Trace elements in meconium from preterm and full-term infants

Meconium samples from 23 preterm infants (birth weight = 1,097 +/- 359 g; gestational age 29 +/- 3 weeks, mean +/- SD) and 27 full-term infants (3,453 +/- 476 g; 39.5 +/- 1 weeks) were analyzed for zinc, copper, manganese, chromium and iron by atomic absorption spectrometry. Compared to meconium from preterm infants, full-term infants had an elevated (p less than 0.05) total excretion (microgram) of zinc (957 +/- 545 vs. 503 +/- 506), copper (245 +/- 256 vs. 128 +/- 94) and manganese (62 +/- 55 vs. 29 +/- 29), but not iron (190 +/- 147 vs. 332 +/- 532) or chromium (0.4 +/- 0.19 vs. 0.75 +/- 1.0). Two preterm infants had high losses (1.5 and 2 mg) of iron in their meconium. Zinc, copper and manganese losses into meconium appear to increase with gestation, whereas iron and chromium losses occur early in gestation and may be reabsorbed by term.     

Anti-oxidant enzymes and related elements in term and preterm newborns

Background:  Although oxidative stress-related diseases mostly affect neonates with extremely low birthweight, healthy preterm newborns might also be at risk of oxidative damages. The aim of the present study was to verify this possibility.
Methods:  Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), erythrocyte glutathione peroxidase (GSHPx) and superoxide dismutase (SOD), plasma and erythrocyte concentrations of selenium, zinc and copper were measured until 100 days of life in 30 preterm infants with mean ± SD birthweight and gestational age of 1605 ± 122 g and 34.5 ± 0.5 weeks. The control group included 30 term infants with birthweight 3123 158 g and gestational age 39.6 0.7 weeks.
Results:  Throughout the study period urinary 8-OHdG, taken as a marker of oxidative stress, was significantly higher in the preterm than in the term group. Up until 20 days of life, GSHPx activity was significantly lower in the preterm than in the term infants but this was not associated with any apparent selenium deficiency. Conversely, up until 100 days, preterm infants had significantly reduced SOD levels that appeared to reflect a shortage of the elements needed for this enzyme's activity, notably copper, the plasma concentrations of which were constantly and significantly below the control values.
Conclusion:  The nutritional status of the elements related to the anti-oxidant enzymes, especially zinc and copper, should be carefully assessed in preterm infants, even if their birthweight is not extremely low.     

Zinc, copper, selenium and manganese blood levels in preterm infants

Objective

To measure the zinc, copper, selenium and manganese blood levels in a cohort of 68 preterm infants, and to establish any associations with growth and/or dietary intake.

Design

Blood samples were collected at an infant''s expected date of delivery (term) and 6 months later. Serum zinc, plasma copper and whole blood manganese were analysed by atomic absorption spectrometry, plasma and red cell selenium were determined by mass spectrometry. Growth and dietary intake determinations have been previously published.

Setting

Hampshire, England.

Results

Mean (SD) birth weight of the infants was 1.47 (0.434) kg and mean gestation was 31.4 (2.9) weeks. Mean blood levels at term and 6 months were: serum zinc 12.0 (2.6) µmol/l and 13.8 (2.5) µmol/l; plasma copper 10.1 (2.6) µmol/l and 19.2 (3.6) µmol/l; plasma selenium 0.49 (0.15) µmol/l and 0.72 (0.14) µmol/l; red blood cell selenium 1.68 (0.40) µmol/l and 1.33 (0.19) µmol/l; and blood manganese 320 (189) nmol/l and 211 (68) nmol/l, respectively. There were no significant associations between levels of zinc and copper and dietary intakes of those nutrients at either age (dietary intakes of selenium and manganese were not determined). Only copper levels at term were significantly associated (r = 0.31; p = 0.05) with a growth parameter (head circumference).

Conclusion

These results provide new information about trace element status in this vulnerable population.Trace elements are essential nutrients for metabolism, growth, and neurological and immunological function.1,2,3 Zinc is an important micronutrient that supports normal growth.2 Preterm infants are especially vulnerable to zinc deficiency.4,5 Selenium is an essential component of selenoproteins including the antioxidant glutathione peroxidase. At birth, blood levels of selenium are lower in preterm infants than in term infants and continue to fall until weaning is commenced.6,7,8 Copper is a cofactor in several metalloproteins, essential for oxidative metabolism, myelination and the metabolism of several steroid hormones.2 Clinical copper deficiency is a recognised hazard among preterm infants.9 Manganese is an essential micronutrient component of several enzymes including pyruvate carboxylase, mitochondrial superoxide dismutase and enzymatic systems of matrix turnover in skeletal growth.10,11 The measurement of the variation in trace element blood levels in preterm infants throughout infancy, and the range of levels associated with good development are important areas of research.We have previously reported a randomised clinical trial of a specially devised nutritional strategy in preterm infants.12 The trial aimed to analyse blood mineral levels at term (expected date of delivery) and 6 months'' gestation corrected age (GCA), and assess dietary intake and growth at these ages. As we did not find any significant differences in the blood levels of trace elements in the two arms of the trial, in this paper we report on the combined results of all infants enrolled in the trial to provide information on zinc, selenium, copper and manganese blood levels in a healthy population of UK preterm infants. The interaction between growth and dietary intake and blood biochemistry is also explored.     

Trace elements (copper, zinc, manganese, and selenium) in plasma and erythrocytes in relation to dietary intake during infancy

All determinations of copper, zinc, manganese, and selenium were performed with a flameless atomic absorption spectrophotometer. Seventy-three full-term infants aged 1 to 52 weeks were divided into three age groups. Each age group contained two subgroups, breast-fed and formula-fed. No statistically significant differences between formula-fed and breast-fed subgroups were found in regard to the levels of copper and zinc in plasma and erythrocytes. At 1 to 5 weeks of age, the manganese concentration of erythrocytes was higher in formula-fed than in breast-fed infants (p less than 0.001). This might be due to the high dietary intake of this element in the formula-fed subgroup. On the other hand, plasma selenium concentrations were significantly higher in breast-fed than in formula-fed infants of all ages (p less than 0.01 at 1 to 5 weeks and p less than 0.05 at 6 to 52 weeks). This suggests that selenium compounds are biologically more available for infant nutrition in breast milk than in formula.     

Zinc, copper, manganese, and selenium metabolism in patients with human growth hormone deficiency or acromegaly

This study was designed to evaluate trace metal metabolism in patients with known abnormalities of human growth hormone (hGH). The mean concentration of zinc in plasma and urine decreased in patients with hGH deficiency after hGH injection, whereas, after adenomectomy, in patients with acromegaly, zinc increased in plasma, remained the same in erythrocytes, and decreased in urine. There was a negative correlation between plasma zinc and serum hGH levels and a positive correlation between urinary zinc excretion and serum hGH levels in acromegaly. In hGH deficiency, the copper content remained unchanged in plasma and erythrocytes and rose in urine after treatment; however, in acromegaly, the copper content increased in plasma and remained unchanged in erythrocytes and urine after surgery. The mean concentration of erythrocyte manganese did not change significantly after treatment in patients with hGH deficiency or acromegaly, but the pre-hGH treatment level of erythrocyte manganese in hGH deficiency was lower than in the controls. Plasma selenium concentrations were decreased in hGH deficiency and increased in acromegaly patients after therapy. These results suggest that hGH affects the metabolism of zinc, copper, manganese, and selenium.     

The role of trace elements in juvenile diabetes mellitus

There is accumulating evidence that the metabolism of several trace elements is altered in insulin-dependent diabetes mellitus and that these nutrients might have specific roles in the pathogenesis and progress of this disease. Magnesium deficiency is the most evident disturbance of metal metabolism in diabetes mellitus. Hypomagnesemia might increase the risk of ischemic heart disease and severe retinopathy. Increased urinary loss of zinc is a commonly encountered feature of diabetes. High-dose oral zinc might enhance wound healing, although data regarding diabetes are lacking. Chromium increases tissue sensitivity to insulin and tends to raise high-density lipoprotein (HDL) cholesterol and the HDL:low-density lipoprotein ratio. Selenium is involved in processes which protect the cell against oxidative damage by peroxides produced from lipid metabolism. There is one report of elevated serum selenium in diabetic children although the clinical significance of this finding is still unclear. An insulin-like effect has recently been attributed to vanadium in experimental animals, a finding of potential interest to man. Current knowledge does not implicate iron, iodine, manganese, cobalt, nickel, silicone, fluoride, molybdenum or tin in the pathophysiology of diabetes. Appropriate trace element supplementation might prove beneficial in ameliorating some physiological deficiencies associated with diabetes and prevent or retard secondary complications. However, properly designed and well-documented trials, especially on magnesium supplementation, need to be performed before rationales for such supplementation are developed. The potential roles of vanadium, chromium and selenium in diabetes constitute challenging areas for further experimental and clinical research.     

IRON REQUIREMENT IN LOW BIRTHWEIGHT INFANTS

Siimes, M.A. (Children's Hospital, University of Helsinki, Finland). Iron requirement in low birthweight infants. Acta Paediatr Scand, Suppl. 296: 101, 1982.—Since full-size newborns have adequate iron stores, severe iron deficiency anaemia rarely develops in these infants. If it develops, it is usually due to intestinal blood loss. Low birthweight infants have reduced iron stores resulting in higher nutritional iron requirements. Despite supplementation preterm infants reach at about two months lower Hb values than full-term infants, but sebsequent anaemia is prevented. Iron supplementation should at least during the first six weeks be combined with vitamin E supplementation. Different iron dosages are suggested for different birthweights.     

Meeting zinc and copper intake requirements in the parenterally fed preterm and full-term infant

To determine the intravenous zinc and copper intakes required to build up body stores in the preterm infant and achieve positive retention in full-term infants, balance studies were completed in 38 preterm, full-term, and full-term SGA infants who received complete intravenously delivered nutrient formulations excluding zinc and copper. Zinc as ZnSo4 and copper as CuCl2 were then added to individual infants' formulations, with intakes ranging from 91 to 824 micrograms/kg/day (zinc) and 8 to 92 micrograms/kg/day (copper). Samples of infusate as well as urine, stool, and aspirate were collected for 72 hours and analyzed for zinc and copper by atomic absorption spectrophotometry. Zinc and copper retention correlated significantly with intake (r = 0.89; 0.82, P less than 0.01) and were independent of gestational age, postnatal age, and birth weight. In full-term and full-term SGA infants, intakes of zinc at greater than 150 and copper at greater than 16 micrograms/kg/day were adequate to replace ongoing losses and prevent acute deficiencies. The dosage for copper is similar to the current recommendation of the American Medical Association; the zinc dosage is 50% higher. Preterm infants receiving intakes of zinc at 438 and copper at 63 micrograms/kg/day achieve in utero retention rates. These dosages are significantly higher than AMA recommendations. Both combinations can be delivered by peripheral or central line without complications.     

A Comparison of the Zinc, Copper and Manganese Status of Very Low Birth Weight Pre-Term and Full-Term Infants during the First Twelve Months

During a longitudinal study, hair samples and dietary intake data were collected from 50 preterm (mean birth weight = 1054 ± 234 g, mean gestational age = 29 ± 2.5 weeks) and 60 full-term infants (mean birth weight = 3 509 ± 269 g, mean gestational age = 40+1 weeks) at 3, 6 and 12 months of age. Mean daily zinc, copper and manganese intakes were calculated using three-day dietary records and test-weight data for the breast-fed infants. Hair samples were analyzed for these elements by instrumental neutron activation analyses. The medium hair zinc concentration in the pre-term group at six months (81 μg/g) was lower ( p < 0.05) than that of the full-term group (144 μg/g) and was associated with lower mean dietary zinc intakes at 3 and 6 months. At 12 months, the median hair copper (12.5 μg/g) and manganese (0.18 μg/g) concentrations for the pre-term were lower ( p < 0.05) than those of the full-term infants (Cu = 16.5 μg/g; Mn = 0.25 μg/g) and were also associated with low dietary copper and manganese intakes     

Zinc and copper balances in preterm infants

Preterm infants are at risk for copper and zinc depletion if sufficient quantities of these nutrients are not provided in a bioavailable form in postnatal life. The purpose of this study was to determine whether the use of a whey-predominant, 50% medium chain triglyceride formula with relatively high concentrations of zinc and copper would promote the achievement of the in utero accretion rate for zinc and copper in the preterm infant. Two groups of five preterm infants were fed a diet containing 12.5 mg/L of zinc and either 0.9 mg/L or 2.1 mg/L of copper. Seventy-two-hour metabolic balance studies were performed at an average postconceptual age of 34 weeks and an average weight of 1,549 g. All infants were in positive zinc balance and nine of ten achieved the in utero accretion rate for zinc for a 34-week gestation fetus (greater than or equal to 0.432 mg/d). Three infants receiving the high copper formula and two receiving the lower copper formula were in positive copper balance. Two infants from each group achieved the in utero accretion rate for copper for a 34-week gestation fetus (0.088 mg/d). A formula that provides 12.5 mg/L of zinc permits positive zinc balance and zinc retention similar to in utero rates. A formula that provides as much as 2.1 mg/L of copper, however, may not always permit positive copper balance.     

Zinc absorption by infants

Zinc is a vital mineral in human nutrition and rare cases of overt zinc deficiency are well described in term and preterm infants. A variety of methods have been developed to assess zinc absorption, retention and balance in humans, either using mass (metabolic) balance or stable isotope-based METHODS: The different methods have different benefits and disadvantageous. Many studies have used such methods to examine zinc absorption in term and preterm infants. In preterm infants the main interest has been establishing whether different diets lead to positive zinc balance and approached in utero accretion rates. The earliest studies were concerning as they suggested that preterm infants may be in negative zinc balances for prolonged periods after birth. Subsequent studies have been more contradictory and it remains unclear from the literature how much zinc preterm infants absorb early in life. Nor is it clear whether poor zinc absorption during this period has any long-term consequences. Studies in term infants have suggested no such prolonged period of negative zinc balance. Generally the absorption values are in line with those used by the Institute of Medicine in the most recent edition of the Dietary Reference Intakes. Other studies have been designed to assess the effect of changes in formula composition on zinc intake (e.g. the presence or absence of lactose, high vs low zinc contents, etc.). Ho-wever, despite almost 20 studies of zinc absorption in infants many physiologically important questions remain unanswered, especially in preterm infants.     

Contents of trace elements in the human liver before birth

A multielement analysis was carried out in nine fetal livers (age: 23 weeks of gestation to term) in comparison to an adult control group (n = 37). 15 elements (phosphorus to lead) were analyzed by proton-induced X-ray emission (PIXE). Significant differences between the two groups, expressed as ratios (R) of fetal to adult liver values were observed for copper (R = 16), zinc (R = 2.0), iron (R = 1.5), calcium (R = 1.34), selenium (R = 1.22), manganese (R = 0.7), and molybdenum (R = 0.13). An interesting point seems to be the inverse relation of copper and molybdenum. The negative correlation of these two trace elements which is known from animal experiments has now been confirmed in the human liver.     

Supplementation of milk with iron bound to lactoferrin using weanling mice. II: Effects on tissue manganese, zinc, and copper

Iron supplementation is recommended for formula-fed infants, and it is currently suggested that iron be supplemented in formulas at a minimum of 6 mg/L. A negative side effect of iron supplementation, however, may be a reduction in the absorption of elements with similar physicochemical properties. We investigated this possibility by evaluating the impact of iron supplementation at 6 mg/L on tissue concentrations of zinc, copper, and manganese. Weanling mice fed a supplemented diet for 4 weeks had markedly lower tissue manganese concentrations than mice fed a nonsupplemented diet. Tissue zinc and copper levels were only marginally affected. The potential negative effect of iron supplementation on manganese status in the human infant should be evaluated.     

The late preterm infant

Late preterm birth refers to birth at 34–36 weeks of gestation, which can occur for many different maternal and fetal reasons. Infants born late preterm represent almost three quarters of all preterm births, yet they have been studied much less than their more immature counterparts born at the limits of viability. Whilst problems of late preterm infants are generally fewer and milder than those of the most immature infants, nevertheless they are at increased risk of adverse neonatal outcomes. Mortality rates are higher than term infants and common morbidities in the neonatal period for late preterm infants include hypothermia, hypoglycaemia, difficulties in establishing oral feeding, jaundice and respiratory compromise. Long term health and neurodevelopmental problems, as well as educational difficulties are also known to occur, and effects of prematurity in this group may extend into adolescence and adulthood. Currently neonatal care for late preterm infants is delivered in a variety of settings and management varies between centres. This review aims to identify some of the key themes in the available evidence for late preterm babies and consider how this may impact upon health outcomes for these babies now and in future life.     

CRITICAL VITAMINS FOR LOW BIRTHWEIGHT INFANTS

Orzalesi, M. and Colarizi, P. (Department of Child Health, University of Sassari and the Department of Paediatrics, University of Rome, Italy). Critical vitamins for low birthweight infants. Acta Paediatr Scand, Suppl. 296: 00, 1982.—All vitamins are "critical" by definition for the growing infant. However, some of them are particularly relevant to the preterm or low birthweight (LBW) infant in whom a deficiency can occur more frequently than in a full-term newborn. In LBW infants vitamin deficiency may develop due to (1) low body stores at birth, (2) low intake, (3) limited absorption, (4) increased need or utilization, (5) presence of certain clinical conditions. The first reason concerns all lipid-soluble vitamins, and particularly vitamin E and K, which cross the placenta with some difficulty. Among hydro-soluble vitamins, cord-blood levels of vitamin B₆ have been shown to be abnormally low in preterm infants. Low intake can occur because of low vitamin levels in milk or because of delayed and/or insufficient feeding. Limited intestinal absorption of vitamins in LBW infants has only been demonstrated for vitamin E and folic acid. The rapid post-natal growth may lead to increased vitamin utilization. In some clinical conditions particularly high intakes of certain vitamins are indicated. In our opinion, the really "critical" vitamins in LBW infants are vitamin D, E, K and folic acid, for which routine supplementation can be recommended, and possibly vitamins C and B₆ under special circumstances.     

Reference range for micronutrients and nutritional marker proteins in cord blood of neonates appropriated for gestational ages

BACKGROUND: Reference values of numerous micronutrients at different gestational ages (GA) have not been yet reported based on large series. AIMS: This study aimed to establish the reference range for zinc, copper, selenium, vitamin A, vitamin E, retinol binding protein, transthyretin, albumin, transferrin and ceruloplasmin in neonates and to give the profiles according to gestational age. STUDY DESIGN: A total of 510 infants appropriate for gestational age were included in the study. The determinations were done using the serum cord blood of 262 term and 248 preterm infants (gestational age of 37 to 42 and 26 to 36 weeks, respectively). RESULTS: All nutrients correlated significantly with birth weight and gestational age but different patterns were highlighted. Vitamin A, retinol binding protein and prealbumin showed a triphasic pattern with a cut-off at about 36 to 39 weeks. In this period, these parameters rised significantly (P<0.001). Albumin and selenium showed a biphasic pattern with a significant positive correlation (P<0.001) between weeks 26 to 38. Transferrin and ceruloplasmin associated with copper showed a continuous increase with GA (P<0.001). On the opposite, zinc and vitamin E decreased. Zinc showed a biphasic pattern with a significant negative correlation (P<0.001) between the 26th to 34th weeks. Vitamin E presented a triphasic pattern with a cut-off at about 32 to 35 weeks (P<0.001). CONCLUSION: The large number of data allow the build-up of reference ranges and charts for the evaluation of micronutrients and proteins in high-risk neonates.     

Review of fortified food and beverage products for pregnant and lactating women and their impact on nutritional status

Fortified beverages and supplementary foods, when given during pregnancy, have been shown to have positive effects on preventing maternal anaemia and iron deficiency. Studies show that use of micronutrient fortified supplementary foods, especially those containing milk and/or essential fatty acids during pregnancy, increase mean birthweight by around 60-73 g. A few studies have also shown that fortified supplementary foods have impacts on increasing birth length and reducing preterm delivery. Fortification levels have ranged generally from 50% to 100% of the recommended nutrient intake (RNI). Iron, zinc, copper, iodine, selenium, vitamins A, D, E, C, B1, B2, B6, and B12, folic acid, niacin and pantothenic acid are important nutrients that have been included in fortified beverages and supplemental foods for pregnant and lactating women. While calcium has been shown to reduce the risk of pre-eclampsia and maternal mortality, calcium, phosphorus, potassium, magnesium and manganese can have negative impacts on organoleptic properties, so many products tested have not included these nutrients or have done so in a limited way. Fortified food supplements containing milk and essential fatty acids offer benefits to improving maternal status and pregnancy outcome. Fortified beverages containing only multiple micronutrients have been shown to reduce micronutrient deficiencies such as anaemia and iron deficiency.     

Vitamin A and preterm infants: what we know, what we don't know, and what we need to know

Vitamin A is essential for optimal growth and development. In the developing world, vitamin A supplementation of the newborn infant reduces mortality. In the developed world, extremely preterm infants are born with low body stores of vitamin A and are at high risk of vitamin A deficiency. Optimal vitamin A supplementation for this population is not clearly defined, however, and, despite evidence of benefit, early vitamin A supplementation of extremely preterm infants is not uniformly practised in the United Kingdom. There is an urgent need for studies in preterm infants that include quantification of hepatic stores and functional assessment of vitamin A status as well as long term outcome.     

Taurine in infant nutrition

The importance of taurine in diet is poorly understood. The present evidence suggests that it is a conditionally essential aminoacid in man wherein deficiency states may result in adverse changes which will be improved with supplementation. It has a role in fat absorption in preterm infants and children with cystic fibrosis, retinal dysfunction in patients receiving TPN and those with blind loop gut syndromes. Taurine is also reported to improve maturation of ABER in pre-term infants and has a role in osmoregulation of CNS and may act as neuroinhibitor.     

Zinc-deficiency dermatitis in breast-fed infants

We report ten infants (mean gestational age: 30 weeks; range: 25 to 40 weeks) with zinc deficiency dermatitis who developed erosive, impetiginized periorificial dermatitis at 10 weeks of age (corresponding to a mean gestational age of 41.4 weeks, with a range of 36-44 weeks), but who were otherwise well. Cutaneous symptoms were initially misdiagnosed as eczema or impetigo in 8/10 (80%) children who received either topical (4/8) and/or systemic (6/8) antibiotics. Topical corticosteroids were applied in 4/10 infants for a mean time of 4 weeks (range: 2 to 5 weeks) before the correct diagnosis was established by decreased serum zinc levels; skin atrophy (telangiectasia, thinning) as a complication of topical steroid treatment (class II steroids) was observed in two infants. All children responded to oral therapy with zinc sulfate or zinc gluconate (1.5-4 mg/kg/d). Skin lesions started to clear within 24 h after the initiation of therapy and had completely cleared in all infants after 14 days of therapy (range: 3-14 days). We conclude that nutritional zinc deficiency is a frequently misdiagnosed problem in thriving, fully breast-fed preterm babies. It is attributable to the decreased zinc content of human milk as compared to cow's milk, and the increased demand of zinc in rapidly thriving preterm infants. It seems advisable to routinely check serum zinc levels in fully breast-fed preterm infants who do not receive regular oral zinc supplementation once they reach a gestational age of 40 weeks.