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      The Influence of Omega-3 Long-Chain Polyunsaturated Fatty Acid, Docosahexaenoic Acid, on Child Behavioral Functioning: A Review of Randomized Controlled Trials of DHA Supplementation in Pregnancy, the Neonatal Period and Infancy

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          Abstract

          This is a review of randomized controlled trials using docosahexaenoic acid (DHA) interventions in the first 1000 days of life with assessments of behavioral functioning in childhood. Electronic databases were searched for trials with a DHA intervention (compared with a placebo group that received no or less DHA) at any time to either women or infants during the first 1000 days, with a subsequent assessment of child behavior. There were 25 trials involving 10,320 mother–child pairs, and 71 assessments of behavior in 6867 of the children (66.5% of those originally enrolled). From the 71 assessments administered, there were 401 comparisons between a DHA group and a control group, with most reporting a null effect. There were no findings of a positive effect of DHA, and 23 instances where the DHA group had worse scores compared with the control group. There was limited evidence that DHA supplementation had any effect on behavioral development, although two of the largest trials with behavioral measures detected adverse effects. Future trials, and future follow-ups of existing trials, should make an effort to evaluate the effect of DHA intervention on behavioral functioning.

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          Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

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            Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis.

            The cognitive and behavioral outcomes of school-aged children who were born preterm have been reported extensively. Many of these studies have methodological flaws that preclude an accurate estimate of the long-term outcomes of prematurity. To estimate the effect of preterm birth on cognition and behavior in school-aged children. MEDLINE search (1980 to November 2001) for English-language articles, supplemented by a manual search of personal files maintained by 2 of the authors. We included case-control studies reporting cognitive and/or behavioral data of children who were born preterm and who were evaluated after their fifth birthday if the attrition rate was less than 30%. From the 227 reviewed studies, cognitive data from 15 studies and behavioral data from 16 studies were selected. Data on population demographics, study characteristics, and cognitive and behavioral outcomes were extracted from each study, entered in a customized database, and reviewed twice to minimize error. Differences between the mean cognitive scores of cases and controls were pooled. Homogeneity across studies was formally tested using a general variance-based method and graphically using Galbraith plots. Linear meta-analysis regression models were fitted to explore the impact of birth weight and gestational age on cognitive outcomes. Study-specific relative risks (RRs) were calculated for the incidence of attention-deficit/hyperactivity disorder (ADHD) and pooled. Quality assessment of the studies was performed based on a 10-point scale. Publication bias was examined using Begg modified funnel plots and formally tested using the Egger weighted-linear regression method. Among 1556 cases and 1720 controls, controls had significantly higher cognitive scores compared with children who were born preterm (weighted mean difference, 10.9; 95% confidence interval [CI], 9.2-12.5). The mean cognitive scores of preterm-born cases and term-born controls were directly proportional to their birth weight (R(2) = 0.51; P<.001) and gestational age (R(2) = 0.49; P<.001). Age at evaluation had no significant correlation with mean difference in cognitive scores (R(2) = 0.12; P =.20). Preterm-born children showed increases in externalizing and internalizing behaviors in 81% of studies and had more than twice the RR for developing ADHD (pooled RR, 2.64; 95% CI, 1.85-3.78). No differences were noted in cognition and behaviors based on the quality of the study. Children who were born preterm are at risk for reduced cognitive test scores and their immaturity at birth is directly proportional to the mean cognitive scores at school age. Preterm-born children also show an increased incidence of ADHD and other behaviors.
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              Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments.

              Nonpharmacological treatments are available for attention deficit hyperactivity disorder (ADHD), although their efficacy remains uncertain. The authors undertook meta-analyses of the efficacy of dietary (restricted elimination diets, artificial food color exclusions, and free fatty acid supplementation) and psychological (cognitive training, neurofeedback, and behavioral interventions) ADHD treatments. Using a common systematic search and a rigorous coding and data extraction strategy across domains, the authors searched electronic databases to identify published randomized controlled trials that involved individuals who were diagnosed with ADHD (or who met a validated cutoff on a recognized rating scale) and that included an ADHD outcome. Fifty-four of the 2,904 nonduplicate screened records were included in the analyses. Two different analyses were performed. When the outcome measure was based on ADHD assessments by raters closest to the therapeutic setting, all dietary (standardized mean differences=0.21-0.48) and psychological (standardized mean differences=0.40-0.64) treatments produced statistically significant effects. However, when the best probably blinded assessment was employed, effects remained significant for free fatty acid supplementation (standardized mean difference=0.16) and artificial food color exclusion (standardized mean difference=0.42) but were substantially attenuated to nonsignificant levels for other treatments. Free fatty acid supplementation produced small but significant reductions in ADHD symptoms even with probably blinded assessments, although the clinical significance of these effects remains to be determined. Artificial food color exclusion produced larger effects but often in individuals selected for food sensitivities. Better evidence for efficacy from blinded assessments is required for behavioral interventions, neurofeedback, cognitive training, and restricted elimination diets before they can be supported as treatments for core ADHD symptoms.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                28 January 2021
                February 2021
                : 13
                : 2
                : 415
                Affiliations
                [1 ]Women and Kids, South Australian Health and Medical Research Institute, 72 King William Road, 5006 Adelaide, Australia; maria.makrides@ 123456sahmri.com
                [2 ]School of Psychology and Discipline of Paediatrics, Faculty of Health and Medical Sciences, The University of Adelaide, 5005 Adelaide, Australia
                [3 ]School of Psychology, Faculty of Health and Medical Sciences, The University of Adelaide, 5005 Adelaide, Australia; Rachel.roberts@ 123456adelaide.edu.au
                [4 ]Discipline of Paediatrics, Faculty of Health and Medical Sciences, The University of Adelaide, 5005 Adelaide, Australia
                Author notes
                [* ]Correspondence: jacqueline.gould@ 123456sahmri.com ; Tel.: +61-8128-4423
                Author information
                https://orcid.org/0000-0002-9547-9995
                https://orcid.org/0000-0003-3832-541X
                Article
                nutrients-13-00415
                10.3390/nu13020415
                7911027
                33525526
                d6135b68-cdd0-4b86-8865-8aeed59716c9
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 14 January 2021
                : 25 January 2021
                Categories
                Review

                Nutrition & Dietetics
                dha,omega-3 fatty acids,supplementation,behavior,behavioral problems,prenatal,postnatal,neonatal,infant

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