Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: A prospective, randomized controlled trial

Deborah L. O'Connor, Robert Hall, David Adamkin, Nancy Auestad, Marcella Castillo, William E. Connor, Sonja L. Connor, Kathleen Fitzgerald, Sharon Groh-Wargo, E. Eugenie Hartmann, Joan Jacobs, Jeri Janowsky, Alan Lucas, Dean Margeson, Patricia Mena, Martha Neuringer, Mirjana Nesin, Lynn Singer, Terence Stephenson, Joanne SzaboVance Zemon

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    Objectives. A randomized, masked, controlled trial was conducted to assess effects of supplementing premature infant formulas with oils containing the long-chain polyunsaturated fatty acids, arachidonic acid (AA; 20:4n6), and docosahexaenoic acid (DHA; 22: 6n3) on growth, visual acuity, and multiple indices of development. Methods. Infants (N = 470) with birth weights 750 to 1800 g were assigned within 72 hours of the first enteral feeding to 1 of 3 formula groups with or without long-chain polyunsaturated fatty acids: 1) control (N = 144), 2) AA+DHA from fish/fungal oil (N = 140), and 3) AA+DHA from egg-derived triglyceride (egg-TG)/fish oil (N = 143). Infants were fed human milk and/or Similac Special Care with or without 0.42% AA and 0.26% DHA to term corrected age (CA), then fed human milk or NeoSure with or without 0.42% AA and 0.16% DHA to 12 months' CA. Infants fed exclusively human milk to term CA (EHM-T; N = 43) served as a reference. Results. Visual acuity measured by acuity cards at 2, 4, and 6 months' CA was not different among groups. Visual acuity measured by swept-parameter visual-evoked potentials in a subgroup from 3 sites (45 control 50 AA+DHA [fish/fungal]; 39 AA+DHA [egg-TG/fish]; and 23 EHM-T) was better in both the AA+DHA (fish/fungal; least square [LS] means [cycle/degree] ± standard error [SE; octaves] 11.4 ± 0.1) and AA+DHA (egg-TG/fish; 12.5 ± 0.1) than control (8.4 ± 0.1) and closer to that of the EHM-T group (16.0 ± 0.2) at 6 months' CA. Visual acuity improved from 4 to 6 months' CA in all but the control group. Scores on the Fagan test of novelty preference were greater in AA+DHA (egg-TG/fish; LS means ± SE, 59.4 ± 7.7) than AA+DHA (fish/fungal; 57.0 ± 7.5) and control (57.5 ± 7.4) at 6 months' CA, but not at 9 months' CA. There were no differences in the Bayley Mental Development Index at 12 months' CA. However, the Bayley motor development index was higher for AA+DHA (fish/fungal; LS means ± SE, 90.6 ± 4.4) than control (81.8 ± 4.3) for infants ≤1250 g. When Spanish-speaking infants and twins were excluded from the analyses, the MacArthur Communicative Development Inventory revealed that control infants (LS means ± SE, 94.1 ± 2.9) had lower vocabulary comprehension at 14 months' CA than AA+DHA (fish/fungal) infants (100.6 ± 2.9) or AA+DHA (egg-TG/fish) infants (102.2 ± 2.8). There were no consistent differences in weight, length, head circumference, or anthropometric gains. Conclusion. These results showed a benefit of supplementing formulas for premature infants with AA and DHA from either a fish/fungal or an egg-TG/fish source from the time of first enteral feeding to 12 months' CA.

    Original languageEnglish (US)
    Pages (from-to)359-371
    Number of pages13
    Issue number2 II
    Publication statusPublished - 2001



    • Arachidonic acid
    • Docosahexaenoic acid
    • Infant formulas
    • Long-chain polyunsaturated fatty acids
    • Premature infants

    ASJC Scopus subject areas

    • Pediatrics, Perinatology, and Child Health

    Cite this

    O'Connor, D. L., Hall, R., Adamkin, D., Auestad, N., Castillo, M., Connor, W. E., ... Zemon, V. (2001). Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: A prospective, randomized controlled trial. Pediatrics, 108(2 II), 359-371.