Vitamin E supplementation for prevention of morbidity and mortality in preterm infants.
BACKGROUND
Treating very low birth weight (VLBW) infants with pharmacologic doses of vitamin E as an antioxidant agent has been proposed for preventing or limiting retinopathy of prematurity, intracranial hemorrhage, hemolytic anemia, and chronic lung disease. However, excessive doses of vitamin E may result in side effects.


OBJECTIVE
The aim of this systematic review was to assess the effects of vitamin E supplementation on morbidity and mortality in preterm infants.


METHODS
We searched MEDLINE (October 2002), EMBASE (March 2002), the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library, 2003, Issue 1, and personal files for clinical trials assessing vitamin E in preterm infants.


METHODS
We selected trials analyzing primary outcomes (mortality or combined long-term morbidity) or secondary outcomes (other morbidity) in infants with gestational age less than 37 weeks or birth weight less than 2500 grams. The intervention was allocation to routine supplementation with vitamin E in the treatment group versus placebo, no treatment or another type, dose or route of administration of vitamin E.


METHODS
We used standard methods of the Cochrane Collaboration and of the Cochrane Neonatal Review Group.


RESULTS
Twenty-six randomized clinical trials fulfilled entry criteria. No study assessed combined long-term morbidity. Routine vitamin E supplementation significantly reduced the risk of germinal/intraventricular hemorrhage (typical relative risk [RR] 0.85, 95% confidence interval [CI] 0.73, 0.99), increased the risk of sepsis (typical RR 1.52, CI 1.13, 2.04) and increased hemoglobin concentration by a small amount, but did not significantly affect mortality and other morbidity. In VLBW infants, vitamin E supplementation increased the risk of sepsis, and reduced the risk of severe retinopathy and blindness among those examined. Subgroup analyses in VLBW infants showed (1) an association between serum tocopherol levels greater than 3.5 mg/dl and increased risk of sepsis and reduced risk for severe retinopathy among those examined; and (2) an association between intravenous, high-dose administration of vitamin E and increased risk of sepsis.


CONCLUSIONS
Vitamin E supplementation in preterm infants reduced the risk of intracranial hemorrhage but increased the risk of sepsis. In very low birth weight infants it increased the risk of sepsis, and reduced the risk of severe retinopathy and blindness among those examined. Evidence does not support the routine use of vitamin E supplementation by intravenous route at high doses, or aiming at serum tocopherol levels greater than 3.5 mg/dl.
Brion
L P
LP
Pediatrics, Section of Neonatology, Albert Einstein College of Medicine, Children's Hospital at Montefiore, Weiler Hospital Room 725, 1825 Eastchester Road, Bronx, NY 10461, USA.
Bell
E F
EF
Raghuveer
T S
TS
D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000401:mortality* / Q000517:prevention & control*; D019102:Infant, Very Low Birth Weight; D009017:Morbidity; D016032:Randomized Controlled Trials as Topic; D014810:Vitamin E / Q000008:administration & dosage*
D014810:Vitamin E