Vitamin E supplementation reduces frequency of periventricular haemorrhage in very preterm babies. Protective effect of vitamin E (DL-alpha-tocopherol) against intraventricular haemorrhage in premature babies. Vitamin E and selenium in preterm infants: lack of effect on clinical patency of ductus arteriosus. Vitamin E requirements of preterm infants. Effect of intramuscular vitamin E on mortality and intracranial hemorrhage in neonates of 1000 grams or less. The effect of vitamin E on erythrocyte hemolysis and lipid peroxidation in newborn premature infants. Vitamin E supplementation in very-low-birth-weight infants: long-term follow-up at two different levels of vitamin E supplementation. Effects of vitamin E supplementation during erythropoietin treatment of the anaemia of prematurity. Retrolental fibroplasia and vitamin E in the preterm infant--comparison of oral versus intramuscular:oral administration.
231 babies, born at less than or equal to 32 weeks' gestation were enrolled in a randomised, controlled trial to assess the efficacy of vitamin E (dl-alpha-tocopherol acetate) in the prevention of periventricular haemorrhage. Daily supplementation with 20 mg/kg vitamin E intramuscularly during the first 3 days of life was associated with a rise in plasma vitamin E concentration and a reduction in hydrogen peroxide haemolysis of red blood cells in vitro. Among babies without haemorrhage on entry to the trial (n = 210), supplemented babies had a lower frequency of intraventricular haemorrhage than controls (8.8% v 34.3%; p less than 0.005) and a lower combined frequency of intraventricular and parenchymal haemorrhage (10.8% v 40.7%; p less than 0.0001) on the final ultrasound brain scan. This protective effect was observed in both inborn and referred babies but was stronger in the former. Supplementation had no effect on mortality, but among survivors fewer supplemented babies than controls had intraventricular or parenchymal haemorrhage (10.7% v 32.6%; p less than 0.001). Possibly, vitamin E scavenges free radicals generated during ischaemic injury of the subependymal region and thereby limits tissue damage and the extent of periventricular haemorrhage on reperfusion. Forty four babies, of less than 32 weeks' gestation, were either randomly given 25 mg/kg vitamin E (DL-alpha-tocopherol acetate) intramuscularly after birth (day 0) and on days 1, 2, and 3 or served as controls. Frequent real time ultrasound examinations of the brain were made in each baby during the first week and less frequently thereafter. In babies under 32 weeks' gestation the incidence of intraventricular haemorrhage was lower in supplemented babies (18.8%) compared with the controls (56.3%). On days 0, 1, 2, and 3 median plasma vitamin E concentrations in babies without haemorrhage and in those with subependymal haemorrhage only were similar. Babies with intraventricular haemorrhage had lower median concentrations on day 1 (p less than 0.002) and day 2 (p less than 0.05) compared with those with subependymal haemorrhage and lower concentrations on day 0 (p less than 0.02) and day 1 (p less than 0.05) compared with those without haemorrhage. These findings suggest that in premature babies vitamin E, an antioxidant, protects endothelial cell membranes from oxidative damage and disruption and limits the magnitude of haemorrhage and its spread from the subependyma into the ventricles. Levels of antioxidant defenses, which include vitamin E and Se-dependent GSH-Px, are generally relatively low in the fetus and neonate. Se-dependent GSH-Px and vitamin E are known to modulate biosynthesis of eicosanoids and therefore could have the potential for affecting patency or closure of the ductus arteriosus after birth. We evaluated some indices of antioxidant defense in sick LBW infants in relationship to one another as well as to clinical PDA, and investigated the effects of producing a rapid rise in serum vitamin E levels in some of these infants. Twenty-nine sick preterm infants (B. W. 750-1750 g) were randomized into control and vitamin E supplemented groups; the latter received dl-alpha-tocopherol IM., commencing within 12 hours of birth, to a total dosage of 175 mg/kg over four weeks. Most E-supplemented infants attained serum tocopherol levels greater than 0.50 mg/dl (12 mumol/l) within 24 hours of the first dose. Vitamin E supplementation did not influence clinical patency or closure of the ductus arteriosus, and no correlation could be established between serum levels of alpha-tocopherol, Se, GSH-Px or NPS and PDA. At 4 weeks vitamin E-supplemented infants had serum levels of the other antioxidant indices that were not significantly different from the non-supplemented babies. Differences between feeding practices in earlier investigations prompted the present study of iron and vitamin E supplementation in breast milk fed preterm infants. A new and highly sensitive technique for quantitation of alpha-tocopherol in serum was used. Studies on 34 infants with a birth weight below 2000 g or gestational age less than or equal to 35 weeks showed that supplementation with 16.5 mg tocopheryl acetate/day from 10 days of age resulted in a significantly higher haemoglobin concentration and lower reticulocyte count at 8-10 weeks than supplementation with 1.5 mg/day (p is less than 0.05). Studies on 23 infants with a birth weight of 2000-2499 g revealed subnormal alpha-tocopherol levels in 2 of the infants given 1.5 mg tocopheryl acetate/day but there was no effect on the haemoglobin concentration at 8-10 weeks. There were no untoward effects of an early iron supplementation with 2-3 mg Fe++ (as ferrous succinate)/kg/day. It is concluded that extra supplementation with vitamin E is advisable also in breast milk fed preterm infants. A low dosage iron supplementation from 3 weeks of age is safe. A randomized, double-blind study to determine the effect of intramuscular vitamin E on mortality and intracranial hemorrhage (ICH) was performed. One hundred forty-nine neonates with birth weights less than or equal to 1000 g and less than or equal to 24 hours of age were grouped by weight (501 to 750 g and 751 to 1000 g) and randomized to treatment or control. The treatment group received intramuscular injections of vitamin E (dl-alpha-tocopherol) on days 1, 2, 4, and 6 of life. The control group received intramuscular injections of placebo on the same schedule. All neonates initially received oral vitamin E (100 mg/kg/day dl-alpha-tocopheryl acetate), which was subsequently adjusted to keep serum levels at 0.5 to 3.5 mg/dL. Ultrasonographic examinations of the head were performed as possible on days 1, 5 to 7, and 12 to 14. Hemorrhage was defined as mild if less than or equal to grade II ICH, or severe if grade III or IV. No significant differences in neonatal or total hospital mortality between groups were found. However, all ICH, as well as severe ICH, were significantly less in the vitamin E-treated 501 to 750-g subgroup (all ICH: 60% vs 29%; severe ICH: 32% vs 4%). When survivors were analyzed separately, a significant decrease in severe ICH was seen in the vitamin E-treated neonates (25% vs 5%). Necrotizing enterocolitis and sepsis did not occur more frequently in the neonates treated with intramuscular injections of vitamin E. Other than two cases of mild induration at injection sites, no deleterious side effects of treatment were identified. Vitamin E may have a role in the prevention of severe ICH in premature neonates weighing between 501 and 750 g. The biochemical effect of vitamin E supplementation to mothers with threatened premature delivery and to premature infants after birth has been studied. Although a weak correlation was found between maternal and cord blood vitamin E levels at birth, cord blood levels were not significantly higher in the infants from supplemented mothers than those from unsupplemented mothers. Furthermore, maternal vitamin E treatment did not prevent either erythrocyte hemolysis or lipid peroxide formation in the premature infants after birth. On the other hand, intramuscular vitamin E to infants after birth produced a marked biochemical effect, with both zero erythrocyte hemolysis and low lipid peroxide formation when serum vitamin E increased above 2 mg/100 ml. We conclude that intramuscular vitamin E immediately after birth is necessary to achieve a biochemical effect of vitamin E in the early neonatal period. (No cases of retrolental fibroplasia occurred in the present study.) This study evaluates the need of vitamin E supplementation in very-low-birth-weight infants by long-term follow-up of plasma vitamin E status during the first 15 mo of life, with two different levels of supplementation. The subjects were 51 newborn infants with birth weights less than or equal to 1520 g. During hospitalization the infants were fed human milk. On the third day of life oral vitamin E supplementation of less than or equal to 10 mg/d was started in all infants. In addition, 23 infants selected at random were given intramuscular vitamin E (20 mg/kg/d) during the first 3 d. The data indicate that the 10 mg/d supplement resulted in an adequate plasma concentration of vitamin E. After cessation of supplementation at age 3 mo, the risk of low plasma vitamin E levels increased. Although intramuscular administration resulted in long-lasting increments in mean plasma vitamin E values, some later levels in these infants were marginal. To evaluate the effects of vitamin E supplementation on haemoglobin concentration and the requirement for transfusion in premature infants treated with erythropoietin and iron.
                Randomised, double blind, placebo controlled trial. Thirty infants </=32 weeks gestation and </=1250 g birth weight, who were defined as stable based on minimal requirements for respiratory support and phlebotomy, and absence of major congenital anomalies were enrolled. All were treated with erythropoietin and iron, and were randomised to receive, in addition, either vitamin E 50 IU/day or placebo for eight weeks or until discharge, whichever came first.
                Despite higher vitamin E (alpha-tocopherol) levels in the experimental group in weeks 3 (49.0 v 28.1 micro mol/l) and 8 (66.2 v 38.5 micro mol/l), there were no differences in haemoglobin, reticulocyte count, iron concentration, or transfusion requirement.
                Oral vitamin E supplementation at 50 IU/day does not increase the response of preterm infants to erythropoietin and iron. Vitamin E obtained through standard nutrition may have been sufficient or higher doses may be required. To evaluate the efficacy of four early intramuscular injections of vitamin E given in addition to continuous minimal oral vitamin E supplementation, 168 very low-birth-weight infants (less than or equal to 1,500 g) have enrolled in a randomized, double-masked, clinical study. All infants received vitamin E orally, 100 mg/kg/d. In addition, on days 1, 2, 4, and 6, seventy-nine infants received vitamin E intramuscularly, 15, 10, 10, and 10 mg/kg, respectively. On the same days, 89 control infants received placebo intramuscular injections. Multivariate analysis of the 135 infants who survived greater than or equal to 10 weeks showed no significant difference in the development of severe retrolental fibroplasia between these two supplementation schedules (P = .86). Plasma vitamin E levels never exceeded a mean of 3.3 mg/100 mL, and no toxicity was observed. Ultrastructural analyses of seven pairs of whole eye donations from infants receiving IM vitamin E demonstrated identical kinetics of gap junction formation between adjacent spindle cells as compared with 13 pairs of whole eye donations from control infants (P greater than .3). Therefore, oral vitamin E supplementation affords retinal protection against the development of severe retrolental fibroplasia when initiated on the first day of life and maintained continuously until retinal vascularization is complete.
Vitamin E supplementation in preterm infants reduced the risk of intracranial hemorrhage but increased the risk of sepsis. In very low birth weight infants, vitamin E 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.