PROJECT SUMMARY/ABSTRACT
One in 10 children in the U.S. is born preterm and consequently at high risk for long-term cognitive deficits and
poor academic performance. While omega-3 docosahexaenoic fatty acid (DHA) dietary supplements have been
touted to promote cognitive development in children born preterm, several recent studies have produced
suggestive evidence of long-term adverse effects. The long-term goal is to ensure that interventions to help
children born preterm succeed in school are safe and effective. The objective of this application is to determine
the long-term effects of DHA supplementation on general cognitive ability, language, and executive function, and
to examine genetic explanations for treatment effects, by continuing to follow the children from the fully blind,
randomized, placebo-controlled trial called Omega Tots. The central hypothesis is that children born preterm
who were randomized to 180 days of DHA at age 1 will exhibit poorer general cognitive ability, greater language
deficits, and more impaired executive function at age 9-10 versus children randomized to placebo. The rationale
for this project is that a careful examination of the long-term effects of DHA supplementation will offer valuable
clarification about the appropriateness of DHA as an intervention to promote neurodevelopment among children
born preterm. The central hypothesis will be tested by pursuing 2 specific aims: 1) Determine the long-term effect
of DHA supplementation at age 1 year by comparing general cognitive ability, language, and multiple facets of
executive function between the DHA and placebo arms at age 9-10. 2) Determine the role of variability in fatty
acid metabolism genetics en masse on the effect of DHA supplementation on short and long-term outcomes,
and further focus on 2 previously published FADS2 genetic variants. Under Aim 1, the approach will be an
innovative prospective cohort of children from Omega Tots who will participate in detailed, in-person
assessments at age 9-10 including evaluation by blind assessors and parent and teacher reports of outcomes.
For Aim 2, SNP-based heritability methods will examine the role of fatty acid metabolism genes as measured in
stored blood or saliva to explain observed treatment effects. The proposed research is innovative, in the
applicant's opinion, because it represents a substantive departure from the status quo by conducting robust,
multi-informant follow-up assessment of general cognitive development, language and executive function of a
large child cohort who participated in a DHA supplementation trial, as well as integrating, for the first time ever,
consideration of fatty acid metabolism genetics as possible explanatory factors for short and long-term adverse
effects. The expected outcome is the determination of the effects of DHA supplementation at age 1 on cognitive
ability, language, and multiple facets of executive function at age 9-10, and new insight into the role of specific
genetic contributors as explanatory mechanisms for short and long-term effects. This contribution is expected to
be significant because, if DHA supplementation has persistent, adverse effects on the neurodevelopment of US
children born preterm, such findings would directly inform clinical recommendations about supplementation.