research reported to be descriptive/prevalence survey or analytic/association (cross-sectional) study designs. Synthesis included quantitative and qualitative analysis. RESULTS: Of the 4556 records screened, 90 were selected for inclusion; 67 (74%) described the development of, or validation process for, appraisal tools, 15 (17%) described methodological content or theory relevant to RoB for cross-sectional studies and 8 (9%) records of methodological systematic reviews. Review of methodological reports identified important RoB concepts for both descriptive/prevalence and analytic/association studies. Tools identified (n = 64 unique tools) were either intended to appraise quality or assess RoB in multiple study designs including cross-sectional studies (n = 21; 33%) or cross-sectional designs alone (n = 43; 67%). Several existing tools were modified (n = 17; 27%) for application to cross-sectional studies. The RoB items most frequently addressed in the RoB tools were validity and reliability of the exposure (53%) or outcome (65%) measurement and representativeness of the study population (59%). Most tools did not consider nonresponse or missingness appropriately or at all. CONCLUSION: Assessing cross-sectional studies involve unique RoB considerations. We identified RoB tools designed for broad applicability across various study designs as well as those specifically tailored for cross-sectional studies. However, none of the identified tools comprehensively address all potential biases pertinent to cross-sectional studies. Our findings indicate a need for continued improvement of RoB tools and suggest that the development of context-specific or more precise tools for this study design may be necessary.

Timing of standard chow exposure determines the variability of mouse phenotypic outcomes and gut microbiota profile.

Standard chow diet contributes to reproducibility in animal model experiments since chows differ in nutrient composition, which can independently influence phenotypes. However, there is little evidence of the role of timing in the extent of variability caused by chow exposure. Here, we measured the impact of diet (5V5M, 5V0G, 2920X, and 5058) and timing of exposure (adult exposure (AE), lifetime exposure (LE), and developmental exposure (DE)) on growth & development, metabolic health indicators, and gut bacterial microbiota profiles across genetically identical C57BL6/J mice. Diet drove differences in macro- and micronutrient intake for all exposure models. AE had no effect on measured outcomes. However, LE mice exhibited significant sex-dependent diet effects on growth, body weight, and body composition. LE effects were mostly absent in the DE model, where mice were exposed to chow differences from conception to weaning. Both AE and LE models exhibited similar diet-driven beta diversity profiles for the gut bacterial microbiota, with 5058 diet driving the most distinct profile. Diet-induced beta diversity profiles were sex-dependent for LE mice. Compared to AE, LE drove 9X more diet-driven differentially abundant genera, majority of which were the result of inverse effects of 2920X and 5058. Our findings demonstrate that lifetime exposure to different chow diets has the greatest impact on reproducibility of experimental measures that are common components of preclinical mouse model studies. Importantly, weaning DE mice onto a uniform diet is likely an effective way to reduce unwanted phenotypic variability among experimental models.

Ultra-processed foods and human health: An umbrella review and updated meta-analyses of observational evidence.

BACKGROUND & AIMS: Ultra-processed food (UPF) intake has increased sharply over the last few decades and has been consistently asserted to be implicated in the development of non-communicable diseases. We aimed to evaluate and update the existing observational evidence for associations between ultra-processed food (UPF) consumption and human health. METHODS: We searched Medline and Embase from inception to March 2023 to identify and update meta-analyses of observational studies examining the associations between UPF consumption, as defined by the NOVA classification, and a wide spectrum of health outcomes. For each health outcome, we estimated the summary effect size, 95% confidence interval (CI), between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. These metrics were used to evaluate evidence credibility of the identified associations. RESULTS: This umbrella review identified 39 meta-analyses on the associations between UPF consumption and health outcomes. We updated all meta-analyses by including 122 individual articles on 49 unique health outcomes. The majority of the included studies divided UPF consumption into quartiles, with the lowest quartile being the reference group. We identified 25 health outcomes associated with UPF consumption. For observational studies, 2 health outcomes, including renal function decline (OR: 1.25; 95% CI: 1.18, 1.33) and wheezing in children and adolescents (OR: 1.42; 95% CI: 1.34, 1.49), showed convincing evidence (Class I); and five outcomes were reported with highly suggestive evidence (Class II), including diabetes mellitus, overweight, obesity, depression, and common mental disorders. CONCLUSIONS: High UPF consumption is associated with an increased risk of a variety of chronic diseases and mental health disorders. At present, not a single study reported an association between UPF intake and a beneficial health outcome. These findings suggest that dietary patterns with low consumption of UPFs may render broad public health benefits.

Universal Free School Meals and School and Student Outcomes: A Systematic Review.

Importance: The White House National Strategy on Hunger, Nutrition, and Health included expanding free school meals to all students, regardless of income, which has sparked debate in the United States. Objective: To assess the association between universal free school meals (UFSMs) and school and student outcomes in the United States. Evidence Review: An expert panel-informed protocol was developed to evaluate intervention or cohort studies comparing UFSM programs, such as the Community Eligibility Provision (CEP), with non-UFSM programs in US schools from August 2012 (excluding 2020-2021 due to the COVID-19 pandemic) in peer-reviewed publications or government reports. Outcomes included meal participation rates, attendance, dietary intake and quality, food waste, economic impact, food insecurity, anthropometrics, disciplinary actions, stigma, and shaming. A search of Medline, Econlit, Business Source Ultimate, ERIC, Agricola, Cab Abstracts, and CINAHL was performed in April 2024. Two researchers screened articles for inclusion, extracted data, and assessed risk of bias, using the Risk of Bias in Nonrandomized Studies of Interventions tool, for each included study. Grading of Recommendations, Assessment, Development, and Evaluations was used to assess the certainty of evidence for each outcome. Findings: The search identified 2784 records, with 6 studies included, representing more than 11 000 elementary, middle, and high schools. Nonrandomized intervention studies performed difference-in-difference or rate ratio analysis to investigate CEP participation rates, attendance, anthropometrics, and/or suspensions. CEP was associated with increased lunch (3 studies; moderate certainty) and breakfast (1 study; very low certainty) participation. School attendance was unchanged or improved in schools with CEP compared with schools without UFSM (2 studies; low certainty). CEP was associated with lower obesity prevalence (1 study; very low certainty) and fewer suspensions (1 study; very low certainty). Reasons for downgrading the certainty ratings included indirectness (data not fully representative of the United States) and inconsistency (small number of studies limiting ability to assess consistency). Despite the limitations, the evidence reflected well-designed longitudinal intervention studies appropriate for decision-making. Conclusions and Relevance: In this systematic review, UFSMs were associated with increased meal participation, no or slight improvements in attendance, and decreased obesity prevalence and suspension rates; certainty of evidence was moderate for lunch participation and low or very low for other outcomes. Studies did not report several important outcomes, such as diet quality and food security, suggesting the need for more high-quality research encompassing policy-relevant indicators.

The Association between Long-Term DDT or DDE Exposures and an Altered Sperm Epigenome-a Cross-Sectional Study of Greenlandic Inuit and South African VhaVenda Men.

BACKGROUND: The organochlorine dichlorodiphenyltrichloroethane (DDT) is banned worldwide owing to its negative health effects. It is exceptionally used as an insecticide for malaria control. Exposure occurs in regions where DDT is applied, as well as in the Arctic, where its endocrine disrupting metabolite, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) accumulates in marine mammals and fish. DDT and p,p'-DDE exposures are linked to birth defects, infertility, cancer, and neurodevelopmental delays. Of particular concern is the potential of DDT use to impact the health of generations to come via the heritable sperm epigenome. OBJECTIVES: The objective of this study was to assess the sperm epigenome in relation to p,p'-DDE serum levels between geographically diverse populations. METHODS: In the Limpopo Province of South Africa, we recruited 247 VhaVenda South African men and selected 50 paired blood serum and semen samples, and 47 Greenlandic Inuit blood and semen paired samples were selected from a total of 193 samples from the biobank of the INUENDO cohort, an EU Fifth Framework Programme Research and Development project. Sample selection was based on obtaining a range of p,p'-DDE serum levels (mean=870.734±134.030 ng/mL). We assessed the sperm epigenome in relation to serum p,p'-DDE levels using MethylC-Capture-sequencing (MCC-seq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq). We identified genomic regions with altered DNA methylation (DNAme) and differential enrichment of histone H3 lysine 4 trimethylation (H3K4me3) in sperm. RESULTS: Differences in DNAme and H3K4me3 enrichment were identified at transposable elements and regulatory regions involved in fertility, disease, development, and neurofunction. A subset of regions with sperm DNAme and H3K4me3 that differed between exposure groups was predicted to persist in the preimplantation embryo and to be associated with embryonic gene expression. DISCUSSION: These findings suggest that DDT and p,p'-DDE exposure impacts the sperm epigenome in a dose-response-like manner and may negatively impact the health of future generations through epigenetic mechanisms. Confounding factors, such as other environmental exposures, genetic diversity, and selection bias, cannot be ruled out. https://doi.org/10.1289/EHP12013.