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.     

Plasma homocysteine levels in children and adolescents with type 1 diabetes

OBJECTIVE: Hyperhomocysteinemia has been established as a risk factor for cardiovascular disease. The objective was to investigate total plasma homocysteine concentrations in children and adolescents with type 1 diabetes and a control group. METHOD: Twenty-seven children with type 1 diabetes and 27 subjects of an age- and sex-matched control group were recruited. Fasting samples were collected for plasma total homocysteine, serum vitamin B12, folate, and creatinine. RESULTS: Fasting total homocysteine concentrations showed no difference between patients and controls (5.6 +/- 2.9 micromol/L vs 5.7 +/- 2.2 micromol/L; p greater than 0.05). The diabetic patients had significantly higher serum folate than the healthy controls (11.4 +/- 3.3 ng/mL vs 9.4 +/- 4.1 ng/mL; P = 0.02 and higher serum B12 than the control group (282.8 +/- 119 pg/mL vs 228.5 +/- 50.9 pg/mL; P = 0.03). Total plasma homocysteine concentration correlated with age (r = 0.44, P = 0.02), weight (r = 0.56, P = 0.002), body mass index (r = 0.57, P = 0.002), folate (r = -0.48, P = 0.01), and creatinine (r = 0.41, P = 0.03) in diabetic patients. In stepwise multivariate regression model for diabetics, the independent correlates for total plasma homocysteine concentration was folate (P = 0.002). CONCLUSION: We concluded that fasting plasma total homocysteine concentrations were within normal limits in children and adolescents with type 1 diabetes who were without any clinical evidence of microvascular and macrovascular complications.     

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.     

Prevalence and treatment of vitamin D deficiency in children on anticonvulsant drugs

Bone metabolism was studied in a group of adolescent epileptic children given anticonvulsant drugs and compared with a matched group of nonepileptic children living in the same institutional environment. Biochemical evidence of vitamin D deficiency was more common in treated children than in controls, and 3 out of 60 children taking anticonvulsants had radiological evidence of rickets. The signs of vitamin D deficiency could not be corrected by giving 5 μg (200 IU) cholecalciferol daily for 12 weeks, but disappeared after treatment with 75 μg (3000 IU) cholecalciferol weekly for a further 12 weeks. Thus, in a residential home in southeast England the increased nutritional requirement for vitamin D caused by the administration of anticonvulsants to adolescent epileptic children was of the order of 10 μg cholecalciferol per day. It is likely that all epileptic subjects on anticonvulsants have increased needs for vitamin D and we advise regular supplementation of their diets.It is also shown that serum concentrations of γ-glutamyl transpeptidase, 5′nucleotidase, and leucine aminopeptidase are raised in children taking anticonvulsants. It seems likely that this is caused by drug induction of membrane-bound enzymes in the liver.     

Plasma homocysteine levels and folate status in children with sickle cell anemia.

PURPOSE: A sensitive inverse relationship between plasma homocysteine concentration and folate status has been demonstrated. Although children with sickle cell anemia (SCA) are at potential risk for folate deficiency, plasma homocysteine levels have not been reported in such patients. Therefore, a study was designed to assess plasma homocysteine levels as a marker of folate status. DESIGN: Plasma homocysteine concentrations were measured in 120 children with SCA (102 in steady state and 18 during an acute complication) who had never received supplemental folic acid. Folate status was directly assessed in 34 of these patients. RESULTS: Plasma homocysteine levels in the patients with SCA and control subjects were similar. The mean value +/- 1 SD was 5.8+/-2.5 micromol/L (range, 1.6 to 14.1 micromol/L) in the patients with SCA and 6.1+/-2.7 micromol/L (range, 1.7 to 15.3 micromol/L) in 73 pediatric control subjects. In a subpopulation of the study group (34 children), simultaneous serum folate, red cell folate, and total homocysteine concentrations were also measured. Their serum folate and red cell folate concentrations were normal: 12.4+/-10.0 nmol/L (range, 1 to 42 nmol/L) and 604+/-374.7 nmol/L (range, 205 to 1741 nmol/L), respectively. There was no correlation of plasma homocysteine concentration with various clinical or laboratory measures or with red cell folate concentration. CONCLUSION: Folate stores in children with SCA not receiving folic acid supplements are adequate despite an underlying hemolytic anemia.     

Congenital heart defects and maternal derangement of homocysteine metabolism

Methionine loading tests and folate, vitamin B(6), and vitamin B(12) analyses were performed in 27 mothers of children with congenital heart defects. Median fasting plasma homocysteine concentrations were significantly higher in the study group as compared with 56 control subjects (P =.0001). Maternal hyperhomocysteinemia may be a risk factor for congenital heart defects.     

Homocysteine and other vascular risk factors in patients with phenylketonuria on a diet

The aim of this study was to investigate the known risk factors, such as lipids, homocysteine and endothelin, for the development of coronary artery disease (CAD) in phenylketonuria (PKU) patients, depending on their diet. The PKU patients (n = 74) were divided into two groups. Group A (n = 34; mean age 6.78 +/- 1.5 y) adhered strictly to a diet and group B (n = 40; mean age 8.0 +/- 3.2 y) did not comply with the diet. The control group comprised 50 healthy non-PKU children. All groups were evaluated for blood levels of homocysteine and vitamin B6 by high-performance liquid chromatography, vitamin B12 and folate in serum by a radioassay, lipids by a routine method, and lipoprotein(a) and endothelin-1 with an immunoassay. Homocysteine levels (28.65 +/- 3.3 micromol l(-1)) were increased in group A compared with group B (6.86 +/- 1.6 micromol l(-1)) and the controls (6.9 +/- 2.0 micromol l(-1)) (p < 0.001). Vitamin B6 (10.7 +/- 10.9 nmol l(-1)), vitamin B12 (98.5 +/- 22.3 pmol l(-1)), folate (2.35 +/- 1.3 nmol l(-1)) and lipids were decreased in group A. The other vascular risk factors, which were not dependent on diet [lipoprotein(a) and endothelin-1], did not differ among the three groups. Conclusion: PKU patients on a strict diet had low vitamin B6, vitamin B12 and folate levels resulting in moderate hyperhomocysteinaemia. The evaluation of these vitamins at short intervals and their supplementation could be an early measure in the prevention of CAD.     

Red blood cell folate and serum vitamin B12 status in children with sickle cell disease

PURPOSE: To determine red blood cell (RBC) folate and serum vitamin B12 levels in children with sickle cell disease, SS-type, and to evaluate the associations of these nutrient levels with growth and hematologic parameters. PATIENTS AND METHODS: Subjects enrolled in this prospective, cross-sectional study were recruited from one tertiary care setting. Complete blood counts, measurement of red blood cell (RBC) folate and serum vitamin B12, anthropometric measures (height, weight, skinfold measurements), pubertal status, and 24-hour dietary recalls were obtained from 70 patients ages 1 to 19 years. RESULTS: Low RBC folate levels were found in 15% of the children. Fifty-seven percent of the sample had inadequate dietary folate intake. Three percent of the children had low serum vitamin B12 levels. All children and adolescents sampled had adequate dietary intake of vitamin B12. Both RBC folate (P = 0.01) and serum vitamin B12 levels (P < 0.01) decreased with increasing age. CONCLUSIONS: More than half of the subjects had inadequate intake of folate from food, and despite daily folate supplementation, 15% had low RBC folate levels. Low serum vitamin B12 levels were rare, and dietary vitamin B12 intake was adequate. Additional research is needed to explore the effects of improved folate status, the need for folate supplementation, and the relationship of folate, vitamin B12, and homocysteine levels and the risk for vascular damage and stroke in children with sickle cell disease.     

Homocysteine,folate, vitamin B12 and B6 in mothers of children with neural tube defects in Xinjiang,China

Aim: To investigate the maternal homocysteine (Hcy), folate, vitamin B₁₂ and B₆, and their relations to neural tube defects (NTDs). Methods: Thirty mothers of NTDs offspring and another 60 mothers of normal children were enrolled as the patient and control groups from Xinjiang, China, from January 2008 to May 2011. The plasma levels of Hcy, folate, vitamin B₁₂ and B₆ were measured and compared between the two groups. Results: The morbidity of NTDs was 2.44% in Xinjiang. The Hcy was significantly higher in patient group than in control group (15.1 ± 7.8 vs. 8.5 ± 4.0 μmol/L, p < 0.001). The folate in patient group (9.7 ± 8.1 μg/L) was lower than in control group (15.0 ± 8.1 μg/L, p < 0.001). The vitamin B₁₂ was 181.3 ± 107.7 and 394.3 ± 386.3 ng/L in patient and control groups, respectively, with a significant difference (p < 0.001). The abnormal frequency of Hcy and vitamin B₁₂ was statistically different in two groups. The difference of vitamin B₆ between the patients and controls was marginal (48.7 ± 16.5 vs. 42.0 ± 10.5 mg/L, p = 0.051). Moreover, folate and vitamin B₁₂ levels were negatively correlated with Hcy while vitamin B₆ was positively correlated with Hcy. Positive correlation was observed between folate and vitamin B₁₂ levels. Conclusion: Our data confirm that higher Hcy, lower folate and vitamin B₁₂ are risk factors for NTDs. Besides folate, vitamin B₁₂ should be supplied to decrease NTDs occurrence. Further study is required to investigate the levels and accurate role of vitamin B₆.     

Serum asymmetric dimethylarginine (ADMA), homocysteine,vitamin B<Subscript>12</Subscript>, folate levels,and lipid profiles in epileptic children treated with valproic acid

Recent reports have demonstrated elevated serum homocysteine (Hcy) levels in children receiving valproic acid (VPA) therapy. Elevated Hcy levels might play a potential role in the resistance to antiepileptic drugs, and might lead to an increased risk for a vascular disease. It has been reported that elevated total homocysteine (tHcy) levels are associated with elevated asymmetric dimethylarginine (ADMA) levels, which are factors that may be better indicators of endothelial dysfunction compared to serum homocysteine levels, because they are less sensitive to changes, such as fasting status, physical activity, and other factors. In this study, we aim to evaluate serum ADMA, Hcy, lipid, folate, and vitamin B₁₂ levels in epileptic children, receiving VPA monotherapy. Forty-four epileptic children, receiving VPA monotherapy for at least 6 months and 28 healthy children aged between 4 and 16 years, were recruited. Serum lipids, lipoproteins, folate, vitamin B₁₂, Hcy, and ADMA levels were analyzed in both study groups. Serum Hcy, ADMA, and vitamin B₁₂ levels were higher in patients than in controls (p < 0.001 for tHcy and ADMA levels; p < 0.05 for vitamin B₁₂ levels); however, serum lipid, lipoprotein, and folate levels were similar. According to the duration of epilepsy, serum tHcy, ADMA, and triglyceride (TG) levels were higher in patients with epilepsy for ≥2 years than in patients with epilepsy for <2 years (p < 0.001 for serum ADMA levels, p < 0.01 for tHcy levels, and p < 0.05 for serum TG levels). Similarly, with respect to the duration of VPA therapy, serum tHcy, ADMA, and TG levels were higher in patients who had received VPA therapy for more than 2 years (p < 0.001 for serum ADMA levels, p < 0.05 for serum tHcy levels, p < 0.01 for TG levels). Serum ADMA levels were significantly higher in patients receiving VPA at the dose of 25–30 mg/kg/day than in those receiving 20 mg/kg/day (p < 0.01). In conclusion, our study found increased serum ADMA levels and increased tHcy levels in epileptic children receiving VPA monotherapy. Increased serum ADMA levels were demonstrated in epileptic children who have had a seizure history greater than 2 years, and have used VPA therapy for more than 2 years, and have received higher doses of VPA. Routine monitoring of serum ADMA and tHcy levels might have beneficial effects for patients receiving long-term VPA therapy, especially in children who have other potential risk factors for vascular diseases. Further studies are needed to investigate serum ADMA and Hcy levels, and the presence of vascular disease, as well as the potential interactions between serum ADMA levels and seizure control.     

Evaluation of the levels of folate, vitamin B12, homocysteine and fluoride in the parents and the affected neonates with neural tube defect and their matched controls

The aim of this study is to evaluate the folate, vitamin B12, fluoride and homocysteine levels in newborns with neural tube defect (NTD) and their parents. The study included 35 neonates with NTD and their parents, 31 neonates with congenital anomalies other than NTD formed control 1, 24 neonates with no anomalies, with the highest birth order and normal siblings formed control 2. These groups matched for socio-economic and nutritional status. Demographic, antenatal history, parental habits, folate (RBC, whole blood and serum), serum vitamin B12 and homocysteine levels were estimated using chemiluminescence technology. Chi-square test was used to assess association between factors and the outcome. One-way ANOVA was used to compare means in the three groups. To determine the risk factors for NTD, odds ratios (95% CI) was computed using bivariate and multivariate logistic regression analysis (STATA 9.0). No difference was found between NTD group and 'control 1' group. The fathers in NTD group had significantly lower folate and vitamin B12 and a higher homocysteine, in comparison to 'control 2' group (i.e. with normal babies). The babies with NTD had higher homocysteine while their mothers had significantly low folate levels in comparison to 'control 2' mothers. Low RBC folate, low serum vitamin B12 and high plasma homocysteine in both the parents had an association with NTD. Multivariate logistic regression revealed high homocysteine of father as the only independent significant risk factor [OR(95% CI):2.6(2.6, 226)] for NTD and also for other anomalies. NTD (and other congenital anomalies) may not only be due to nutritional deficiency in the mothers but also due to more intricate gene-nutrient interaction defects in the affected families, probably some abnormal folate-homocysteine metabolism. These defects seem to be affect the fathers more severely and in all likelihood, get transmitted to the babies from either or both the parents. The emergence of father's serum homocysteine levels as an independent risk factor for NTD and also other congenital anomalies calls for further studies to evaluate if this can be taken as a marker for congenital anomalies in the fetus during antenatal screening.     

A prospective study of maternal fatty acids,micronutrients and homocysteine and their association with birth outcome

Our earlier studies both in animals and in humans have indicated that micronutrients (folic acid, vitamin B12) and long‐chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), are interlinked in the one‐carbon cycle, which plays an important role in fetal ‘programming’ of adult diseases. The present study examines the levels of maternal and cord plasma fatty acids, maternal folate, vitamin B12 and homocysteine in healthy mothers at various time points during pregnancy and also examine an association between them. A longitudinal study of 106 normal pregnant women was carried out, and maternal blood was collected at three time points, viz., T1 = 16–20th week, T2 = 26–30th week and T3 = at delivery. Cord blood was collected at delivery. Fatty acids were estimated using a gas chromatograph. Levels of folate, vitamin B12 and homocysteine were estimated by the chemiluminescent microparticle immunoassay (CMIA) technology. Maternal plasma folate (P < 0.05), vitamin B12 (P < 0.01) and DHA (P < 0.05) levels were lowest, while maternal homocysteine levels were highest (P < 0.01) at T3. There was a negative association between maternal DHA and homocysteine at T2 (P < 0.05) and T3 (P < 0.01). There was a positive association between plasma DHA in maternal blood at T3 and cord blood. Furthermore, there was a positive association between maternal folate and vitamin B12 at T3 and baby weight, whereas maternal homocysteine at T1 were inversely associated with baby weight at delivery. Our study provides evidence for the associations of folic acid, vitamin B12, homocysteine with DHA and baby weight, suggesting that a balanced dietary supplementation of folate–vitamin B12–DHA during pregnancy may be beneficial.     

Changes in serum lipids and lipoproteins in epileptic children treated with anticonvulsants

Objective: To assess the effect of long-term treatment of phenobarbital, carbamazepine and sodium valproate on serum lipids and lipoproteins in epileptic children.
Methodology: One hundred and fourteen (55 male, 59 female) children and adolescents suffering from various types of epilepsy who received different antiepileptic drugs were studied. The patients were subdivided into three groups according to their therapy: (i) carbamazepine (35 patients); (ii) phenobarbital (34 patients); and (iii) sodium valproate (45 patients). One-hundred healthy sex- and age-matched children served as controls. Lipids and lipoprotein profile were evaluated before the beginning of the anticonvulsant therapy and after at least 2.5 years. In the patients receiving phenobarbital, we re-evaluated 12 children (seven male, five female) at the end of therapy.
Results: The children receiving phenobarbital showed high levels of serum total cholesterol and low-density lipoprotein (LDL) cholesterol and low levels of triglycerides, while children treated with carbamazepine had high levels of total cholesterol, triglycerides, LDL and high-density lipoprotein (HDL) cholesterol. Children treated with valproate had low triglycerides and LDL cholesterol levels with high levels of HDL cholesterol. The patients treated with phenobarbital showed a normalization of all parameters after the end of therapy.
Conclusions: Anticonvulsant drugs significantly modify serum lipids and lipoproteins in epileptic children. The changes due to phenobarbital seem to be transient.     

亚甲基四氢叶酸还原酶缺陷导致学童精神分裂症

亚甲基四氢叶酸还原酶（MTHFR）缺陷是一种少见的常染色体隐性遗传性疾病,是高同型半胱氨酸血症的常见类型之一。该文通过对1例MTHFR缺陷导致的精神障碍的临床经过、生化特点、MTHFR 基因突变进行回顾性研究,探讨该病的临床特点与诊疗方法。患儿11岁起出现精神异常,恐惧、幻听、学习困难、入睡困难、脾气暴躁、发呆、傻笑,符合精神分裂症诊断。多种精神科药物治疗无效,休学。13岁时来院就诊,血、尿总同型半胱氨酸明显升高。血浆和脑脊液叶酸均显著降低。血液蛋氨酸水平正常。患儿MTHFR基因存在665C>T纯合突变。经亚叶酸钙、维生素B12、维生素B6、甜菜碱补充治疗1周后,患儿血清及尿液总同型半胱氨酸降至正常,病情逐步改善,3个月后复学。晚发型MTHFR缺陷合并继发性脑叶酸缺乏症的患儿可表现为精神分裂症;血液及尿液总同型半胱氨酸测定、血液氨基酸测定、血清及脑脊液叶酸测定及基因分析对患者的病因诊断非常重要;补充叶酸、维生素B6、维生素B12、甜菜碱治疗有效。     

Homocysteine,vitamin B<Subscript>12</Subscript> and folate status in pediatric acute lymphoblastic leukemia

Objective  The cause of majority of acute leukemias is unknown, but likely to involve interaction of environment, hematopoitic development and weak susceptibility loci within an individual’s genetic constitution. The present study evaluates the association between plasma levels of homocysteine, folate and vitamin B₁₂ and acute lymphoblastic leukemia. Methods  Plasma levels of homocysteine, folate and vitamin B₁₂ were compared between cases of acute lymphoblastic leukemia and age and sex matched normal controls. Homocysteine levels were measured by solid immunoassay, while folate and vitamin B₁₂ levels were determined by radioassay. Results  Folate levels were significantly among cases as compared to control group (8.56 ± 4.35) vs (14.04 ± 2.62) ng/ml, P<0.001). Although individually vitamin B₁₂ and homocysteine were not significant different between cases and controls, the combined effect of all three parameters was significantly different (P<0.001), with 83.3% of correct classification of cases and controls was obtained by discriminate function analysis. Conclusion  The data provide evidence for the role of folate, vitamin B₁₂ and homocysteine levels in acute lymphoblastic leukemia, suggesting that gene-environment interaction may be an important factor in the development of acute lymphoblastic leukemia.     

Plasma homocysteine concentrations in adolescents with subclinical hypothyroidism

OBJECTIVE: Hyperhomocysteinemia is a risk factor for premature atherosclerotic vascular disease and venous thrombosis. The aim of the present study was to assess plasma total homocysteine (tHCys) concentrations in adolescent patients with subclinical hypothyroidism. PATIENTS AND METHODS: Nineteen patients with subclinical hypothyroidism and 19 healthy children were studied. Fasting plasma concentrations of tHCys and its putative determinants (plasma concentrations of free thyroxine [FT4], folate, vitamin B12 and renal function) were measured. RESULTS: tHCys concentrations showed no statistical difference between patients and controls (p > 0.05). Moreover, the difference in tHCys and total cholesterol concentrations was not significant between patients with mild TSH elevations (< or = 10 mIU/l) and patients with prominent TSH elevations (> 10 mIU/l). No correlation was found between tHCys concentrations and its putative determinants. CONCLUSIONS: We concluded that plasma tHCys concentrations were not increased in adolescent patients with subclinical hypothyroidism.     

Folate,vitamin B12, and homocysteine in smoking‐exposed pregnant women: A systematic review

Smoking exposure is associated with pregnancy complications, as are levels of folate, vitamin B12, and homocysteine. In nonpregnant adults, smoking exposure is associated negatively with folate and vitamin B12 levels and positively with homocysteine levels. A complete overview of the literature on this topic in pregnant women is lacking. To evaluate evidence of associations of maternal smoking exposure during pregnancy and levels of folate, homocysteine, and vitamin B12 in pregnancy and in cord blood, we searched MEDLINE, Embase, CINAHL, Cochrane, Scopus, Web of Science, and reference lists of relevant studies until August 2017. We selected studies in pregnant women describing the association of passive or active smoking and levels of folate, homocysteine, and/or vitamin B12. Data were extracted by two independent reviewers. We included 32 studies of 2,015 identified references with a total of 37,822 participants and more than 6,000 smokers. Twenty‐eight studies measured folate, 14 measured vitamin B12, and 13 measured homocysteine. Nineteen out of 28 studies assessing folate reported significantly lower levels in pregnant women exposed to smoking compared with those unexposed. Vitamin B12 levels were lower in smoking mothers in eight out of 14 studies. Homocysteine levels tended to be higher in mothers exposed to smoking. Smoking exposure during pregnancy is generally associated with lower folate and vitamin B12 levels and higher homocysteine levels. This may help raise further awareness about the consequences of smoking and the need to encourage stopping smoking in all, especially in pregnant women.     

Folate,Vitamin B12, Vitamin B6 and homocysteine: impact on pregnancy outcome

Good clinical practice recommends folic acid supplementation 1 month prior to pregnancy and during the first trimester to prevent congenital malformations. However, high rates of fetal growth and development in later pregnancy may increase the demand for folate. Folate and vitamins B12 and B6 are required for DNA synthesis and cell growth, and are involved in homocysteine metabolism. The primary aim of this study was to determine if maternal folate, vitamin B12, vitamin B6 and homocysteine concentrations at 18–20 weeks gestation are associated with subsequent adverse pregnancy outcomes, including pre‐eclampsia and intrauterine growth restriction (IUGR). The secondary aim was to investigate maternal B vitamin concentrations with DNA damage markers in maternal lymphocytes. A prospective observational study was conducted at the Women's and Children's Hospital, Adelaide, South Australia. One hundred and thirty‐seven subjects were identified prior to 20 weeks gestation as at high or low risk for subsequent adverse pregnancy outcome by senior obstetricians. Clinical status, dietary information, circulating micronutrients and genome damage biomarkers were assessed at 18–20 weeks gestation. Women who developed IUGR had reduced red blood cell (RBC) folate (P < 0.001) and increased plasma homocysteine concentrations (P < 0.001) compared with controls. Maternal DNA damage, represented by micronucleus frequency and nucleoplasmic bridges in lymphocytes, was positively correlated with homocysteine (r = 0.179, P = 0.038 and r = 0.171, P = 0.047, respectively). Multivariate regression analysis revealed RBC folate was a strong predictor of IUGR (P = 0.006). This study suggests that low maternal RBC folate and high homocysteine values in mid pregnancy are associated with subsequent reduced fetal growth.     

Calcium metabolism and vitamin D metabolite levels in children receiving anticonvulsant drugs

Calcium metabolism and plasma concentrations of vitamin D metabolites were investigated in 27 children on long-term anticonvulsant therapy. Serum calcium was in the low normal range, phosphorus was normal, parathyroid hormone concentrations and alkaline phosphatase were elevated. Plasma 25-hydroxyvitamin D (25-OH D) and 24,25-dihydroxyvitamin D (24,25-(OH)₂D) were decreased, but 1,25-dihydroxyvitamin D (1,25-(OH)₂D) was normal when compared with a synchronous control group. The serum concentrations of all anticonvulsant drugs given were measured. The decreases in 25-OH D and 24,25-(OH)₂D did not depend on the blood level of a single drug, or any combination of drugs given, or on the duration of therapy. The 25-OH D levels were negatively correlated with the number of different drugs used, which may reflect the severity of the neurologic disorder, and therefore with non-specific factors such as exposure to sunlight, nutrition, or physical activity.Our data do not support the hypothesis that anticonvulsant drugs act on vitamin D metabolism.Dedicated to Prof. Dr. G.-A. von Harnack on occasion of his 65th birthday     

Homocysteine, cysteine, and related metabolites in maternal and fetal plasma in preeclampsia

Homocysteine is associated with endothelial dysfunction and cardiovascular disease, and elevated concentrations of homocysteine have been found in preeclampsia. The purpose of this study was to investigate maternal and fetal concentrations of total homocysteine and related metabolites (including cysteine, choline, and betaine), and possible associations with infant birth weight. Women with preeclampsia (n=47) and controls (n=51), who underwent cesarean section, were included. Maternal plasma, umbilical vein, and artery plasma were analyzed. Median concentrations of homocysteine, cysteine, choline, and betaine were significantly higher in women with preeclampsia than controls, both in maternal and fetal plasma. There were no differences in folate and vitamin B12 concentrations between the groups, neither for maternal nor fetal samples. Maternal homocysteine concentration was a negative predictor for birth weight only in the preeclampsia group. Elevated homocysteine and cysteine concentration in maternal circulation in preeclampsia is reflected in the fetal circulation. The clinical significance of elevated homocysteine and cysteine concentrations in maternal and fetal compartments in preeclampsia remain to be explored, both regarding fetal growth and development of disease later in life.