Vitamin A Supplementation for Extremely-Low-Birth-Weight Infants
Jon E. Tyson, M.D., M.P.H., Linda L. Wright, M.D., William Oh, M.D., Kathleen A. Kennedy, M.D., Lisa Mele, Sc.M., Richard A. Ehrenkranz, M.D., Barbara J. Stoll, M.D., James A. Lemons, M.D., David K. Stevenson, M.D., Charles R. Bauer, M.D., Sheldon B. Korones, M.D., Avroy A. Fanaroff, M.B., B.Ch., Edward F. Donovan, M.D., M.P.H., Waldemar A. Carlo, M.D., Seetha Shankaran, M.D., Ann R. Stark, M.D., Lu-Ann Papile, M.D., Alan Jobe, M.D., Ph.D., Maria Stacewicz-Sapuntzakis, Ph.D., Joel Verter, Ph.D., for The National Institute of Child Health Human Development Neonatal Research Network
Background Vitamin A supplementation may reduce the risk ofchronic lung disease and sepsis in extremely-low-birth-weightinfants. The results of our pilot study suggested that a doseof 5000 IU administered intramuscularly three times per weekfor four weeks was more effective than the lower doses givenin past trials.
Methods We performed a multicenter, blinded, randomized trialto assess the effectiveness and safety of this regimen as comparedwith sham treatment in 807 infants in need of respiratory support24 hours after birth. The mean birth weight was 770 g in thevitamin A group and 769 g in the control group, and the respectivegestational ages were 26.8 and 26.7 weeks.
Results By 36 weeks' postmenstrual age, 59 of the 405 infants(15 percent) in the vitamin A group and 55 of the 402 infants(14 percent) in the control group had died. The primary outcome death or chronic lung disease at 36 weeks' postmenstrualage occurred in significantly fewer infants in the vitaminA group than in the control group (55 percent vs. 62 percent;relative risk, 0.89; 95 percent confidence interval, 0.80 to0.99). Overall, 1 additional infant survived without chroniclung disease for every 14 to 15 infants who received vitaminA supplements. The proportions of infants in the vitamin A groupand the control group who had signs of potential vitamin A toxicitywere similar. The proportion of infants with serum retinol valuesbelow 20 µg per deciliter (0.70 µmol per liter)was lower in the vitamin A group than in the control group (25percent vs. 54 percent, P<0.001).
Conclusions Intramuscular administration of 5000 IU of vitaminA three times per week for four weeks reduced biochemical evidenceof vitamin A deficiency and slightly decreased the risk of chroniclung disease in extremely-low-birth-weight infants.
Source Information
From the University of Texas Southwestern Medical Center, Dallas (J.E.T., K.A.K.); the National Institute of Child Health and Human Development, Bethesda, Md. (L.L.W.); Women and Infant's Hospital, Providence, R.I. (W.O.); George Washington University Biostatistics Center, Rockville, Md. (L.M.); Yale University, New Haven, Conn. (R.A.E.); Emory University, Atlanta (B.J.S.); Indiana University, Indianapolis (J.A.L.); Stanford University, Stanford, Calif. (D.K.S.); University of Miami, Miami (C.R.B.); University of Tennessee, Memphis (S.B.K.); and Case Western Reserve University, Cleveland (A.A.F.). Other authors were Edward F. Donovan, M.D., M.P.H., University of Cincinnati, Cincinnati; Waldemar A. Carlo, M.D., University of Alabama, Birmingham; Seetha Shankaran, M.D., Wayne State University, Detroit; Ann R. Stark, M.D., Brigham and Women's Hospital, Boston; Lu-Ann Papile, M.D., University of New Mexico, Albuquerque; Alan Jobe, M.D., Ph.D., Children's Hospital Medical Center, Cincinnati; Maria Stacewicz-Sapuntzakis, Ph.D., University of Illinois at Chicago, Chicago; and Joel Verter, Ph.D., George Washington University Biostatistics Center, Rockville, Md.
Address reprint requests to Dr. Tyson at UT Houston, 6431 Fannin, Suite 3.228, Houston, TX 77030.
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