Mother's iron status, breastmilk iron and lactoferrin--are they related?

OBJECTIVE: Exclusive breastfeeding is recommended till 6 months age. Factors regulating the breastmilk iron and lactoferrin levels are incompletely known. Considering high prevalence of nutritional anemia in lactating mothers, we studied the iron status of lactating mothers, their breastmilk iron and lactoferrin levels to determine any relationship between them. DESIGN: Prospective study with 6 months follow-up. SETTING: Tertiary care referral hospital. SUBJECTS: Hundred nonanemic and 100 anemic mothers with their babies recruited at birth. Fifty-two nonanemic and 50 anemic mothers and their babies completed the 6-month follow-up. INTERVENTIONS: Hemoglobin (Hb), total iron binding capacity (TIBC), percent transferrin saturation (%TS), serum iron (SI) and serum ferritin measured on day 1 and 6 months postpartum. Breastmilk iron and lactoferrin measured on day 1, 14 weeks and 6 months after delivery. RESULTS: Breastmilk iron decreased progressively from day 1 to 14 weeks and at 6 months in both groups, but no significant difference was noted between nonanemic and anemic mothers (P>0.05). Significant decline in breastmilk lactoferrin concentration from day 1 to 14 weeks in nonanemic and anemic mothers (P<0.001) noted. Hemoglobin, TIBC, %TS, SI and serum ferritin of both groups had no correlation with breastmilk iron and lactoferrin concentration on day 1, 14 weeks and 6 months after delivery. CONCLUSIONS: Breastmilk iron and lactoferrin concentration had no relationship with the mother's Hb and iron status.

Evaluation of serum ferritin in screening for iron deficiency in tuberculosis.

Serum ferritin (SF) values

Utility of haematological parameters and C-reactive protein in the detection of neonatal sepsis.

OBJECTIVE: To evaluate various haematological parameters, individually and in combination, to formulate a haematological scoring system (HSS, defined by Rodwell et al.), which can then be used to screen for sepsis in neonates who are clinically suspected of infection.1 METHODS: The study cohort consisted of 150 neonates (from birth to 3 days old) with clinically suspected infection. Blood was collected by peripheral venepuncture in all neonates. A complete blood count, differential leucocyte count, total leucocyte count (TLC), total neutrophil count (TNC), immature neutrophil count, band form count and platelet count were performed. Immature total neutrophil count (I/T) and immature/mature neutrophil count (I/M) ratios were then obtained. C-reactive protein (CRP) was measured semiquantitatively and blood culture and antibiotic sensitivity were performed in each case. The haematological parameters were compared individually and in combination (by HSS) with CRP. RESULTS: Twenty-one (14%) neonates had blood culture proven sepsis. On evaluation of various haematological parameters, TLC < 10 x 109/L, TNC < 8 x 109/L, I/M > 0.25, I/T > 0.14, band count > 15% and platelet count < 150 x 109 were found to have optimal sensitivities and negative predictive values (NPV). Using these values, an HSS was formulated. A haematological score > or = 3 had a sensitivity of 86% and NPV of 96%. C-reactive protein as a single test had a sensitivity of 76% and NPV of 96%. A combination of CRP with haematological parameters decreased the sensitivity and NPV of the HSS. CONCLUSIONS: A haematological score can be obtained by a complete blood count and examination of peripheral blood smear, thus permitting an objective assessment of haematological changes that occur in a neonate suspected of sepsis. C-reactive protein does not have any advantage over HSS, either as a single test or in combination.

Acute and chronic toxicity studies on partially purified hypoglycemic preparation from water extract of bark ofFicus bengalensis.

Acute and chronic toxicity studies were conducted to assess toxicity of a partially purified preparation from the water extract of the bark ofFicus bengalensis, which was demonstrated in our earlier studies to have significant hypoglycemic and hypocholesteroiemic effect on alloxan induced, mild and severe diabetes in rabbits. LD(50) of this preparation was found to be ∼1 gm/kg in rats when given orally. For chronic toxicity studies 3 doses of aqueous preparation were given to 3 groups of rats. First group received 5 times ED(50) (50 mg/kg), second group 10 times ED(50) (100 mg/kg) and the third group 15 times ED(50) (150 mg/kg) for 3 months. Fourth group which served as control was given water. After three months, blood was collected for studying biochemical and hematological parameters. Blood glucose, serum cholesterol, liver and kidney function tests, haemoglobin, total and differential leukocyte count were determined. Animals were sacrificed and histopathological examination of liver, heart and kidneys was carried out. Results of the study showed that partially purified preparation fromFicus bengalensis is not toxic by all the above mentioned parameters.

Effect of electroconvulsive therapy on hematological parameters.

Although a complete blood count is part of the evaluation before the use of electroconvulsive therapy (ECT), there are no known hematological contraindications for the procedure. A preliminary study was done on 31 randomly selected psychiatric patients (chronic schizophrenia, n=10; acute depression, n=8; acute mania, n=6; acute psychosis, n=6; delusional disorder, n=1) receiving ECT to study its hematological effects. Blood samples were drawn just before and 0, 1 and 2 h after ECT. Hemoglobin (Hb%), total and differential leukocyte count (TLC and DLC), red blood cell (RBC) count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and platelet count were measured on a fully automated hematology analyzer (Sysmex K-1000). Significant changes were found in TLC, percentage of polymorphs and lymphocytes, and Hb%. Changes in other parameters were not statistically significant. More such studies are needed to substantiate these observations and to understand the mechanism and implication of these effects.

Serum transferrin receptors in detection of iron deficiency in pregnancy.

A prospective hospital-based study was conducted to evaluate the efficacy of serum transferrin receptors in the detection of iron deficiency in pregnant women. The iron status of 100 pregnant women with single uncomplicated term pregnancies in the first stage of labor was established using standard laboratory measures. These included complete hemogram, red cell indices, serum iron, percent transferrin saturation, and serum ferritin. In addition, serum transferrin receptor (STFR) was estimated. The results of 81 women with complete laboratory profiles were analyzed. Thirty-five (43.2%) women were anemic (hemoglobin <11 g/dl). Hemoglobin (Hb) showed a significant correlation with MCH, MCHC, serum iron, and percent transferrin saturation, suggesting that the anemia was likely to be due to iron deficiency. The mean STFR level was 18.05+/-9.9 mg/l in the anemic women and was significantly raised (p<0.001) compared with that of the nonanemic women. STFR correlated significantly with Hb (p<0.001), MCH (p<0.05), MCHC (p<0.01), serum iron (p<0.01), and percent transferrin saturation (p<0.01) and also showed a highly significant correlation with the degree of anemia. Serum ferritin in these women did not correlate with Hb, and only 54.4% of the women had levels <12 ng/ml, which does not reflect the true prevalence of iron deficiency. Serum transferrin receptor estimation is thus a useful measure for detecting iron deficiency in pregnancy.

Monitoring oral iron therapy with protoporphyrin/heme ratios in pregnant women.

Assessment of the efficacy of iron therapy has usually been done in populations/patients by monitoring changes in hemoglobin concentration, serum iron, percent transferrin saturation, and serum ferritin. In this study the protoporphyrin heme (P/H) ratio (a measure of free erythrocyte protoporphyrin) was measured before and after iron therapy in three groups of pregnant women, who received 60 mg (group A), 120 mg (group B), and 240 mg (group C) of elemental iron with folic acid (0.5 mg) per day for a period of 12 weeks, to evaluate its efficacy to monitor iron therapy. The three groups were comparable regarding the initial mean Hb concentration and serum ferritin levels. The initial mean P/H ratios were markedly elevated in all three groups and were different in the three groups, being highest in group A (113.2+/-92.6), intermediate in group B (87.5+/-62.5), and lowest in group C (69.8+/-43.3). The initial P/H ratio was significantly higher in group A than in group C (p<0.05). This probably affected the efficacy of iron therapy in the three groups. The P/H ratio decreased significantly in each of the three groups after iron therapy (A and B: p<0.001; C p<0.01). Mean Hb concentration and serum ferritin increased in all three groups post therapy; however, the magnitude of change in P/H ratio in all three groups was much greater. This indicated that the predominant contributory factor for anemia was iron deficiency in this group of pregnant women. Serum iron and percent transferrin saturation are difficult to interpret in our population, as iron is freely available over the counter and is prescribed as soon as anemia is detected in patients; therefore, the reduction in P/H ratio may be used to monitor response to iron therapy in population groups.

Red cell indices and discriminant functions in the detection of beta-thalassaemia trait in a population with high prevalence of iron deficiency anaemia.

Red cell indices and discriminant functions were studied in 463 heterozygous beta-thalassaemics (337 without iron deficiency, 126 with iron deficiency) and 195 patients of iron deficiency anaemia (IDA) to ascertain their utility in the detection of betathalassaemia trait (BTT). Majority of traits in both groups had an elevated RBC count (> or = 5.0 x 10(12)/L). The counts were significantly higher than of patients with IDA, only 4.6% of whom had this degree of erythrocytosis. Mean Hb concentration was significantly higher in traits as compared to iron deficient subjects (p < 0.0001). Mean MCV and MCH were significantly (p < 0.0001) lower in traits more so in those with ID as compared to patients of IDA. MCV < 80 fl and MCH < 27 pg were found to be sensitive markers in the detection of traits even in the presence of ID. Of the four discriminant functions studied MCSQ was found to be most sensitive in detection of BTT and it identified 97.9% traits. DF of England and Fraser was most specific for BTT being < 8.4 in only 6.2% patients with IDA. Detection of erythrocytosis especially in the presence of mild anaemia and calculation of discriminant functions derived from red cell indices were found to play an important role in screening for BTT even in the presence of ID and helped identify those patients who required further laboratory evaluation.

Haematological parameters and HbA2 levels in beta-thalassaemia trait with coincident iron deficiency.

Iron status was estimated in 463 heterozygous beta-thalassaemics to delineate the effect of iron deficiency (ID) on the haematological parameters and expression of HbA2 in these patients. One hundred and twenty six (27.2%) traits had coincident ID. These iron deficient traits had a significantly (p < 0.0002), higher prevalence of anaemia (90.5%) as compared to iron replete traits (71.5%). Mean haemoglobin concentration was significantly lower (p < 0.0001) in beta-thalassaemics with ID (10.7 +/- 1.5) g/al as compared to those without ID (11.6 +/- 1.6 g/dl). Mean MCV and MCH were significantly lowered (p < 0.0001) in patients of beta-thalassaemia trait (BTT) with ID than in these without ID. Mean HbA2 was not significantly different in the two groups of traits and was elevated (> or = 3.5%) in all except one patient. However, mean HbA2/cell was significantly (p < 0.05) lower in traits with ID. The effect of ID in BTT was apparent with significant lowering of haemoglobin concentration and increased prevalence of anaemia. Iron therapy is warranted in iron deficient traits and would help in significantly raising their haemoglobin concentration. Elevation in HbA2 values was striking and could be used with reliability for diagnosis of BTT even in the presence of ID.

Phenotypic expression of hemoglobin A2 in beta-thalassemia trait with iron deficiency.

Iron status was estimated in 463 heterozygous beta-thalassemics to delineate the effect of iron deficiency on the expression of hemoglobin A2 (HbA2) in these patients. One hundred and twenty-six (27.2%) patients with the trait were iron deficient. These iron-deficient patients had a significantly (p < 0.0002) higher prevalence of anemia (90.5%) compared with iron-replete patients with the trait (71.5%). The mean hemoglobin (Hb) concentration, MCV, and MCH were significantly (p < 0.0001) lower in patients with beta-thalassemia traits (BTT) who had iron deficiency than in those without iron deficiency. Mean RBC count and MCHC did not differ in the two groups. Mean HbA2 was not significantly different in the two groups of patients with the trait and was elevated (>3.5%) in all but one heterozygote investigated. Mean HbA2/cell was significantly (p < 0.05) lower in BTT patients with iron deficiency than in patients without iron deficiency. The presence of iron deficiency did not preclude the detection of BTT in this population. The effect of iron deficiency in BTT was apparent as a significant lowering of the Hb concentration and an increased prevalence of anemia. Iron therapy is warranted for BTT patients with iron-deficiency traits and would help to significantly raise their Hb concentration. The elevation of HbA2 was striking and could be used with reliability in making the diagnosis of BTT even in the presence of iron deficiency.

Prevalence & etiology of nutritional anaemias in early childhood in an urban slum.

The present study was carried out to find out the prevalence and etiology of nutritional anaemia among preschool children from an urban slum. Randomly selected 300 children aged 3 months-3 yr were analysed over a period of one year for estimating prevalence of nutritional anaemia. Prevalence was also assessed by the rise in haemoglobin after 8 wk of haematinic supplementation in 159 of the 300 subjects. Ninety anaemic children were evaluated for the etiology of anaemia. Prevalence of anaemia, as judged by WHO recommended 'cut-off' value of haemoglobin < 11 g/dl, was 76 per cent while comparable value of 74.8 per cent was derived by response to haematinic supplementation. Pure iron deficiency anaemia (IDA) was detected in 41.4 per cent (37/90) of anaemic children. Vitamin B12 deficiency alone or in combination with iron was diagnosed in 14.4 and 22.2 per cent anaemic children respectively. Similarly folate deficiency, IDA with infection and anaemia of chronic diseases (ACD) was diagnosed in 2.2, 3.3 and 12.2 per cent cases respectively. Childhood anaemia continues to be a significant public health problem in preschoolers and iron deficiency is by far the commonest nutritional cause of anaemia. Vitamin B12 deficiency per se or in combination with iron is an important yet not commonly recognised cause of anaemias in preschool children in the community.

Beta-thalassaemia mutations in northern India (Delhi).

The present study was undertaken to define beta-thalassaemia mutations prevalent in northern India (Delhi). Forty six children of beta-thalassaemia major and their families were investigated. DNA was extracted from leucocytes and screened for mutations prevalent in the Indian population. These mutations included 619bp deletion, IVS 1-1 (G-T), IVS 1-5 (G-C), frameshift mutations FS 8/9 (+G), FS 41/42 (-CTTT), Codon 16(-C), Codon 15 (G-A), codon 30 (G-C), IVS 1-110 (G-A) and -88 (C-T). 619 bp deletion mutation was detected directly by amplification of DNA by PCR followed by agarose gel electrophoresis. Other mutations were studied by DNA amplification and dot blot hybridization using synthetic normal and mutant oligonucleotide probes labelled at 5' end with gamma-32 P-ATP. Five mutations accounted for all the chromosomes in 46 patients. 619 bp deletion mutation was found to be the commonest mutation (34.8%) followed by IVS 1-5 (G-C) in 22.8 per cent, IVS 1-1 (G-T) in 19.6 per cent, FS 8/9 (+G) in 13 per cent and FS 41/42 (-CTTT) in 9.8 per cent. Nineteen (41.3%) patients were homozygous and 27 (58.7%) double heterozygous for different beta-thalassaemia mutations. This observation of limited number of mutations is significant and will be useful in planning strategies for prenatal diagnosis of beta-thalassaemia in northern India.

Haemostatic function in coronary artery disease (CAD).

Tests to evaluate haemostatic function bleeding time (BT), prothrombin time (PT) partial thromboplastin time with kaolin (PTTK), thrombin time (TT), platelet count, platelet function tests (platelet adhesiveness and microthrombus index) and plasma fibrinogen levels were performed in 30 patients of coronary artery disease (14 myocardial infarction, 16 angina pectoris) and 20 age and sex matched controls. There was no statistically significant difference in platelet adhesiveness and mean microthrombus index in patients and controls. The BT, PT, PTTK and TT were normal in all patients and controls. Stepwise logistic regression analysis showed that plasma fibrinogen was an independent risk factor in the production of CAD.

Proliferating cell nuclear antigen immunostaining in breast carcinoma and its relationship to clinical and pathological variables.

Tumour proliferative activity of 74 breast lesions was assessed by determining mitotic index and immunostaining for proliferative cell nuclear antigen using Peroxidase antiperoxidase method. The indices were correlated with histomorphology and clinical stage of the disease. Positively stained nuclei and mitotic figures were counted per 1000 cells to calculate Proliferating Cell Nuclear Antigen (PCNA) and mitotic index respectively. Sixty four cases stained positive for PCNA. The index ranged between 0 to 98. PCNA index was significantly low in benign lesions as compared to malignant lesions (p < 0.0002). There was a linear correlation between the mitotic index and PCNA index. PCNA index also showed significant correlation with tumour size and histologic grade; however, it had no correlation with axillary lymph node status.

ESR and iron status in pregnancy.

ESR (Westergen) correlated significantly with the iron status (as measured by Hb concentration, haematocrit, red cell count, MCH, P/H ratio, serum iron, TIBC and percent saturation of transferrin) in a group of pregnant women (PW) at term. Serum ferritin correlated negatively with the ESR but the correlation was not statistically significant. Serum ferritin levels of < 50 micrograms/L were present in 9 (34.6%) PW with ESR > or = 50 mm 1st hour and 5 (19.2%) PW with ESR < 50 mm 1st hour. The mean ESR in PW was 55.7 (+/- 22.9) and was > or = 50 mm 1st hour in 50% and < 75 mm 1st hour in 82.7%. The difference in the mean ESR in anaemic and nonanaemic PW was highly significant (p < 0.001), 87.5% anaemic PW with serum ferritin > 50 micrograms/L had ESR > or = 50 mm 1st hour, suggesting the possible effect of chronic infection in raising ferritin levels in these PW.

Serum transferrin receptor levels in the evaluation of iron deficiency in the neonate.

Iron deficiency anemia (IDA) is a major global problem. Early onset of iron deficiency in developing countries makes it imperative to identify iron deficiency in neonates. Most conventional laboratory parameters of iron status fail to distinguish neonates with iron deficient erythropoiesis. Serum transferrin receptor (STFR) levels are a recent sensitive measure of iron deficiency and the present study was carried out to evaluate the usefulness of cord serum transferrin receptors in identifying iron deficient erythropoiesis in neonates. A complete hemogram, red cell indices, iron profile: serum iron (SI), percent transferrin saturation (TS%) and serum ferritin (SF) was carried out in 100 full-term neonates and their mothers at parturition. Cord and maternal STFR levels were estimated using a sensitive enzyme-linked immunosorbent assay (ELISA) technique. Anemic women had a significantly lower SI, their TS% and high STFR levels suggesting that iron deficiency was responsible for the anemia. In the neonates of iron deficient mothers, cord SI, TS% and cord ferritin were not significantly different from those of neonates born to non-anemic mothers. Cord STFR level correlated well with hemoglobin (Hb) and laboratory parameters of iron status, and its level was significantly higher in neonates born to anemic mothers than in those born to non-anemic mothers. It was the only laboratory parameter to differentiate between neonates born to anemic and non-anemic mothers. Therefore, STFR is a sensitive index of iron status in neonates and identifies neonates with iron deficient erythropoiesis.

Autologous fibrin adhesive in experimental tubal anastomosis.

OBJECTIVE: To evaluate autologous fibrin in rabbit oviduct anastomosis versus 7-0 vikryl, a conventional suture material used in tubal anastomosis. METHODS: Thrombin was added to the autologous fibrinogen at the site of anastomosis to obtain a tissue adhesive. The anastomotic time, pregnancy rate, and litter size were evaluated. Three months later, a relaparotomy was done to evaluate patency and degree of adhesions, and a tubal biopsy was taken from the site of anastomosis. RESULTS: Analysis of results showed a statistically significant (P < .001) shortened anastomotic time and superior histopathological union in the tissue adhesive group. Patency rate, pregnancy rate, and degree of adhesions were comparable in both groups.