Published biochemical reference data on trace element status in low birthweight infants is limited and needs updating for use in the clinical setting; that which is published indicates that preterm infants routinely have low stores of essential minerals such as zinc, copper, selenium and manganese. In this paper, the blood levels of the trace elements zinc, selenium, manganese and copper are reported at two points in infancy.
Our study population was generally representative of preterm infants in the UK. Only 4% of study families chose not to complete the study and their characteristics were typical of the study population. The initial human milk feeding rate (94%) among the study infants was higher than the nationally reported rate (71%) for full term infants,13
but comparable with that reported (84%) in a recent survey of low birthweight feeding practices.25
Even so, the high initial human milk feeding rate in our study may not be typical of UK preterm infants. Thus, some caution may be needed in using these trace elements levels as norms for other populations of preterm infants.
Most of the blood tests (68%) were performed within the time period of ±1.4 weeks of term or 6 months GCA and all were performed within 3 weeks of the specified age.
Clinical interventions in the neonatal unit had no observable effects on blood trace element analyses, with the exception of plasma selenium levels at term, which were lower in infants who had received blood transfusions or who had received total parenteral nutrition than in the rest of the cohort. The use of plasma depleted red cells in current transfusions and/or the babies receiving blood transfusions or total parenteral nutrition (TPN) being among the most premature could account for this effect. These differences were transitory and had disappeared by 6 months GCA.
We found a wide range of values of all analytes at term. This may be a reflection of the heterogeneous population (wide range of birth weights, gestational ages and severity of postnatal illness) in the study, or of variations in intrauterine nutrient accretion rates, or a combination of factors. By 6 months GCA, the range of values of analytes, with the exception of copper, was narrower than at term indicating that the effects of the intrauterine environment and early postnatal complications had dissipated. In addition, mean values of plasma zinc, selenium and copper increased significantly by the time of the second blood test, indicative of improved body stores. It is not clear why the range of copper values increased between term and 6 months GCA—it could be the result of variations in environmental exposure to copper.
Our observations of a decrease in blood manganese levels between term and 6 months GCA are in accord with other published values.22
High blood manganese levels around birth result from in utero accumulation.26
The subsequent decrease in blood manganese levels with age is believed to indicate the gradual movement of manganese from the blood to tissue storage. Hence, the transition in the manganese blood:tissue partition gave rise to lower manganese values for the study infants at 6 months GCA compared with those at term.
The mean values of plasma zinc were comparable with published values for preterm infants at both test points whereas the mean plasma copper value (10.1 μmol/l) was higher than the reference value at term.22
The difference between the mean copper level of the subjects at term and previously published values might have been due to the recent increase in copper content of infant milk formulations in line with the infant formula and follow‐on formula regulations and/or the variation in the copper content of water supplies with geographical location.28
The mean plasma levels of selenium at term and 6 months GCA fall within the normal ranges for infants of the same GCA.29
In general, any lack of comparability between study values and previously published data may be explained by changes in the nutritional management of preterm infants in recent years or by differences in cohort characteristics.
We did not find any gender differences in blood results at term or 6 months GCA, with the exception of a significantly higher mean whole blood selenium level, at term, and a significantly higher mean red blood cell selenium level, at 6 months GCA, in girls than in boys. Two measures of selenium status, Se‐dependent glutathione peroxidase activity and erythrocyte selenium, have previously been found to be higher in female compared with male preterm infants.30
Red blood cell and whole blood selenium levels are indicative of selenium status over a longer time than plasma selenium values.22
Thus, it could be hypothesised that boys have a higher physiological requirement for selenium than girls, such that plasma selenium levels, which reflected current nutrient intakes, were similar for both sexes but the whole and red blood cell selenium levels were lower for boys because of greater metabolic need. Alternatively, preterm girls may begin life with better selenium stores than preterm boys.
We found no associations between the trace element levels in blood and dietary intakes of protein, iron, zinc and copper at term or 6 months GCA and only one association between growth and trace element blood levels. This lack of association may be due to the wide ranges of both micronutrient intakes and the trace element blood levels, or due to not all infants having achieved metabolic equilibrium by term or that preterm infants may have marginal body stores of trace element minerals during infancy. In addition, at term, the infants' mean intake of copper was below the current recommendation and would probably not increase body stores,19
the strong homoeostatic control of body zinc status renders a correlation between blood levels and zinc intakes unlikely, except at extremes of intake, and for formula‐fed infants the copper content of the water supply may be the main determinant of copper status. Hence, the lack of an association between mineral intakes from food and milk, and plasma mineral levels is not surprising.
The association between copper intake at term and head circumference is not readily explained. This may be a chance finding or it is possible that copper may be the limiting nutrient for brain enlargement at this point but not for somatic growth. Further research is needed to elucidate the complex interactions between nutrition and brain development