Does vitamin C cause hemolysis in premature newborn infants? Results of a multicenter double-blind, randomized, controlled trial.
OBJECTIVE
We tested the hypothesis that vitamin C supplementation of premature neonates is associated with hemolysis.


METHODS
A double-blind, randomized, controlled trial of vitamin C supplementation (50 mg/day) was undertaken in premature neonates (birth weight, 1000 to 1500 gm). Infants were randomly assigned to receive vitamin C (Ce-Vi-Sol) (n = 32) or placebo (n = 24) for 14 days. Twenty-three subjects per group were required to detect a difference of 1 SD in corrected carboxyhemoglobin values (alpha = 0.05, beta = 0.10).


RESULTS
Day 14 vitamin C levels were lower in control subjects than in supplemented neonates (62 +/- 24 vs 125 +/- 62 micromol/L, p = 0.005). There was no difference in corrected blood carboxyhemoglogin concentrations (0.72 +/- 0.44 vs 0.72 +/- 0.23%; p = 0.95), other parameters of hemolysis, weight gain, blood sampled, presumed septic episodes, necrotizing enterocolitis, feeding intolerance, or transfusion. On day 14, bilirubin values were higher in control subjects than in the supplemented group (77 +/- 37 vs 55 +/- 33 micromol/L; p = 0.04). When a distant outlier in the nonsupplemented group was excluded (163 micromol/L), statistical significance was lost (73 +/- 32 vs 55 +/- 33 micromol/L; p = 0.09).


CONCLUSIONS
Oral supplementation of premature infants with vitamin C is not associated with evidence of increased erythrocyte destruction, hyperbilirubinemia, or other morbidity.
Doyle
J
J
Hospital for Sick Children, Women's College Hospital, and Mount Sinai Hospital Department of Pediatrics, University of Toronto, Ontario, Canada.
Vreman
H J
HJ
Stevenson
D K
DK
Brown
E J
EJ
Schmidt
B
B
Paes
B
B
Ohlsson
A
A
Boulton
J
J
Kelly
E
E
Gillie
P
P
Lewis
N
N
Merko
S
S
Shaw
D
D
Zipursky
A
A
D000743:Anemia, Hemolytic / Q000139:chemically induced; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology*; D007235:Infant, Premature, Diseases / Q000139:chemically induced; D008297:Male
D001205:Ascorbic Acid