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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 [+ or -] 134.030 ng/mL). We assessed the sperm epigenome in relation to serump,p'-DDE levels using MethylC-Capture-sequencing (MCCseq) 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, Introduction Dichlorodiphenyltrichloroethane (DDT) is a lipophilic organochlorine pollutant that is listed under the Stockholm Convention, with the objective to eliminate its use so as to protect human health and the [...]

Folate, an essential nutrient found naturally in foods in a reduced form, is present in dietary supplements and fortified foods in an oxidized synthetic form (folic acid). There is widespread agreement that maintaining adequate folate status is critical to prevent diseases due to folate inadequacy (e.g., anemia, birth defects, and cancer). However, there are concerns of potential adverse effects of excess folic acid intake and/or elevated folate status, with the original concern focused on exacerbation of clinical effects of vitamin B-12 deficiency and its role in neurocognitive health. More recently, animal and observational studies have suggested potential adverse effects on cancer risk, birth outcomes, and other diseases. Observations indicating adverse effects from excess folic acid intake, elevated folate status, and unmetabolized folic acid (UMFA) remain inconclusive; the data do not provide the evidence needed to affect public health recommendations. Moreover, strong biological and mechanistic premises connecting elevated folic acid intake, UMFA, and/or high folate status to adverse health outcomes are lacking. However, the body of evidence on potential adverse health outcomes indicates the need for comprehensive research to clarify these issues and bridge knowledge gaps. Three key research questions encompass the additional research needed to establish whether high folic acid or total folate intake contributes to disease risk. 1) Does UMFA affect biological pathways leading to adverse health effects? 2) Does elevated folate status resulting from any form of folate intake affect vitamin B-12 function and its roles in sustaining health? 3) Does elevated folate intake, regardless of form, affect biological pathways leading to adverse health effects other than those linked to vitamin B-12 function? This article summarizes the proceedings of an August 2019 NIH expert workshop focused on addressing these research areas.

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. [ABSTRACT FROM AUTHOR]

Dietary Reference Intakes (DRIs) are used in Canada and the United States in planning and assessing diets of apparently healthy individuals and population groups. The approaches used to establish DRIs on the basis of classical nutrient deficiencies and/or toxicities have worked well. However, it has proved to be more challenging to base DRI values on chronic disease endpoints; deviations from the traditional framework were often required, and in some cases, DRI values were not established for intakes that affected chronic disease outcomes despite evidence that supported a relation. The increasing proportions of elderly citizens, the growing prevalence of chronic diseases, and the persistently high prevalence of overweight and obesity, which predispose to chronic disease, highlight the importance of understanding the impact of nutrition on chronic disease prevention and control. A multidisciplinary working group sponsored by the Canadian and US government DRI steering committees met from November 2014 to April 2016 to identify options for addressing key scientific challenges encountered in the use of chronic disease endpoints to establish reference values. The working group focused on 3 key questions: 1) What are the important evidentiary challenges for selecting and using chronic disease endpoints in future DRI reviews, 2) what intake-response models can future DRI committees consider when using chronic disease endpoints, and 3) what are the arguments for and against continuing to include chronic disease endpoints in future DRI reviews? This report outlines the range of options identified by the working group for answering these key questions, as well as the strengths and weaknesses of each option.

Fetal and child development are shaped by early life exposures, including maternal health states, nutrition and educational and home environments. We aimed to determine if suboptimal pre-pregnancy maternal body mass index (BMI; underweight, overweight, obese) would associate with poorer cognitive outcomes in children, and whether early life nutritional, educational and home environments modify these relationships. Self-reported data were obtained from mother-infant dyads from the pan-Canadian prospective Maternal-Infant Research on Environmental Chemicals cohort. Relationships between potential risk factors (pre-pregnancy maternal BMI, breastfeeding practices and Home Observation Measurement of the Environment [HOME] score) and child cognitive development at age three (Weschler's Preschool and Primary Scale of Intelligence, Third Edition scale and its subcategories) were each evaluated using analysis of variance, multivariable regression models and moderating analyses. Amongst the 528 mother−child dyads, increasing maternal pre-pregnancy BMI was negatively associated with scores for child full-scale IQ (β [95% CI]; −2.01 [−3.43, −0.59], p = 0.006), verbal composite (−1.93 [−3.33, −0.53], p = 0.007), and information scale (−0.41 [−0.70, −0.14], p = 0.003) scores. Higher maternal education level or HOME score attenuated the negative association between maternal pre-pregnancy BMI and child cognitive outcome by 30%–41% and 7%–22%, respectively, and accounted for approximately 5%–10% greater variation in male children's cognitive scores compared to females. Maternal education and higher quality home environment buffer the negative effect of elevated maternal pre-pregnancy BMI on child cognitive outcomes. Findings suggest that relationships between maternal, social and environmental factors must be considered to reveal pathways that shape risk for, and resiliency against, suboptimal cognitive outcomes in early life. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Mandatory folic acid fortification was implemented in Canada in 1998 to reduce the risk of neural tube defects (NTD). Our objective was to assess the relationship between socio-demographic factors and folate status in non-supplement-consuming Canadian women of childbearing age. METHODS: Data on demographic factors, lifestyle factors, physical measures and red blood cell (RBC) folate concentration were collected from 1,008 non-supplement-consuming women aged 15-49 years in the Canadian Health Measures Survey (2007-2009). RBC folate ≥906 nmol/L was used as a cut-off for optimal folate status for protection from NTD. RESULTS: Approximately 75% of non-supplement consuming women had an RBC folate concentration ≥906 nmol/L. Young age (15-19 years), White ethnicity, less than secondary education, lowest income adequacy, smoking and high body mass index were associated with a higher prevalence of lower folate status. After adjustment, only young age (adjusted odds ratio [OR] 1.99-95% confidence interval [CI]: 1.25-3.18) was associated with lower folate status. Less than secondary education (adjusted OR 5.66, 95% CI: 1.10-29.04) and lowest income adequacy (adjusted OR 4.77, 95% CI: 1.06-21.49) were associated with lower folate status in women aged 15-24 and 25-49 years, respectively. CONCLUSIONS: Many risk factors for lower folate status identified before food fortification was implemented were not associated with folate status in our representative sample of non-supplement-consuming Canadian women. However, younger women, women aged 15-24 with less than secondary education and women aged 25-49 with low income adequacy remain at risk of lower folate status, supporting the continued promotion of folic acid supplement use to women of childbearing age. KEY WORDS: Folate; folic acid; fortification; neural tube defects; Canadian Health Measures Survey OBJECTIF : Applique au Canada depuis 1998, l'enrichissement obligatoire en acide folique vise a reduire le risque d'anomalies du tube neural (ATN). Notre objectif etait d'evaluer la relation entre les facteurs sociodemographiques et le statut en folates chez les Canadiennes en age de procreer ne consommant pas de supplements. METHODE : Des donnees sur les facteurs demographiques, les facteurs lies au mode de vie, les indicateurs physiques et la concentration en folates erythrocytaires ont ete recueillies aupres de 1 008 femmes de 15 a 49 ans ne consommant pas de supplements et ayant participe a l'Enquete canadienne sur les mesures de la sante (2007-2009). Un seuil de folates erythrocytaires ≥906 nmol/L a servi a delimiter le statut optimal en folates qui protege contre les ATN. RESULTATS : Environ 75 % des femmes ne consommant pas de supplements avaient une concentration en folates erythrocytaires [greater than or equal to]906 nmol/L. La jeunesse (15-19 ans), l'ethnicite blanche, le fait d'avoir moins qu'un diplome d'etudes secondaires, la categorie inferieure de revenu adequat, le tabagisme et un indice de masse corporelle eleve etaient associes a une prevalence accrue du faible statut en folates. Apres correction, seule la jeunesse (rapport de cotes ajuste [RC] 1,99, intervalle de confiance de 95 % [IC] : 1,25-3,18) etait associee au faible statut en folates. Le fait d'avoir moins qu'un diplome d'etudes secondaires (RC ajuste 5,66, IC de 95 % : 1,10-29,04) et la categorie inferieure de revenu adequat (RC ajuste 4,77, IC de 95 % : 1,06-21,49) etaient associes au faible statut en folates chez les femmes de 15 a 24 ans et de 25 a 49 ans, respectivement. CONCLUSIONS : De nombreux facteurs de risque de faible statut en folates, identifies avant la mise en oeuvre de l'enrichissement des aliments, n'etaient pas associes au statut en folates dans notre echantillon representatif de Canadiennes ne consommant pas de supplements. Toutefois, les jeunes femmes, les femmes de 15 a 24 ans n'ayant pas termine leurs etudes secondaires et les femmes de 25 a 49 ans dans la categorie inferieure de revenu adequat courent encore le risque d'avoir un faible statut en folates, ce qui justifie que l'on continue a promouvoir la supplementation en acide folique chez les femmes en age de procreer. MOTS CLES : folates; acide folique; aliments enrichis; anomalies du tube neural; Enquete canadienne sur les mesures de la sante, La traduction du resume se trouve a la fin de l'article. The risk of a woman having a child affected by a neural tube defect (NTD) is partially dependent on [...]