Giardiasis: haematological status and the absorption of vitamin B12 and folic acid

The haematological status, as well as the fractional absorptions of folic acid (FAFol) and vitamin B12 (FAB12) were studied in 29 children aged 0.7-13.5 years (mean 3.3 years) with chronic diarrhoea due to giardiasis. Small intestinal biopsies revealed mucosal damage in 20 children; the biopsies of the remaining nine children were normal. At the initial investigation the FAFol and FAB12 values were below normal in approximately one-sixth and one-third of patients, respectively. Bacterial overgrowth of the small intestinal tract did not seem to play a role in FAB12 malabsorption. About one-fifth of patients had mild anaemia. None of the patients showed FAB12 insufficiency and only one patient suffered from folate depletion. At follow-up, FAFol, FAB12, haemoglobin and Erc-folate concentrations increased significantly while P-B12 and P-folate remained unchanged. Iron status, as well as dietary intake of iron, appeared insufficient prior to, as well as after treatment. Serum iron, transferrin saturation and haemoglobin concentrations were lower in patients who had acquired the disease abroad or suffered from persistent diarrhoea.     

The role of the exocrine pancreas in early-onset vitamin B12 malabsorption in gluten-challenged celiac children

The fractional absorption of vitamin B12 (FAB12) was measured by a double-isotope technique specially adapted for children. In six celiac children on a strict gluten-free diet and with a normal small intestinal biopsy, the FAB12 performed in the fasting patient averaged 30% (23-40%). After gluten challenge for a mean of 2 months (range 1-4), when mucosal damage was demonstrated by biopsy, the average fasting FAB12 in these patients decreased to 10% (0-17%) (p less than 0.05). However, when the FAB12 test was repeated by means of stimulation by a B12-free meal 1-3 weeks later, while the patients were still on a diet containing gluten, a significant increase was observed (mean 21%, range 14-27%) (p less than 0.05). In four of the six patients the B12 absorption was further evaluated by repeating the FAB12 test by means of intravenous cholecystokinin (CCK) stimulation (n = 3) or by administration of exocrine pancreas enzyme supplementation (EPES) (n = 2) or cobinamide (n = 1). These tests all showed FAB12 values within the range of the meal-stimulated FAB12. Moreover, in eight gluten-free celiac children with normal biopsies, no difference was found between fasting and meal-stimulated FAB12 values. Therefore, it is likely that the early-onset B12 malabsorption observed in the gluten-challenged celiac child with upper-small-intestinal mucosal damage is in part due to an insufficient stimulation of the exocrine pancreas when using the standard fasting B12 absorption test.(ABSTRACT TRUNCATED AT 250 WORDS)     

Folic acid absorption determined by a single stool sample test--a double-isotope technique. The folic acid absorption capacity in children

The fractional folic acid absorption (FAFol) was determined in 66 patients with various gastrointestinal diseases by a double-isotope technique, employing a single stool sample test (SSST) as well as a complete stool collection. The age of the patients ranged from 2.5 months to 16.8 years (mean 6.3 years). The test dose was administered orally and consisted of 50 micrograms of [3H]folic acid (monoglutamate) (approximately 20 muCi), carmine powder, and 2 mg 51CrCl3 (approximately 1.25 muCi) as the unabsorbable tracer. The whole-body radiation given to a 1-year-old child averaged 4.8 mrad only. The stool and napkin contents were collected and homogenized by the addition of 300 ml chromium sulfuric acid. A 300-ml sample of the homogenized stool and napkin contents, as well as 300 ml chromium sulfuric acid (75% vol/vol) containing the standards, were counted for the content of 51Cr in a broad-based well counter. The quantity of [3H]folic acid was determined by liquid scintillation, after duplicate distillation. Estimated by SSST, the FAFol, which employs the stool with the highest content of 51Cr corresponding to the most carmine-colored stool, correlated closely with the FAFol based on complete stool collection (r = 0.96, n = 39, p less than 0.0001). The reproducibility of FAFol determined by SSST was assessed from repeated tests in 18 patients. For a mean of 81%, the SD was 4.6%, which corresponded to a coefficient of variation of 5.7%.(ABSTRACT TRUNCATED AT 250 WORDS)     

叶酸对苯妥英钠所致癫痫患儿认知功能障碍的改善

目的探讨苯妥英钠（PHT）对癫痫儿认知功能的影响及叶酸制剂对其认知功能障碍的改善作用。方法14名患儿采用自身前后对照，于PHT治疗3mo后加服叶酸制剂，分析PHT治疗前、治疗3mo、治疗6mo后认知功能及血清叶酸、维生素B12的变化。结果PNT治疗3mo后，患儿的记忆力、注意力、精细运动及视觉保持能力明显降低。接受叶酸制剂后患儿认知功能明显改善。血清叶酸、维生素B12与认知功能之间有显著相关性。结论PHT对癫痫患儿认知功能的影响与PHT引起患儿血清维生素B12水平降低有关。加服叶酸制剂对癫痫患儿的认知功能有显著的改善作用。     

Effect of long-term carbamazepine therapy on serum lipids,vitamin B12 and folic acid levels in children

Serum triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), vitamin B12 and folic acid levels were studied in 16 children with epilepsy who had been receiving carbamazepine (CBZ), and in 16 healthy children. Our purpose was to determine whether there was any effect of CBZ therapy on serum lipids, vitamin B12 and folic acid levels. Age ranged from 5 to 19 years (12.25 +/- 3.79 years) and 5.5 to 18 years (12.16 +/- 3.53 years) in the study and control groups, respectively. The duration of CBZ therapy in the patients was between 1 and 4.5 years (3.01 +/- 1.04 years). Serum CBZ level varied between 4 and 12 microg/ml (6.26 +/- 2.07 microg/ml). There was no statistically significant difference in serum triglycerides, TC, HDL-C, LDL-C, VLDL-C or vitamin B12. However, mean folic acid level was found to be lower in the study group than that of the control group (p < 0.05). Nonetheless, serum folic acid levels were within the normal range in all patients. Our study demonstrated that CBZ therapy does not affect serum lipids, vitamin B12 and folic acid levels, and may safely be used with regard to these parameters in children.     

The Impact of Gluten on Haematological Status, Dietary Intakes of Haemopoietic Nutrients and Vitamin B12 and Folic Acid Absorption in Children with Coeliac Disease

ABSTRACT. The haematological status, as well as the fractional absorptions of folic acid-and of vitamin B₁₂ (FAFol and FAB₁₂) were studied longitudinally in 20 coeliac children aged 1.2-16.6 yr (mean 7.5 yr) during periods of gluten-free and gluten containing diets. The absorption methods were specially adapted to use in children, and age-related reference limits were established. Also, dietary intakes of iron, folate and B₁₂ were registered. The haemoglobin concentrations did not show any significant differences in relation to shifts in diet. A few had mild anaemia while the haemoglobin concentrations in the other patients remained within normal range. The iron status, as judged from mean corpuscular volume (MCV), serum (S)-iron, S-transferrin and saturation %, appeared to be generally insufficient. However, the only significant change related to shifts in diet was an increase of S-iron during the first period of gluten-free diet. Dietary intakes of iron proved to be insufficient, regardless of the type of diet. Plasma (P)-B₁₂ concentrations demonstrated a wide range of values above the lower normal limit, whereas the level in a single patient was within the “intermediate range” of B₁₂ insufficiency (150-200 pmol/l). The folate status (erythrocyte-folate) showed significant variations related to dietary changes. However, few patients were folate depleted. FAFol and FAB₁₂ demonstrated rapidly occurring, and significant decreases and increases in relation to gluten challenge and gluten-free diet, respectively. Bacterial overgrowth of the small intestinal tract was not found to be a plausible cause of the B₁₂ malabsorption in the case of 5 patients observed. In conclusion, it is recommended that the dietary management of coeliac patients with regard to haemopoietic nutrients focus on an appropriate iron intake. While a few patients failing to keep a strict gluten-free diet risk folate depletion due to malabsorption and to inadequate intake, these patients are, on the other hand, unlikely to develop vitamin B₁₂ deficiency.     

Vitamin B12 absorption capacity in healthy children

B12 absorption was investigated in 47 healthy children aged 7 months to 15.8 years (median 4.9 years). The patients had either recovered from giardiasis, the post-gastroenteritis syndrome, or had celiac disease in remission (treated with a gluten-free diet). The B12 absorption was measured by a double-isotope technique using 57CoB12 and 51CrCl3, the latter being the inabsorbable marker. The radiation dose was minimal. The results were presented as fractional absorption of B12 (FAB12). Within the different age groups, the absorption test was performed by means of the following oral amounts of B12: 0- less than 1 year, 0.5 microgram; 1-3 years: 1.7 micrograms, 4-6 years, 2.5 micrograms; 7-10 years; 3.3 micrograms; and 11-15 years, 4.5 micrograms. When using these oral amounts of B12, the medians (and ranges) of FAB12 were found to be: 1-3 years (n = 18), 37% (16-80%); 4-6 years (n = 10), 27% (19-40%); 7-10 years (n = 9), 32% (21-44%); and 11-15 years (n = 8), 27% (19-59%). The FAB12 in two children aged 7 and 11 months was 31% and 32%, respectively. These results may be interpretated as reference values for B12 absorption in children. Further absorption tests were performed in seven children representing the four age groups from 1 to 15 years. When a high oral amount of B12 was given (i.e., three times the saturation dose), the FAB12 ranged from 0 to 20% (median 9%), whereas a low amount (i.e., one-ninth of the saturation dose) produced fractional absorptions from 65 to 82% (median 74%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Maternal Milk and Serum Vitamin B12, Folic Acid,and Protein Levels in Indian Subjects

Serum vitamin B12 and folic acid activity levels were studied in 47 mothers. The mean serum vitamin B12 value in non-vegetarian mothers was 228 μμg./ml. ± 38·9 SE, as compared to mean values 97 μμg./ml. ± 20·7 SE in lacto-vegetarians. There was no significant difference in folic acid levels, haemoglobin, and total proteins among the different dietetic groups. Analysis of milk revealed mean vitamin B12 values of 103 μμg./ml. in non-vegetarians as compared to 91 μμg./ml. in lacto-vegetarians; the difference was not statistically significant. Mean total protein and folic acid levels for milk were similar in different dietetic groups. The figures obtained for vitamin B12 content of human milk in these mothers are considerably lower than those reported in similar studies from Western countries.     

Gastric function and absorption of vitamin B12 in children with celiac disease

Gastric acid secretion in nineteen children with celiac disease remained almost unchanged and the level of fasting serum gastrin was comparable with that of a control group of the same age. The absorption of vitamin B₁₂ was significantly decreased, most clearly in the infants with celiac disease as compared with their controls. The serum B₁₂ level, however, was decreased only in the oldest children. The results suggest that the mucosal lesion in the small intestine is most extensive in the youngest children, but the absorption defect of vitamin B₁₂ becomes clinically significant only after a long duration of the disease and not in childhood.     

Elevated plasma homocysteine in obese schoolchildren with early atherosclerosis

Elevated plasma homocysteine is widely seen as an independent risk factor of cardiovascular disease in adults. In order to investigate the role of homocysteine in a paediatric population at risk for early atheroclerosis, we studied plasma homocysteine in obese schoolchildren and non-obese peers. Plasma homocysteine, serum vitamin B12 and serum folic acid were determined in 41 obese and 27 control subjects and related to carotid intima-media thickness and flow-mediated dilatation measured on high-resolution ultrasonography. Homocysteine, vitamin B12 and folic acid were all significantly elevated in obese children. In girls, plasma homocysteine correlated significantly with body mass index (r=0.56, p=0.002), increased ICA intima-media thickness (r=0.39, p=0.035) and flow-mediated dilatation (r=−0.40, p=0.031). In boys, none of these associations reached significance (all p>0.234). No independent association of homocysteine with IMT and FMD was seen after adjustment for BMI. Conclusion: Plasma homocysteine is elevated in obese schoolchildren with hypertension and dyslipidaemia, particularly in girls. This may indicate a high-risk constellation, so that plasma homocysteine should be monitored in these children.     

Vitamin status in treated patients with cystic fibrosis.

The water-soluble (B1, B2, B6, C, folic acid) and fat-soluble vitamin (A, carotene, E, and D) status of 36 patients with cystic fibrosis was assessed and compared with a control group of 21 age-matched normal children. Twenty-seven of the patients were receiving vitamin supplements (except folic acid and vitamin E) at the time of investigation. Vitamin B1, B2, and B6 status was adequate in all patients, and there was little evidence of folic acid deficiency. Vitamin C stores might not have been adequate in some of these patients, despite daily supplements with 50 mg of the vitamin. Steatorrhoea, often severe, was present in most of them. Serum carotene and vitamin E concentrations were low in over 90% of patients and were related to the severity of steatorrhoea. Vitamin A was low in over 40% of the patients despite daily vitamin supplements of 4000 IU and correlated with the serum retinol-binding protein level. Serum 25-OH cholecalciferol was low in some patients whether or not they were receiving a daily supplement of 400 IU vitamin D. In a short-term supplementation trial with water-miscible preparations of vitamin A and E in 14 patients, the serum levels of both vitamins responded well to 2 weeks of treatment with 50 mg vitamin E and 4000 IU vitamin A. Except for serum vitamin A, which was lowest in patients with the poorest clinical grading, the other vitamins were not influenced by the clinical grade of the patients.     

Effect of carbamazepine therapy on homocysteine, vitamin B12 and folic acid levels in children with epilepsy

Objectives

To compare the levels of homocysteine, vitamin B12 and folic acid before and after 6 months of carbamazepine therapy and to correlate them with carbamazepine level at 6 months.

Design

Prospective comparative study.

Setting

Tertiary care centre in North India.

Participants

51 children (2–12 years of age) presenting with motor partial seizures.

Intervention

Carbamazepine (10–20 mg/μ/day) for 6 months.

Main outcome measure

Change in serum homocysteine, B₁₂, folic acid level.

Methods

Fasting venous samples were collected before carbamazepine therapy and after six months. Homocysteine was analyzed using homocysteine enzyme immunoassay. Vitamin B₁₂ and folic acid were estimated using electrochemiluminesence technique. Carbamazepine levels were measured at 6 months.

Results

Of the 51 children, 36 (males-21), were followed up and their data analyzed. Mean homocysteine level was 11.51±3.95 μmol/L at recruitment and 11.77±6.65 μmol/L at six months (P=0.785). At recruitment 6(16%) children had homocysteine level above 15 μmol/L which increased to 10(27%) at 6 months. Mean vitamin B₁₂ at recruitment was 292.1±111.2 pg/mL and 297.8±82.9 pg/mL at 6 months (P=0.764). Mean folic acid at recruitment was 9.98±3.45 ng/mL and 10.66±3.97 ng/mL at 6 months (P=0.358). There was no correlation between carbamazepine levels with homocysteine, vitamin B₁₂ and folic acid (P>0.05). There was no effect of age, sex or dietary pattern on homocysteine levels.

Conclusion

Hence 6 months of carbamazepine therapy did not cause significant change in serum levels of homocysteine, vitamin B₁₂ and folic acid.     

Nature and nurture in vitamin B12 deficiency.

We report on a child in whom severe nutritional vitamin B12 deficiency was exacerbated by a genetic impairment of the folate cycle, causing reduced CSF concentrations of the methyl group donor 5-methyltetrahydrofolate. Some patients with vitamin B12 deficiency may benefit from high dose folic acid supplementation, even if plasma concentrations are high.     

Nature and nurture in vitamin B12 deficiency

We report on a child in whom severe nutritional vitamin B12 deficiency was exacerbated by a genetic impairment of the folate cycle, causing reduced CSF concentrations of the methyl group donor 5-methyltetrahydrofolate. Some patients with vitamin B12 deficiency may benefit from high dose folic acid supplementation, even if plasma concentrations are high.     

Folic acid supplements in vitamin tablets: a determinant of hematological drug tolerance in maintenance therapy of childhood acute lymphoblastic leukemia

Methotrexate (MTX) is an antifolate that inhibits cell division by reducing intracellular amounts of reduced tetrahydrofolates. Of 53 children with acute lymphoblastic leukemia (ALL) in maintenance treatment with MTX and 6-mercaptopurine (6-MP), 25 had received daily folic acid supplements in vitamin tablets containing 75-200 micrograms folic acid for at least the preceding 3-month period. Experimental data have shown that increased folate concentrations intracellularly inhibit MTX metabolism and toxicity. Therefore we found it relevant to investigate the extent to which folic acid supplements affect hematological tolerance to MTX and 6-MP in children during maintenance therapy for ALL. The erythrocyte folate (ery-folate) concentration was significantly higher in children who received extra folic acid than in those who did not (p less than 0.001). The ery-folate in MTX-treated children was only marginally reduced compared with the controls. The erythrocyte methotrexate (ery-MTX) concentration correlated with the weekly dose of MTX but not with any of the investigated hematological parameters. Children who received vitamin tablets containing folic acid had higher thrombocyte counts (p = 0.0056), higher leukocyte counts (p = 0.06), higher neutrophil counts (p = 0.05), and lower erythrocyte mean cell volumes (p = 0.05) than children who received no folic acid. We conclude that folic acid supplements of 75-200 micrograms/day affect the proliferative capacity of the bone marrow. Since none of the children was folate deficient as judged by the ery-folate, we recommend that vitamins given to children in maintenance treatment with MTX and 6-MP for ALL should not contain folic acid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduced total plasma homocyst(e)ine in children and adolescents with type 1 diabetes

OBJECTIVES: The objective was to investigate total plasma homocyst(e)ine (tHcy), methylenetetrahydrofolate reductase (MTHFR) genotype, and the contribution of diet to homocysteine values in children and adolescents with type 1 diabetes and a control group. STUDY DESIGN: A total of 78 children with type 1 diabetes and 59 members of an age- and sex-matched control group were recruited. Fasting samples were collected for tHcy, MTHFR genotype, serum vitamin B(12), serum folate, red cell folate, and plasma creatinine. Food frequency questionnaires targeted intake of folate, vitamin B(6), and vitamin B(12). RESULTS: Fasting tHcy was reduced in patients compared with the control group (4.7 vs 5.9 micromol/L, P <.001). Serum folate (P =.002), red cell folate(P <.001), and serum vitamin B(12) (P =.005) were higher, and plasma creatinine was lower. A significant difference in tHcy values between patients and the control group persisted after correction was done for these factors (r = 0.1, P =.02). No difference was seen in the frequency of MTHFR polymorphisms. tHcy was not elevated in those patients with the 677TT or 677T/1298C genotypes, although red cell folate was significantly higher in members of the case (P =.01) and control groups (P =.05) with a 677 TT genotype. Dietary intake of folate correlated with serum folate (r = 0.4,P =.005). CONCLUSION: tHcy values are lower in children and adolescents with type 1 diabetes. Higher serum levels of folic acid and vitamin B(12), reflecting differences in dietary intake between children with diabetes and members of a control group, partially account for this difference.     

注意缺陷多动障碍患儿血清B族维生素水平及其与社会功能的相关性

目的探讨儿童注意缺陷多动障碍(ADHD)与血清B族维生素水平间的关系。方法选取2018年9月至2019年4月来苏州大学附属儿童医院儿童保健科就诊的ADHD患儿103例设为ADHD组,另选取同期在儿童保健科进行健康体检的同年龄段儿童89例设为健康对照组。采用电化学法测定2组儿童血清维生素B1、维生素B2、维生素B6、维生素B9、维生素B12水平。采用Weiss功能缺陷程度评定量表父母版(WFIRS-P)对ADHD患儿各社会功能评分与B族维生素水平进行相关性分析。结果 ADHD组中维生素B9水平[(12.55±2.22) nmol/L比(13.26±2.54) nmol/L]和维生素B12水平[(278.54±32.00) ng/L比(288.90±31.32) ng/L]均明显低于健康对照组,差异均有统计学意义(t=-2.064、-2.261,均P<0.05)。2组血清维生素B1、维生素B2、维生素B6水平比较,差异均无统计学意义(均P>0.05)。相关性分析显示,仅维生素B12水平与学习/学校维度的社会功能显著负相关(r=-0.208,P=0.035),其余血清B族维生素与各社会功能之间均未发现显著相关性(均P>0.05)。结论 ADHD患儿血清维生素B9和B12水平显著低于健康同龄儿童,血清维生素B12缺乏对ADHD患儿学习/学校维度的社会功能具有影响。儿童期注重B族维生素尤其是维生素B9和B12水平的监测并及时补充,在一定程度上对防治ADHD的发生发展可能有积极意义。     

Neutrophil hypersegmentation in children with iron deficiency anemia

Neutrophil hypersegmentation (NH) is usually associated with vitamin B12 or folic acid deficiency. NH is seen in iron deficiency anemia but there are very few case studies about this. Neutrophil hypersegmentation was evaluated in 94 children with iron deficiency anemia; 23 healthy children comprised the control group with similar ages. NH was found in 76/94 (81%) in the study group and 2/23 (9%) of the control group. The difference was statistically significant (p < .01).     

UNRELATED CORD BLOOD TRANSPLANT EXPERIENCE BY THE PEDIATRIC BLOOD AND MARROW TRANSPLANT CONSORTIUM

Neutrophil hypersegmentation (NH) is usually associated with vitamin B 12 or folic acid deficiency. NH is seen in iron deficiency anemia but there are very few case studies about this. Neutrophil hypersegmentation was evaluated in 94 children with iron deficiency anemia; 23 healthy children comprised the control group with similar ages. NH was found in 76/94 (81%) in the study group and 2/23 (9%) of the control group. The difference was statistically significant ( p < .01).     

Anti-Epileptic drug treatment in children: Hyperhomocysteinaemia, B-Vitamins and the 677C→T Mutation of the Methylenetetrahydrofolate Reductase Gene

The aim of the study was to observe the influence of carbamazepine and valproic acid on plasma total homocysteine and B-vitamin status and the gene-drug interaction with the 677C-->T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. Plasma total homocysteine concentrations were determined in 136 epileptic children taking anti-epileptic drugs as monotherapy. Nutritional (folate, B12 and B6 vitamins) and genetic (MTHFR 677 C-->T) determinants of plasma homocysteine were studied in a random sample of 59 of the 136 epileptic children. Total homocysteine concentrations were significantly increased (p < 0.05) and folate and vitamin B6 levels were significantly decreased (p < 0.01) in the children taking anti-epileptic drugs compared with our reference ranges. In the carbamazepine-treated group, significantly positive correlation was found between duration of treatment and homocysteine concentration (p < 0.01). Homocysteine concentrations showed a significantly negative correlation with vitamin levels (folate: p = 0.002, and vitamin B12: p = 0.017) only in the carbamazepine treated group. In children treated with carbamazepine up to 3 years, total homocysteine concentration correlated negatively only with folate (p = 0.003), while in patients treated for more than 3 years, total homocysteine correlated negatively only with vitamin B12 values (p = 0.007). The lowering action of carbamazepine treatment on folate levels seems to be associated with hyperhomocysteinaemia, which seems to be related to the homozygous condition for the MTHFR 677C-->T mutation. Valproic acid treatment, although also associated with hyperhomocysteinaemia, only shows a lowering effect on vitamin B6 levels, which seems to be independent of the MTHFR genotype.