Fatty Acid Supplementation and Socioemotional Outcomes: Secondary Analysis of a Randomized Trial

Abstract

BACKGROUND AND OBJECTIVES: Children born preterm experience socioemotional difficulties, including increased risk of autism spectrum disorder (ASD). In this secondary analysis, we tested the effect of combined docosahexaenoic acid (DHA) and arachidonic acid (AA) supplementation during toddlerhood on caregiver-reported socioemotional outcomes of children born preterm. We hypothesized that children randomly assigned to DHA 1 AA would display better socioemotional outcomes compared with those randomly assigned to a placebo. METHODS: Omega Tots was a single-site randomized, fully masked, parallel-group, placebocontrolled trial. Children (N = 377) were 10 to 16 months at enrollment, born at ,35 weeks' gestation, and assigned to 180 days of daily 200-mg DHA 1 200-mg AA supplementation or a placebo (400 mg corn oil). Caregivers completed the Brief Infant-Toddler Social and Emotional Assessment and the Pervasive Developmental Disorders Screening Test-II, Stage 2 at the end of the trial. Liner mixed models and log-binomial regression compared socioemotional outcomes between the DHA 1 AA and placebo groups.RESULTS: Outcome data were available for 83% of children (n treatment = 161; n placebo = 153). Differences between DHA 1 AA and placebo groups on Brief Infant-Toddler Social and Emotional Assessment scores were of small magnitude (Cohen's d # 0.15) and not statistically significant. Children randomly assigned to DHA 1 AA had a decreased risk of scoring at-risk for ASD on the Pervasive Developmental Disorders Screening Test-II, Stage 2 (21% vs 32%; risk ratio = 0.66 [95% confidence interval: 0.45 to 0.97]; risk difference = 20.11 [95% confidence interval: 20.21 to 20.01]) compared with children randomly assigned to a placebo. CONCLUSIONS:No evidence of benefit of DHA 1 AA supplementation on caregiver-reported outcomes of broad socioemotional development was observed. Supplementation resulted in decreased risk of clinical concern for ASD. Further exploration in larger samples of preterm children and continued follow-up of children who received DHA 1 AA supplementation as they approach school age is warranted.WHAT'S KNOWN ON THIS SUBJECT: Preterm children are at increased risk for socioemotional difficulties, including autism spectrum disorder (ASD). Docosahexaenoic acid (DHA) supplementation may reduce ASD behaviors, but effects on socioemotional development more broadly are less clear.WHAT THIS STUDY ADDS: Differences between the DHA 1 arachidonic acid and placebo groups on socioemotional development were not statistically significant, and effects were small. Children randomly assigned to DHA 1 arachidonic acid had a decreased risk of clinical concern for ASD compared with children randomly assigned to a placebo.

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

“…Our search identified a total of 25 RCTs as eligible for inclusion, with relevant trial outcomes or details published between 1999 and 2020 across 36 publications [ 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 ]. We excluded two potentially eligible trials, one that intervened with eggs (which contain DHA as well as other nutrients that contribute to neurodevelopment) vs. no control eggs [ 116 ] and another that commenced the intervention for the majority of children after the first 1000 days period (18–38 months, mean 27 months) [ 117 ].…”

“…There were eight studies that included a parent-rated measure of general behavior [ 84 , 85 , 86 , 87 , 88 , 90 , 92 , 100 , 102 , 111 , 113 , 114 ], an additional trial that included a parent-rated measure of development with a behavior score [ 93 ], and two trials that included parent-rated measures of temperament [ 81 , 99 ].…”

“…The Conners was used in two trials [ 88 , 100 ]. The Brief Infant Toddler Social and Emotional Assessment (BITSEA) assesses socioemotional and behavioral problems in toddlerhood and was completed by parents in one of the preterm trials [ 102 ]. The BITSEA is comprised of seven scales (Competence, Problem, Externalizing, Internalizing, Dysregulation, Red Flag, ASD) which authors compared between groups as mean scores as well as dichotomized according to cut-off scores indicating a possible behavioral problem [ 102 ].…”

“…The Brief Infant Toddler Social and Emotional Assessment (BITSEA) assesses socioemotional and behavioral problems in toddlerhood and was completed by parents in one of the preterm trials [ 102 ]. The BITSEA is comprised of seven scales (Competence, Problem, Externalizing, Internalizing, Dysregulation, Red Flag, ASD) which authors compared between groups as mean scores as well as dichotomized according to cut-off scores indicating a possible behavioral problem [ 102 ]. This same trial also asked parents to complete the Pervasive Developmental Disorders Screening Test-II (PDDST) to screen for ASD in children with developmental concerns and again compared both the mean score and proportion scoring over the cut off [ 102 ].…”

“…The BITSEA is comprised of seven scales (Competence, Problem, Externalizing, Internalizing, Dysregulation, Red Flag, ASD) which authors compared between groups as mean scores as well as dichotomized according to cut-off scores indicating a possible behavioral problem [ 102 ]. This same trial also asked parents to complete the Pervasive Developmental Disorders Screening Test-II (PDDST) to screen for ASD in children with developmental concerns and again compared both the mean score and proportion scoring over the cut off [ 102 ]. The Vineland Adaptive Behavior Scales (VABS) is a parent-completed questionnaire that measures adaptive behavior and was administered in one trial of preterm infants [ 105 ].…”