Objective: To determine if docosahexaenoic acid (DHA) and arachidonic acid (ARA) supplementation influences growth or visual acuity of formula-fed premature infants. Study design: Double-blind, multi-center study of 194 premature infants given preterm formula with no DHA or ARA (control), 0.15% energy DHA, or 0.14% DHA + 0.27% ARA from single-cell triglycerides for at least 28 days and then fed term formula (no DHA or ARA) to 57 weeks postmenstrual age (PMA), with 90 breast-fed term infants as reference. Results: Infants fed DHA+ARA formula gained weight significantly faster (post-hoc analysis) during preterm formula feeding than control infants (34.7 vs. 30.7 g/d) and had weights and weight:length ratios not different from term breast- fed infants at 48 and 57 weeks PMA. Infants fed control or DHA formula had lower body weights than term infants. Red blood cell phosphatidylethanolamine ARA was significantly correlated to weight gain during preterm formula feeding and to weight and length at 40, 48, and 57 weeks PMA (r = 0.19 to 0.24, P = .004-.02). Providing DHA or DHA+ARA during the preterm period had no effect on subsequent visual acuity or incidence of adverse events. Conclusions: Feeding DHA+ARA from single-cell triglycerides enhances weight gain in formula-fed premature infants with no evidence of adverse effects. (J Pediatr 2002;140:547-54) 547 and retina and are accumulated in large amounts during the last trimester of ges- tation. 1 Although the neurochemical basis for the importance of DHA is un- clear, reduced brain DHA results in de- creased visual function and performance in learning tasks and altered serotonin and dopamine metabolism in animals. 1-3 ARA is found in membrane phospho- lipids throughout the body, and is impor- Docosahexaenoic acid and arachidonic acid enhance growth with no adverse effects in preterm infants fed formula Sheila M. Innis, PhD, RDN, David H. Adamkin, MD, Robert T. Hall, MD, Satish C. Kalhan, MD, Cheryl Lair, RD, Mary Lim, MD, Dennis C. Stevens, MD, Paul F. Twist, DO, Deborah A. Diersen-Schade, PhD, Cheryl L. Harris, MS, Kimberly L. Merkel, RPh, and James W. Hansen, MD From the Department of Pediatrics, University of British Columbia, Vancouver, Canada; Department of Pediatrics, University of Louisville, Kentucky; Children’s Hospital, Kansas City, Missouri; Rainbow Babies and Children’s Hos- pital, Cleveland, Ohio; Southwestern Medical Center, Dallas, Texas; Pomona Valley Hospital, Pomona, California; University of South Dakota Medical School, Sioux Falls; Winthrop University Hospital, Minneola, New York; and Mead Johnson Research Center, Evansville, Indiana. All funding for this study as well as infant formulas studied, was provided by Mead Johnson Nu- tritionals. A preliminary report of this work was presented at the Fourth International Congress on Essen- tial Fatty Acids and Eicosanoids and appeared in the conference proceedings in Essential Fatty Acids and Eicosanoids, Invited Papers from the Fourth International Congress. Riemersma RA, Armstrong R, Kelly RW, Wilson R, editors. Champaign (IL): AOCS Press; 1998. Submitted for publication Jan 17, 2001; revisions received July 3, 2001, and Dec 17, 2001; ac- cepted Jan 23, 2002. Reprint requests: Sheila M. Innis, PhD, RDN, British Columbia Research Institute for Chil- dren’s and Women’s Health, University of British Columbia, 950 West 28th Ave, Vancouver, BC, Canada V5Z 4H4. Copyright © 2002, Mosby, Inc. All rights reserved. 0022-3476/2002/$35.00 + 0 9/21/123282 doi:10.1067/mpd.2002.123282 ANOVA Analysis of variance ARA Arachidonic acid DHA Docosahexaenoic acid EPA Eicosapentaenoic acid LA Linoleic acid LCPUFA Long-chain polyunsaturated fatty acids LNA α-linoleic acid PC Phosphatidylcholine PE Phosphatidylethanolamine PMA Postmenstrual age RBC Red blood cell acid (ARA, 20:4n-6) has been an inten- sively studied area of infant nutrition. ARA and DHA are the major LCPUFA in the nonmyelin membranes of the brain The physiologic significance of a dietary supply of the long-chain polyunsaturated fatty acids (LCPUFA), docosahexaenoic acid (DHA, 22:6n-3), and arachidonic