Serial changes in selected serum constituents in low birth weight infants on peripheral parenteral nutrition with different zinc and copper supplements.

One hundred and five infants of birth weight 2000 g or less who received peripherally administered parenteral nutrition for periods of three or more weeks, were randomly assigned to groups receiving different amounts of zinc and copper supplement. The blood concentrations of zinc, copper, retinol-binding protein, prealbumin, alkaline phosphatase and aspartate transaminase were followed weekly. Mean serum zinc, retinol-binding protein and prealbumin declined significantly over time while alkaline phosphatase rose. Only the group receiving the highest zinc supplement maintained a mean serum zinc concentration within the normal range at seven weeks. No difference in the protein or enzyme concentrations was found between the different zinc supplement groups. No difference was seen in serum copper or ceruloplasmin between copper dose groups although one intravenous supplement was double that of the other.

The effect of red cell and plasma transfusion on serum zinc and copper levels in the neonate.

Transfusion of packed red cells (15 to 20 ml/kg) in 11 preterm infants resulted in a slight increase in mean serum zinc levels on the 3rd post transfusion day but no effect was noted on serum copper levels. No significant difference was found between the changes in serum zinc in 141 paired specimens collected a week apart when zero, one, two or three packed cell transfusions were given in the intervening week. A slight decrease in the mean copper level was noted when one transfusion was given. Transfusion of fresh frozen plasma in six newborns with abdominal wall defects resulted in initial serum copper levels two to three times greater than the reference mean for newborns. No effect was noted on zinc levels. Serum copper results should be interpreted with caution in infants who have been transfused with plasma.

Cardiomyopathy associated with nonendemic selenium deficiency in a Caucasian adolescent.

We describe a girl aged 17 y who died after a cardiac arrest secondary to septic shock. At autopsy, the enlarged, soft, and flabby heart showed microscopic evidence of acute myocardial infarction, myocardial edema, myocardiocyte loss, replacement fibrosis in the interventricular septum, and right and left ventricular hypertrophic nucleomegaly. The pathological diagnosis was that of cardiomyopathy due to prolonged selenium deficiency. The patient had been on total parenteral nutrition for 17 mo, following extensive bowel resection for intractable pain, nausea, and vomiting caused by chronic idiopathic intestinal pseudoobstruction. Seven months before death, when severe biochemical selenium deficiency was diagnosed, supplemental selenium was added to the infusion, and plasma selenium concentrations increased. In long-standing selenium deficiency, sepsis may contribute the final insult to a damaged myocardium, triggering symptomatic cardiac failure and sudden death.

Pulse oximetry advantages in infants with bronchopulmonary dysplasia.

We studied 12 infants with a clinical and radiologic diagnosis of bronchopulmonary dysplasia who were oxygen dependent and older than 30 days. Simultaneous readings of hemoglobin oxygen saturation (SaO2) determined by two pulse oximeters (Nellcor 100, BTI Biox III) and transcutaneous (tc) PO2 (Sensor Medics, Transend) were correlated with SaO2 (Radiometer, OSM 2 Hemoximeter) and PaO2 (Corning 178) measured on blood from an indwelling arterial catheter. For each infant, the fractional inspiratory oxygen (FiO2) was adjusted to obtain three to five sets of data in the range of 70% to 95% SaO2. Fifty-three data points were generated and pooled for analysis. The slope of the regression line generated for the Nellcor 100 was .86; for the BTI Biox III, it was .91; and for the Sensor Medics Transend, it was .55, resulting in average errors of +2.5%, +1.0%, and -29%, respectively, when comparing corresponding transcutaneous and arterial values. When SaO2 was equal to or less than 95%, no infants were hyperoxic. These data confirm reports by others that tcPO2 values do not accurately represent PaO2 values in older infants with bronchopulmonary dysplasia. Pulse oximeters do not require user calibration, and their sensor is unheated so they will not cause skin burns. We conclude that pulse oximetry offers major advantages over tcPO2 measurements in the management of infants with bronchopulmonary dysplasia.

Perspectives on lead toxicity.

Lead toxicity causes hematological, gastrointestinal, and neurological dysfunction in adults and children. Symptoms are usually noted with blood lead greater than 1.93 mumol/L. Severe or prolonged exposure may also cause chronic nephropathy, hypertension, and reproductive impairment. Lead inhibits enzymes; alters cellular calcium metabolism; stimulates synthesis of binding proteins in kidney, brain, and bone; and slows nerve conduction. Less severe exposure to lead, designated by blood lead levels of 0.48-0.96 mumol/L, has been implicated in poor pregnancy outcome, impaired neurobehavioral development, reduced stature in young children, and higher blood pressure in adults. Biochemical and systemic effects of high and low level lead toxicity are described. Dust, water, and paint chips are still major sources of lead but lead from folk remedies, cosmetics, food supplements, food preparation utensils, and improperly prepared infant formula has caused epidemic and sporadic severe lead toxicity. Screening for pediatric low level lead exposure requires measurement of blood lead.

Beyond the umbilical cord: interpreting laboratory tests in the neonate.

Interpretation of biochemical testing in the neonatal period is challenging because of the complexity of perinatal physiology, the difficulty of establishing appropriate laboratory reference ranges, and the technical aspects of analyzing microvolume specimens that are often hemolyzed, lipemic, or have a high hematocrit or bilirubin concentration. Metabolic problems such as hyperbilirubinemia and hypoglycemia in the full-term neonate occur as the infant adapts from an intrauterine metabolism to extrauterine life. Pathophysiological processes in the premature infant vary with the severity of prematurity and the immaturity of metabolic systems. Interpreting neonatal biochemistry requires age- and gestation-specific reference ranges but technical, ethical, and philosophical concerns continue to impair the development of the needed reference data.

Timing of specimen collection is crucial in urine screening of drug dependent mothers and newborns.

We compared results of urine drug analysis with clinical data and history to test the usefulness of peripartum drug screening and to establish guidelines for optimal testing. Urine from 28 mothers and 52 babies was analysed. Drugs not suspected by history were found in 10 mothers and six babies. Results assisted in the management of neonatal withdrawal in three babies. Drugs suspected by history were not found in 11/22 mothers and 23/35 babies. About half of these results were associated with delayed urine collection. In 12/28 mothers, drugs administered in hospital could have confused interpretation of screen results. We conclude that urine drug screening without strict protocols for specimen collection is of limited usefulness for management of drug abuse in pregnancy and neonatal drug withdrawal. We favour testing of maternal urine obtained before drugs are administered in hospital. Neonatal urine, if used, should be collected in the first day of life.

Biochemical investigation of a child with molybdenum cofactor deficiency.

A girl aged eight months, who presented with developmental delay and dislocated optic lenses, was diagnosed as having combined sulfite oxidase and xanthine dehydrogenase deficiencies consistent with molybdenum cofactor deficiency. The diagnosis was confirmed by demonstrating the absence in urine of urothione, a molybdenum cofactor metabolite. Prenatal diagnosis excluded the disease in the mother's second pregnancy. A summary of an in vitro study of molybdenum cofactor synthesis in the patient is given.

Perinatal and pediatric nutrition.

Nutritional deficiencies develop rapidly in the very low birth weight infants because of a lack of third-trimester accumulation of fat, minerals, trace elements, and fat-soluble vitamins. Symptomatic zinc deficiency and hypernatremic dehydration may occur unexpectedly in the wholly breast-fed full-term or premature infant, and nutritional adequacy should be carefully monitored even in breast-fed full-term infants.

Iron and copper-associated cirrhosis in infants. Acquired metal toxicity or genetic disorder?

Iron and Copper are essential trace elements for growth and development of the human infant but are toxic in excess. Lethal cirrhotic syndromes in the neonate and infant have been associated with both copper and iron overload. The relative importance of underlying genetic susceptibility and acquired excess of iron or copper in the pathogenesis of these chronic metal toxicity states is controversial and both syndromes probably encompass a spectrum of conditions.

Trace elements in nutrition for premature infants.

Ten trace elements that are nutritionally essential include: zinc, copper, selenium, chromium, manganese, molybdenum, cobalt, fluoride, iodine, and iron. This article briefly reviews the biochemistry of these trace elements, describes clinical deficiency states, and provides a rationale for recommended enteral and parenteral intakes for preterm infants.

Trace elements in pediatrics.

This review discusses biologic roles, metabolism, and clinical aspects of three essential trace elements, zinc, copper, and selenium. Clinical situations that result in disturbed trace element metabolism, and signs or symptoms that may suggest a trace element problem are listed. Important issues for trace element assay development are emphasized, and examples of pediatric reference ranges provided.

Clinical biochemistry of pregnancy.

Major adaptations in maternal physiology and metabolism are required for successful pregnancy outcome. Hormonal changes initiated even before conception significantly alter maternal biochemistry early in pregnancy. Steroid hormones, peptide hormones, and prostaglandins interact to expand blood and plasma volume and modulate the maternal capacity to supply energy and nutrients to the fetoplacental unit. As gestation progresses, reference ranges for the concentration of many biochemical parameters change significantly from those found in the nonpregnant state. Gestation-specific reference ranges are essential for correct interpretation of tests used in screening, diagnosis, and monitoring during pregnancy. The use of clinical laboratory tests in the management of high-risk pregnancy are discussed from the perspective of testing before conception and during pregnancy.

Selenium: clinical significance and analytical concepts.

Selenium is an essential trace element in humans and animals. Its only established function in humans is the antioxidant activity of glutathione peroxidase, a selenoenzyme. Severe prolonged deficiency may cause a fatal cardiomyopathy. Iatrogenic causes of selenium deficiency include parenteral and enteral nutrition. Low plasma selenium is also found in malabsorption, cystic fibrosis, rheumatoid arthritis, neoplasia, and other varied clinical disorders. Death has resulted from a single massive ingestion of selenium, while chronic excessive intake causes skin, nail, and hair pathology. Extreme geographical variation in population blood and urine selenium levels and a marked age-specific variation in population reference intervals are important factors in understanding selenium nutrition. Nutritional requirements, biological availability, and metabolism are discussed in relation to geographical, age, and method variability. Sampling, processing procedures, and methods for selenium quantitation are reviewed. Selenium content in different biological matrices and reference values for pediatric, adult, and obstetric populations are provided.

Rapid, semi-quantitative assay of C-reactive protein evaluated.

We evaluated a new rapid semi-quantitative immunometric assay of C-reactive protein (CRP) as a screening test for sepsis by comparison with an automated nephelometric method. Plasma samples (n = 101) from preterm infants during the first week of life were saved for CRP analyses. We measured CRP by the Nycocard semiquantitative method and compared the results with those obtained with a Behring Nephelometer. A CRP value less than 10 mg/L was considered to be negative for infection. All CRP results read as less than 10 mg/L (negative) by the Nycocard method were also less than 10 mg/L by the comparison method, and all CRP values found to be greater than 20 mg/L (positive) by the Nycocard method were also positive by the comparison method. Results in the 10-20 mg/L range were considered equivocal. We conclude that the Nycocard CRP semi-quantitative method is a rapid and useful screening test for sepsis in preterm infants.

Direct determination of selenium in serum by graphite-furnace atomic absorption spectrometry with deuterium background correction and a reduced palladium modifier: age-specific reference ranges.

We describe the development of a direct method for determination of selenium in serum by graphite-furnace atomic absorption spectrophotometry with deuterium background correction. We include palladium modifier to stabilize selenium in the presence of a strong reducing agent. Spectral interferences from iron are not evident in this system. Because an analysis requires only 20 microL of serum or plasma, the method is applicable to neonatal populations. At a selenium concentration of 0.75 mumol/L (approximately the mean found in our pre-term infants), the within-run CV is 5.3%. For a concentration of 1.83 mumol/L, which approximates our normal adult mean, within-run and between-run CVs are 2.7% and 3.4%. Accuracy is demonstrated by analytical recoveries ranging from 96% to 102%. We present reference values for pre-term and term infants, and age-specific ranges for infants to adults.

Improved sample preparation for accurate determination of low concentrations of lead in whole blood by graphite furnace analysis.

The effect of low concentrations of lead on pre- and post-natal growth and development is a current concern. We describe a simple method of sample preparation for direct determination of lead in whole blood by Zeeman graphite-furnace atomic absorption spectrometry. This procedure improves analytical precision and accuracy of lead determinations at low concentrations as compared with published furnace data. At blood lead concentrations of 0.25, 1.98, and 3.76 mumol/L, within-run CVs were 3.2%, 1.8%, and 1.4% respectively; between-run CVs were 7.3%, 2.9%, and 2.2%. Accuracy, as demonstrated by analytical recovery, ranged from 99% to 102%. Our reproducibility/accuracy score in the 1989 Quebec interlaboratory comparison program was 96% compared with the target, second best of 66 participating laboratories.

Blood lead levels in children aged 24 to 36 months in Vancouver.

OBJECTIVES: To determine the blood lead levels in children and to identify risk factors for elevated levels. DESIGN: Cross-sectional study. SETTING: Vancouver. PARTICIPANTS: Random sample of children aged 24 to 36 months, born and still resident in Vancouver. The sample was stratified proportionally by the median annual family income in the census tract where each family resided. OUTCOME MEASURES: Blood lead levels and risk factors for elevated blood lead levels, determined from a questionnaire administered to parents. RESULTS: Of the children in the sample, 42% (178/422) were ineligible or could not be located. Of the remaining children, 73% (177/244) participated and adequate blood specimens were obtained from 172. The mean blood lead level was 0.29 mumol/L (standard deviation 0.13 mumol/L). (A blood lead level of 1 mumol/L is equivalent to 20.7 micrograms/dL.) The lowest level was 0.06 mumol/L, and the highest was 0.85 mumol/L. Of children with adequate samples, 8.1% (14/172) had blood lead levels of 0.48 mumol/L or higher, and 0.6% (1/172) had a level higher than 0.72 mumol/L. The logarithms of the levels were normally distributed, with a geometric mean (GM) of 0.26 mumol/L (geometric standard deviation 1.56). Of approximately 70 possible predictors of blood lead levels analysed, those that showed a statistically significant association (p < 0.05) with increased blood lead levels were soldering performed in the home as part of an electronics hobby (GM blood lead level 0.34 mumol/L, 95% confidence interval [CI] 0.27 to 0.39 mumol/L), aboriginal heritage (GM blood lead level 0.33 mumol/L, 95% CI 0.28 to 0.39 mumol/L), dwelling built before 1921 (GM blood lead level 0.32 mumol/L, 95% CI 0.28 to 0.37 mumol/L), age of water service connection to dwelling (predicted blood lead level 0.00087 mumol/L [95% CI 0.00005 to 0.00169 mumol/L] higher per year since service connection) and decreased stature (predicted blood lead level 0.018 mumol/L [95% CI 0.0353 to 0.0015 mumol/L] higher for every standard deviation below the age-specific mean height). CONCLUSIONS: This study found much lower blood lead levels in children than those found in previous Canadian studies. The authors believe that this result is not an artefact due to differences in population sampling or methods of collection of blood specimens. The study showed no clear risk factors for elevated blood lead levels: although a few factors had a statistically significant association with increased blood lead levels, the differences in levels were small and unimportant.

Blood serotonin concentrations and fenfluramine therapy in autistic children.

Whole-blood serotonin concentrations of 31 autistic children, aged 2 1/2 to 16 years, 10 non-autistic retarded children, and 18 children with Down syndrome were measured by a fluorometric method and compared with those of normal children of similar age range. No significant difference in the serotonin concentration per milliliter of whole blood or per 1000 platelets was found between groups for autistic, retarded, or normal children, but the values for those with Down syndrome were significantly lower. A double-blind cross-over study on the effect of fenfluramine versus placebo in seven autistic boys over a period of 8 months demonstrated a significant decrease in blood serotonin levels during the fenfluramine phase in all subjects. Slight improvements were found in short-term auditory memory and some measures of receptive language skills, particularly in children functioning at a high level. There was no significant change in global psychometric measurements of general intelligence during therapy. No adverse clinical effect was observed other than weight loss of 6% in one child. We conclude that fenfluramine may have some selective favorable effects on increasing attention in high-functioning autistic children. Blood serotonin concentration may be followed as an indication of drug compliance during fenfluramine therapy, but does not appear to reflect clinical efficacy.

Age- and sex-specific pediatric reference intervals: study design and methods illustrated by measurement of serum proteins with the Behring LN Nephelometer.

We analyzed blood from 450 healthy children and adolescents, ages one to 19 y, as well as term and preterm infants, to define age- and sex-specific reference intervals for numerous blood constituents. Reference intervals were derived by using nonparametric methods to determine the 0.025 and 0.975 fractiles. Ten serum proteins were measured with the Behring LN Nephelometer. Girls over 10 years of age had higher concentrations of ceruloplasmin and alpha 1-antitrypsin than other children had. There was no sex-related difference in reference intervals for the other proteins tested. Reference intervals are presented for immunoglobulins G, A, and M, complement fractions C3c and C4, ceruloplasmin, transferrin, alpha 1-antitrypsin, retinol-binding protein, and prealbumin (transthyretin).