Erythrocyte folate, plasma folate and plasma homocysteine during normal pregnancy and postpartum: a longitudinal study comprising 404 Danish women

OBJECTIVE: To assess folate and homocysteine status during normal pregnancy and postpartum in a longitudinal setting. METHODS: This study, performed in 1995-1996, comprised 404 healthy pregnant Danish Caucasian women residential in Copenhagen County. Women taking folic acid tablets or vitamin B12 injections were not included. Dietary multivitamin supplements containing folic acid 100 microg or vitamin B12 1 microg, taken by 34%, were discontinued at inclusion. Participants had normal renal function. Folate status [erythrocyte (Ery-) folate, plasma (P-) folate, P-homocysteine] was measured at 18, 32 and 39 wk of gestation and 8 wk postpartum when the women were lactating. RESULTS: Through 18, 32 and 39 wk of gestation and postpartum, P-folate demonstrated a significant fall: median values were 14.4, 10.2, 9.3 and 8.9 nmol/L, respectively (P < 0.0001). The prevalence of low P-folate <6 nmol/L increased during pregnancy from 0.7% to 19.0% postpartum (P < 0.0001). Ery-folate displayed a similar, significant fall: median value was 0.84, 0.75, 0.65 and 0.55 micromol/L, respectively (P < 0.0001). The prevalence of low Ery-folate <0.40 micromol/L increased during pregnancy from 0.5% to 17.2% postpartum (P < 0.0001). P-homocysteine demonstrated a significant increase: median value was 6.4, 7.0, 7.7 and 10.8 micromol/L, respectively (P < 0.0001). The prevalence of P-homocysteine >13 micromol/L increased during pregnancy from 0.7% to 20.8% postpartum (P < 0.0001). The prevalence of low folate status (defined as P-folate <6 nmol/L and P-homocysteine >13 micromol/L) was 0%, 0%, 1.2%, and 8.4% at 18, 32 and 39 wk of gestation and 8 wk postpartum, respectively. CONCLUSION: Low folate status occurs among Danish pregnant women, especially in late pregnancy and postpartum during lactation. Despite new guidelines for folic acid supplement since 1997, only 13% of pregnant women followed the guidelines in 2003. The official recommendations for periconceptional folic acid supplement should be reconsidered and reinforced.     

Serum Ferritin is a Reliable, Non-invasive Test for Iron Status in Pregnancy: Comparison of Ferritin with Other Iron Status Markers in a Longitudinal Study on Healthy Pregnant Women; Erythropoiesis

Background and Aims: To assess the true positive and false positive rates of the iron status markers (serum iron, serum transferrin, transferrin saturation, haemoglobin, haematocrit, mean corpuscular volume (MCV), mean cell haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), erythrocyte count) in the diagnosis of depleted iron stores (iron depletion) during normal pregnancy and postpartum. Methods: Among 120 pregnant women, 58 were randomised to placebo-treatment and 62 to iron-treatment (66 mg ferrous iron daily from 14 weeks of gestation). Iron status markers were measured every 4th week during pregnancy and 8 weeks postpartum. Iron depletion was defined by a serum ferritin concentration < 16 &mgr;g/L. The 5th percentiles for the other iron status markers in the group of iron-treated women were used as cut-off values. Calculations were made in the 2nd and 3rd trimester, praepartum and postpartum. Results: In general, the true positive rates of other iron status markers in the diagnosis of iron depletion (serum ferritin < 16 &mgr;g/L) were low ranging from 0% to 52% during pregnancy and from 9% to 64% postpartum. Transferrin saturation and MCH displayed the highest true positive rates. The false positive rates ranged from 0% to 13% during pregnancy and from 4% to 17% postpartum. Haemoglobin and MCH displayed the highest false positive rates. Conclusions: The sensitivities of the other iron status markers were too low and the false positive rates too high to be of clinical value in the diagnosis of iron depletion. Despite physiologic variations due to haemodilution, the serum ferritin concentration is currently the most reliable non-invasive marker of iron status in pregnancy and postpartum.     

Cobalamin status during normal pregnancy and postpartum: a longitudinal study comprising 406 Danish women

OBJECTIVES: To assess cobalamin (vitamin B(12)) status during normal pregnancy and postpartum in a longitudinal setting. METHODS: This study was performed in 1995-1996. It comprised 406 healthy, pregnant Danish Caucasian women, living in Copenhagen County. Cobalamin status, i.e. plasma (P-) cobalamin, P-methylmalonic acid and P-homocysteine was measured at 18, 32 and 39 wk gestation and 8 wk postpartum during lactation. RESULTS: P-cobalamin showed a gradual, significant decline during pregnancy (P < 0.0001) followed by a significant increase postpartum (P < 0.0001); at 18, 32, 39 wk gestation and 8 wk postpartum median values were 225, 172, 161 and 319 pmol/L, respectively. P-methylmalonic displayed a gradual, significant increase during pregnancy as well as postpartum (P < 0.001) with median values of 0.11, 0.13, 0.14, and 0.16 micromol/L, respectively. P-homocysteine demonstrated a significant increase during pregnancy and postpartum (P < 0.001). The frequency of P-cobalamin values <150 pmol/L increased during pregnancy from 15% at 18 wk to 43% at 39 wk gestation and subsequently declined to 3% postpartum. CONCLUSION: Low cobalamin status may occur among pregnant women, especially in late pregnancy. The recommendations for periconceptional vitamin B(12) supplementation should be reconsidered.     

Hyperhomocysteinemia in inflammatory bowel disease patients without past intestinal resections: correlations with cobalamin, pyridoxine, folate concentrations, acute phase reactants, disease activity, and prior thromboembolic complications

OBJECTIVE: Homocysteine is a sulfur-containing amino acid formed during the demethylation of methionine and high levels of this amino acid is a known risk factor for both arterial and also venous thromboembolic complications. Deficiencies of cobalamin, folate, and pyridoxine may predispose subjects to hyperhomocysteinemia, a common phenomenon in inflammatory bowel disease (IBD) patients. The aim of this study was to identify the prevalence, risk factors of hyperhomocysteinemia and its correlation with prior thromboembolic events in an IBD cohort without past intestinal resections. METHODS: In this prospective study, we studied the concentrations of homocysteine, cobalamin, folate, and pyridoxine in 105 consecutive patients with IBD, of whom 11 had a prior history of thromboembolic complications. Data regarding smoking habits, medication use, disease location, and severity were gathered and patients with past intestinal resections were excluded. Age-matched and sex-matched 85 healthy volunteers served as controls and multivariate regression analysis was performed to find out independent predictors of hyperhomocysteinemia. RESULTS: The mean age (+/-SD) in the IBD cohort was 38.69+/-12.13 years, and 51% were male. The mean age in the control group was 37.61+/-10.05 years, and 52% were male. Homocysteine concentrations in patients were higher [16.35 micromol/L (range 6.82 to 48.15) vs. 9.60 micromol/L (range 4.97 to 17.39), P=0.000] and hyperhomocysteinemia had a higher prevalence in patients than in the controls (56.2% vs. 4.7%, chi2=56.179, P=0.000), thus IBD significantly increased the risk of hyperhomocysteinemia [odds ratio=25.973 (95% confidence interval: 8.861-76.128)]. Homocysteine concentrations in patients with a history of thrombosis were not higher than those without a history of thrombosis [16.29 micromol/L (range 8.45 to 34.75) vs. 16.36 micromol/L (range 6.82 to 48.15), not significant]. Hyperhomocysteinemia was found in 54.5% of patients with thrombosis and 56.4% of patients without thrombosis (not significant). On stepwise regression analysis, plasma cobalamin level, albumin concentration, erythrocyte sedimentation rate, and platelet count were found to be independent predictors of elevated homocysteine levels. CONCLUSIONS: IBD patients have a higher prevalence of hyperhomocysteinemia than do healthy controls and elevated homocysteine levels are independently associated with lower serum cobalamin, albumin levels and elevated erythrocyte sedimentation rate, and platelet count. There is no correlation between hyperhomocysteinemia and a history of prior thromboembolic events.     

Haematological reference values in Spanish adolescents: the AVENA study

Objectives: To provide reference values for haematological indices in Spanish adolescents according to age and gender. Methods: A cross sectional study conducted in five Spanish cities was performed. Blood was drawn from a representative sample of 581 adolescents with age ranging from 13 to 17–18.5 yr. Age‐ and gender‐specific means, standard deviations and percentiles were determined for the following parameters: total red blood cell counts (RBC), haemoglobin concentration (Hb), haematocrit percentage (Hct), mean corpuscular volume (MCV), mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, red cell distribution width and total white blood cell (WBC) counts as well as counts and percentage of neutrophils, lymphocytes, monocytes, eosinophils and basophils; platelet count (PLT), mean platelet volume and plateletcrit percentage. Results: Younger male subjects presented lower RBC, Hb, Hct and MCV means that their older counterpart. By contrast these differences were not observed in female subjects. As expected, RBC, Hb and Hct mean values in males were found significantly higher than in girls for all studied age groups. No significant differences were observed in WBC by age and gender. PLT values gradually decreased with age, except for females aged 17–18.5 yr. Conclusion: The present study provides reference data on the distribution of haematological indices of Spanish adolescents. These data can be useful biomarkers of the nutritional status in adolescents.     

Erythropoiesis: Correlations Between Iron Status Markers During Normal Pregnancy in Women with and without Iron Supplementation

The aim was to evaluate relationships between iron status markers (haemoglobin, erythrocyte indices, serum iron, serum transferrin, serum transferrin saturation, serum ferritin) in normal pregnancy. Iron status markers were measured at 4-week-intervals during pregnancy and postpartum in 120 healthy women; 62 had daily treatment with tablets containing 66 mg ferrous iron, 58 were treated with placebo. Placebo-treated: Ferritin displayed positive correlations with transferrin saturation during 2nd and 3rd trimester. There were positive correlations between ferritin, erythrocyte MCV and MCH during 2nd and 3rd trimester and postpartum. Prior to delivery and postpartum, ferritin demonstrated positive correlations with haemoglobin. Transferrin saturation showed positive correlations with MCV, MCH and MCHC during 2nd and 3rd trimester and postpartum. Transferrin saturation displayed positive correlations with haemoglobin prior to delivery and postpartum. Iron-treated: In general, there were no correlations between iron status markers. Positive correlations appeared postpartum between ferritin, transferrin saturation and MCHC but not with haemoglobin. Transferrin saturation showed a positive correlation with MCH postpartum, but not with haemoglobin. Conclusion: The patterns of relationships in placebo-treated women were consistent with iron deficient erythropoiesis.     

Serum cobalamin, folate, methylmalonic acid and total homocysteine as vitamin B12 and folate tissue deficiency markers amongst elderly Swedes--a population-based study

OBJECTIVES: The possibilities of detecting tissue cobalamin and folate deficiency are under debate. In this report the levels of serum cobalamin, folate, methylmalonic acid (MMA) and total homocysteine (tHcy) and their interrelations in a representative random population sample are presented. DESIGN: Cohort study. SETTING: A general mid-Swedish population. SUBJECTS: A 20% random sample of persons 70 years or older in a defined geographical area were invited to a survey. A total of 235 (85%) persons responded, out of whom 224 had no interfering diseases. MAIN OUTCOME MEASURES: Serum cobalamin, folate, MMA and tHcy. RESULTS: The serum levels of cobalamin, folate, MMA and tHcy were all correlated to cobalamin and folic acid treatment. They were also correlated to the intake of multivitamin preparations. In addition, serum cobalamin was higher in untreated women than in men but not correlated to age. Serum folate was correlated neither to sex nor age. Serum tHcy and MMA were both directly correlated to age but MMA not to sex. MMA was inversely correlated to serum cobalamin but not to serum folate, whereas serum tHcy was inversely correlated to serum cobalamin, folate and creatinine. Neither serum cobalamin, folate, MMA nor tHcy had any significant correlation to haemoglobin, erythrocyte volume fraction (EVF) or mean red cell volume. Half of the study population had abnormal MMA or tHcy levels, suggesting a latent or overt tissue deficiency of cobalamin or folate. CONCLUSIONS: A substantial proportion of the elderly general population had signs of low tissue levels of cobalamin or folate. Amongst those who took multivitamin preparations this proportion was much lower.     

Correlations Between Iron Status Markers During Normal Pregnancy in Women with and without Iron Supplementation

The aim was to evaluate relationships between iron status markers (haemoglobin, erythrocyte indices, serum iron, serum transferrin, serum transferrin saturation, serum ferritin) in normal pregnancy. Iron status markers were measured at 4-week-intervals during pregnancy and postpartum in 120 healthy women; 62 had daily treatment with tablets containing 66 mg ferrous iron, 58 were treated with placebo. Placebo-treated: Ferritin displayed positive correlations with transferrin saturation during 2nd and 3rd trimester. There were positive correlations between ferritin, erythrocyte MCV and MCH during 2nd and 3rd trimester and postpartum. Prior to delivery and postpartum, ferritin demonstrated positive correlations with haemoglobin. Transferrin saturation showed positive correlations with MCV, MCH and MCHC during 2nd and 3rd trimester and postpartum. Transferrin saturation displayed positive correlations with haemoglobin prior to delivery and postpartum. Iron-treated: In general, there were no correlations between iron status markers. Positive correlations appeared postpartum between ferritin, transferrin saturation and MCHC but not with haemoglobin. Transferrin saturation showed a positive correlation with MCH postpartum, but not with haemoglobin. Conclusion: The patterns of relationships in placebo-treated women were consistent with iron deficient erythropoiesis.     

Haematological and biochemical profile of uncomplicated pregnancy in nulliparous women; a longitudinal study

Background: Most laboratory parameters change during pregnancy. A serial study of a large number of routine haematological and biochemical blood parameters and biochemical urine parameters was conducted in a group of 66 healthy nulliparous pregnant women, who had an uncomplicated pregnancy.Methods: Blood samples and 24-h urine samples were obtained at four weeks intervals during pregnancy and at 1 (1P) and 6 (6P) weeks after delivery.Results: During pregnancy, haemoglobin concentration, haematocrit and erythrocyte count were lower, mean cell volume was not different, and mean cell haemoglobin and mean cell haemoglobin concentration were enhanced. The platelet count during pregnancy was not different from the level at 6P but increased 60% at 1P. Serum ferritin decreased 50% whereas plasma fibrinogen increased 100%. Serum creatinine (−28%), uric acid (−35%) and urea (−40%) concentrations were reduced during pregnancy. The serum concentrations of sodium (−4 mmol/1) and potassium (−0.2 mmol/1) were lower, but serum chloride was unaltered. Serum protein and albumen concentrations declined by 7.8 and 9.4 g/1 respectively. The serum concentrations of bilirubin, ALAT, ASAT and γ-GT remained unaltered. Serum LDH was 30% above normal non-pregnant values at 1P. The heat-stable alkaline phosphatase level increased in the third trimester. Heat-stable and heat-labile fractions were both elevated at 1P. The serum osmolality was 9 mosmol/kg lower and urine volume was about 25% higher during pregnancy. The creatinine excretion was unaltered but creatinine clearance increased by 25%.Conclusions: The concentrations of most components change during pregnancy. The interpretation of results of laboratory tests in pregnant women should be made with caution.     

The impact of vegetarianism on some haematological parameters

OBJECTIVE: Subjects adopting a vegetarian diet are liable to vitamin B12 and iron deficiencies. Co-existing vitamin B12 and iron deficiencies may give an equivocal haematological picture, which may, in turn, delay making an early diagnosis. The current work was undertaken to investigate some haematological parameters in relation to vitamin B12 and iron status in vegetarians. SUBJECTS AND METHODS: Twenty-nine vegans, 64 lacto- and lacto-ovo-vegetarians, in addition to 20 occasional meat eaters, were enrolled for this study. The total group included 49 males and 64 females aged [mean (SD) = 46(15) yr]. Complete blood count, methylmalonic acid (MMA), homocysteine (HCY), ferritin, and transferrin concentrations and percentage transferrin saturation were assayed, using conventional methods. RESULTS: Vegans displayed the highest MMA and HCY levels (median MMA = 708 nmol L(-1); HCY = 12.8 micromol L(-1)). A lower lymphocyte count and a higher mean corpuscular volume (MCV) were found in vegans compared with lacto- or lacto-ovo-vegetarians (median = 1.51 x 10(9) vs. 1.83 x 10(9) L(-1); 92 vs. 89 fL, respectively). Vitamin B12-deficient subjects in the higher range of transferrin saturation percentage had higher MCV than vitamin B12-deficient subjects in the lower transferrin saturation range (mean MCV = 92 vs. 89 fL). A lower platelet count was found in the highest quartile of MMA (mean = 211 x 10(9) L(-1)) and in the highest quartile of HCY (mean = 215 x 10(9) L(-1)), compared with the other quartiles. Lower lymphocyte and platelet counts and higher MCV were found in subjects with elevated MMA and HCY, compared to those with normal metabolites. Factors that explained the variations in MCV were red blood cell count, ferritin, transferrin saturation, and methylmalonic acid levels. CONCLUSION: vitamin B12 and iron status were compromised by a vegetarian diet. Variations in mean corpuscular volume were determined by iron and vitamin B12 status. Lower lymphocyte and platelet count were accompanied by metabolic evidence that indicated vitamin B12 deficiency.     

Effect of a Red Blood Cell Transfusion on Biological Markers Used to Determine the Cause of Anemia: A Prospective Study

Background

Blood test results required for the evaluation of anemia are considered difficult to interpret after red blood cell transfusion. However, this hypothesis is neither supported by a strong physiological rationale nor is it evidence based.

Long-term effect of Helicobacter pylori eradication on plasma homocysteine in elderly patients with cobalamin deficiency

BACKGROUND: Helicobacter pylori gastritis may lead to impairment of the production of pepsinogen and acid, which are essential to cobalamin absorption. In turn, cobalamin deficiency leads to hyperhomocysteinaemia, a risk factor for cardio and cerebrovascular diseases. AIM: To evaluate the effect of H pylori eradication on plasma homocysteine levels in elderly patients. PATIENTS: Sixty-two H pylori-positive elderly patients with cobalamin deficiency were prospectively studied. METHODS: Homocysteine and cobalamin concentrations were determined before, 6 and 12 months after H pylori eradication. RESULTS: Corpus atrophy was observed in a few patients; otherwise, in most of them, the degree of corpus gastritis was moderate to severe. The initial homocysteine mean (SD) levels decreased from 41.0 (27.1) to 21.6 (10.1) micromol/l at the 6 month follow-up (p<0.001) and to 13.1 (3.8) micromol/l 12 months after H pylori eradication (p<0.001). Conversely, initial cobalamin mean levels increased from 145.5 (48.7) pmol/l to 209.8 (87.1) pmol/l and to 271.2 (140.8) pmol/l, 6 and 12 months after treatment, respectively (p<0.001 for both). Although the erythrocyte mean corpuscular volume was within reference intervals, it decreased significantly 6 (p = 0.002) and 12 (p<0.001) months after treatment. CONCLUSIONS: The results of the current study demonstrated that the eradication of H pylori in elderly patients with cobalamin deficiency is followed by increasing of cobalamin and decreasing of homocysteine blood levels.     

Low cobalamin (vitamin B12) levels in multiple myeloma: a retrospective study

BACKGROUND: In patients with multiple myeloma a variety of metabolic events may occur. One of these are changes in the serum cobalamin (vitamin B12) concentration. Elevated as well as decreased serum cobalamin levels have been reported. The prevalence and clinical consequences of low cobalamin levels are largely unknown. OBJECTIVE: To investigate the prevalence of low serum cobalamin levels in patients with multiple myeloma and to describe the clinical features, haematological parameters and outcome in patients with multiple myeloma with low and normal serum cobalamin levels. METHODS: A retrospective study was conducted in the Deaconess Hospital in Eindhoven. Thirty-two patients were identified who fulfilled the diagnostic criteria for multiple myeloma and had at least one serum cobalamin level tested during the diagnostic or treatment period. A number of clinical characteristics, haematological parameters and outcome were scored. RESULTS: Twenty-one (66%) patients had a normal serum cobalamin level, nine (28%) patients had a low one and two (6%) patients had an elevated serum cobalamin level. Between the group with a normal and a low serum cobalamin level there were no differences in patients characteristics such as sex and age, tumour characteristics such as the type of paraprotein, tumour load or tumour stage nor in haematological parameters such as haemoglobin level, mean corpuscular volume and megaloblastic changes in the bone marrow. The median survival was not statistically different between both groups.     

Abnormal biochemistry and morphology of erythrocytes in a case of transcobalamin II deficiency during treatment

Metabolic studies on a transcobalamin II deficient child during apparent haematological remission revealed abnormally low erythrocyte levels of cobalamin- and folate-coenzymes and highly unusual morphology of erythrocytes. Transfusion with hydroxocobalamin-supplemented plasma temporarily normalized the child's erythrocyte adenosylcobalamin and methylcobalamin. Subsequent oral leucovorin increased erythrocyte levels of low-polyglutamate folate. These findings provide further evidence that TCII may be involved not only in cellular cobalamin uptake but also in intracellular conversion of the cobalamin coenzymes and polyglutamate folates.     

Erythrocyte vitamin B12 activity in lactovegetarian pregnant Indian women

Plasma and erythrocyte vitamin B12 levels were studied in pregnant Indian women consuming very little food of animal origin and compared with healthy non-pregnant women from the same dietetic group. The comparison of the mean values for routine haematological parameters revealed distinct fall in haemoglobin, packed cell volume, plasma vitamin B12, and albumin levels in pregnant women. However, the mean erythrocyte vitamin B12 levels in pregnant women with haemoglobin of more than 10 g/dl did not differ significantly from the corresponding mean observed in non-pregnant subjects. It seems that in normal pregnancy, the fall in erythrocyte vitamin B12 is much less marked than the fall in plasma levels of this vitamin.     

Helicobacter pylori eradication lowers serum homocysteine level in patients without gastric atrophy

AIM: To determine whether Helicobacter pylori (H pylori) infection caused hyperhomocysteinemia by altering serum vitamin B_(12), serum folate and erythrocyte folate levels and whether eradication of this organism decreased serum homocysteine level. METHODS: The study involved 73 dyspeptic H pylork positive patients, none of them had gastric mucosal atrophy based on rapid urease test and histology. Out of 73 patients, 41 (56.2%) showed a successful eradication of H pylori 4 wk after the end of treatment. In these 41 patients, fasting serum vitamin B_(12) folate and homocysteine levels, and erythrocyte folate levels before and 4 wk after H pylori eradication therapy were compared. RESULTS: The group with a successful eradication of H pylori had significantly higher serum vitamin B_(12) and erythrocyte folate levels in the post-treatment period compared to those in pre-treatment period (210±97 pg/mL vs 237±94 pg/mL,P＜0.001 and 442±212 ng/mL vs 539±304 ng/mL, P=0.024, respectively), but showed no significant change in serum folate levels (5.6±2.6 ng/mL vs 6.0+2.4 ng/mL, P=0.341). Also, the serum homocysteine levels in this group were significantly lower after therapy (13.1±5.2 μmol/L vs 11.9±6.2 μmol/L, P=0.002). Regression analysis showed that serum homocysteine level was positively correlated with age (P=0.01) and negatively with serum folate level before therapy (P=0.003). CONCLUSION: Eradication of H pylori decreases serum homocysteine even in patients who do not exhibit gastric mucosal atrophy. It appears that the level of homocysteine in serum is related to a complex interaction among serum vitamin B_(12), serum folate and erythrocyte folate levels.     

Helicobacter pylori eradication lowers serum homocysteine level in patients without gastric atrophy

AIM: To determine whether Helicobacter pylori ( H pylori)infection caused hyperhomocysteinemia by altering serum vitamin B12, serum folate and erythrocyte folate levels and whether eradication of this organism decreased serum homocysteine level.METHODS: The study involved 73 dyspeptic H pylori-positive patients, none of them had gastric mucosal atrophy based on rapid urease test and histology. Out of 73 patients, 41 (56.2%) showed a successful eradication of Hpylori4 wk after the end of treatment. In these 41 patients, fasting serum vitamin B12, folate and homocysteine levels, and erythrocyte folate levels before and 4 wk after Hpylorieradication therapy were compared.RESULTS: The group with a successful eradication of Hpylori had significantly higher serum vitamin B12 and erythrocyte folate levels in the post-treatment period compared to those in pre-treatment period (210&#177;97 pg/mL vs237&#177;94pg/mL, P&lt;0.O01 and 442&#177;212 ng/mL vs 539&#177;304 ng/mL,P = 0.024, respectively), but showed no significant change in serum folate levels (5.6&#177;2.6 ng/mL vs 6.0&#177;2.4 ng/mL,P= 0.341). Also, the serum homocysteine levels in this group were significantly lower after therapy (13.1&#177;5.2 μmol/L vs 11.9&#177;6.2 μmol/L, P = 0.002). Regression analysis showed that serum homocysteine level was positively correlated with age (P = 0.01) and negatively with serum folate level before therapy (P = 0.003).CONCLUSION: Eradication of H pylori decreases serum homocysteine even in patients who do not exhibit gastric mucosal atrophy. It appears that the level of homocysteine in serum is related to a complex interaction among serum vitamin B12, serum folate and erythrocyte folate levels.     

Serum cobalamin concentration in sickle cell disease (HbSS)

The serum cobalamin, serum folate, erythrocyte folate concentrations and total leucocyte and neutrophil counts have been studied in sickle cell children (with HbSS) during the steady state. There was a significant reduction in serum cobalamin concentration with significant increases in both the total leucocyte count and neutrophil differential. A relationship was also observed between the serum cobalamin and erythrocyte folate. The lowest erythrocyte folate levels were observed in patients with the lowest serum cobalamin concentration. These abnormalities are discussed in relation to the possible role of cobalamin in the synthesis of erythrocyte folate polyglutamate and possible immunological role of cobalamin among these children. These results lend support to the view that daily cobalamin supplementation along with folate (which is being given) may prove beneficial to the sickle cell patients as it may lower the frequency and severity of infections.     

Folate-responsive homocystinuria and megaloblastic anaemia in a female patient with functional methionine synthase deficiency (cblE disease)

This first detailed report of a female patient with functional methionine synthase deficiency due to the cblE defect describes treatment with several vitamins and cofactors and clinical progress for 17 years. Before treatment, major findings were microcephaly, psychomotor retardation, episodic reduced consciousness, megaloblastic anaemia, increased plasma free homocystine (> 20 µmol/L), low plasma methionine (< 10 µmol/L) and increased excretion of formiminoglutamate. On high-dose folic acid, biochemical abnormalities such as formiminoglutamate excretion and homocystinuria nearly normalized, but clinical and haematological abnormalities remained. On replacement of folate with methylcobalamin, alertness, motor function, speech and the electroencephalogram improved, biochemical features were similar, but the mean corpuscular volume increased. The best control was observed on a combination of folate and methylcobalamin. At 17 years of age she remains severely mentally retarded.In cultured fibroblasts methionine synthesis was reduced (0.03 nmol/mg/per 16h, controls 2.4-6.9); methionine synthase activity was normal under high reducing conditions but decreased on limiting the reducing agent, dithiothreitol, to 5 mmol/L (18% of total, controls 51-81%); formation of methylcobalamin was low (4.5% of total cobalamins, control 57.5%) and complementation studies indicated the cblE defect. Methionine formation showed only minor increases in cells grown in folate- or cobalamin-supplemented medium. Serine synthesis, which was low in normal medium, increased with cobalamin supplementation. These studies suggest further heterogeneity within cblE mutants, show the difficulty of establishing the enzyme defect in vitro, and indicate a role for folate in addition to cobalamin in treatment.     

Levels of iron, vitamin B12, folic acid and their binding proteins during pregnancy

One hundred pregnant women, not anemic and not receiving iron or vitamin supplements, were chosen at random among the three trimesters of pregnancy to determine the incidence of unexpected iron, plasma folate and/or cobalamin deficiency, and the significance of fluctuating levels of their respective binding proteins. Pregnant females had a nonsignificant fall in serum iron and a fourfold decline in serum ferritin in the 3rd trimester compared with 1st trimester values. There was a steady decrease in plasma cobalamin and cobalophilin levels in every trimester but no difference in transcobalamin II values. Unsaturated cobalamin (UBBC) and unsaturated transcobalamin binding capacity (UTCBC) were lower in the 1st trimester fully recovering afterwards. Plasma folate levels were not lower, although there was a steady reduction in total and unsaturated folate binding capacity throughout pregnancy.