Strengthening Research that Answers Nutrition Questions of Public Health Importance: Leveraging the Experience of the USDA Nutrition Evidence Systematic Review Team.

The Nutrition Evidence Systematic Review (NESR) team conducts nutrition- and public health-related systematic reviews and is within the USDA's Center for Nutrition Policy and Promotion. NESR has collaborated with scientific experts to conduct systematic reviews on nutrition and public health topics for more than a decade and is uniquely positioned to share recommendations with the research community to strengthen research quality and impact, especially the evidence base that supports public health nutrition guidance, including future editions of the Dietary Guidelines for Americans. Leveraging the expertise of NESR and its systematic review process resulted in the following recommendations for the research community: a) use the strongest study design feasible with sufficient sample size(s); b) enroll study participants who reflect the diversity of the population of interest and report participant characteristics; c) use valid and reliable dietary assessment methods; d) describe the interventions or exposures of interest and use standard definitions to promote consistency; e) use valid and reliable health outcome measures; f) account for variables that may impact the relationship between nutrition-related interventions or exposures and health outcomes; g) carry out studies for a sufficient duration and include repeated measures, as appropriate; and h) report all relevant information to inform accurate interpretation and evaluation of study results. Implementing these recommendations can strengthen nutrition and public health evidence and increase its utility in future public health nutrition systematic reviews. However, implementation will require additional support from the entire research community, including scientific journals and funding agencies.

Omega-3 Fatty Acid Dietary Supplements Consumed During Pregnancy and Lactation and Child Neurodevelopment: A Systematic Review.

BACKGROUND: Maternal nutrition during pregnancy and lactation has profound effects on the development and lifelong health of the child. Long-chain PUFAs are particularly important for myelination and the development of vision during the perinatal period. OBJECTIVES: We conducted a systematic review to examine the relationship between supplementation with omega-3 fatty acids during pregnancy and/or lactation and neurodevelopment in children, to inform the Scientific Report of the 2020 Dietary Guidelines Advisory Committee. METHODS: We identified articles on omega-3 fatty acid supplementation in pregnant and lactating women that included measures of neurodevelopment in their children (0-18 y) by searching PubMed, CENTRAL, Embase, and CINAHL Plus. After dual screening articles for inclusion, we qualitatively synthesized and graded the strength of evidence using pre-established criteria for assessing risk of bias, consistency, directness, precision, and generalizability. RESULTS: We included 33 articles from 15 randomized controlled trials (RCTs) and 1 prospective cohort study. Of the 8 RCTs that delivered omega-3 fatty acid dietary supplements during pregnancy alone (200-2200 mg/d DHA and 0-1100 mg/d EPA for approximately 20 wk), 5 studies reported ≥1 finding that supplementation improved measures of cognitive development in the infant or child by 6%-11% (P < 0.05), but all 8 studies also reported ≥1 nonsignificant (P > 0.05) result. There was inconsistent or insufficient evidence for other outcomes (language, social-emotional, physical, motor, or visual development; academic performance; risks of attention deficit disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, anxiety, or depression) and for supplementation during lactation or both pregnancy and lactation. Populations with a lower socioeconomic status and adolescents were underrepresented and studies lacked racial and ethnic diversity. CONCLUSIONS: Limited evidence suggests that omega-3 fatty acid supplementation during pregnancy may result in favorable cognitive development in the child. There was insufficient evidence to evaluate the effects of omega-3 fatty acid supplementation during pregnancy and/or lactation on other developmental outcomes.

Maternal postpartum plasma folate status and preterm birth in a high-risk US population.

OBJECTIVE: While maternal folate deficiency has been linked to poor pregnancy outcomes such as neural tube defects, anaemia and low birth weight, the relationship between folate and preterm birth (PTB) in the context of the US post-folic acid fortification era is inconclusive. We sought to explore the relationship between maternal folate status and PTB and its subtypes, i.e. spontaneous and medically indicated PTB. DESIGN: Observational study. SETTING: Boston Birth Cohort, a predominantly urban, low-income, race/ethnic minority population at a high risk for PTB.ParticipantsMother-infant dyads (n 7675) enrolled in the Boston Birth Cohort. A sub-sample (n 2313) of these dyads had maternal plasma folate samples collected 24-72 h after delivery. RESULTS: Unadjusted and adjusted logistic regressions revealed an inverse relationship between the frequency of multivitamin supplement intake and PTB. Compared with less frequent use, multivitamin supplement intake 3-5 times/week (adjusted OR (aOR) = 0·78; 95 % CI 0·64, 0·96) or >5 times/week (aOR = 0·77; 95 % CI 0·64, 0·93) throughout pregnancy was associated with reduced risk of PTB. Consistently, higher plasma folate levels (highest v. lowest quartile) were associated with lower risk of PTB (aOR = 0·74; 95 % CI 0·56, 0·97). The above associations were similar among spontaneous and medically indicated PTB. CONCLUSIONS: If confirmed by future studies, our findings raise the possibility that optimizing maternal folate levels across pregnancy may help to reduce the risk of PTB among the most vulnerable US population in the post-folic acid fortification era.

Maternal Multivitamin Intake, Plasma Folate and Vitamin B12 Levels and Autism Spectrum Disorder Risk in Offspring.

BACKGROUND: To examine the prospective association between multivitamin supplementation during pregnancy and biomarker measures of maternal plasma folate and vitamin B12 levels at birth and child's Autism Spectrum Disorder (ASD) risk. METHODS: This report included 1257 mother-child pairs, who were recruited at birth and prospectively followed through childhood at the Boston Medical Center. ASD was defined from diagnostic codes in electronic medical records. Maternal multivitamin supplementation was assessed via questionnaire interview; maternal plasma folate and B12 were measured from samples taken 2-3 days after birth. RESULTS: Moderate (3-5 times/week) self-reported supplementation during pregnancy was associated with decreased risk of ASD, consistent with previous findings. Using this as the reference group, low (≤2 times/week) and high (>5 times/week) supplementation was associated with increased risk of ASD. Very high levels of maternal plasma folate at birth (≥60.3 nmol/L) had 2.5 times increased risk of ASD [95% confidence interval (CI) 1.3, 4.6] compared to folate levels in the middle 80th percentile, after adjusting for covariates including MTHFR genotype. Similarly, very high B12 (≥536.8 pmol/L) showed 2.5 times increased risk (95% CI 1.4, 4.5). CONCLUSION: There was a 'U shaped' relationship between maternal multivitamin supplementation frequency and ASD risk. Extremely high maternal plasma folate and B12 levels at birth were associated with ASD risk. This hypothesis-generating study does not question the importance of consuming adequate folic acid and vitamin B12 during pregnancy; rather, raises new questions about the impact of extremely elevated levels of plasma folate and B12 exposure in-utero on early brain development.

Biomarkers of Nutrition for Development-Folate Review.

The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-based advice to anyone with an interest in the role of nutrition in health. Specifically, the BOND program provides state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutrients in body tissues at the individual and population level. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, iron, zinc, folate, vitamin A, and vitamin B-12. This review represents the second in the series of reviews and covers all relevant aspects of folate biology and biomarkers. The article is organized to provide the reader with a full appreciation of folate's history as a public health issue, its biology, and an overview of available biomarkers (serum folate, RBC folate, and plasma homocysteine concentrations) and their interpretation across a range of clinical and population-based uses. The article also includes a list of priority research needs for advancing the area of folate biomarkers related to nutritional health status and development.

Biomarkers of nutrition for development--iodine review.

The objective of the Biomarkers of Nutrition for Development (BOND) project is to provide state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. Specifically, the BOND project seeks to develop consensus on accurate assessment methodologies that are applicable to researchers (laboratory/clinical/surveillance), clinicians, programmers, and policy makers (data consumers). The BOND project is also intended to develop targeted research agendas to support the discovery and development of biomarkers through improved understanding of nutrient biology within relevant biologic systems. In phase I of the BOND project, 6 nutrients (iodine, vitamin A, iron, zinc, folate, and vitamin B-12) were selected for their high public health importance because they typify the challenges faced by users in the selection, use, and interpretation of biomarkers. For each nutrient, an expert panel was constituted and charged with the development of a comprehensive review covering the respective nutrient's biology, existing biomarkers, and specific issues of use with particular reference to the needs of the individual user groups. In addition to the publication of these reviews, materials from each will be extracted to support the BOND interactive Web site (http://www.nichd.nih.gov/global_nutrition/programs/bond/pages/index.aspx). This review represents the first in the series of reviews and covers all relevant aspects of iodine biology and biomarkers. The article is organized to provide the reader with a full appreciation of iodine's background history as a public health issue, its biology, and an overview of available biomarkers and specific considerations for the use and interpretation of iodine biomarkers across a range of clinical and population-based uses. The review also includes a detailed research agenda to address priority gaps in our understanding of iodine biology and assessment.

Distribution and correlates of plasma folate, vitamin B12, and homocysteine in a sample of low-income minority children aged 6 months to 9 years in the U.S.

Background: Precision nutrition emphasizes tailoring dietary requirements across populations and life stages. Optimal folate and vitamin B12 levels are important for normal growth and development, but data are lacking for low-income minority U.S. children during early life periods. This study aimed to describe folate, vitamin B12, homocysteine (Hcy) levels, and influencing factors to address the gaps. Methods: Blood samples from children aged 6 months to 9 years and mothers 48-72 hours postpartum in the Boston Birth Cohort (BBC) were tested for folate, vitamin B12, and Hcy. Maternal and child characteristics, sociodemographic factors, and feeding status were obtained from a standard maternal questionnaire interview at the enrollment and follow-up, and medical records. The distribution of children's folate, vitamin B12, and Hcy were described and factors influencing these biomarkers were analyzed. Results: A wide distribution of folate, vitamin B12, and Hcy levels was observed in this sample, with longitudinal trends consistent with National Health and Nutrition Examination Survey (NHANES) data. Multivariate analysis showed that very preterm birth correlated with higher folate levels (adjusted ß 4.236; 95% CI: 1.218, 7.253; p=0.006). Children aged 1-2 years and 3-8 years had lower folate levels compared to those <1 year (adjusted ß -10.191 and -7.499 respectively; p<0.001). Vitamin B12 levels were higher in Black children (adjusted fold change 1.139; 95% CI: 1.052, 1.233; p=0.001) and those children whose mothers' B12 levels were at the highest quartile (Q4) (adjusted fold change 1.229; 95% CI: 1.094, 1.380; p=0.001). Delayed solid food introduction (> 6 months) correlated with lower children's B12 levels (adjusted fold change 0.888; 95% CI: 0.809, 0.975; p=0.013). Hcy levels were lower in Black children (adjusted fold change 0.962; 95% CI: 0.932, 0.993; p=0.018), higher in children with maternal Hcy levels in Q4 (adjusted fold change 1.081; 95% CI: 1.03, 1.135; p=0.002) and in children aged 3-8 years (adjusted fold change 1.084; 95% CI: 1.040, 1.131; p< 0.001). Conclusions: This study revealed wide variations in plasma folate, vitamin B12, and Hcy levels among low-income minority U.S. children and identified race, maternal levels, child's age, prematurity, and timing of solid food introduction as significant correlates.

Dietary Patterns and Health: Insights From NESR Systematic Reviews to Inform the Dietary Guidelines for Americans.

This perspective article shares unique insights from the extensive experience of the US Department of Agriculture Nutrition Evidence Systematic Review branch in conducting systematic reviews on dietary patterns and health outcomes to inform the Dietary Guidelines for Americans. Methodological approaches for reviewing dietary patterns research are described, including approaches to operationalizing definitions and analyzing labeled dietary patterns. The review also describes techniques for synthesizing dietary patterns research across life stages in systematic reviews that inform food-based, federal dietary guidance. Current research activities and recommendations for how to improve or address gaps in dietary patterns research in the future are also discussed.

Biomarkers in growth.

BACKGROUND: The current approaches to assess growth are limited to anthropometry, are insensitive and nonspecific, and do not enable an improved understanding of how nutrition might impact growth. Consequently, new tools to develop better standards of care and programs to address ongoing concerns about nutrition and health are needed. METHODS: The Biomarkers of Nutrition for Development (BOND) project is designed to support the discovery, development, and use of current and new biomarkers of nutritional exposure, status, function, and effect. The Biomarkers in Growth (BIG) project was initiated as a BOND program to develop a roadmap for moving the nutrition and growth agenda forward. The first step in this project was a session jointly organized by the BOND Secretariat and Sight and Life at the 20th International Congress on Nutrition in Granada, Spain. RESULTS: The BIG session outlined current approaches to evaluating growth and understanding of the role of nutrition in linear growth, body composition, and long-term health outcomes and the potential role of systems biology in the assessment of the nutrition-growth relationship. CONCLUSION: The session presentations and deliberations highlighted the need for a concerted effort to address the critical gaps in our understanding of the biology and assessment of growth.

Independent and joint association of cord plasma pantothenate and cysteine levels with autism spectrum disorders and other neurodevelopmental disabilities in children born term and preterm.

Background: Pantothenate (vitamin B5) is a precursor for coenzyme A (CoA) synthesis, which serves as a cofactor for hundreds of metabolic reactions. Cysteine is an amino acid in the CoA synthesis pathway. To date, research on the combined role of early life pantothenate and cysteine levels in childhood neurodevelopmental disabilities is scarce. Objective: To study the association between cord pantothenate and cysteine levels and risk of autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and other developmental disabilities (DD) in children born term and preterm. Methods: The study sample (n = 996, 177 born preterm) derived from the Boston Birth Cohort included 416 neurotypical children, 87 ASD, 269 ADHD, and 224 other DD children, who were mutually exclusive. Participants were enrolled at birth and were followed up prospectively (from October 1, 1998, to June 30, 2018) at the Boston Medical Center. Cord blood sample was collected at birth. Plasma pantothenate and cysteine levels were measured using liquid chromatography-tandem mass spectrometry. Results: Higher cord pantothenate (≥50th percentile vs. <50th percentile) was associated with a greater risk of ASD (adjusted odds ratio [aOR]: 1.94, 95% confidence interval [CI]: 1.06, 3.55) and ADHD (aOR: 1.66, 95% CI: 1.14, 2.40), after adjusting for potential confounders. However, cord cysteine alone was not associated with risk of ASD, ADHD, or other DD. When considering the joint association, greater ASD risk was noted when both cord pantothenate and cysteine levels were elevated (≥50th percentile) (aOR: 3.11, 95% CI: 1.24, 7.79), when compared to children with low cord pantothenate (<50th percentile) and high cysteine. Even though preterm and higher pantothenate independently increased the ASD risk, the greatest risk was found in preterm children who also had elevated pantothenate (≥50th percentile), which was true for all three outcomes: ASD (aOR: 5.36, 95% CI: 2.09, 13.75), ADHD (aOR: 3.31, 95% CI: 1.78, 6.16), and other DD (aOR: 3.39, 95% CI: 1.85, 6.24). Conclusions: In this prospective birth cohort, we showed that higher cord pantothenate individually and in combination with higher cysteine or preterm birth were associated with increased risk of ASD and ADHD. More study is needed to explore this biologically plausible pathway.

USDA Nutrition Evidence Systematic Review's collaborative approach for conducting systematic reviews: Promoting diversity of expertise while managing potential conflicts of interest.

U.S. Department of Agriculture's (USDA) Nutrition Evidence Systematic Review (NESR) Branch develops food-and nutrition-related systematic reviews and other evidence synthesis products. NESR has established itself as a key resource for the Federal government when making evidence-informed decisions related to public health nutrition, such as the development of the Dietary Guidelines for Americans. NESR's systematic review methodology is rigorous, protocol-driven, and highly collaborative. NESR's systematic reviews examine the complex interplay between diet and health with input and support from various collaborators, including Federal stakeholders, expert groups, and public stakeholders. Implementing NESR's rigorous methodology ensures that the appropriate steps are taken to minimize conflict of interest, producing systematic reviews that are high-quality, trustworthy, and useful to end users who make decisions based on their findings. This article describes how NESR's systematic review process leverages a diversity of expertise and experience, while managing potential conflicts of interest. It describes the groups who collaborate to conduct NESR systematic reviews, their expertise, and why their involvement is critical for ensuring the rigor and utility of NESR's work.

Vitamin D status and prevalence of metabolic syndrome by race and Hispanic origin in US adults: findings from the 2007-2014 NHANES.

BACKGROUND: Vitamin D status has been found to be inversely associated with metabolic syndrome (MetS) in some studies. Vitamin D status varies by race and ethnicity, and the association of MetS with vitamin D status in US adults and by race and Hispanic origin has not been evaluated extensively. OBJECTIVES: We aimed to examine the associations between vitamin D status and MetS overall, and across race and Hispanic origin groups, in a nationally representative sample of US adults who participated in the NHANES from 2007 to 2014. METHODS: The total sample included 8639 adults, ≥20 y of age. Serum vitamin D was measured using a standardized LC-tandem MS method and was categorized using data-driven tertiles. MetS was defined using measured waist circumference, triglycerides, HDL cholesterol, blood pressure, and fasting glucose. Multivariable logistic regression models were fitted [accounting for sociodemographic and lifestyle factors, dietary supplement use, and BMI (in kg/m2)] to examine the associations of serum vitamin D with MetS among adults overall, and by race and Hispanic origin. RESULTS: Serum vitamin D in the lowest tertile (≤56 nmol/L) was significantly associated with increased odds of MetS compared with the highest tertile (>77.9 nmol/L) (fully adjusted model OR: 1.85; 95% CI: 1.51, 2.27). Inverse associations were noted for all race-Hispanic origin groups: non-Hispanic white (NHW) (OR: 2.24; 95% CI: 1.67, 3.01), non-Hispanic black (OR: 1.56; 95% CI: 1.06, 2.29), and Hispanic (OR: 1.48; 95% CI: 1.03, 2.14) adults. CONCLUSIONS: Lower vitamin D status was significantly associated with MetS among US adults after adjusting for sociodemographic and lifestyle factors, dietary supplement use, and BMI. This finding was noted across all race and Hispanic origin groups, although the strength of the association varied, being strongest for NHW adults.

Perspective: USDA Nutrition Evidence Systematic Review Methodology: Grading the Strength of Evidence in Nutrition- and Public Health-Related Systematic Reviews.

The USDA's Nutrition Evidence Systematic Review (NESR) team conducts food- and nutrition-related systematic reviews used to inform US Federal guidelines and programs, including the Dietary Guidelines for Americans. NESR's systematic review methodology includes a step to grade the strength of the evidence underlying conclusion statements, which is critical for ensuring that end users understand the level of certainty in conclusions when using them to make decisions. Over time, NESR has ensured its grading process not only remains state of the art but is also designed specifically for systematic reviews that inform Federal guidelines and programs on nutrition and public health. The NESR grading process used by the 2020 Dietary Guidelines Advisory Committee included 5 grading elements: risk of bias, consistency, directness, precision, and generalizability. Evidence was grouped by study design and assessed against these elements, and the grade assigned to the entire body of evidence took into consideration the strengths and limitations of each design. Based on this assessment, 1 of 4 grades was assigned: strong, moderate, limited, or grade not assignable. The grade was clearly communicated by integrating specific language into each conclusion statement (e.g., "strong evidence demonstrates" or "limited evidence suggests"), and supported by rationale documented in the review. NESR's grading process aligns with approaches used by other organizations that conduct systematic reviews, while retaining aspects unique to NESR's role in informing Federal nutrition and public health guidelines and programs. It provides a framework that promotes consistency in grading across food- and nutrition-related reviews, while offering flexibility that allows for thorough consideration of the body of evidence underlying an individual conclusion statement. NESR's rigorous and transparent methods for grading the strength of evidence in food- and nutrition-related systematic reviews ensure that decisions related to nutrition and public health are based on the strongest available evidence.

Association between cord blood metabolites in tryptophan pathway and childhood risk of autism spectrum disorder and attention-deficit hyperactivity disorder.

Alterations in tryptophan and serotonin have been implicated in various mental disorders; but studies are limited on child neurodevelopmental disabilities such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). This prospective cohort study examined the associations between levels of tryptophan and select metabolites (5-methoxytryptophol (5-MTX), 5-hydroxytryptophan (5-HTP), serotonin, N-acetyltrytophan) in cord plasma (collected at birth) and physician-diagnosed ASD, ADHD and other developmental disabilities (DD) in childhood. The study sample (n = 996) derived from the Boston Birth Cohort, which included 326 neurotypical children, 87 ASD, 269 ADHD, and 314 other DD children (mutually exclusive). These participants were enrolled at birth and followed-up prospectively (from October 1, 1998 to June 30, 2018) at the Boston Medical Center. Higher levels of cord 5-MTX was associated with a lower risk of ASD (aOR: 0.56, 95% CI: 0.41, 0.77) and ADHD (aOR: 0.79, 95% CI: 0.65, 0.96) per Z-score increase, after adjusting for potential confounders. Similarly, children with cord 5-MTX ≥ 25th percentile (vs. <25th percentile) had a reduction in ASD (aOR: 0.27, 95% CI: 0.14, 0.49) and ADHD risks (aOR: 0.45, 95% CI: 0.29, 0.70). In contrast, higher levels of cord tryptophan, 5-HTP and N-acetyltryptophan were associated with higher risk of ADHD, with aOR: 1.25, 95% CI: 1.03, 1.51; aOR: 1.32, 95% CI: 1.08, 1.61; and aOR: 1.27, 95% CI: 1.05, 1.53, respectively, but not with ASD and other DD. Cord serotonin was not associated with ASD, ADHD, and other DD. Most findings remained statistically significant in the sensitivity and subgroup analyses.

Perinatal Acetaminophen Exposure and Childhood Attention-Deficit/Hyperactivity Disorder (ADHD): Exploring the Role of Umbilical Cord Plasma Metabolites in Oxidative Stress Pathways.

Oxidative stress mechanisms may explain associations between perinatal acetaminophen exposure and childhood attention-deficit hyperactivity disorder (ADHD). We investigated whether the changes in umbilical cord plasma amino acids needed to synthesize the antioxidant glutathione and in the oxidative stress biomarker 8-hydroxy-deoxyguanosine may explain the association between cord plasma acetaminophen and ADHD in the Boston Birth Cohort (BBC). Mother-child dyads were followed at the Boston Medical Center between 1998 and 2018. Cord plasma analytes were measured from archived samples collected at birth. Physician diagnoses of childhood ADHD were obtained from medical records. The final sample consisted of 568 participants (child mean age [SD]: 9.3 [3.5] years, 315 (52.8%) male, 248 (43.7%) ADHD, 320 (56.3%) neurotypical development). Cord unmetabolized acetaminophen was positively correlated with methionine (R = 0.33, p < 0.001), serine (R = 0.30, p < 0.001), glycine (R = 0.34, p < 0.001), and glutamate (R = 0.16, p < 0.001). Children with cord acetaminophen levels >50th percentile appeared to have higher risk of ADHD for each increase in cord 8-hydroxy-deoxyguanosine level. Adjusting for covariates, increasing cord methionine, glycine, serine, and 8-hydroxy-deoxyguanosine were associated with significantly higher odds for childhood ADHD. Cord methionine statistically mediated 22.1% (natural indirect effect logOR = 0.167, SE = 0.071, p = 0.019) and glycine mediated 22.0% (natural indirect effect logOR = 0.166, SE = 0.078, p = 0.032) of the association between cord acetaminophen >50th percentile with ADHD. Our findings provide some clues, but additional investigation into oxidative stress pathways and the association of acetaminophen exposure and childhood ADHD is warranted.

Maternal prenatal selenium levels and child risk of neurodevelopmental disorders: A prospective birth cohort study.

Selenium (Se) is an essential trace element involved in various biological processes, including neurodevelopment. Available literature indicates that both Se deficiency and excess may be detrimental to health. It is also known that Se can cross the placenta from maternal to fetal circulation. To date, the role of maternal Se status in child long-term neurodevelopment is largely unexplored. This study investigated the temporal and dose-response associations between maternal Se status and child risk of neurodevelopmental disorders including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). It consisted of 1550 mother-infant dyads from the Boston Birth Cohort. Maternal red blood cell (RBC) Se levels were measured in samples collected within 72 h of delivery (biomarker of third trimester Se status). Pediatric neurodevelopmental diagnoses were obtained from electronic medical records. Data analyses showed that maternal RBC Se levels were positively associated with child risk of developing ASD, with an adjusted odds ratio of 1.49 for ASD (95% CI: 1.09, 2.02) per IQR increase in Se. There was also a positive association between maternal Se and ADHD (OR: 1.29; 95% CI: 1.04, 1.56, per IQR increase in Se). These associations remained robust even after adjusting for pertinent covariables; and there was no significant interaction between Se and these covariables. Our findings suggest that prenatal exposure to high maternal Se levels may adversely affect child neurodevelopment. Our findings warrant further investigation; if confirmed, optimizing maternal prenatal Se levels may be necessary to maximize its health benefits while preventing undue risk. LAY SUMMARY: Selenium (Se) is an essential nutrient for the health of the pregnant mother and her baby. While Se can readily cross the placenta from maternal to fetal circulation, little is known about maternal Se status on her child's neurodevelopmental outcomes. We studied over 1500 mother-child dyads from birth to school age of the child. We found that babies born from mothers with high blood Se levels may be at increased risk of developing autism spectrum disorder or attention deficit hyperactivity disorder. Given this is the first study of the kind, more study is needed to confirm our findings.

A prospective birth cohort study on cord blood folate subtypes and risk of autism spectrum disorder.

BACKGROUND: We previously reported that extremely high concentrations of maternal plasma folate were associated with increased risk of autism spectrum disorder (ASD) in children. This study explored whether specific types of folate in cord blood have differential association with ASD. OBJECTIVES: In the Boston Birth Cohort (BBC), we assessed the association between cord blood unmetabolized folic acid (UMFA), 5-methyl tetrahydrofolate (THF), and total folate and a child's ASD risk. In a subset, we explored whether the association between UMFA and ASD risk can be affected by the dihydrofolate reductase (DHFR) genotype and cord plasma creatinine. We also examined prenatal correlates of cord UMFA concentrations. METHODS: This report included 567 BBC children (92 ASD, 475 neurotypical), who were recruited at birth and prospectively followed at the Boston Medical Center. ASD was defined from International Classification of Diseases (ICD)-9 and ICD-10 codes documented in electronic medical records. RESULTS: Children with cord UMFA in the highest, versus lowest quartile, had a greater ASD risk (adjusted OR, aORquartile4: 2.26; 95% CI: 1.08, 4.75). When stratified by race/ethnicity, the association was limited to 311 (45 ASD) Black children (aORquartile4: 9.85; 95% CI: 2.53, 38.31); a test of interaction between race/ethnicity and cord UMFA concentrations was significant (P = 0.007). The UMFA-ASD association in Black children slightly attenuated after adjusting for cord plasma creatinine (P = 0.05). There was no significant association between cord 5-methyl THF, total folate, DHFR genotype, and ASD risk. Cord total folate and maternal supplement intake during second trimester were associated with higher cord UMFA. CONCLUSIONS: Higher concentrations of cord UMFA, but not 5-methyl THF or total folate, were associated with a greater risk of ASD in Black children. This study in a preterm-birth-enriched cohort raises more questions than it could answer and underscores the need for additional investigations on the sources and role of cord UMFA in children's neurodevelopmental outcomes and underlying mechanisms.

Household coverage of vitamin A fortification of edible oil in Bangladesh.

Mandatory fortification of edible oil (soybean and palm) with vitamin A was decreed in Bangladesh in 2013. Yet, there is a dearth of data on the availability and consumption of vitamin A fortifiable oil at household level across population sub-groups. To fill this gap, our study used a nationally representative survey in Bangladesh to assess the purchase of fortifiable edible oil among households and project potential vitamin A intake across population sub-groups. Data is presented by strata, age range and poverty-the factors that potentially influence oil coverage. Across 1,512 households, purchase of commercially produced fortifiable edible oil was high (87.5%). Urban households were more likely to purchase fortifiable oil (94.0%) than households in rural low performing (79.7%) and rural other strata (88.1%) (p value: 0.01). Households in poverty were less likely to purchase fortifiable oil (82.1%) than households not in poverty (91.4%) (p <0.001). Projected estimates suggested that vitamin A fortified edible oil would at least partially meet daily vitamin A estimated average requirement (EAR) for the majority of the population. However, certain population sub-groups may still have vitamin A intake below the EAR and alternative strategies may be applied to address the vitamin A needs of these vulnerable sub-groups. This study concludes that a high percentage of Bangladeshi population across different sub-groups have access to fortifiable edible oil and further provides evidence to support mandatory edible oil fortification with vitamin A in Bangladesh.

Cord and Early Childhood Plasma Adiponectin Levels and Autism Risk: A Prospective Birth Cohort Study.

Emerging research suggests that adiponectin, a cytokine produced by adipose tissue, may be implicated in ASD. In this prospective birth cohort study (n = 847), we assessed the association between cord, early childhood plasma adiponectin and the risk of developing ASD. ASD was defined based on ICD codes of physician diagnosis. Cord adiponectin levels were inversely associated with ASD risk (aOR 0.50; 95% CI 0.33, 0.77), independent of preterm birth, early childhood adiponectin and other known ASD risk factors. Early childhood adiponectin, assessed prior to ASD diagnosis, was associated with lower risk of ASD, which attenuated after adjusting for cord adiponectin, indicating the relative importance of cord adiponectin in ASD risk. Further research is warranted to confirm our findings and elucidate biological mechanisms.

Preterm birth subtypes, placental pathology findings, and risk of neurodevelopmental disabilities during childhood.

INTRODUCTION: Preterm birth (PTB) and in-utero inflammation are recognized risk factors of neurodevelopmental disabilities (NDDs); however, their combined role in NDDs is unknown. We examined the independent and joint association of PTB and placental histological findings with the childhood risk of NDDs (overall and by subgroups including autism spectrum disorder (ASD) and ADHD). METHODS: We analyzed data from the Boston Birth Cohort, where mother-infant pairs were enrolled at birth and followed from birth onwards. Birth outcomes, placental pathology and NDDs were obtained from electronic medical records. Placental pathology was categorized using a standardized classification system proposed by the Amsterdam Placental Workshop Group. RESULTS: PTB (all, including spontaneous, medically indicated) was an independent risk factor for NDDs. Placental histological chorioamnionitis (CA) and PTB additively increased the odds of NDDs (aOR: 2.16, 95% CI: 1.37, 3.39), as well as ADHD (aOR: 2.75, 95% CI: 1.55, 4.90), other developmental disabilities (aOR: 1.96, 95% CI: 1.18, 3.25) and possibly ASD (aOR: 2.31, 95% CI: 0.99, 5.39). The above associations were more pronounced in spontaneous than medically indicated PTB. PTB alone in the absence of CA only had a moderate association with ASD and ADHD. Placental maternal vascular malperfusion alone or in combination with PTB was not associated with the risk of NDDs. DISCUSSION: Our study provided new insights on PTB and NDDs by further considering preterm subtypes and placental histology. We revealed that children of spontaneous PTB along with histological CA were at the highest risk for a spectrum of NDDs.