Maternal Plasma Vitamin Research Articles

The association of maternal vitamin D status with infant birth outcomes, postnatal growth and adiposity in the first 2 years of life in a multi-ethnic Asian population: the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study.

Maternal vitamin D status during pregnancy has been associated with infant birth and postnatal growth outcomes, but reported findings have been inconsistent, especially in relation to postnatal growth and adiposity outcomes. In a mother-offspring cohort in Singapore, maternal plasma vitamin D was measured between 26 and 28 weeks of gestation, and anthropometric measurements were obtained from singleton offspring during the first 2 years of life with 3-month follow-up intervals to examine birth, growth and adiposity outcomes. Associations were analysed using multivariable linear regression. Of a total of 910 mothers, 13·2 % were vitamin D deficient (<50 nmol/l) and 26·5 % were insufficient (50-75 nmol/l). After adjustment for potential confounders and multiple testing, no statistically significant associations were observed between maternal vitamin D status and any of the birth outcomes - small for gestational age (OR 1·00; 95 % CI 0·56, 1·79) and pre-term birth (OR 1·16; 95 % CI 0·64, 2·11) - growth outcomes - weight-for-age z-scores, length-for-age z-scores, circumferences of the head, abdomen and mid-arm at birth or postnatally - and adiposity outcomes - BMI, and skinfold thickness (triceps, biceps and subscapular) at birth or postnatally. Maternal vitamin D status in pregnancy did not influence infant birth outcomes, postnatal growth and adiposity outcomes in this cohort, perhaps due to the low prevalence (1·6 % of the cohort) of severe maternal vitamin D deficiency (defined as of <30·0 nmol/l) in our population.

The relation between vitamin D level and increased risk for early-onset neonatal sepsis in full-term infants

Objectives The aim of the study was to determine the role of maternal and neonatal plasma vitamin D levels in early-onset sepsis (EOS) and in its severity in term infants. Methods This study was performed on 60 neonates and their mothers who were divided into two groups. Group 1 comprised 30 full-term neonates with EOS. Group 2 comprised 30 healthy neonates of matched age and sex who served as the control group. All participants were subjected to the following investigations: complete blood count, C-reactive protein, blood culture and serum vitamin D levels in both neonates and their mothers. Results Maternal and neonatal vitamin D levels were lower in the study group compared with the control group and their levels were significantly higher in the summer season. We found a significant negative correlation between infant vitamin D level and C-reactive protein in the patient group. In contrast, there was a significant positive correlation between maternal and neonatal vitamin D levels in both groups. The best cutoff value of neonatal vitamin D for the risk of sepsis was 14.4 ng. Conclusion Lower maternal and neonatal vitamin D levels are associated with EOS. However, there was no significant relation between vitamin D deficiency and outcome.

Increased homocysteine levels exist in women with preeclampsia from early pregnancy

Objective: The present prospective study examines the levels of maternal plasma folate, vitamin B12 and homocysteine in normotensive control (NC) women and women with preeclampsia (PE) from early pregnancy till delivery.Methods: The present study includes 126 NC and 62 PE women. Maternal blood was collected at 3 time points during pregnancy (T1 = 16th–20th weeks, T2 = 26th–30th weeks and T3 = at delivery). Levels of folate, vitamin B12 and homocysteine were estimated by the chemiluminescent microparticle immunoassay technology.Results: Maternal plasma folate levels were similar between NC and PE women at all the time points across gestation. Maternal plasma vitamin B12 levels were significantly higher in PE (p < 0.05) as compared with NC at T2. Maternal plasma homocysteine levels were higher in PE as compared with NC at all the time points, i.e. T1, T2 (p < 0.05 for both) and T3 (p < 0.01).Conclusion: Our results indicate that higher homocysteine levels exist in women with PE from early pregnancy and continue till delivery.

The association between leukocyte telomere length and mitochondrial DNA copy number in pregnant women: a pilot study.

Both short telomere length and mitochondrial dysfunction have been associated with pregnancy complications, such as preeclampsia and intrauterine growth restriction. However, the relationship between these two biomarkers of oxidative stress, during pregnancy, is unknown. This study investigated the association of leukocyte telomere length with mitochondrial DNA (mtDNA) copy number, an indicator of mitochondrial density and possible mitochondrial dysfunction, using maternal blood samples collected from women with pregnancies uncomplicated by gestational diabetes or hypertensive disorders. Leukocyte telomere length and mtDNA copy number were determined in 75 pregnant women using quantitative real-time quantitative PCR. Bivariate and multivariable linear regression procedures were used to evaluate associations of these two biomarkers. Leukocyte mtDNA copy number (natural-logarithm) was positively associated with telomere length (Pearson correlation coefficient = 0.30, p-value = 0.009). After adjusting for maternal age and plasma vitamin B12, natural-log mtDNA copy number increased by 0.80 (f = 0.80; 95% CI 0.25 - 1.34, p-value = 0.005) for every 1 unit increase of telomere length. Approximately 11% of the variation in natural-long mtDNA copy number was explained by the model (adjusted R2 = 0.11). This cross sectional data suggests an association of mtDNA copy number with telomere length, two emergent biological markers of potential importance in perinatal health research. The consequences of oxidative stress, cellular senescence (as reflected by relatively shorter telomere length) and mitochondrial dysfunction, on the course and outcomes of pregnancy remain to be elucidated in larger prospective studies that include these biological markers.

Ascorbic Acid concentration and preterm premature rupture of membranes.

Preterm premature rupture of membranes (PPROM) complicates 1-5% of all pregnancies and is the major contributory factor for perinatal morbidity and mortality. Micronutrient deficiency (vitamin C) is associated with increased risk of PPROM. This study was conducted to establish the association between maternal plasma vitamin C concentration in women with PPROM and women without PPROM and to study the difference in maternal morbidity, neonatal morbidity, and mortality. A prospective study was conducted where 40 women (20 in each study and control group) with singleton pregnancies between 28 and 37weeks gestation were recruited. Women with anemia, diabetes, UTI, RTI, vaginal infection, bleeding, h/o PPROM in previous pregnancy, polyhydramnios, and smoker were excluded from the study. Maternal plasma vitamin C levels were measured. Ascorbic acid levels were low in women with PPROM 0.41±0.08 versus 0.84±0.19mg/dl. There is a linear decline in plasma vitamin C levels as the pregnancy advances. Inverse relationship was observed between duration of rupture of membranes and vitamin C levels. There was a significant difference in maternal morbidity, neonatal morbidity, and mortality. Ascorbic acid concentration was low in women with PPROM. Thus, vitamin C supplementation should be made mandatory along with iron and calcium to antenatal women to avoid the complications of PPROM.

Imbalance of folic acid and vitamin B12 is associated with birth outcome: an Indian pregnant women study

Maternal nutrient supplementation in developing countries is generally restricted to provision of iron and folic acid. Along with folic acid, vitamin B12 is also an important determinant of fetal growth and development. During pregnancy, the increased requirement of folic acid is met with supplementation, while vitamin B12 remains untreated and possibly deficient. The objective of our study was to study the combined effect of maternal plasma folate and vitamin B12, and their ratio on birth anthropometrics. We carried out an observational study on 49 full-term pregnant women at KEM Hospital, Pune, India, during 2006-2008, and measured plasma folate, vitamin B12 and homocysteine in venous blood at 36 weeks of gestation. Neonatal anthropometrics (birth weight, length, head circumference, abdominal circumference, mid arm circumference, chest circumference, triceps skinfold and subscapular skinfold thickness) were measured within 24 h of birth. Maternal plasma folate and vitamin B12 were not correlated to neonatal anthropometrics. The combined association of folate and vitamin B12 expressed as folate to vitamin B12 ratio was correlated to the neonatal anthropometrics. Imbalance in the maternal micronutrients with increasing ratio of folate to vitamin B12 was associated with an increase in plasma homocysteine (P=0.014), lowering of neonatal birth weight (P=0.009), birth length (P=0.034), head circumference (P=0.018) and chest circumference (P=0.009), while no significant association to other anthropometrics was observed. Supplementation of vitamin B12 in addition to supplementation of folic acid in pregnancy may be important for improving birth weight, birth length, head circumference and chest circumference.

319: The association of maternal plasma vitamin D with expression of angiogenic factors in early onset severe preeclamptic (EOSPE) placenta

319: The association of maternal plasma vitamin D with expression of angiogenic factors in early onset severe preeclamptic (EOSPE) placenta

Low plasma vitamin B-12 is associated with a lower pregnancy-associated rise in plasma free choline in Canadian pregnant women and lower postnatal growth rates in their male infants

Choline needs are increased in pregnancy. Choline can be used as a source of methyl for homocysteine remethylation to methionine, but choline synthesis requires methyls from methionine. Vitamin B-12 deficiency increases choline use for homocysteine methylation. We investigated whether poor vitamin B-12 status occurs and contributes to low plasma choline and altered biomarkers of choline synthesis in pregnant women. With the use of a post hoc analysis, we addressed the association of maternal plasma vitamin B-12 status with postnatal growth rates in term infants. Blood was analyzed for a prospective study of 264 and 220 pregnant women at 16 and 36 wk of gestation, respectively, and 88 nonpregnant women as a reference. The proportion of women with a plasma total vitamin B-12 concentration <148 pmol/L (deficient) or 148-220 pmol/L (marginal) increased with pregnancy and pregnancy duration, which affected 3% and 9% of nonpregnant women, 10% and 21% of women at 16 wk of gestation, and 23% and 35% of women at 36 wk of gestation, respectively. Plasma free choline, betaine, and dimethylglycine were lower in women at 36 wk of gestation with a deficient or marginal compared with sufficient plasma total vitamin B-12 concentration (>220 pmol/L). Plasma total vitamin B-12 was positively associated with the increase in plasma free choline from midgestation to late gestation (P < 0.001). The postnatal growth rate to 9 mo was lower in infant boys of women classified as total vitamin B-12 deficient compared with sufficient. This study shows that maternal vitamin B-12 status is related to choline status in late gestation in a folate-replete population and may be a determinant of infant growth even in the absence of undernutrition.

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.

Vitamin D levels in Malawian infants from birth to 24 months

We measured longitudinal levels of vitamin D in unsupplemented Malawian infants at 0 (birth), 2, 12, 15, 18 and 24 months of age. Matched maternal plasma and breast milk vitamin...

Effects of antioxidant vitamins on newborn and placental traits in gestations at high altitude: comparative study in high and low altitude native sheep

The present study evaluated the hypothesis that the effects of hypoxia on sheep pregnancies at high altitude (HA) are mediated by oxidative stress and that antioxidant vitamins may prevent these effects. Both HA native and newcomer ewes were maintained at an altitude of 3,589 m during mating and pregnancy. Control low altitude (LA) native ewes were maintained at sea level. Half of each group received daily oral supplements of vitamins C (500 mg) and E (350 IU) during mating and gestation. Near term, maternal plasma vitamin levels and oxidative stress biomarkers were measured. At delivery, lambs were weighed and measured, and placentas were recovered for macroscopic and microscopic evaluation. Vitamin concentrations in supplemented ewes were two- or threefold greater than in non-supplemented ewes. Plasma carbonyls and malondialdehyde in non-supplemented ewes were consistent with a state of oxidative stress, which was prevented by vitamin supplementation. Vitamin supplementation increased lamb birthweight and cotyledon number in both HA native and newcomer ewes, although placental weight and cotyledon surface were diminished. Placentas from vitamin-supplemented HA ewes were similar to those from ewes at sea level, making these placental traits (weight, number and diameter of cotyledons) similar to those from ewes at sea level. Vitamin supplementation had no effect on LA pregnancies. In conclusion, supplementation with vitamins C and E during pregnancy at HA prevents oxidative stress, improving pregnancy outcomes.

Relation between hypomethylation of long interspersed nucleotide elements and risk of neural tube defects

Impaired one-carbon metabolism is thought to be associated with the risk of neural tube defects (NTDs); however, the role of methylation in NTDs remains unclear. Long interspersed nucleotide element-1 (LINE-1) constitutes 17-25% of the human genome. LINE-1 hypomethylation correlates with global DNA methylation levels in cancerous cells, but limited information is available on LINE-1 methylation in NTDs. We determined whether LINE-1 methylation patterns were associated with neural tube development and the possible relations between DNA methylation and key maternal metabolites involved in folate-mediated one-carbon metabolism. Global methylation, maternal plasma folic acid, vitamin B-12, and total homocysteine (tHcy) concentrations were assessed in 48 NTD and 49 control samples by immunoassay, and LINE-1 methylation levels were evaluated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Methylation levels of genomic DNA and LINE-1 decreased significantly in the neural tissue of NTD samples. The risk of NTDs increased with decreasing levels of LINE-1 methylation, with an odds ratio of 5.246 (95% CI: 1.519, 18.124; P = 0.009) for the lowest quartile (methylation level < or = 57.94%) compared with the highest quartile (methylation level > or = 60.94%). Compared with control subjects, case subjects had lower maternal plasma concentrations of vitamin B-12. Hypomethylation of LINE-1 and genomic DNA was associated with an increased risk of NTDs. Functional insufficiency of maternal plasma vitamin B-12 was associated with NTDs, although no significant correlation could be established between maternal folic acid, vitamin B, tHcy, and LINE-1 methylation.

Higher Maternal Plasma Folate but Not Vitamin B-12 Concentrations during Pregnancy Are Associated with Better Cognitive Function Scores in 9- to 10- Year-Old Children in South India1–3

Folate and vitamin B-12 are essential for normal brain development. Few studies have examined the relationship of maternal folate and vitamin B-12 status during pregnancy and offspring cognitive function. To test the hypothesis that lower maternal plasma folate and vitamin B-12 concentrations and higher plasma homocysteine concentrations during pregnancy are associated with poorer neurodevelopment, 536 children (aged 9–10 y) from the Mysore Parthenon birth cohort underwent cognitive function assessment during 2007–2008 using 3 core tests from the Kaufman Assessment Battery, and additional tests measuring learning, long-term storage/retrieval, attention and concentration, and visuo-spatial and verbal abilities. Maternal folate, vitamin B-12, and homocysteine concentrations were measured at 30 ± 2 wk gestation. During pregnancy, 4% of mothers had low folate concentrations (<7 nmol/L), 42.5% had low vitamin B-12 concentrations (<150 pmol/L), and 3% had hyperhomocysteinemia (>10 μmol/L). The children’s cognitive test scores increased by 0.1–0.2 SD per SD increase across the entire range of maternal folate concentrations (P < 0.001 for all), with no apparent associations at the deficiency level. The associations with learning, long-term storage/retrieval, visuo-spatial ability, attention, and concentration were independent of the parents’ education, socioeconomic status, religion, and the child’s sex, age, current size, and folate and vitamin B-12 concentrations. There were no consistent associations of maternal vitamin B-12 and homocysteine concentrations with childhood cognitive performance. In this Indian population, higher maternal folate, but not vitamin B-12, concentrations during pregnancy predicted better childhood cognitive ability. It also suggests that, in terms of neurodevelopment, the concentration used to define folate deficiency may be set too low.

Vigabatrin (VGB) administered during late gestation lowers maternal folate concentration and causes pregnancy loss, fetal growth restriction and skeletal hypoplasia in the mouse

Vigabatrin (VGB) has several therapeutic advantages over older antiepileptic drugs (AED), but there is a lack of information about its potential reproductive toxicologic effects. Our aim was to evaluate the consequences of VGB administered during late gestation on fetal growth and development in the mouse. Based on the results of our previous study, we administered groups of mice a single dose of 450 mg/kg VGB on one of gestation days (GD) 15, 16 or 17. Fetuses were collected on GD 18. VGB groups had a significant incidence of fetal death, abortion, intrauterine growth restriction (IUGR), and hypoplasia of the axial skeleton, metacarpals, metatarsal and phalanges. Abortion was characterized by visible hemorrhagic expulsion of the embryos with their membranes. Maternal plasma folate (FA) and vitamin B12 concentrations were found to be markedly reduced within 12 h of VGB treatment. Mice were supplemented with FA from GD 12 through GD 17 with or without a single dose of VGB on GD 15. This group had no abortions. Their fetuses had better body weight and lower frequency of IUGR than those of the non-supplemented VGB group. These data suggest that reductions in maternal FA and vitamin B12 concentrations play an important role in fetal loss, IUGR and skeletal hypoplasia induced by VGB during late gestation in the mouse. In view of the finding that a significant maternal toxicity is associated with this dose regimen, additional groups of mice were treated with 350 mg/kg VGB during embryogenesis and late gestation. This treatment was found to be maternally nontoxic. However, this low dose also resulted in significant fetal loss and IUGR when treatment occurred during late gestation. These data support the hypothesis that late gestation is particularly susceptible to VGB-induced fetal loss and IUGR in the mouse.

Vitamin A deficiency in an infant with PAGOD syndrome

PAGOD syndrome is a rare condition characterized by multiple congenital anomalies including pulmonary artery and lung hypoplasia, agonadism, diaphragmatic abnormalities, cardiac defects, omphalocele, and various genital anomalies. The etiology of this condition is unknown but the spectrum of birth defects is similar to the developmental anomalies observed in vitamin A deficiency animal models. We describe an infant with PAGOD syndrome phenotype. The patient had a normal male karyotype and no copy number changes were seen on chromosome genomic hybridization (CGH) microarray. Endocrine evaluation was consistent with primary hypogonadism. The testes and Müllerian structures were absent by imaging studies, raising the possibility of arrest of early gonadogenesis. The plasma free vitamin A was low, consistent with moderate to severe vitamin A deficiency; the maternal plasma vitamin A level was normal. During pregnancy maternal vitamin A is taken up by retinol binding protein 4 (RBP4) which is expressed in the embryonic visceral endoderm from pregastrulational stages. This transport is mediated via the specific membrane receptor for RBP, stimulated by retinoic acid 6 (STRA6). STRA6 is widely expressed in human organ systems including the placenta during embryonic development. Mutations in the STRA6 gene result in Matthew-Wood syndrome, which demonstrates significant phenotypic overlap with PAGOD syndrome. Sequencing of STRA6 coding regions in our patient, revealed no mutations. We present a case of PAGOD syndrome with a review of the literature, posing the hypothesis that a vitamin A metabolic defect, other than transport mediated by STRA6 receptor, might have an etiological role in the development of this multiple congenital anomalies syndrome.

Vitamin B12 status of pregnant Indian women and cognitive function in their 9-year-old children.

Recent research has highlighted the influence of maternal factors on the health of the offspring. Intrauterine experiences may program metabolic, cardiovascular, and psychiatric disorders. We have shown that maternal vitamin B12 status affects adiposity and insulin resistance in the child. Vitamin B12 is important for brain development and function. We investigated the relationship between maternal plasma vitamin B12 status during pregnancy and the child's cognitive function at 9 years of age. We studied children born in the Pune Maternal Nutrition Study. Two groups of children were selected on the basis of maternal plasma vitamin B12 concentration at 28 weeks of gestation: group 1 (n = 49) included children of mothers with low plasma vitamin B12 (lowest decile, < 77 pM) and group 2 (n = 59) children of mothers with high plasma vitamin B12 (highest decile, > 224 pM). Children from group 1 performed more slowly than those from group 2 on the Color Trail A test (sustained attention, 182 vs. 159 seconds; p < .05) and the Digit Span Backward test (short-term memory, p < .05), after appropriate adjustment for confounders. There were no differences between group 1 and group 2 on other tests of cognitive function (intelligence, visual agnosia). Maternal vitamin B12 status in pregnancy influences cognitive function in offspring.

The effect of maternal and cord-blood vitamin C, vitamin E and lipid peroxide levels on newborn birth weight

Background Newborn birth weight has been shown to significantly correlate with the blood levels of vitamin C. Objective This study was planned to answer the question of why vitamin C levels correlate with birth weight; does such correlation reflect a protective effect of vitamin C on fetal growth, by its antioxidant characteristics or does it correspond to the nutritional status of both the mother and the fetus. We examined the hypothesis that maternal blood levels of vitamin C, but not vitamin E influence newborn birth weight. We determined maternal and newborn blood levels of vitamin C, vitamin E, and lipid peroxides (an index of oxidative insult) and the birth weights of full-term newborns delivered at our hospital. Results Compared with maternal blood levels, newborns have higher levels of vitamin C and lipid peroxides, but lower levels of vitamin E. There was a significant correlation in levels between mothers and their newborns for blood levels of vitamin C (r = 0.82, P < 0.01) and vitamin E (r = 0.61, P < 0.02) but not for lipid peroxides (r = 0.001). This suggests that maternal vitamin C and vitamin E intake can influence fetal vitamin C and vitamin E levels. Linear regression analysis shows a significant positive relationship between newborn birth weight and maternal plasma vitamin C (r = 0.51, P < 0.02). Similarly, there was a modest but significant positive relationship between newborn birth weights and newborn vitamin C levels (r = 0.61, P < 0.05). However, there was no relationship between maternal or fetal vitamin E or lipid peroxides levels and the newborn birth weight. Conclusions This study with a small number of subjects suggests a significant association between newborn birth weight and maternal and newborn plasma vitamin C levels. Lack of relationship between birth weight and vitamin E and lipid peroxides suggest that antioxidant function of vitamin C does not appear to have a major role in the effect of vitamin C on birth weight.

Effectiveness of an early supplementation scheme of high-dose vitamin A versus standard WHO protocol in Gambian mothers and infants: a randomised controlled trial

Most developing countries have adopted a standard WHO dosing schedule for vitamin A supplementation. However, in 2002 the International Vitamin A Consultative Group (IVACG) Annecy Accord recommended a new high-dose regimen for mothers and infants. Our aim was to test whether the new high-dose regimen of vitamin A supplementation would increase maternal and infant plasma vitamin A, reduce infant Helicobacter pylori infection and nasopharyngeal pneumococcal carriage, and improve infant gut epithelial integrity. In an area of moderate vitamin A deficiency in rural Gambia, 220 mother-infant pairs were enrolled in a randomised double-blind trial between September, 2001, and October, 2004, that compared the IVACG high dose with the WHO dose. The primary endpoints were levels of maternal and infant plasma vitamin A, H pylori infection, pneumococcal carriage, and gut epithelial integrity. The trial is registered as ISRCTN 98554309. 197 infants completed follow-up to 12 months (99 high dose and 98 WHO dose). There were no adverse events at dosing. No differences were found in the primary outcomes for high-dose versus WHO schedule: maternal vitamin A concentration at 2 months +0.02 micromol/L (95% CI -0.10 to 0.15); infant vitamin A at 5 months +0.01 micromol/L (-0.06 to 0.08); H pylori infection at 12 months -0.3% (-14.7 to 14.2); maternal pneumococcal carriage at 12 months -2.0% (-13.7 to 9.7); infant pneumococcal carriage at 12 months -4.1% (-15.8 to 7.6); infant gut mucosal damage at 12 months 5.2% (-8.7 to 19.2). There were more clinic attendances by the high-dose group in the first 6 months of life (p=0.018). Our results do not lend support to the proposal to increase the existing WHO standard dosing schedule for vitamin A in areas of moderate vitamin A deficiency. Caution is urged for future studies because trials have shown possible adverse effects of higher doses of vitamin A, and potential negative interactions with the expanded programme on immunisation (EPI) vaccines.

Prevalent Vitamin B-12 Deficiency in Twelve-Month-Old Guatemalan Infants Is Predicted by Maternal B-12 Deficiency and Infant Diet

Approximately one-third of low-income women and children studied in Guatemala are reported to have deficient (<148 pmol/L) or marginal (148–220 pmol/L) plasma vitamin B-12 concentrations. Because vitamin B-12 deficiency can adversely affect infant development and cognitive function, the present study examined predictors of deficient plasma vitamin B-12 concentrations at the age of 12 mo. Analyses were performed on baseline data from a randomized clinical trial in 304 Guatemalan infants, 80% of whom were partially breast-fed, and their mothers. Exclusion criteria for infants included twins, severe stunting or moderate wasting, reported major health problems, severe developmental delay, hemoglobin <95 g/L, maternal age <17 y, and maternal pregnancy >3 mo. Data collected included socio-economic status, infant anthropometry, vitamin B-12 intake from complementary foods, and breast-feeding frequency reported by mothers. A complete blood count and plasma vitamin B-12, folate, ferritin, and C-reactive protein were measured. Deficient or marginal plasma vitamin B-12 concentrations were found in 49% of infants and 68% of mothers. The mean intake of maternal vitamin B-12 was 3.1 μg/d, and infants consumed 2.2 μg/d from complementary foods. In linear regression analysis, infant plasma B-12 concentration was strongly and positively associated with maternal plasma vitamin B-12 and B-12 intake from complementary foods (predominantly powdered cow’s milk), and inversely associated with frequency of breast-feeding and larger household size (P < 0.0001). Vitamin B-12 supplementation of lactating women, food fortification, and education to improve infant’s vitamin B-12 status are potential interventions that can improve the vitamin B-12 status of mothers and infants in this population.

Evaluation of transcobalamin II polymorphisms as neural tube defect risk factors in an Irish population

Decreased maternal folate levels are associated with having a child with a neural tube defect (NTD), and periconceptual folic acid supplementation reduces this risk by >50%. Vitamin B(12) (as methylcobalamin) is a cofactor for methionine synthase, an enzyme that plays a key role in folate metabolism. Alterations in vitamin B(12) metabolism may influence the development of NTDs. Low levels of maternal plasma vitamin B(12) and reduced binding of vitamin B(12) by transcobalamin II (TCII) are independent risk factors for NTDs. TCII levels are altered in the amniotic fluid of pregnancies affected by NTDs. Given this evidence, inherited variants in genes involved in vitamin B(12) trafficking such as TCII are candidate NTD risk factors. We used case/control and family-based association methods to investigate whether six common polymorphisms in the TCII gene influence NTD risk. TCII genotypes were determined for more than 300 Irish NTD families and a comparable number of Irish controls. Allele and genotype frequencies for each polymorphism did not differ between family members and controls. These six TCII polymorphisms do not strongly influence NTD risk in the Irish population. The Supplementary Material for this article can be found on the Birth Defects Research (Part A) website: http://www.mrw.interscience.wiley.com/suppmat/1542-0752/suppmat/2005/73/v73.4.swanson.html