Neurodevelopmental outcomes at 7 years’ corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: a follow-up of a randomised controlled trial
What this study found
High-DHA feeding did not improve IQ or other neurodevelopmental outcomes at 7 years' corrected age compared with standard-DHA feeding. For the primary outcome, Full Scale IQ was 98.3 (14.0) in the high-DHA group and 98.5 (14.9) in the standard-DHA group, with an adjusted treatment effect of -0.3 (95% CI -2.9 to 2.2; p=0.79). There were no significant differences in verbal IQ, performance IQ, attention, memory, executive function, behavior, visual perception, educational progress, or quality of life. Parent-reported ADHD, autism spectrum disorder, and cerebral palsy outcomes also did not…
- Study & population
- Follow-up of a randomized controlled trial in very preterm infants born before 33 weeks' gestation at five Australian tertiary hospitals.
- Intervention
- The high-DHA arm received enteral DHA from the first week of life until 40 weeks' corrected age, with infant feeds providing about 50 mg/kg/day of DHA and preterm formula containing approximately 1.0% DHA and 0.6% AA.
- Key limitation
- Follow-up was incomplete relative to the original randomized cohort, with attrition from 657 randomized to 604 consenting and fewer children analyzed for the primary outcome.
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Open PDFOriginal abstract
Objective To determine if improvements in cognitive outcome detected at 18 months’ corrected age (CA) in infants born <33 weeks’ gestation receiving a high-docosahexaenoic acid (DHA) compared with standard-DHA diet were sustained in early childhood. Design Follow-up of a multicentre randomised controlled trial. Randomisation was stratified for sex, birth weight (<1250 vs ≥1250 g) and hospital. Setting Five Australian tertiary hospitals from 2008 to 2013. Participants 626 of the 657 participants randomised between 2001 and 2005 were eligible to participate. Interventions High-DHA (≈1% total fatty acids) enteral feeds compared with standard-DHA (≈0.3% total fatty acids) from age 2–4 days until term CA. Primary outcome Full Scale IQ of the Wechsler Abbreviated Scale of Intelligence (WASI) at 7 years CA. Prespecified subgroup analyses based on the randomisation strata (sex, birth weight) were conducted. Results 604 (92% of the 657 originally randomised) consented to participate (291 high-DHA, 313 standard-DHA). To address missing data in the 604 consenting participants (22 for primary outcome), multiple imputation was performed. The Full Scale IQ was not significantly different between groups (high-DHA 98.3, SD 14.0, standard-DHA 98.5, SD 14.9; mean difference adjusted for sex, birthweight strata and hospital −0.3, 95% CI −2.9 to 2.2; p=0.79). There were no significant differences in any secondary outcomes. In prespecified subgroup analyses, there was a significant sex by treatment interaction on measures of parent-reported executive function and behaviour. Scores were within the normal range but girls receiving the high-DHA diet scored significantly higher (poorer outcome) compared with girls receiving the standard-DHA diet. Conclusions Supplementing the diets of preterm infants with a DHA dose of approximately 1% total fatty acids from days 2–4 until term CA showed no evidence of benefit at 7 years’ CA. Trial registration number Australian New Zealand Clinical Trials Registry: ACTRN12606000327583.