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

C.T. Collins, R.A. Gibson, P.J. Anderson, A.J. Mcphee, T.R. Sullivan, J.F. Gould, P.F. Ryan, L. Doyle, P.G. Davis, J.E. Mcmichael, Noel French, P.B. Colditz, Karen Simmer, S.A. Morris, M. Makrides

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    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.

    Original languageEnglish
    Pages (from-to)1-12
    JournalBMJ Open
    Volume5
    Issue number3
    DOIs
    Publication statusPublished - 18 Mar 2015

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