Developmental and Behavioral Follow-up at Age 2 Years of Preterm Children Supplemented with Docosahexaenoic and Arachidonic Acid at Age 1 Year: The Omega Tots Trial

Sarah Keim ^1,2,3 Kelly Boone ⁴ Krista Pattison ⁵ Taniqua Ingol ² Grace Pelak ² Kelly Sheppard ² Mary Ann Nelin ⁶ Mark Klebanoff ^1,3,6,7 Joseph Rausch ^1,2 Keith Yeates ^8,9 Abigail Norris Turner ^3,10 Lynette Rogers ^1,6

¹Pediatrics, The Ohio State University College of Medicine, USA
²Center for Biobehavioral Health, Nationwide Children's Hospital, USA
³Epidemiology, The Ohio State University College of Public Health, USA
⁴Crane Center for Early Childhood Research and Policy, The Ohio State University, USA
⁵Pediatrics, Pennsylvania State University College of Medicine, USA
⁶Center for Perinatal Research, Nationwide Children's Hospital, USA
⁷Obstetrics and Gynecology, The Ohio State University College of Medicine, USA
⁸Alberta Children's Research Institute, University of Calgary, Canada
⁹Hotchkiss Brain Institute, University of Calgary, Canada
¹⁰Internal Medicine, The Ohio State University College of Medicine, USA

Background: Toddlers consume low amounts of docosahexaenoic acid (DHA) post-weaning. The Omega Tots randomized, blind, placebo-controlled trial of children born at

Objective: To determine whether daily DHA and arachidonic acid (AA) supplementation at age 1 year improves development and behavior at age 2 years among children born preterm.

Methods: Omega Tots participants were followed up at 26-35 months’ chronological age to assess longer-term outcomes. Parents remained blind to treatment assignment and completed the Developmental Profile-3 (global cognitive); MacArthur-Bates Communicative Development Inventory (expressive language); Behavior Rating Inventory of Executive Function (BRIEF-P); Child Behavior Checklist 1.5-5 ADHD, PDD, attention; and reported diagnoses. Analyses were intent-to-treat. Mixed models compared treatment groups, controlling for clustering and baseline scores whenever possible. Sub-group effects for language by birthweight and for executive function by income were explored because adverse effects were observed in the original trial.

Results: Parents of 261/328 (80%) eligible children participated. No benefits of supplementation were observed at age 2 (see Table). The DHA+AA group had lower standard cognitive scores than the placebo group, but this was not statistically significant (median=107 vs 114, P=0.28). The DHA+AA group was twice as likely to have a current developmental/behavioral diagnosis (OR=2.02, 95% CI: 1.01, 4.05). In exploratory sub-group analyses, children with birthweight P=0.03, effect size=-0.44). Effects observed in the original trial on executive function by income were no longer present.

Conclusion: Long-term, robust assessment is needed to clarify the long-term effects of DHA+AA supplementation in toddlerhood for children born preterm.

Table