Unusual Syndrome with Fatalities among Premature Infants:
Association with a New Intravenous Vitamin E Product
Since March 9, 1984, CDC has received reports from two
hospitals
of clusters of an unusual illness occurring among low-birthweight
(less than 1,500 grams), premature infants in neonatal
intensive-care
units. Thirteen affected infants in these two hospitals developed
clinically significant ascites, in addition to some or all of the
following abnormalities: hepatomegaly, splenomegaly, cholestatic
jaundice, azotemia, and thrombocytopenia. Eight infants have died.
All affected infants had received parenteral nutrition therapy, in
addition to other supportive measures and therapeutic interventions
common to the care of low-birthweight infants. An intravenous
vitamin
E preparation, containing 25 mg/ml vitamin E, 9% polysorbate 80 and
1%
polysorbate 20 in 2-ml vials (E-Ferol Aqueous SolutionR,
distributed
by O'Neal, Jones & Feldman, St. Louis, Missouri), was introduced in
each hospital for addition to parenteral nutrition solutions
approximately 1 month before the onset of illness in the first
infant
in both clusters. All affected infants received E-Ferol; some
affected infants received up to 1 ml or more daily. Both outbreaks
ceased shortly after use of E-Ferol was discontinued.
In collaboration with the state health departments, CDC is
conducting ongoing epidemiologic investigations at both
institutions.
Although the etiology and pathophysiology of this syndrome are
presently unclear, the U.S. Food and Drug Administration (FDA) and
CDC
recommend that E-Ferol not be used. FDA and the distributor have
initiated a voluntary recall of the product. The product, which
has
been marketed since December 1983, is not the subject of an
Approved
New Drug Application by FDA.
Reported by V Lorch, MD, MD Murphy, MD, University of Tennessee
Research Center and Hospital, Knoxville, RH Hutcheson, MD, State
Epidemiologist, Tennessee Dept of Health and Environment; N
Kosmetatos, MD, D Frank, MD, Good Samaritan Hospital, Cincinnati,
TJ
Halpin, MD, State Epidemiologist, Ohio State Dept of Health; Center
for Drugs and Biologics, US Food and Drug Administration; Hospital
Infections Program, Div of Viral Diseases, Center for Infectious
Diseases, Center for Environmental Health, CDC.
Editorial Note
Editorial Note: Premature neonates are reported to have a relative
deficiency of vitamin E at birth, which has been associated with
hemolytic anemia in premature infants (1). Although vitamin E is
reported to have a therapeutic benefit in treating this form of
hemolytic disease in premature infants and may have a role in
preventing the development of retrolental fibroplasia and
bronchopulmonary dysplasia in infants requiring oxygen therapy, the
benefit, risk, and dosage relationships are, at present, uncertain
(1,2).
Other vitamin E preparations are available for enteral,
subcutaneous, and intramuscular administration. Vitamin E is a
component, at lower concentrations, of multivitamin preparations
for
intravenous use. Use of these alternative vitamin E preparations
has
not been temporally associated with the severe clinical syndrome
described above. However, other complications, such as cholestatic
jaundice, have been associated with total parenteral nutrition
therapy
(3), and thrombocytopenia with lipid emulsion therapy (4).
Additional reports of similar severe illness should be reported
through appropriate state health officials to the Epidemiology
Development Branch, Division of Drug and Biologic Experience, FDA
(301) 443-6410 or the Hospital Infections Program, Center for
Infectious Diseases, CDC (404) 329-3406.
References
Ehrenkranz RA. Vitamin E and the neonate. Am J Dis Child
1980;134:1157-66.
Hittner HM, Godio LB, Rudolph AJ, et al. Retrolental
fibroplasia: efficacy of vitamin E in a double blind clinical
study of preterm infants. N Eng J Med 1981;305:1365-71.
Bernstein J, Chang CH, Brough AJ, Heidelberger KP. Conjugated
hyperbilirubinemia in infancy associated with parenteral
alimentation. J Pediatr 1977;90;361-7.
Lipson AH, Pritchard J, Thomas G. Thrombocytopenia after
intralipid infusion in a neonate. Lancet 1974;I:1462-3.
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