High-dose Docosahexaenoic Acid Supplementation in Preterm Infants Does Not Improve Behavioral Functioning at 5 years of age

1. Docosahexaenoic acid supplementation at the in utero dose for infants born at less than 29 weeks gestation did not improve behavioral and emotional functioning at 5 years of age.

2. No differences in executive functioning or health were found between the children who had received high-dose docosahexaenoic acid and the children who had not.

Evidence Rating Level: 2 (Good)       

Study Rundown: Following preterm birth, children are at increased risk of developing behavioral problems, neurobehavioral disability, impaired executive functioning, chronic disease, and poor quality of life. Those born at less than 30 weeks’ gestation have decreased exposure to docosahexaenoic acid (DHA) which is hypothesized to be important for intellectual and behavioral development. Recent work has demonstrated that DHA supplementation improves IQ at five years of age. As such, this study sought to determine if it has similarly positive effects on behavioral functioning, executive functioning, and health in long term follow up. Infants born at less than 29 weeks’ gestation were given either daily DHA supplementation or a placebo until 36 weeks postmenstrual age or discharge home, whichever came first. The study team  assessed these infants five years later using the Strengths and Difficulties Questionnaire (SDQ) and the Pediatric Quality of Life Inventory (PedsQL). Parents were asked to report various health outcomes and whether their child had accessed allied health care or school support services. At five year follow-up, no difference was found in behavioral functioning as assessed by the SDQ or  health-related quality of life as assessed by the PedsQL.  Similarly,  no difference was noted in rates of surgeries, disability, respiratory-related hospitalizations, and use of allied health or school support services. This study contributes to our understanding of the role of DHA in prenatal development, suggesting that DHA supplementation does not improve behavioral and emotional functioning, executive functioning, and health at five years of age. Future work should distinguish whether there is a dose related effect to the benefit of DHA supplementation or if DHA is unrelated to this aspect of development. 

Click to read the study in JAMA Pediatrics

Relevant Reading: Neonatal docosahexaenoic acid in preterm infants and intelligence at 5 years

In-Depth [retrospective cohort]: This study was a five year follow-up of a multi-center, double-blind parallel-placebo randomized clinical trial to evaluate the effect of DHA supplementation in preterm infants. Infants received either the DHA emulsion or a placebo three times daily, from within three days of their first enteral feed until 36 weeks’ postmenstrual age or discharge home, whichever occurred first. Parents completed the SDQ, PedsQL, and reported whether their child had been diagnosed with any medical conditions, had been hospitalized due to respiratory illness, had undergone surgery, or had accessed allied health care or school support services. Analyses were performed using Stata on an intention-to-treat basis. Subgroup analyses were conducted to determine if the effects of DHA supplementation were mediated by sex and gestational age. Exploratory post hoc comparisons were performed to evaluate whether DHA supplementation influenced the proportion of abnormal SDQ scores. Of the 1028 children who were enrolled at the 10 centers, 731 (76% of the surviving children) had scores for the primary outcome. Between the intervention and control groups, there were no significant differences in the SDQ Total Difficulties scores (adjusted mean difference of 0.01, 95% CI -0.87 to 0.89, P = 0.98) and PedsQL scores (adjusted effect of 0.59, 95% CI -1.92 to 3.09, P = 0.65). No significant difference was found between groups in their rates of surgeries, disability, hospitalizations due to respiratory illness, or use of allied health or school support services. 

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