Folate, leptin, adiponectin and development of Autism Spectrum Disorder: A prospective birth cohort study

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in social interaction and communication, and by the presence of restrictive repetitive behavior. The precise cause of ASD is largely unknown, but is thought to be due to genetic predisposition combined with environmental factors. Emerging epidemiological studies have identified several non-genetic risk factors for ASD, many of which may have their origins during prenatal and early postnatal periods. Among these, nutritional and metabolic factors during critical early life windows may be important, but they have not been well studied in a prospective birth cohort. To address some of these knowledge gaps, this dissertation focused on the prospective associations between: 1) maternal folate and vitamin B12 status and development of ASD in children (specific aim 1); and 2) child’s leptin and adiponectin levels and development of ASD (specific aims 2 and 3). Data from the Boston Birth Cohort (BBC), a large prospective birth cohort, consisting of a predominantly urban, low-income minority population, were used. The BBC recruited mother-child pairs at birth and followed them from birth onwards for pediatric outcomes including ASD. Electronic Medical Records were used to identify children with ASD and other neurodevelopmental disorders. For specific aim 1, maternal folate status was defined using two complementary measures: maternal self-reported intake via questionnaire and maternal plasma biomarker of folate and vitamin B12 levels. Mothers’ supplement intake during pregnancy was associated with a ‘U-shaped’ relationship in ASD risk in their children. In addition, extremely high maternal plasma folate and vitamin B12 levels were associated with a greater risk of developing ASD in children. For specific aims 2 and 3, the child’s plasma leptin and adiponectin levels were measured at two-time points: cord blood collected at delivery and venous blood collected in early childhood. Children with highest early childhood leptin levels (quartile 4), when compared to those with lowest levels (quartile 1), showed an increased risk of developing ASD. Extremely rapid weight gain during 1st year of life was associated with a greater ASD risk, when compared to those children whose growth was on track and this association persisted after adjusting for pertinent confounders. Early childhood leptin partially mediated the association between 1st year weight gain and ASD. However, no association with ASD was found for fetal growth pattern and cord leptin levels. On the other hand, cord adiponectin levels were inversely associated with ASD risk and this was independent of preterm birth, early childhood adiponectin and other known ASD risk factors. While higher early childhood adiponectin was also associated with a lower risk of ASD, the association attenuated after adjusting for cord adiponectin. The findings from this dissertation, if confirmed by future studies, could have important clinical and public health implications. Notably, findings from specific aim 1 underscore the need to 1) regularly monitor folate levels in women of reproductive age (both at clinical and population level); and 2) identify an optimal plasma folate levels, so that adverse effects of both low and high levels of folate can be averted. Findings from specific aims 2 and 3 provide a basis to further explore whether biomarkers such as leptin and adiponectin, in combination with early life growth pattern can improve our ability to detect children at high risk of developing ASD at the earliest possible age, to inform targets for early prevention

Tracking Trainees to Success

Atlanta Conference on Science and Innovation Policy 2009This presentation was part of the session : Science and Innovation WorkforceThis material is presented to ensure timely dissemination of scholarly and technical work. Copyright and all rights therein are retained by authors or by other copyright holders. All persons copying this information are expected to adhere to the terms and constraints invoked by each author's copyright. In most cases, these works may not be reposted without the explicit permission of the copyright holder. ©2009 IEEE. Personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution to servers or lists, or to reuse any copyrighted component of this work in other works must be obtained from the IEEE

Tracking Trainees to Success

Atlanta Conference on Science and Innovation Policy 2009This presentation was part of the session : Science and Innovation WorkforceThis material is presented to ensure timely dissemination of scholarly and technical work. Copyright and all rights therein are retained by authors or by other copyright holders. All persons copying this information are expected to adhere to the terms and constraints invoked by each author's copyright. In most cases, these works may not be reposted without the explicit permission of the copyright holder. ©2009 IEEE. Personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution to servers or lists, or to reuse any copyrighted component of this work in other works must be obtained from the IEEE

Vitamin D status and prevalence of metabolic syndrome by race and Hispanic origin in U.S. adults: findings from 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 U.S. adults and by race and Hispanic origin has not been evaluated extensively. OBJECTIVES: To examine the associations between Vitamin D status and MetS overall, and across race and Hispanic origin groups in a nationally representative sample of U.S. adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2014. DESIGN: The total sample included 8,639 adults, 20 years of age and over. Serum Vitamin D was measured using a standardized liquid chromatography-tandem mass spectrometry 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) 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 to the highest tertile (\u3e 77.9 nmol/L); fully adjusted model OR: 1.85 and 95% CI: 1.51, 2.27. Inverse associations were noted for all race-Hispanic origin groups: non-Hispanic White (OR: 2.24; and 95% CI: 1.67, 3.01), non-Hispanic Black (OR: 1.56; and 95% CI: 1.06, 2.29) and Hispanic (OR: 1.48; and 95% CI: 1.03, 2.14) adults. CONCLUSIONS: Lower Vitamin D status was significantly associated with MetS among U.S. 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 non-Hispanic White adults

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

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

BackgroundMaternal 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.ObjectivesWe 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.MethodsWe 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.ResultsWe 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.ConclusionsLimited 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