Illness with fatalities in premature infants: association with an intravenous vitamin E preparation, E-Ferol.

Three clusters of an unusual syndrome in premature infants were investigated in three intensive care nurseries in 1984. A retrospective cohort study of 68 infants weighing less than or equal to 1,250 g at birth and surviving at least 72 hours revealed that in 13 infants ascites developed and in four at least two of the following abnormal laboratory values were found within a seven-day period: serum direct bilirubin greater than or equal to 2 mg/dL, blood urea nitrogen greater than or equal to 40 mg/dL or serum creatinine greater than or equal to 2 mg/dL, and platelet count less than or equal to 60,000/microL. All cases occurred after the introduction and use of intravenous E-Ferol, a vitamin E preparation that was new on the market when the clusters were reported. All 17 case infants but only 23 of 51 (45%) noncase infants received E-Ferol (P less than .0001). Case and noncase infants were similar with respect to other complications and to receipt of medications and parenteral nutrition. A dose-response relationship was found; cases occurred in infants receiving E-Ferol dosages of greater than 20 U/kg/d. Case infants who had higher daily doses of E-Ferol had a shorter latency. No new cases were reported after use of E-Ferol was stopped. Results of these investigations led to a nationwide recall of intravenous E-Ferol.

Vasculopathic hepatotoxicity associated with E-Ferol syndrome in low-birth-weight infants.

A fatal syndrome characterized by progressive clinical deterioration with unexplained thrombocytopenia, renal dysfunction, cholestasis, and ascites developed in certain infants throughout the United States who had received E-Ferol, an intravenous vitamin E supplement. We reviewed the clinical course of all 36 infants from one (index) nursery who had received E-Ferol, which contains 25 units per milliliter of dl-alpha-tocopheryl acetate solubilized with 9% polysorbate 80 and 1% polysorbate 20. The syndrome was recognized in eight of the 36 infants; affected infants had a lower birth weight (less than 1,200 g) and had received a higher total dose of E-Ferol for longer periods than the unaffected cases. We reviewed autopsy-derived tissue from 20 infants (six from the index nursery and 14 from three other collaborating nurseries) who had received the intravenous vitamin E preparation in a reported dose of 25 to 137 units/kg/day for six to 45 days between October 1983 and March 1984. The hepatic histology in the affected cases indicated a progressive injury characterized initially by Kupffer cell exfoliation, central lobular accumulation of cellular debris, and centrally accentuated panlobular congestion. Prolonged exposure to E-Ferol was associated with progressive intralobular cholestasis, inflammation of hepatic venules, and extensive sinusoidal veno-occlusion by fibrosis. We propose that vasculocentric hepatotoxicity is the basis for the observed clinical syndrome that represents the cumulative effect of one or more of the constituents of E-Ferol.

Intracranial hemorrhage in the premature. Its predictive features and outcome.

Sixty-four infants with birth weights of 500 to 1,500 g were studied to determine the incidence and outcome of intracranial hemorrhage. Thirty-seven (58%) had hemorrhage and of these 60% died. Of the survivors, progressive hydrocephalus requiring treatment developed in only two infants. Serial computerized tomographic scans with measurement of ventricular-brain width ratios were found to be useful in objectively evaluating hydrocephalus. Review of perinatal data showed no association of maternal or obstetrical factors with neonatal hemorrhage but the infants who had intracranial bleeding showed a high incidence of low Apgar scores, respiratory distress syndrome, acidosis, hypoxia, apnea, hypotension, seizures, and requirement for respiratory support. Multiple regression analysis of potentially causative factors assigned importance to low gestational age, respiratory distress syndrome, birth asphyxia (low Apgar score), and vaginal delivery.

Congenital, complete heart block in the infant of a woman with collagen vascular disease. A case report.

Persistent fetal bradycardia may have multiple etiologies. The following represents a case of persistent fetal bradycardia due to congenital heart block in the infant of a woman with suspected collagen vascular disease. A review of the literature and a discussion of the association of maternal collagen vascular disease and congenital heart block is presented. The prognosis of infants with congenital heart block is reviewed and the possible association with growth retardation discussed.

Newborn head size and neurological status. Predictors of growth and development of low birth weight infants.

One hundred eighteen infants with birth weights of 2,000 g or less were evaluated for growth and development at approximately 5 years of age. Review of neonatal data indicated that head circumference less than the tenth percentile at birth and abnormal neurological examination in the newborn period were important predictors of outcome. Both of these factors were associated with poor growth, later microcephaly, and neurological deficit. In addition, neonatal microcephaly was substantially related to poor intellectual attainment. Other associations were seen between microcephaly at birth and intrauterine growth retardation, low Apgar score, and low socioeconomic status, factors that also correlated with poor outcome.