Brief clinical and laboratory observation

Vitamin E in placental blood and its interrelationship to maternal and newborn levels of vitamin E

In evaluating vitamin E (VE) nutritional status of preterm infants, it is essential that any data should be compared with those of healthy term infants, and never with those of adults. Moreover, it should be evaluated in terms of gestational age (GA), not birth weight (BW), because placental transfer of most nutrients from mother to fetus is dependent on GA, not BW. Judging from the limited data during the last 75 years, there was no significant correlation between GA and VE concentrations in circulation or in the red blood cells (RBCs), leukocytes, and buccal mucosal cells. In addition, the oxidizability of polyunsaturated fatty acids (PUFAs) in plasma or RBCs, as targets for protection by VE chain-breaking ability, was lower in preterm infants. However, because of the minimal information available about hepatic VE levels, which is considered a key determinant of whole body VE status, the decision on whether VE status of preterm infants is comparable with that of term infants should be postponed.

Clinical trials of VE supplementation in preterm infants were repeatedly undertaken to investigate whether VE reduces severity or inhibits development of several diseases specific to preterm infants, namely retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and germinal matrix hemorrhage - intraventricular hemorrhage (GMH-IVH). Most of these trials resulted in a misfire, with a few exceptions for IVH prevention. However, almost all these studies were performed from 1980s to early 1990s, in the pre-surfactant era, and the study populations were composed of mid-preterm infants with GAs of approximately 30 weeks (wks). There is considerable difference in ‘preterm infants’ between the pre- and post-surfactant eras; modern neonatal medicine mainly treats preterm infants of 28 wks GA or less. Therefore, these results are difficult to apply in modern neonatal care.

Before considering new trials of VE supplementation, we should fully understand modern neonatal medicine, especially the recent method of oxygen supplementation. Additionally, a deeper understanding of recent progress in pathophysiology and therapies for possible target diseases is necessary to decide whether VE administration is still worth re-challenging in modern neonatal intensive care units (NICUs). In this review, we present recent concepts and therapeutic trends in ROP, BPD, and GMH-IVH for those unfamiliar with neonatal medicine.

Numerous studies have reported the possible involvement of reactive oxygen species (ROS)-induced damage in relation to supplemental oxygen use, inflammation, and immature antioxidant defense in the development of both BPD and ROP. Various antioxidants effectively prevented the exacerbation of BPD and ROP in animal models. In the future, VE should be re-attempted as a complementary factor in combination with various therapies for BPD, ROP, and GMH-IVH. Because VE is a natural and safe supplement, we are certain that it will attract attention again in preterm medicine.

We measured plasma and erythrocyte vitamin E (VE) and plasma vitamin A (VA) profiles in 48 full-term and 8 preterm pairs of neonates and their mothers at birth and we determined whether there is any relationship between maternal and umbilical cord for the nutrients measured. At the same time, we assessed the influence of the delivery type and neonate anthropometric measurements on maternal and cord blood VA and VE levels. We measured vitamin levels in vein and arterial blood in order to establish differences due to fetal metabolism. To determine the influence of pregnancy on vitamin levels, we compared the maternal results with data from a group of 13 non-pregnant women. Cord blood had lower plasma VE (arterial 275.8±71.7 μg/dl and vein 282.89±64.4 μg/dl values), erythrocyte VE (arterial 256.96±50.41 μg/dl packet cells and vein 257.41±44.35 μg/dl values), and VA levels (arterial 26.72±11.83 μg/dl and 27.15±10.05 μg/dl values) and a lower vitamin E/total lipids ratio (VE/LT) (arterial 1.60±0.4 and vein 1.62±0.3 values) than maternal blood (1474.62±424.51 μg/dl, 305.94±54.75 μg/dl packet cells, 41.03±18.83 μg/dl, 2.34±0.5, respectively). VA levels were higher in preterm than full-term neonates (P<0.05). Plasma and erythrocyte VE levels were not correlated in maternal blood but were correlated in neonates and infants (r>0.40; P<0.01). We found a good correlation between erythrocyte tocopherol of maternal and cord blood (r>0.40; P<0.01), although there was no correlation with plasma VE values. Cord vein plasma VE levels were higher than cord arterial blood measurements (P<0.01). The plasma VE and VE/LT of the mother and cord following vaginal delivery were higher than measurements from caesarean delivery (P<0.05), although erythrocyte levels were similar. The plasma VE level was higher in mothers at delivery than non-pregnant women.

OBJECTIVE: The purpose was to establish which blood characteristics of vitamin E status were highly correlated between mothers and fetuses during gestation.

STUDY DESIGN: Twenty-four pregnant women were selected because of suspicion of toxoplasmosis or other disease and malformation or intrauterine growth delay justifying cord blood puncture. After maternal and fetal blood was collected, analyses of plasma and red blood cell vitamin E contents were performed together with analyses of standard lipid parameters and lipoprotein (a) in maternal plasma and fatty acid compositions of maternal and fetal red blood cells.

RESULTS: The maternal population was characterized by a plasma lipid-normalized vitamin E mean content higher (3.5 mmol/mol lipids) than usually found in nonpregnant adults. There was no relationship between plasma and red blood cell vitamin E contents. This was also true for fetuses. When the vitamin E status of mothers was compared with that of fetuses, we found no correlation in plasma vitamin E in the whole population and in the high lipoprotein (a) (>300 mg/L) and low lipoprotein (a) (<300 mg/L) groups. In contrast, statistically significant correlations appeared between maternal and fetal red blood cell contents and red blood cell relative changes in vitamin E in the whole population, whereas still higher correlations occurred in the high lipoprotein (a) group (r = 0.94 for the red blood cell content). Improved correlations were also found in the high lipoprotein (a) group for the interrelationship between vitamin E and plasma lipid contents (cholesterol and triglycerides), whereas improvement was noted in the low lipoprotein (a) group by positive correlation between age and vitamin E red blood cell content or red blood cell relative charge.

CONCLUSION: Determination of red blood cell vitamin E and plasma lipoprotein (a) in mothers could be useful in antenatal blood analysis in cases of ris of prematurity at birth, to prevent peroxidative membrane damage in neonates, and > 85% of the mothers in the current population would benefit from vitamin E supplementation from the viewpoint of the fetal red blood cell vitamin E requirement in spite of the rather high maternal lipid-normalized vitamin E plasma content.

Following the advice given by the Department of Health to women who are, or may become pregnant, not to eat liver and liver products because of the risk of vitamin A toxicity, the concentrations of vitamins A and E, and copper, magnesium and zinc in cord blood were investigated. The study was conducted in Hackney, an inner city area of London. Esters of vitamin A were not detected in any of the samples, indicating that there was no biochemical evidence of a risk of toxicity. Indeed, vitamin A correlated significantly with birthweight, head circumference, length, and gestation period. There was also a significant positive relationship between zinc and birthweight. In contrast, copper showed a negative correlation with birth-weight and head circumference. Vitamin E and magnesium were not associated with any of the anthropometric measurements, although magnesium showed an increasing trend with birthweight. The data suggest that most of the mothers of the subjects studied may have been marginal with respect to vitamins A and E and zinc. In those with low birthweight babies, a higher intake would have improved their nutritional status and possibly the outcome of their pregnancy. For these low-income mothers, liver and liver products are the cheapest and the best source of vitamins A and E, haem iron, B vitamins and several other essential nutrients; hence the advice of the Department of Health may have been misplaced.