Plasma Copper Concentrations Research Articles

Copper and zinc status during acute inflammation: studies on blood, liver and kidneys metal levels in normal and inflamed rats.

The concentrations of copper and zinc in plasma, blood cells, liver and kidneys were determined in a study performed on normal female rats, and in female rats with carrageenan induced pleurisy. In the normal rat, the total amount of both metals increases, from 51 to 79 days of age, in all the compartments examined. This increase was mostly, and in some case exclusively, dependent upon the growth of the animal, although high individual and day to day variations in both copper and zinc values were observed in all the compartments studied. In the blood of inflamed rats a statistically significant increase in copper was measured during the crucial hours of the experiment (i.e. from 6 to 72 h); over 90% of the increase found was attributable to variations in plasma copper concentration values. In the liver of inflamed rats a statistically significant increase in zinc was measured at 6, 22 and 48 h after the carrageenan injection. The induction of the acute non-infective inflammatory process did not cause quantitative changes of both copper and zinc in all the other compartments considered in the present study. These results seem to suggest that, during acute inflammation, the organism increases its requirement for copper and zinc, and that this demand is fulfilled by enhanced intestinal absorption and/or decreased intestinal excretion of both metals.

Use of orally administered oxidised copper wire particles for copper therapy in cattle

Oxidised copper wire particles (OCWP) were given per os to cattle as an alternative to subcutaneous copper glycinate injections. OCWP were recovered from the stomachs of cattle slaughtered 3 months after treatment. OCWP (50g) treatment resulted in sustained higher plasma copper concentrations than subcutaneous injections of copper glycinate. OCWP given at high doses (300g) raised liver copper concentrations to 16 mmol/kg without clinical effects, it is concluded that OCWP could be a practical alternative to current injection methods of copper therapy.

Studies on lambs from lines genetically selected for low and high copper status 2. Incidence of hypocuprosis on improved hill pasture

ABSTRACTGrowth rate and the concentrations of various biochemical constituents were measured in 2 years in lambs from two lines, selected on low (L) and high (H) copper (Cu) concentrations in plasma, and from two unselected pure breeds, Scottish Blackface (B) and Welsh Mountain (W). The lambs grazed improved hill pastures and half were given Cu supplements.H lambs were always heavier and were fattened for slaughter earlier than were L lambs, differences that were not completely eliminated when supplementary Cu was given. In both years, the improvements in growth rate due to supplementary Cu varied with genetic type (average L 20·5 (s.e. 2·5); H 5·7 (s.e. 2·6); B 25·1 (s.e. 3·7); W 8·1 (s.e. 3·3) g/day). Growth rates of supplemented lambs were L 100 (s.e. 2), H 104 (s.e. 2), B 134 (s.e. 5), W 103 (s.e. 3) g/day.At 6 weeks of age, unsupplemented lambs trom all genetic types were hypocupraemic and, at all ages, unsupplemented L and B lambs had lower concentrations of Cu in plasma and superoxide dismutase (SOD) activity than had unsupplemented H and W lambs. Supplemented lambs always had greater concentrations of Cu in plasma and SOD activities than had their unsupplemented counterparts. Supplementation increased the haemoglobin concentration for B (in year 2) and L lambs but not for H and W lambs. Cholesterol concentrations in plasma were unaffected by selection but were slightly higher in unsupplemented lambs. The concentration of total protein and the activity of aspartate transaminase were unaffected by genotype or Cu supplementation. In the liver of lambs at slaughter, the concentration of Cu was lower for unsupplemented lambs and inversely related to the concentration of iron.It was concluded that (i) genotype was an important determinant of hypocuprosis; (ii) the degree of hypocuprosis could not be predicted from herbage analyses alone, but instead may be predicted from biochemical assessment of the lamb; and (iii) the dose of Cu supplement used was inadequate for L and B lambs and recommended levels could be increased, within limits, without risk of toxicity.

THE EFFECTS OF SULPHATE REMOVAL FROM THE DRINKING WATER ON THE PLASMA AND LIVER COPPER AND ZINC CONCENTRATIONS OF BEEF COWS AND THEIR CALVES

Pregnant Hereford cows (n = 99) and heifers (n = 98) whose ration contained 10 mg Cu kg−1 DM and 20 mg Zn kg−1 DM were assigned to two treatments. The water supply (sulphated water) for one group contained 500 mg S L−1 as sulphates. The sulphates in the water (desulphated) for the other group had been decreased to 42 mg S L−1 by reverse osmosis. Changes in plasma and liver copper and zinc concentrations were monitored in the cows and their calves during the winter drylot and pasture periods. The initial plasma and liver copper concentrations in all cows indicated a deficient status. At calving, the plasma copper concentration had declined in both groups. The greatest decrease was evident in the cows on sulphated water. At calving, the liver copper concentration had declined in both water treatment groups but was lowest in the cattle on the sulphated water. After calving, plasma and liver copper concentrations in both groups increased; this increase was greatest in the cows drinking the desulphated water. Water treatment had no effect on the copper status of the nursing calves. Water purification had a positive effect on the body weights of first and second calf heifers. Although the zinc status was normal, the plasma zinc declined and liver zinc increased in the cows at calving. These changes were independent of water treatment. When the sulphur in the drinking water was decreased to 42 mg L−1 by reverse osmosis there was a positive effect on the copper status of beef cows. Further research is required into higher dietary copper intakes, as 10 mg Cu kg−1 DM was not adequate in improving the deficient copper status of these cattle. Key words: Water sulphates, copper, zinc, beef cattle

Enzyme immunoassay for ceruloplasmin: application to cancer patient serum

Ceruloplasmin (Cp), a glycoprotein of molecular weight 132 000 contains most of the copper found in human serum [I]. Cp has been proposed to act as a copper transport agent and to carry out enzymatic functions [2]. Serum or plasma copper concentrations rise during many disease states such as cancer [3], arthritis [4] and infection [3,5] as well as during nonpathological stresses such as pregnancy [5], lactation [7] and chronic exercise [8]. Generally, increases in serum or plasma copper have been found to correspond to elevated levels of Cp oxidase activity toward one of several substrates [3-81. In the case of cancer, Cp oxidase reaches highest levels during the most severe stage of the disease [3]. On the other hand, one study found that successful treatment of several types of cancer was accompanied by a return of Cp oxidase activity concentrations toward normal [9]. Despite these various studies, no functional or diagnostic significance has been firmly established for stress-induced elevations in serum or plasma copper and Cp oxidase activity. It is very possible that the mechanisms regulating activity levels as well as the functional consequences of changes may vary for different stress conditions. Further characterization of the different stress-induced increases in serum copper and Cp oxidase activity levels requires comparison of these parameters with immunoreactive Cp levels. Recently, work in this laboratory [lo] showed that lactation raised immunoreactive Cp concentrations to a greater extent than serum copper or Cp oxidase activity. Immunoreactive Cp levels were measured using commercially available radial immunodiffusion (RID) plates (Calbiochem-Behring Diagnostics). The present paper describes an enzyme-linked immunoadsorbant assay (ELISA) for ceruloplasmin. The ELISA is cheaper and faster than the RID approach and utilizes commercially available antibodies. No conjugation synthesis is required of the user. The ELISA was applied to serum from cancer patients and controls but should be sensitive enough for application to appropriate cell cultures.

Zinc and copper in striated muscle and body fluids from subjects with diabetes mellitus type I

Plasma levels of zinc and copper were measured in 68 subjects with diabetes mellitus type I and the results were compared to that of 180 healthy controls. Diabetic subjects had significantly lower levels of zinc and higher of copper in plasma as compared to controls. The concentration of copper in plasma was dependent on the metabolic control of the diabetic disease; a significant correlation was found between plasma levels of copper and levels of glycosylated HbA. The levels of zinc and copper were, in a separate study, measured in plasma and striated muscle obtained from 19 subjects with diabetes mellitus type I. Zinc was also, in this smaller group of diabetics, analysed in erythrocytes and in urine collected during 24 hours. The results were compared to that of 12 healthy controls. Subjects with diabetes mellitus showed higher urinary losses of zinc than controls while the muscular concentration was not significantly different. The level of copper in striated muscle was significantly higher in healthy controls as compared to diabetics.

Copper and zinc distribution in the liver and oviduct of estrogen- and testosterone-treated hens ( Gallus domesticus)

Sexually immature (12 weeks-of-age) and mature (22 weeks-of-age) hens were randomly assigned to one of three hormone treatments (control, 17β-estradiol, or testosterone) in a 2×3 factorial arrangement to determine the effects of exogenous estrogen and testosterone on hepatic intracellular distribution of copper and zinc. Hormone treatments were administered in subcutaneous polydimethylsiloxane implants for five weeks. Plasma copper concentrations were higher (P<.05) in mature than in immature hens, but were not influenced by hormone treatment. Maturity had no effect on hepatic copper concentrations, but hepatic zinc was higher (P<.05) in mature than in immature hens. Copper and zinc distribution within the subcellular fractions of the liver was altered by both sexual maturity and steroid treatment. Immature hens had more (P<.05) copper in the large granule (mitochondria, lysosomes) and microsome fractions and less (P<.05) zinc in the debri (nuclei) and microsome fractions than mature hens. Microsome copper was two-fold greater in estrogen-treated, immature hens than in any other treatment. Gel filtration chromatography of liver cytosol revealed that more zinc was associated with binding proteins of >150,000 and 10,000 daltons in mature hens, but little difference in protein copper content was observed between ages. Whole oviduct copper concentrations in mature control hens were greater than in any other treatment. These results suggest that at sexual maturity in the hen, alterations in copper and zinc distribution and metabolism occur which differ somewhat from the age-related changes observed in mammals. Such shifts may reflect an increased requirement for copper or zinc in egg formation and reproduction.

Supplementation of Copper as Copper Sulfate or Copper Proteinate for Growing Calves Fed Forages Containing Molybdenum

Holstein calves (age>12 wk old) were assigned to dietary treatments of 1) no supplemental copper, 2) copper proteinate, or 3) copper sulfate. The copper supplements were incorporated into premixes and added to a pelleted concentrate. The concentrates were fed at 1.8kg per head per d and contained 5, 19, or 19ppm copper and .6ppm molybdenum by analysis. All calves were fed a grass hay free-choice, which contained 1ppm copper and 5ppm molybdenum. Ratios of copper to molybdenum were .9, 2.8, and 2.8 for diets 1, 2, and 3, respectively. Copper concentrations in plasma were significantly greater at wk 12 in calves fed copper proteinate than control or calves supplemented with copper sulfate. Liver copper also was higher at wk 12 in calves fed copper proteinate. Final body weights, plasma zinc, plasma iron, hemoglobin, and hematocrit were not affected by treatment. Bioavailability of dietary copper from copper proteinate was greater than from copper sulfate for calves fed diets containing molybdenum.

Subclinical cervico-spino-bulbar effects of lead: a study of short-latency somatosensory evoked potentials in workers exposed to lead, zinc, and copper.

Subclinical central and peripheral nervous system dysfunction among lead-exposed workers was studied by measuring short-latency somatosensory evoked potentials (SSEP) and maximal motor and sensory nerve conduction velocities (MCV and SCV) following stimulation of the median nerve at the wrist. The examinations were conducted in 20 gun-metal foundry workers exposed to lead, zinc, copper, and tin, with blood lead (BPb) concentrations of 16 to 64 micrograms/dl (mean, 42 micrograms/dl). The interpeak latency of SSEP in the cervico-spino-bulbar region [N9(Erb)-N13 latency] was significantly prolonged, and the MCV and SCV in the forearm were significantly slowed. Multiple regression analysis revealed that the yield of urinary lead following challenge with calcium disodium ethylenediamine tetraacetate (CaEDTA) and packed red blood cell volume were the major factors associated with the prolongation of SSEP latency in the cervico-spino-bulbar region. Similarly, the interpeak latency in the upper central nervous system (N13-N20 latency) was inversely related to the zinc concentration in erythrocytes; latency up to the Erb's point [N9(Erb) latency], which reflects conduction time in a long pathway of the sensory median nerve, was inversely related to urinary zinc level; the MCV and SCV in the palm were positively related to erythrocyte zinc concentration and plasma copper concentration, respectively. These findings suggest that the subclinical neurophysiological effects of lead occur not only in peripheral nerves but also in the central nervous system. It appears that zinc antagonizes the central and peripheral neurologic dysfunction caused by lead; similarly, copper antagonizes the peripheral sensory nerve dysfunction.

Development of copper deficiency in rats fed fructose or starch: weekly measurements of copper indices in blood.

Copper deficiency was induced in weanling rats fed diets whose sole source of carbohydrates was starch or fructose for 7 weeks. Conventional parameters of copper status, plasma copper concentrations, ceruloplasmin activity, and erythrocyte superoxide dismutase (SOD) activity were longitudinally monitored weekly to follow the development of the deficiency and to correlate these indices with the degree of severity of the deficiency. Although 30% of the rats fed a copper-deficient fructose diet died and no deaths occurred in rats fed the copper-deficient starch diet, plasma copper, ceruloplasmin, and SOD activities were reduced to a similar extent in all rats fed copper-deficient diets regardless of the type of dietary carbohydrate. Thus, none of the indices used accurately reflected the greater degree of deficiency or mortality in rats fed the fructose diet deficient in copper. The results of the present study underscore the need for more sensitive tests or alternative parameters to assess copper status in living animals.

Electrolytes and nitrogen compounds of body fluids and tissues ofOctopus vulgaris Lam.

1. The water content ofOctopus vulgaris blood was found to be about 870 g/kg of wet tissue, while that of solid tissue was between 720–800 g/kg of wet tissue, except for the hepatopancreas that was 680 g/kg. 2. Blood plasma was hyperosmotic to the seawater environment. Urine was isosmotic. 3. The total cation (or anion) charge of blood plasma was 624 mEq/l, of urine 670, and of the seawater environment 646 mEq/l. 4. The ionic concentration of the body fluids was higher than that found in other cephalopods; although in all cephalopods it is within 2% (98%–102%) of the ionic concentration of seawater. 5. Proteins represent the major buffer system inO. vulgaris blood plasma. 6. The concentration of protein and copper in the blood plasma was 10,540 and 25.5 mg% ml respectively, practically all of the copper being bound to proteins and only 0.013 mg/ml being in free form. 7. The ionic concentration in the solid tissues differed slightly according to the tissue examined. High levels of sodium chloride were found in the branchial heart and in the branchial gland. Potassium was higher in the brain and white body, while iron and copper levels were highest in the hepatopancreas. 8. Ammonia and amino acids were the major free compounds inO. vulgaris urine and solid tissue, respectively. The ammonia and urea levels were higher in solid tissues than in blood, and in some tissues (brain and hepatopancreas) they were more than 20 times as high. Uric acid occurred in kidney and hepatopancreas in concentrations above 50 mg/100 g of tissue water, but it was absent from other tissues (except brain).

Psychological performance in relation to central and peripheral nerve conduction in workers exposed to lead, zinc, and copper.

Psychological performance was examined in relation to central and peripheral nerve conduction by means of the Wechsler Adult Intelligence Scale test, short-latency somatosensory-evoked potential (SSEP), and median nerve conduction velocity in 19 male gun-metal foundry workers exposed to lead, zinc, and copper. (Their blood lead concentrations--ie, 16-64 micrograms/dl with a mean of 42--and plasma zinc and copper concentrations were significantly higher than those of control subjects). In these workers, the score of picture completion (psychological performance) was significantly low; indicators of lead absorption, but no indicators of zinc and copper absorption, were significantly correlated with this score. The score of picture completion was significantly correlated with the N11-N13 latency of SSEP (conduction time in the spinobulbar region) in the workers; their N11-N13 latency, together with the N9 and N9-N11 latencies, was significantly prolonged and was significantly correlated with indicators of lead absorption. Furthermore, their maximal motor and sensory conduction velocities of the median nerve were significantly slowed. It is concluded that both psychological performance and central and peripheral nerve conduction may be impaired in lead-exposed workers with BPb's below approximately 60 micrograms/dl.

Zinc and copper metabolism during open-heart surgery.

Zinc and copper changes were studied in plasma, whole blood, urine and myocardium in 15 patients undergoing valve replacement in hypothermic cardiopulmonary bypass with hemodilution. During the cardiopulmonary bypass, a fall in plasma copper and zinc concentration was related to hemodilution. The zinc concentration also decreased in whole blood, but remained unchanged intracellularly. The urinary concentration of both cations, but not the output, decreased at the end of the operation in relation to the baseline values. The myocardial copper and zinc concentrations increased during the aortic cross-clamping period. The possible causes and significance of these changes are considered.

Plasma and erythrocyte copper, zinc, manganese and magnesium concentrations in Wilson's disease

Plasma copper was significantly reduced in Wilson's disease with decreased ceruloplasmin levels, while there was no significant difference in erythrocyte copper levels between Wilson's disease and controls. Mean zinc and manganese levels in plasma were increased in Wilson's disease, but these differences were not significant. Mean magnesium level in plasma was normal. The levels of these metals in erythrocytes showed no difference between Wilson's disease and controls. Our results suggest that the abnormal copper level in plasma is not due to the primary metabolic defects, but is probanly due to the level of the binding proteins in plasma to this metal, ceruloplasmin, in Wilson's disease.

Retention of copper in the liver of sheep genetically selected for high and low concentrations of copper in plasma

ABSTRACTThe extent to which genetic selection to change the concentration of copper (Cu) in plasma also affected the retention of Cu in the liver was assessed in three experiments. In each, the concentration of Cu was measured in samples of liver (taken by biopsy) and of plasma from female sheep of lines selected from a Scottish Blackface × Welsh Mountain population (which had previously been interbred for several generations) for high and low plasma Cu levels (high line and low line) and from purebred Scottish Blackface and Welsh Mountain females.The concentration of Cu in the liver and plasma was found to be consistently greater in high-line and Welsh Mountain than in low-line and Scottish Blackface females (P &lt; 0·01) in the first experiment in which grazing animals were sampled at both 6 and 10 months of age and in the second, where sampling' was at 6 months only. Mean Cu concentrations in the liver ranged from 13 to 115 mg/kg dry matter (DM) and the correlations with those in plasma varied from 0·28 to 0·53 (all P &lt; 0·05) and was highest when the concentration of Cu in the liver was lowest. The correlation between the concentrations of Cu in liver at different ages was 0·57 (P &lt; 0·05).In the third experiment, 10-month-old high- and low-line females were given complete diets containing either 5, 10, 22 or 28 mg Cu per kg DM for 12 weeks. Liver samples were obtained at the beginning and end of this period and blood samples were taken every 3 weeks. The concentration of Cu in the liver was greater in high- than in low-line sheep on all diets and increased linearly with the Cu concentration of the diet but at a greater rate in the high line. At the end, the high line had significantly greater concentrations of Cu in plasma on the 5 and 10 mg Cu per kg DM diets.The experiments showed that high-line females retained more Cu in the liver than low-line females. It is most likely that this was caused by a positive genetic correlation between concentration of Cu in plasma and the efficiency of absorption of Cu.

Postnatal Dependence of Plasma Copper and Zinc Levels on Gestational Age and Maturity Observed in Infants Fed a High Zinc Content Formula

Summary:We studied the effect of gestational age and maturity on plasma zinc and copper levels at 10 and 120 days of age. The association of plasma zinc changes and body growth was also investigated. Infants were receiving a controlled intake of zinc and copper solely through a zinc‐supplemented formula (4.7 mg/L of zinc and 0.16 mg/L of copper). Twenty‐eight low‐birthweight infants (&lt;2,500 g) having gestational ages ranging from 33 to 40 weeks [17 with an appropriate birthweight for gestational age (AGA) and 11 small for gestational age (SGA)] were enrolled in the present study. Measurements of plasma zinc and copper concentration, weight, length, head circumference, and tricipital and subscapular skinfolds were carried out at 10 and 120 days of age. Proton‐induced x‐ray fluorescence technique (PIXE) was used to assess copper and zinc concentrations. At 10 days of age a significant correlation between copper concentration and gestational age was found. At 120 days of age the copper concentration was higher than at 10 days and independent of gestational age and maturity (mean ± SEM = 116 ± 5 μg/dl). At 10 days of age no significant correlation between zinc content and gestational age was found (86 ± 4 μg/dl). The plasma zinc percent change over the period from 10 to 120 days of age was positively correlated with gestational age in the whole sample as well as in AGA and SGA infants separately. The value of gestational age at which the zinc percent change turns from negative to positive was 35.6 ± 0.7 weeks for AGA, 37.4 ± 0.5 weeks for SGA, and 36.2 ± 0.5 weeks for the whole sample. No significant correlation between the increments of the measured body features and the plasma zinc change was found. Length and weight velocities were similar in AGA and SGA infants. These observations indicate that the possibility of increasing plasma zinc level by zinc supplementation depends on gestational age and maturity.

Trace element supplementation of sheep: evaluation of various copper supplements and a soluble glass bullet containing copper, cobalt and selenium.

The effect of 5 different copper supplements on copper status of Merino sheep at pasture was examined. Transient increases in plasma copper concentrations occurred following treatment with copper calcium EDTA, copper sulphate, and glass bullets impregnated with copper, cobalt and selenium, but these increases were not considered to be a reliable indication of changes in liver copper reserves. Sheep receiving the glass bullet or 2.5 g oxidised copper wire particles orally or 50 mg copper as copper calcium EDTA parenterally had liver copper concentrations significantly greater than those of untreated sheep for periods up to 51 weeks. Oral doses of 30 mg copper as copper oxychloride, or 300 mg copper as copper sulphate did not alter the liver copper reserves at any stage. The bodyweight and greasy fleece weights were not significantly altered by any of the copper supplements. Plasma vitamin B12 concentrations in sheep given the glass bullet were increased for about 5 months. Thereafter increased plasma vitamin B12 concentrations were observed in all sheep. Blood selenium concentrations were also high during the experiment thereby preventing the evaluation of the glass bullet as a source of selenium.

Zinc and copper in Asian pregnancies--is there evidence for a nutritional deficiency?

In 92 Hindu Asians, 59% of them vegetarian, and 51 Europeans longitudinal measurements were made during pregnancy of the zinc and copper concentrations in plasma and hair together with urinary zinc excretion, as indices of their zinc and copper status. Maternal diets were assessed once at booking. Zinc intakes ranged from 3.1 to 16.9 mg/day, with average intakes least in vegetarian Hindus and most in Europeans. Average copper intakes ranged between 1.48 and 1.80 mg/day and were similar in the three patient groups. Both ethnic groups showed the pregnancy-associated fall in the plasma concentration of zinc and rise in that of copper but throughout the study Hindus had statistically significant lower levels of zinc and higher levels of copper than Europeans. Urinary zinc excretion was not only significantly lower throughout the study in Hindus than in Europeans but the increase in excretion which occurred after 20 weeks gestation was smaller. There were no ethnic differences in the zinc content of hair. Urinary zinc excretion correlated with both plasma zinc levels and dietary zinc. Mean birthweight in the Hindus was 2912 g and 34% of infants were below the 10th centile, using the Aberdeen standards, compared with 6% of the European babies (mean birthweight 3349 g). No association was found between crude or adjusted birthweight and any of the measures of zinc or copper status in either ethnic group. The Hindus had an apparently lower average zinc status than the Europeans, but there was no evidence that this had acted as a nutritional constraint and was the cause of their slower rate of intrauterine growth.

Genetic selection to produce lines of sheep differing in plasma copper concentrations

ABSTRACTMale lambs were selected annually at 18 and 24 weeks of age for high or low concentrations of copper in plasma to produce two closed lines. The difference between the high and low lines increased to approx. 0·5 mg/1 after 5 years when the experiment ended, indicating appreciable additive genetic variation for the concentration of Cu in plasma. The selection lines were derived from a population of Scottish Blackface × Welsh Mountain crosses which had been interbred for many generations. The two parental breeds contributing to the cross normally differ in a number of aspects of Cu status with that of the Welsh higher than that of the Blackface. Both pure breeds were kept as controls. In the final year, Cu concentrations of the high selection line exceeded the values of the Welsh and the low selection line had values below those of the Blackface. Differences between the selection lines persisted at all ages.There were indications of changes in the frequency of the Hb alleles, associated with the selection for Cu concentrations, but there were no correlated changes in body weight, reproductive performance or lamb mortality during the 5-year selection period when dietary supplies of Cu were not particularly restrictive.

Zinc and copper nutrition in human pregnancy: a longitudinal study in normal primigravidae and in primigravidae at risk of delivering a growth retarded baby

A longitudinal study of plasma zinc and copper concentration and plasma volume was carried out in 33 normal healthy primigravidae for comparison with 31 primigravidae selected as being at risk of delivering a growth retarded baby. Neither group received mineral or vitamin supplements. In Group A, plasma zinc concentration fell as plasma volume increased between 14 weeks and 35 weeks. Intravascular mass of zinc therefore increased and showed significant correlation with intravascular mass of albumin. Both of these were significantly lower in Group B, reflecting poorer plasma volume expansion. Plasma copper concentration mirrored the increase in plasma ceruloplasmin and was comparable in both groups. Plasma zinc and copper concentrations were unaffected by smoking or by method of feeding and there was no correlation found with percentile birth weight distribution. In both groups at 30 weeks daily dietary zinc intake was approximately half the Recommended Dietary Allowance.