Comparison of single and dual latent tuberculosis screening strategies before biologic and targeted therapy in patients with rheumatic diseases: a retrospective cohort study.

PURPOSE: Before biologic and targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) treatment, latent tuberculosis infection (LTBI) screening by tuberculin skin test (TST) or interferon gamma release assay (IGRA) is recommended. However, both tests have reduced reliability in immunosuppressed patients. We investigated whether dual LTBI screening with both tests could reduce the incidence of tuberculosis. METHODS: Consecutive patients receiving b/tsDMARDs for rheumatic diseases in a regional hospital were recruited. All patients underwent either TST/IGRA or both. They were categorised into a single or dual testing group and were followed up for at least 6 months. Isoniazid was prescribed if any one test was positive. RESULTS: In total, 217 patients were included in this study; 121 underwent single LTBI testing and 96 underwent dual testing. Tuberculosis occurred in nine patients in the single testing group and one patient in the dual testing group (7.4% vs 1.0%, P=0.045). However, the difference was not statistically significant when follow-up duration was considered (log rank test). In total, 71 patients tested positive for LTBI with isoniazid treatment (28.9% in the single testing group and 45.8% in the dual testing group, P=0.007). Agreement between the IGRA and TST was 74.4% (Cohen's kappa=0.413); agreement was lower in patients receiving prednisolone. Infliximab use was independently associated with tuberculosis (P=0.032). Mild isoniazid-related side-effects occurred in seven patients. CONCLUSIONS: Dual LTBI testing with both TST and IGRA is effective and safe. It might be useful for patients receiving prednisolone at the time of LTBI screening, or if infliximab therapy is anticipated.

Comparison of a commercial interferon-gamma release assay and tuberculin skin test for the detection of latent tuberculosis infection in Hong Kong arthritis patients who are candidates for biologic agents.

INTRODUCTION: It is universally agreed that screening for latent tuberculosis infection prior to biologic therapy is necessary, especially in endemic areas such as Hong Kong. There are still, however, controversies regarding how best to accomplish this task. The tuberculin skin test has been the routine screening tool for latent tuberculosis infection in Hong Kong for the past decade although accuracy is far from perfect, especially in patients who have been vaccinated with Bacillus Calmette-Guérin, who are immunocompromised, or who have atypical mycobacterium infection. The new interferon-gamma release assays have been shown to improve specificity and probably sensitivity. This study aimed to evaluate agreement between the interferon-gamma release assay and the tuberculin skin test in the diagnosis of latent tuberculosis infection in patients with arthritic diseases scheduled to receive biologic agents. METHODS: We reviewed 38 patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis at a local hospital in Hong Kong from August 2013 to April 2014. They were all considered candidates for biologic agents. The patients underwent both the interferon-gamma release assay (ASACIR.TB; A.TB) and the tuberculin skin test simultaneously. Concurrent medications were documented. Patients who tested positive for either test (ie A.TB+ or TST+) were prescribed treatment for latent tuberculosis if they were to be given biologic agents. All patients were followed up regularly for 1 year and the development of active tuberculosis infection was evaluated. RESULTS: Based on an induration of 10 mm in diameter as the cut-off value, 13 (34.2%) of 38 patients had a positive tuberculin skin test. Of the 38 patients, 11 (28.9%) also had a positive interferon-gamma release assay. The agreement between interferon-gamma release assay and tuberculin skin test was 73.7% (kappa=0.39). Six patients were TST+/A.TB- and four were TST-/A.TB+. When positive tuberculin skin test was defined as an induration of 5-mm diameter, the agreement between the two tests improved with a kappa value of 0.47. In that case, half of the patients had a positive tuberculin skin test; among them, nine were TST+/A.TB-. Only one was TST-/A.TB+. Subgroup analysis showed that the agreement between both tests improved further (kappa=0.69) in patients not taking a concurrent systemic steroid. For patients prescribed systemic steroid, the agreement was only slight with a kappa value of 0.066. Finally, none of the 38 patients, of whom 32 had an exposure to biologic agents, developed active tuberculosis during the 1-year follow-up period. CONCLUSION: In a tuberculosis-endemic population, although 10-mm diameter induration is the usual cut-off for a positive tuberculin skin test, the level of agreement between the interferon-gamma release assay and tuberculin skin test improved from fair to moderate when the cut-off was lowered to 5 mm. A dual testing strategy of tuberculin skin test and interferon-gamma release assays appeared to be effective and should be pursued especially in patients who are on systemic steroid therapy. Nonetheless, the issue of potential overtreatment is yet to be evaluated.

Skiing and snowboarding head injury: A retrospective centre-based study and implications for helmet test standards.

BACKGROUND: Head injury occurs in up to 47% of skiing or snowboarding injuries and is the predominant cause of death in these sports. In most existing literature reporting injury type and prevalence, head injury mechanisms are underreported. Thus, protective equipment design relies on safety evaluation test protocols that are likely oversimplified. This study aims to characterize severity and mechanism of head injuries suffered while skiing and snowboarding in a form appropriate to supplement existing helmet evaluation methods. METHODS: A 6-year, multicentre, retrospective clinical record review used emergency databases from two major trauma centres and Coroner's reports to identify relevant cases which indicated head impact. Records were investigated to understand the relationships between helmet use, injury type and severity, and injury mechanism. Descriptive statistics and odds ratios aided interpretation of the data. FINDINGS: The snow sport head injury database included 766 cases. "Simple fall", "jump impact" and "impact with object" were the most common injury mechanisms while concussion was observed to be the most common injury type. Compared to "edge catch", moderate or serious head injury was more common for "fall from height" (OR = 4.69; 95% CI = 1.44-16.23; P = 0.05), "jump impact" (OR = 3.18; 95% CI = 1.48-7.26; P = 0.01) and "impact with object" (OR = 2.44; 95% CI = 1.14-5.56; P = 0.05). Occipital head impact was associated with increased odds of concussion (OR = 7.46; 95% CI = 4.55-12.56; P = 0.001). INTERPRETATION: Snow sport head injury mechanisms are complex and cannot be represented through a single impact scenario. By relating clinical data to injury mechanism, improved evaluation methods for protective measures and ultimately better protection can be achieved.

Growth hormone and dexamethasone stimulate lipolysis and activate adenylyl cyclase in rat adipocytes by selectively shifting Gi alpha2 to lower density membrane fractions.

GH, in the presence of glucocorticoid, produces a delayed increase in lipolysis in rat adipose tissue, but the biochemical mechanisms that account for this action have not been established. Other lipolytic agents rapidly activate adenylyl cyclase (AC) and the resulting production of cAMP initiates a chain of reactions that culminates in the activation of hormone-sensitive lipase. We compared responses of segments of rat epididymal fat or isolated adipocytes to 30 ng/ml GH and 0.1 microg/ml dexamethasone (Dex) with 0.1 ng/ml isoproterenol (ISO), which evoked a similar increase in lipolysis. All measurements were made during the fourth hour after the addition of GH+Dex or immediately after the addition of ISO to cells or tissues that had been preincubated for 3 h without hormone. Although no significant increases in cAMP were discernible in homogenates of GH+Dex-treated tissues, Rp-cAMPS (Rp-adenosine 3'5'-phosphothioate), a competitive inhibitor of cAMP, was equally effective in decreasing lipolysis induced by GH+Dex or ISO. The proportion of PKA that was present in the active form was determined by measuring the incorporation of 32P from [gamma-32P]ATP into kemptide in the absence and presence of saturating amounts of cAMP. GH+Dex and ISO produced similar increases in protein kinase A activity in tissue extracts. Treatment with GH+Dex did not change the total forskolin-stimulated AC present in either a crude membrane pellet sedimented at 16K x g or a less dense membrane pellet sedimented at 100K x g, but doubled the AC activity in the 16K pellet when assayed in the absence of forskolin. To evaluate possible effects on G proteins, pellets obtained from centrifugation of adipocyte homogenates at 16K x g and 100K x g were solubilized and subjected to PAGE and Western analysis. GH+Dex decreased Gi alpha2 by 44% (P < 0.02) in the 16K pellets and increased it by 52% (P < 0.01) in the 100K pellets. Gs alpha in the 16K pellet was unaffected by GH+Dex and was decreased (P < 0.05) in the 100K pellet. Sucrose density fractionation of the 16K pellets revealed a similar GH+Dex-dependent shift of Gi alpha2 to less dense fractions as determined by both Western analysis and [32P]NAD ribosylation catalyzed by pertussis toxin. No such changes were seen in the distribution of Gs alpha or 5'-nucleotidase. Colchicine (100 microM) blocked the GH+Dex-dependent shift of Gi alpha2 from the 16K to the 100K pellet and blocked the lipolytic effects of GH+Dex, but not those of ISO. We conclude that by modifying the relationship between AC and Gi alpha2, GH+Dex relieves some inhibition of cAMP production and consequently increases lipolysis.

Functional GIP receptors are present on adipocytes.

In addition to its important role in maintaining glucose homeostasis, it has recently become apparent that glucose-dependent insulinotropic polypeptide (GIP) is also involved in different steps of lipid metabolism. GIP has been shown to stimulate the release of lipoprotein lipase from fat, as well as increase the rate of fat incorporation into adipose tissue. Moreover, GIP has been shown to increase the clearance rate of chylomicrons in the circulation and to inhibit the action of glucagon. Despite evidence for GIP effects on fat tissue, GIP receptors have not been identified in fat cells or tissues. The present study was undertaken to identify GIP receptors in isolated adipocytes, as well as to identify GIP receptors in the established fat cell line, differentiated 3T3-L1. RNAse protection analysis demonstrated the presence of GIP receptor transcripts in rat adipocytes. A polyclonal GIP receptor antiserum directed at the N-terminus of the receptor detected the presence of GIP receptors in both rat fat and differentiated 3T3-L1 cells by Western blot analysis. Moreover, [125I] GIP binding assays revealed both specific and displaceable GIP binding sites in differentiated 3T3-L1 cells (IC50 = 10(-9) M). When undifferentiated 3T3-L1 cells, which appear to express relatively few GIP receptors, were incubated in the presence of GIP, no effect on intracellular cAMP accumulation was detected. In contrast, the inclusion of 10 nM GIP in the incubation medium increased cAMP accumulation in rat fat cells and differentiated 3T3-L1 cells. This increase in cAMP accumulation was abolished with the specific GIP receptor antagonist GIP(7-30)NH2. The results of these studies indicate that GIP receptors are present in fat cells and are up-regulated when 3T3-L1 cells undergo differentiation to become adipocytes. Furthermore, the increase in intracellular cAMP accumulation detected upon ligand binding indicates that these receptors are functional.

Significance of an abnormally low or high hemoglobin concentration during pregnancy: special consideration of iron nutrition.

An association between moderate anemia and poor perinatal outcomes has been found through epidemiologic studies, although available evidence cannot establish this relation as causal. Anemia may not be a direct cause of poor pregnancy outcomes, except in the case of maternal mortality resulting directly from severe anemia due to hypoxia and heart failure. Preventing or treating anemia, whether moderate or severe, is desirable. Because iron deficiency is a common cause of maternal anemia, iron supplementation is a common practice to reduce the incidence of maternal anemia. Nevertheless, the effectiveness of large-scale supplementation programs needs to be improved operationally and, where multiple micronutrient deficiencies are common, supplementation beyond iron and folate can be considered. High hemoglobin concentrations are often mistaken as adequate iron status; however, high hemoglobin is independent of iron status and is often associated with poor health outcomes. Very high hemoglobin concentrations cause high blood viscosity, which results in both compromised oxygen delivery to tissues and cerebrovascular complications. Epidemiologic studies have also found an association between high maternal hemoglobin concentrations and an increased risk of poor pregnancy outcomes. Evidence does not suggest that this association is causal; it could be better attributed to hypertensive disorders of pregnancy and to preeclampsia. The pathophysiologic mechanism of these conditions during pregnancy can produce higher hemoglobin concentrations because of reduced normal plasma expansion and cause fetal stress because of reduced placental-fetal perfusion. Accordingly, higher than normal hemoglobin concentrations should be regarded as an indicator of possible pregnancy complications, not necessarily as a sign of adequate iron nutrition, because iron supplementation does not increase hemoglobin higher than the optimal concentration needed for oxygen delivery.

The roles of inflammation and iron deficiency as causes of anemia.

Inflammatory disease as well as iron deficiency may play an important role in the cause of anemia in the United States. We evaluated the relationships between Fe deficiency, inflammatory disease, and anemia using data from of the First National Health and Nutritional Examination Survey (NHANES I). Fe nutrition index was based on the ratio of serum Fe to Fe-binding capacity (Fe:TIBC) and inflammatory index was based on erythrocyte sedimentation rate (ESR). Groups with the highest prevalence of anemia were younger children, young women, and elderly men. Fe deficiency (low Fe:TIBC) was most common among the anemic children and young women but rare in anemic elderly men. Conversely, inflammation (high ESR) was most common among anemic elderly individuals. The prevalence of anemia was more than twice as high in the lowest than in the highest income group. Relative contributions of Fe deficiency and inflammation to anemia did not differ substantially among income groups.

Hemoglobin difference between black and white women with comparable iron status: justification for race-specific anemia criteria.

To determine the appropriateness of race-specific criteria for anemia, we used the sample of women of child-bearing age from the Second National Health and Examination Survey to examine the relationship between hemoglobin and iron status for blacks and whites. After adjustment for major factors known to cause hemoglobin variation, including iron nutrition status, black women overall had a significantly lower mean hemoglobin value (126 +/- 12 g/L) than white women (134 +/- 11 g/L). Comparison of the probability plots of black and white hemoglobin distributions found the difference across the distributions to not be uniform, likely because a subset of black women had lower hemoglobin values rather than because of a generalized lowering. This finding suggests that it may not be appropriate to have a separate criteria for all blacks to accommodate the subset with lower hemoglobin. However, evaluation of the screening performance of hemoglobin found that race-specific anemia criteria (10 g/L difference) yielded a comparable sensitivity and specificity in detecting iron deficiency for both races. In contrast, a fixed anemia criterion did not yield comparable screening performances for the two races. This functional evaluation supports considering race-specific anemia criteria for screening iron deficiency.

Age-related changes in laboratory values used in the diagnosis of anemia and iron deficiency.

Laboratory results from the Second National Health and Nutrition Examination Survey (NHANES II) were used to define age-related changes in laboratory values that are related to the diagnosis of anemia and iron deficiency. Analyses included Hb, hematocrit, red blood cell count, red cell indices, iron, total iron-binding capacity, transferrin saturation, and erythrocyte protoporphyrin. Computation of median values and 95% ranges by age and sex for each laboratory test were performed on 15,093 subjects between 1 and 74 yr of age who had complete laboratory data on venous blood, after excluding those subjects with an abnormality in one or more of three other laboratory tests. Age-related changes in laboratory measurements, such as those described herein, must be taken into consideration in order to optimize the identification of individuals with anemia and iron deficiency.

Prevalence and causes of anemia in the United States, 1976 to 1980.

We estimated the prevalence of anemia in the United States from the results of the Second National Health and Nutrition Examination Survey ( NHANES II, 1976 to 1980). Reference ranges for Hb were first derived from 11,547 subjects in whom laboratory values for serum iron/iron-binding capacity, mean corpuscular volume, and erythrocyte protoporphyrin were all normal (greater than or equal to 16%, greater than or equal to 80 fl, and less than or equal to 75 micrograms/dl red blood cells, respectively). Using these reference standards, the prevalence of anemia (Hb values below the 95% reference range for age and sex) among the 15,093 subjects with complete laboratory results was highest in infants (5.7%), teenage girls (5.9%), young women (5.8%), and elderly men (4.4%). The pattern of laboratory abnormalities in anemic subjects indicated that iron deficiency predominated as a cause in infants and young women in contrast to inflammatory disease in the elderly.

Developmental changes in serum ferritin and erythrocyte protoporphyrin in normal (nonanemic) children.

We studied 4039 children who were 6 months to 12 yr of age to characterize developmental variations of serum ferritin and erythrocyte protoporphyrin. Age-related descriptive statistics were derived. The -2 SD value for serum ferritin was found to increase progressively from 12 to 21 micrograms/1 with increasing age, while the +2 SD value for erythrocyte protoporphyrin was found to decrease progressively from 65 to 42 micrograms/dl whole blood with increasing age. While the mean serum ferritin value was found to continue to rise throughout the first 12 yr of life, erythrocyte protoporphyrin values were highest at 1 to 2 yr of age, then fell to essentially constant levels after 4 to 6 yr of age. These relationships, as well as the linear relationship of increasing hematocrit and serum ferritin with increasing age, suggest that the rise of hematocrit with age, as previously observed, is associated with improving storage and availability of iron for heme synthesis.

Reappraisal of the role of vegetables in the vitamin A status of mothers in Central Java, Indonesia.

Food-based approaches for controlling vitamin A deficiency and its consequences, such as increased mortality, more severe morbidity, and anemia, have become increasingly important, thus prompting a reassessment of the relation between vitamin A intake and status. A nutrition surveillance system in Central Java, Indonesia, assessed the vitamin A intake and serum retinol concentration of women with a child < or =24 mo old with a semiquantitative 24-h recall method that categorized vitamin A-containing foods into 3 categories of plant foods and into 2 categories of animal foods and identified portions as small, medium, or large. Median vitamin A intake was 335 retinol equivalents (RE)/d (n = 600) and vitamin A intake from plant foods was 8 times higher than from animal foods. Serum retinol concentration was related to vitamin A intake in a dose-response manner. The multiple logistic regression model for predicting the chance for a serum retinol concentration greater than the observed median (> or = 1.37 micromol/L) included physiologic factors, vitamin A intake from plant [odds ratio (95% CI) per quartile: 1st, 1.00: 2nd, 1.23 (0.75, 2.02); 3rd, 1.60 (0.97, 2.63); and 4th, 2.06 (1.25, 3.40)] and animal [1st and 2nd, 1.00; 3rd, 1.31 (0.86, 2.02); and 4th, 2.18 (1.40. 3.42)] foods, home gardening [(no, 1.00; yes, 1.71 (1.12, 2.60)], and woman's education level [< or =primary school, 1.00; > or =secondary school, 1.51 (1.02, 2.22)]. Despite the fact that plant foods contributed 8 times as much vitamin A as did animal foods, serum retinol concentrations did not reflect this large difference. Home gardening and woman's education level seemed to reflect longer-term consumption of vitamin A-rich plant and animal foods, respectively.

Does iron supplementation compromise zinc nutrition in healthy infants?

Iron supplements are commonly administered to infants in order to prevent iron deficiency. We wished to determine whether iron administration could compromise zinc nutrition as might be suspected from previous studies. Measures of iron nutrition, serum zinc, and serum copper were measured before and after randomization of 291 healthy 1-yr-old infants to a 3 mo course of placebo or iron treatment (30 mg iron as ferrous sulfate given before a meal). There was no significant difference in serum zinc or copper in the two groups before or after treatment; thus iron administration did not result in any evidence of zinc deficiency in a healthy, well-nourished group of T-yr-old infants.

Evidence of peroxidative damage to the erythrocyte membrane in iron deficiency.

The mechanism responsible for reduced red blood cell (RBC) survival in iron deficient infants or animals is unknown. To investigate the possible role of membrane peroxidation in iron-deficiency anemia, we studied RBC membrane lipids and proteins of rats fed iron-deficient (2 ppm Fe) and control (50 ppm Fe) diets between 21 and 41 days of age. Thin-layer chromatography of lipids showed that iron-deficient rats' RBC contained a novel phospholipid (1.9% of the total phospholipid) which moved between phosphatidylserine and phosphatidylethanolamine. Detailed studies showed that this PL is a Shiff's base adduct of phosphatidylserine, phosphatidyl-ethanolamine, and malonyldialdehyde, an end product of lipid peroxidation. Polyacrylamide gel electrophoresis of RBC proteins of iron-deficient rats also showed presence of high molecular protein complexes similar to that formed in in vitro malonyldialdehyde-treated RBC. To examine the role of such membrane cross-linking on in vivo RBC survival, we have studied survival of in vitro malonyldialdehyde-treated RBC in rabbits, 51Cr-T 1/2 of 5 microM malonyldialdehyde-treated RBC, which contained about the same amount of phospholipid/malonyldialdehyde adducts, was reduced to 6 days as compared to 11 days of sham-treated RBC. The in vitro study suggests that peroxidative damage results in significant reduction in RBC T 1/2 and may be analogous to decreased RBC survival in iron-deficient infants and animals.

A survey of 2,851 patients with hemochromatosis: symptoms and response to treatment.

PURPOSE: Hemochromatosis is a genetic disorder of iron absorption that affects 5 per 1,000 persons and is associated with reduced health and quality of life. We sought to determine the type and frequency of symptoms that patients experienced before the diagnosis and the treatments that they received. METHODS: We mailed a questionnaire to 3,562 patients with hemochromatosis who were located using patient advocacy groups, physicians, blood centers, newsletters, and the Internet. RESULTS: Of the 2,851 respondents, 99% were white and 62% were men. Circumstances that led to diagnosis of hemochromatosis included symptoms (35%), an abnormal laboratory test (45%), and diagnosis of a family member with hemochromatosis (20%). The mean (+/- SD) age of symptom onset was 41 +/- 14 years. Symptoms had been present for an average of 10 +/- 10 years before the diagnosis was made. Among the 58% of patients with symptoms, 65% had physician-diagnosed arthritis and 52% had liver disease. The most common and troublesome symptoms were extreme fatigue (46%), arthralgia (44%), and loss of libido (26%). Physician instructions to patients included treatment with phlebotomy (90%), testing family members (75%), and avoiding iron supplements (65%). CONCLUSIONS: The diagnosis of hemochromatosis in most patients was delayed. Physician education is needed to increase the detection of patients with the disease and to improve its management.

Lack of adverse side effects of oral ferrous sulfate therapy in 1-year-old infants.

An evaluation was made of 278 healthy-appearing 1-year-old infants who were tested for iron deficiency to determine the relative frequency of adverse side effects attributable to oral iron treatment. After obtaining parental informed consent, laboratory tests of iron status were performed on venous blood and infants with hemoglobin level greater than 10.5 g/dL were randomly chosen to receive 1.2 mL of ferrous sulfate (FeSO4) drops (about 3 mg of iron per kilogram per day) or equal volume of placebo for 3 months. After 3 months of treatment, infants were to return to the clinic for repeat blood testing, compliance estimation, and evaluation for possible adverse side effects. There was no significant difference (P greater than .50) in the frequency of vomiting, diarrhea, or fussiness in iron-treated infants (6%) compared with placebo-treated infants (9%). Constipation was slightly more frequently reported (P = .03) in placebo-treated infants (9%) than in iron-treated infants (1%). Compliance with therapy was confirmed in 179 completely evaluated infants by the lack of remaining medication at 3 months, the higher incidence (P less than .0001) of dark stools reported among iron-treated infants, and the changes in laboratory tests of iron status. No parents reported dark stools as an adverse effect of therapy. It is concluded that once daily, moderate-dose FeSO4 therapy given to fasting 1-year-old infants results in no more gastrointestinal side effects than placebo therapy.

Race and birth weight: the Chinese example.

In several studies a race-specific variation in birth weight was suggested between black infants and white infants. The following were compared: (1) the birth weight of Chinese infants born in mainland China, Taiwan, and the United States; and (2) the birth weight of Chinese infants and white infants born in the United States controlled for sociodemographic background. Similar birth weight distributions and incidence of low birth weight were found among Chinese infants born in the three areas with markedly different economic conditions. The women in all three areas appear to have met the basic health and nutritional needs for adequate fetal growth. Similar incidence of low birth weight with different birth weight distribution was found among infants born in the United States to two Chinese parents, to one Chinese parent and one white parent, and to two white parents. The variation in birth weight is greater for white infants than for Chinese infants and, consequently, more white infants had larger birth weight. The possibility of race-specific influences on birth weight distribution is suggested by these findings.

Screening for iron deficiency with the erythrocyte protoporphyrin test.

Elevation of erythrocyte protoporphyrin (EP) level is one of the consequences of iron deficiency. As the EP test has been established to be a screening test for lead poisoning, the screening capability of the EP test for iron deficiency was investigated. A total of 4,160 children between ages 6 months to 12 years had EP determined together with serum ferritin and hematocrit. Comparing the relationship of EP to serum ferritin and using a serum ferritin value less than or equal to 15 micrograms/L as the criterion of iron deficiency, the optimal cutoff limit for the EP test appears to be 35 micrograms/dL of whole blood. At this level, 88% of the subjects with low levels of serum ferritin can be detected (sensitivity), in contrast to the 53% detected at a higher cutoff value (greater than or equal to 50 micrograms/dL) used to screen for lead toxicity, or to the 59% detected by age-related hematocrit value. At an EP screening level of 35 micrograms/dL of whole blood, 90% of the subjects with normal serum ferritin level are correctly determined to be screen negative (specificity). The predictive value of low levels of serum ferritin for all subjects above screening level is 38%. In general, an elevated EP level, by itself, represents inadequate iron supply for hematopoiesis and signals iron deficiency regardless of whether the serum ferritin value is below the diagnostic level or not. A trial course of orally administered iron is suggested for children who are found to have an elevated EP value, with an increase in hemoglobin or hematocrit value serving, retrospectively, as confirmation of prior iron deficiency.

Birth weight and childhood growth.

Most previous studies of the relationship between birth weight and childhood growth have concentrated on the growth of low birth weight infants. To examine this relationship throughout the full range of birth weights, growth data for children less than 5 years of age from the Tennessee Special Supplemental Food Program for Women, Infants, and Children linked to birth certificate records for 1975 to 1985 were used. Growth status was compared for 500-g birth weight categories from 1,000 g to 4,999 g using mean Z scores and the percentage of children more than 2 SD above or less than 2 SD below the median for height for age, weight for age, and weight for height. Infants with lower birth weights were likely to remain shorter and lighter throughout childhood, especially those who were intrauterine growth retarded rather than premature. Conversely, those infants with higher birth weights were likely to remain taller and heavier and to have a higher risk of obesity. Birth weight is a strong predictor of weight and height in early childhood, not only for low birth weight children but also for those of normal and high birth weight.

Declining prevalence of anemia in childhood in a middle-class setting: a pediatric success story?

To study trends of anemia among middle-class children, we collected 6,162 hematocrit measurements from the medical records of 2,432 children, ages 9 months through 6 years, as seen at a private pediatric clinic during the past 18 years. A decline in prevalence of anemia was observed during that period. The overall age-adjusted rate of anemia decreased from 6.2% in 1969 to 1973, 5.8% in 1974 to 1977, 3.8% in 1978 to 1981, and 2.7% in 1982 to 1986. The decline was also observed when trends were determined for three age groups using a single hematocrit measurement per child. The 1982 to 1986 prevalences of anemia for various age groups among this middle-class pediatric population were relatively low: 2.8% among 9- to 23-month-old children, 2.4% among 24- to 47-month-old children, and 2.7% among 48- to 83-month-old children. Most of these recent cases of anemia were mild--most were only slightly less than the hematocrit values used to define anemia--and most did not show strong evidence of iron deficiency based on elevated levels of erythrocyte protoporphyrin. We conclude that iron deficiency is now mild and uncommon in these middle-class children. This improved nutritional status with regard to iron is probably related to increased intake of iron among infants and young children during the past two decades. These findings suggest that the recommended screening schedule for iron deficiency with hemoglobin or hematocrit measurements may need to be reassessed for well-defined populations of low-risk children.