Six-month intervention with wild blueberries improved speed of processing in mild cognitive decline: a double-blind, placebo-controlled, randomized clinical trial.

BACKGROUND: As the sector of the population over 65y increases, cognitive decline and dementia become a public health issue. Interventions to improve brain health and thus, quality of life for older adults are needed. OBJECTIVE: It was hypothesized that those consuming a flavonoid-rich, lyophilized wild blueberry powder would evidence improvements in cognitive performance as measured behaviorally and electrophysiologically compared to those consuming a placebo powder across a 6-month intervention period. DESIGN: In a double-blind, randomized placebo-controlled trial, participants experiencing cognitive issues as determined by scores on the Montreal Cognitive Assessment (MoCA) were randomized to consume either wild blueberry (n = 44) or placebo (n = 42) powder daily for 6 months. Participants who were not experiencing any cognitive issues were included as a reference group (n = 45). Participants were tested at baseline and outcome on the Cambridge Neurological Test Automated Battery (CANTAB) and in an electrophysiological paradigm known as event-related potentials (ERP). RESULTS: Tests of specific cognitive abilities using the CANTAB showed speed of processing not only improved in the blueberry intervention group relative to the placebo group across the 6-month intervention, but blueberries also restored speed of processing to the level of the reference group. The ERP results also showed that, relative to those consuming placebo, speed of processing improved for those in the blueberry group; this improvement was most prominent in those 75-80y. CONCLUSIONS: Consumption of wild blueberries for six months improves cognitive aging sequelae by improving the speed of information processing in older adults.Trial registration: ClinicalTrials.gov identifier: NCT01515098.

Behavioral and Cognitive Differences in Early Childhood related to Prenatal Marijuana Exposure.

Prenatal marijuana exposure (PME) negatively impacts child development and behavior; however, few studies have examined these associations at early ages among children exposed to today's highly potent marijuana. Using a prospective prenatal cohort (Columbus, Ohio, USA), PME was determined from maternal self-report, medical chart abstraction, and urine toxicology from prenatal visits and delivery. At age 3.5 years, 63 offspring children completed tasks assessing executive function (EF), visual spatial ability, emotion regulation, and aggressive behavior. Caregivers reported on children's EF and problem behaviors. Logistic regressions and analyses of covariance controlling for key variables were used to examine associations between PME and child outcomes. Compared to non-exposed children, children with PME had more sleep-related problems, withdrawal symptoms, and externalizing problems, including aggressive behaviors and oppositional defiant behaviors. Children with and without PME did not differ in terms of executive functioning. Findings suggest behavioral problems associated with PME may manifest by age 3.5.

Docosahexaenoic and Arachidonic Acid Supplementation of Toddlers Born Preterm Does Not Affect Short-Term Growth or Adiposity.

BACKGROUND: Dietary DHA intake among US toddlers is low. Healthy physical growth is an important objective for the clinical care of children born preterm. OBJECTIVES: The aim of the trial was to examine the effects of supplementing toddlers born preterm with DHA and arachidonic acid (AA) for 180 d on growth and adiposity. METHODS: Omega Tots, a randomized placebo-controlled trial, was conducted between April 2012 and March 2017. Children born at <35 wk gestation who were 10-16 mo in corrected age were assigned to receive daily oral supplements of DHA and AA (200 mg each, "DHA + AA") or corn oil (placebo) for 180 d. Prespecified secondary outcomes included weight, length, head circumference, mid-upper arm circumference, triceps and subscapular skinfolds, BMI, and their respective z scores, and body fat percentage, which were measured at baseline and trial completion. Mixed-effects regression was used to compare the change in outcomes between the DHA + AA and placebo groups, controlling for baseline values. RESULTS: Among 377 children included in the analysis (median corrected age = 15.7 mo, 48.3% female), 348 (92.3%) had growth or adiposity data at baseline and trial end. No statistically significant differences between the DHA + AA and placebo groups in growth or adiposity outcomes were observed. For instance, the change in weight-for-age z scores was 0.1 for the DHA + AA group and 0.0 for the placebo group (effect size = 0.01, P = 0.99). However, post-hoc subgroup analyses revealed a statistically significant interaction between treatment group and sex, suggesting somewhat slower linear growth for females assigned to the DHA + AA group compared with the placebo group. CONCLUSIONS: Among toddlers born preterm, daily supplementation with DHA + AA for 180 d resulted in no short-term differences in growth or adiposity compared with placebo. If DHA supplementation is implemented after the first year of life, it can be expected to have no effect on short-term growth or adiposity. This trial is registered with clinicaltrials.gov as NCT02199808.

Effect of Docosahexaenoic Acid Supplementation vs Placebo on Developmental Outcomes of Toddlers Born Preterm: A Randomized Clinical Trial.

Importance: Intake of dietary docosahexaenoic acid (DHA) among toddlers is low. Supplementation may benefit developmental outcomes of toddlers who were born preterm. Objective: To determine whether 6 months of daily DHA supplementation improves developmental outcomes of toddlers who were born preterm. Design, Setting, and Participants: A randomized, fully masked, placebo-controlled trial was conducted from April 26, 2012, to March 24, 2017, at a large US pediatric academic center with 9 neonatal intensive care units. Children born at less than 35 weeks' gestation who were 10 to 16 months corrected age underwent 6 months of intervention. Of 2363 children assessed, 982 were eligible, 605 declined, and 377 enrolled and were randomized. Analyses were according to intent to treat. Interventions: One-to-one allocation to receive daily microencapsulated DHA, 200 mg, and arachidonic acid (AA), 200 mg (DHA+AA), or microencapsulated corn oil (placebo). Main Outcomes and Measures: The primary outcome specified a priori was Bayley Scales of Infant and Toddler Development, third edition (Bayley-III), cognitive composite score at 16 to 22 months corrected age. Secondary outcomes were Bayley-III language and motor composite scores and Infant Behavior Questionnaire-Revised and Early Childhood Behavior Questionnaire effortful control and activity level scores. Subgroup analyses defined a priori were by income, sex, and birth weight. Results: Among 377 children randomized and included in the analysis (182 girls and 195 boys; median corrected age, 15.7 months), 338 children (89.7%) had complete data on the primary outcome. Bayley-III cognitive scores did not differ between the DHA+AA and placebo groups (difference in change, 0.5 [95% CI, -1.8 to 2.8]; effect size, 0.05; P = .66). Assignment to the DHA+AA group had a small to medium negative effect on Bayley-III language scores among children with lower birth weights (eg, a child with a birth weight of 1000 g assigned to receive DHA+AA experienced a 4.1-point relative decrease, while a child assigned to placebo did not; P = .03 for interaction). Supplementation had a similar negative effect on effortful control scores among children with annual household incomes greater than $35 000 (difference in change, -0.3 [95% CI, -0.4 to -0.1]; effect size, -0.37; P = .01). Bayley-III motor scores and activity level scores were unaffected. Conclusions and Relevance: Daily supplementation with 200 mg of DHA and 200 mg of AA for 6 months resulted in no improvement in cognitive development and early measures of executive function vs placebo, and may have resulted in negative effects on language development and effortful control in certain subgroups of children. These findings do not support DHA supplementation in the second year of life for children who are born preterm. Trial Registration: ClinicalTrials.gov Identifier: NCT01576783.

Bidirectional effects between parenting sensitivity and child behavior: A cross-lagged analysis across middle childhood and adolescence.

Using a longitudinal, cross-lagged design, this study examined the bidirectional relations between mothers' and fathers' sensitivity and children's externalizing (EXT) and internalizing (INT) behavior from middle childhood into adolescence. The subsample comprised families (N = 578) in which the mother and father cohabitated from the study's first time point (child age = 54 months) through Age 15 in the longitudinal NICHD Study of Early Child Care and Youth Development. Study results revealed differential patterns for mother-child and father-child relations in the full sample and separately for males and females. The full cross-lagged models revealed that child EXT behavior predicted maternal sensitivity, but not vice versa, and fathers' sensitivity and child behavior were reciprocally interrelated. There was a significant indirect pathway from early paternal sensitivity to later EXT in males, and from early maternal sensitivity to INT in females. The results point to the important roles that fathers play in child INT and EXT behaviors and important differences between males and females. (PsycINFO Database Record

ω-3 and ω-6 Fatty Acid Supplementation May Reduce Autism Symptoms Based on Parent Report in Preterm Toddlers.

Background: Children born preterm are at increased risk of autism spectrum disorder (ASD). n-3 (ω-3) Combined with n-6 (ω-6) fatty acids including γ-linolenic acid (GLA) may benefit children born preterm showing early signs of ASD. Previous trials have reported that docosahexaenoic acid (DHA) promotes cognitive development in preterm neonates and n-3 fatty acids combined with GLA improve attention-deficit-hyperactivity disorder. Objectives: The objectives of the pilot Preemie Tots Trial were 1) to confirm the feasibility of a full-scale trial in toddlers born very preterm and exhibiting ASD symptoms and 2) to explore the effects of supplementation on parent-reported ASD symptoms and related behaviors. Methods: This was a 90-d randomized, fully blinded, placebo-controlled trial in 31 children 18-38 mo of age who were born at ≤29 wk of gestation. One group was assigned to daily Omega-3-6-9 Junior (Nordic Naturals, Inc.) treatment (including 338 mg eicosapentaenoic acid, 225 mg DHA, and 83 mg GLA), and the other group received canola oil (124 mg palmitic acid, 39 mg stearic acid, 513 mg linoleic acid, 225 mg α-linolenic acid, and 1346 mg oleic acid). Mixed-effects regression analyses followed intent-to-treat analysis and explored effects on parent-reported ASD symptoms and related behaviors. Results: Of 31 children randomly assigned, 28 had complete outcome data. After accounting for baseline scores, those assigned to treatment exhibited a greater reduction in ASD symptoms per the Brief Infant Toddler Social Emotional Assessment ASD scale than did those assigned to placebo (difference in change = - 2.1 points; 95% CI: - 4.1, - 0.2 points; standardized effect size = - 0.71). No other outcome measure reflected a similar magnitude or a significant effect. Conclusions: This pilot trial confirmed adequate numbers of children enrolled and participated fully in the trial. No safety concerns were noted. It also found clinically-significant improvements in ASD symptoms for children randomly assigned to receive Omega-3-6-9 Junior, but effects were confined to one subscale. A future full-scale trial is warranted given the lack of effective treatments for this population. This trial was registered at www.clinicaltrials.gov as NCT01683565.

Omega-6/omega-3 fatty acid intake of children and older adults in the U.S.: dietary intake in comparison to current dietary recommendations and the Healthy Eating Index.

BACKGROUND: Omega-6 and omega-3 fatty acids (FAs) and their ratio have been shown to affect cognitive function in children and older adults. With these analyses, we aimed to describe omega-6 and omega-3 FA intake among children and older adults in light of FA intake recommendations and with consideration of overall diet. METHODS: Data were merged from two cross-sectional studies with 219 children 7 to 12 years old and one longitudinal study with 133 adults 65 to 79 years old. Demographic data, anthropometric data, and Healthy Eating Index scores were used to study relations among the omega-6 to omega-3 FA ratio and age, education, body mass index, and diet quality. FA intake, demographic, and anthropometric data were examined using partial correlations, t-tests, and analysis of variance. RESULTS: Most children and adults consumed at least the recommended amount of alpha-linolenic acid (LNA; omega-3) for their age and gender without consuming high amounts of linoleic acid (LA; omega-6), but did not consume sufficient eicosapentaenoic acid (EPA; omega-) and docosahexaenoic acid (DHA; omega-3). The average omega-6 to omega-3 ratios in both groups were lower than previously reported. Eating lower ratios was associated with healthier diets and consuming adequate amounts of several other nutrients. No demographic or anthropometric variables were related to FA intake in children. Adults with a college degree had significantly lower ratios than those without a college degree. CONCLUSIONS: American children and older adults are able to consume more balanced omega-6 to omega-3 ratios than has been indicated by commodity data. However, very few American children met even the lowest recommendations for EPA and DHA intake. Research is needed to clarify recommendations for the optimal ratio across development, which may aid in increasing EPA and DHA intake and improving health outcomes in the United States. TRIAL REGISTRATION: ClinicalTrials.gov NCT02199808 13 July 2014, NCT01823419 (retrospectively registered) 20 March 2013, and NCT01515098 18 January 2012.

Effect of Omega-3 and -6 Supplementation on Language in Preterm Toddlers Exhibiting Autism Spectrum Disorder Symptoms.

Delayed language development may be an early indicator of autism spectrum disorder (ASD). Early intervention is critical for children with ASD, and the present study presents pilot data on a clinical trial of omega-3 and -6 fatty acid supplementation and language development, a secondary trial outcome, in children at risk for ASD. We randomized 31 children to receive an omega-3 and -6 supplement or a placebo for 3 months, and measured their language abilities at baseline and after supplementation. Gesture use, but not word production, increased for children in the treatment group more than children in the placebo group. These results suggest possible effectiveness of omega-3 and -6 supplementation for language development in children at risk for ASD.

Executive functions and the ω-6-to-ω-3 fatty acid ratio: a cross-sectional study.

BACKGROUND: The ω-6 (n-6) to ω-3 (n-3) fatty acid (FA) ratio (n-6:n-3 ratio) was previously shown to be a predictor of executive function performance in children aged 7-9 y. OBJECTIVE: We aimed to replicate and extend previous findings by exploring the role of the n-6:n-3 ratio in executive function performance. We hypothesized that there would be an interaction between n-3 and the n-6:n-3 ratio, with children with low n-3 performing best with a low ratio, and those with high n-3 performing best with a high ratio. DESIGN: Children were recruited on the basis of their consumption of n-6 and n-3 FAs. The executive function performance of 78 children aged 7-12 y was tested with the use of the Cambridge Neuropsychological Test Automated Battery and a planning task. Participants provided blood for plasma FA quantification, and the caregiver completed demographic and activity questionnaires. We investigated the role of the n-6:n-3 ratio in the entire sample and separately in children aged 7-9 y (n = 41) and 10-12 y (n = 37). RESULTS: Dietary and plasma n-6:n-3 ratio and n-3 predicted performance on working memory and planning tasks in children 7-12 y old. The interaction between dietary n-6:n-3 ratio and n-3 predicted the number of moves required to solve the most difficult planning problems in children aged 7-9 y and those aged 10-12 y, similar to results from the previous study. There was also an interaction between the plasma n-6:n-3 ratio and n-3 predicting time spent thinking through the difficult 5-move planning problems. The n-6:n-3 ratio and n-3 predicted executive function performance differently in children aged 7-9 y and in those aged 10-12 y, indicating different optimal FA balances across development. CONCLUSIONS: The n-6:n-3 ratio is an important consideration in the role of FAs in cognitive function, and the optimal balance of n-6 and n-3 FAs depends on the cognitive function and developmental period studied. This trial was registered at clinicaltrials.gov as NCT02199808.

Omega-6 to omega-3 fatty acid ratio and higher-order cognitive functions in 7- to 9-y-olds: a cross-sectional study.

BACKGROUND: Biochemical and behavioral evidence has suggested that the ratio of n-6 (omega-6) to n-3 (omega-3) could be an important predictor of executive function abilities in children. OBJECTIVE: We determined the relation between the ratio of n-6 to n-3 and cognitive function in children. We hypothesized that children with lower ratios of n-6 to n-3 fatty acids would perform better on tests of planning and working memory. DESIGN: Seventy 7- to 9-y-old children completed three 24-h diet recalls and a subset of the Cambridge Neuropsychological Test Assessment Battery. Parents provided information on their demographics and children's diet histories. RESULTS: Mean n-3 and mean n-6 intakes were related to the mean time spent on each action taken in the planning problem. The ratio of n-6 to n-3 significantly predicted performance on the working memory and planning problems. There was a significant interaction between the ratio and fatty acid intake; when children had high ratios, a higher intake of n-3 fatty acids predicted a better performance on the planning task than when children had lower n-3 intakes. When children had low ratios, a lower intake of n-3 and lower intake of n-6 predicted better performance than when intakes were higher. CONCLUSIONS: The relation between cognitive abilities and the ratio of n-6 to n-3 may be mediated by an enzymatic affinity for n-3 fatty acids. The ratio of n-6 to n-3 should be considered an important factor in the study of fatty acids and cognitive development. This trial was registered at clinicaltrials.gov as NCT01823419.