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Vitamin E supplementation for prevention of morbidity and mortality in preterm infants
L P Brion1, E F Bell, T S Raghuveer
1Pediatrics, Section of Neonatology, Albert Einstein College of Medicine, Children's Hospital at Montefiore, Weiler Hospital Room 725, 1825 Eastchester Road, Bronx, NY 10461, USA. brionlp@aol.com
Insights
Vitamin E supplementation for preterm infants shows mixed results. It reduces intracranial hemorrhage and severe retinopathy but increases sepsis risk, especially with high-dose intravenous use.
Area of Science:
- Neonatal medicine
- Clinical pharmacology
Background:
- Vitamin E, an antioxidant, is explored for preventing morbidities in very low birth weight (VLBW) infants.
- Potential side effects exist with excessive vitamin E doses.
Purpose of the Study:
- To systematically review the effects of vitamin E supplementation on morbidity and mortality in preterm infants.
Main Methods:
- Searched MEDLINE, EMBASE, and CCTR for randomized clinical trials on vitamin E in preterm infants.
- Included infants <37 weeks gestation or <2500g birth weight, comparing vitamin E to placebo/control.
- Utilized Cochrane Collaboration and Neonatal Review Group methodologies.
Main Results:
- Twenty-six trials were included; none assessed combined long-term morbidity.
- Vitamin E reduced germinal matrix/intraventricular hemorrhage and severe retinopathy/blindness in VLBW infants.
- Increased sepsis risk observed, particularly with intravenous, high-dose vitamin E or serum tocopherol >3.5 mg/dl.
Conclusions:
- Vitamin E supplementation in preterm infants reduces intracranial hemorrhage and severe retinopathy but increases sepsis risk.
- Routine high-dose intravenous vitamin E or targeting serum tocopherol >3.5 mg/dl is not supported.
- Careful consideration of route and dose is crucial for vitamin E use in neonates.
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.
Objectives:
The aim of this systematic review was to assess the effects of vitamin E supplementation on morbidity and mortality in preterm infants.
Search Strategy:
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.
Selection Criteria:
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.
Data Collection And Analysis:
We used standard methods of the Cochrane Collaboration and of the Cochrane Neonatal Review Group.
Main Results:
Twenty-six randomized clinical trials fulfilled entry criteria. No study assessed combined long-term morbidity. Routine vitamin E supplementation significantly increased hemoglobin concentration by a small amount. Vitamin E significantly reduced the risk of germinal matrix/intraventricular hemorrhage and increased the risk of sepsis; however, heterogeneity limits the strength of these latter two inferences. Vitamin E did not significantly affect other morbidity or mortality. In VLBW infants, vitamin E supplementation significantly increased the risk of sepsis, and reduced the risk of severe retinopathy and blindness among those examined. Subgroup analyses showed (1) an association between intravenous, high-dose vitamin E supplementation and increased risk of sepsis and of parenchymal cerebral hemorrhage; (2) an association between vitamin E supplementation by other than the intravenous route and reduced risk of germinal matrix-intraventricular hemorrhage and of severe intraventricular hemorrhage; and (3) 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.
Reviewer'S 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.