Maternal B12 Research Articles

Association of maternal and cord vitamin B12 levels with anthropometry in term neonates born to malnourished mothers in coastal South India.

Malnourished pregnant women are at increased risk of micronutrient deficiency. We assessed the vitamin B12 status in both malnourished and normally nourished pregnant women and their neonates. Additionally, we studied the association between maternal B12 levels, cord B12 levels and neonatal anthropometry. This cross-sectional study enrolled 63 malnourished and 63 normally nourished mothers and neonates. Maternal and cord blood samples were collected at the time of delivery for estimation of vitamin B12 levels. Maternal and cord vitamin B12 levels were compared using the Mann-Whitney U test. Neonatal anthropometry was correlated with maternal and cord B12 levels using Spearman's correlation. Data were analyzed using SPSS version 25. Mean maternal age was 26.58 yrs. The median cord B12 levels were lower than the maternal B12 levels. Maternal B12 levels showed a strong positive correlation with cord B12 levels (rho = 0.879; p < 0.001). Maternal (p < 0.001) and cord (p < 0.001) vitamin B12 levels were significantly lower in the malnourished group than in the normally nourished group. In malnourished group, 66.8% mothers and 95.2% neonates were Vitamin B12 deficient, whereas 1.5% mothers and 4.7% neonates were vitamin B12 deficient in normally nourished group. In the malnourished group, maternal B12 levels were positively correlated with birth weight (rho 0.363, p = 0.003) and length (rho 0.330, p =0.008), whereas cord B12 levels were positively correlated with birth weight in the normally nourished group. (rho 0.277 p= 0.028). High rates of vitamin B12 deficiency were observed in malnourished mothers and neonates. There was a positive correlation between birth weight, length, and maternal vitamin B12 levels in malnourished mothers. These findings emphasize the need to address maternal malnutrition and vitamin B12 deficiency to improve neonatal health.

The Benefit of Detecting Reduced Intracellular B12 Activity through Newborn Screening Remains Unclear.

Vitamin B12 (B12) deficiency (B12D) can have detrimental effects on early growth and development. The Austrian newborn screening (NBS) program targets inborn errors of cobalamin metabolism and also detects B12D. Of 59 included neonates with B12D suspected by NBS, B12D was not further investigated in 16 (27%) retrospectively identified cases, not confirmed in 28 (48%), and confirmed in 15 (25%) cases. NBS and recall biomarkers were recorded. Age at sampling of the dried blood spots for NBS and the 1st-tier methionine/phenylalanine ratio were the strongest parameters to predict B12D (67.4% correct allocations). No differences between cases with confirmed, unconfirmed, or unknown B12D or differences to norms were observed for growth and psychomotor development (Vineland III scales, phone interviews with parents of children between months 10 and 14 of life). B12 intake was below recommendations in most mothers. NBS can detect reduced intracellular B12 activity. No advantage of NBS detection and treatment regarding infant cognitive development or growth could be proven. Since conspicuous NBS findings cannot be ignored, and to prevent exposing newborns to invasive diagnostics, assessment of maternal B12 status during pregnancy seems advisable.

Association of maternal and cord vitamin B12 levels with anthropometry in term neonates born to malnourished mothers in coastal South India

Background Malnourished pregnant women are at increased risk of micronutrient deficiency. We assessed the vitamin B12 status in both malnourished and normally nourished pregnant women and their neonates. Additionally, we studied the association between maternal B12 levels, cord B12 levels and neonatal anthropometry. Methods This cross-sectional study enrolled 63 malnourished and 63 normally nourished mothers and neonates. Maternal and cord blood samples were collected at the time of delivery for estimation of vitamin B12 levels. Maternal and cord vitamin B12 levels were compared using the Mann–Whitney U test. Neonatal anthropometry was correlated with maternal and cord B12 levels using Spearman’s correlation. Data were analyzed using SPSS version 25. Results Mean maternal age was 26.58 yrs. The median cord B12 levels were lower than the maternal B12 levels. Maternal B12 levels showed a strong positive correlation with cord B12 levels (rho = 0.879; p &lt; 0.001). Maternal (p &lt; 0.001) and cord (p &lt; 0.001) vitamin B12 levels were significantly lower in the malnourished group than in the normally nourished group. In malnourished group, 66.8% mothers and 95.2% neonates were Vitamin B12 deficient, whereas 1.5% mothers and 4.7% neonates were vitamin B12 deficient in normally nourished group. In the malnourished group, maternal B12 levels were positively correlated with birth weight (rho 0.363, p = 0.003) and length (rho 0.330, p =0.008), whereas cord B12 levels were positively correlated with birth weight in the normally nourished group. (rho 0.277 p= 0.028) Conclusion High rates of vitamin B12 deficiency were observed in malnourished mothers and neonates. There was a positive correlation between birth weight, length, and maternal vitamin B12 levels in malnourished mothers. These findings emphasize the need to address maternal malnutrition and vitamin B12 deficiency to improve neonatal health.

Effects of vitamin B12 supplementation on oxidative stress markers and pro-inflammatory cytokines during pregnancy and postpartum among Bangladeshi mother–child pairs

BackgroundThere is limited research to determine whether vitamin B12 (B12) supplementation during pregnancy and lactation is protective against oxidative stress and pro-inflammatory cytokines and whether this effect is transferred to breastfed infants via milk. In addition, associations among maternal plasma/ milk and infant B12 status and immune function markers are poorly characterized.ObjectivesTo evaluate effects of oral B12 supplementation during pregnancy and postpartum on maternal and infant 8-hydroxy-2′-deoxyguanosine (8-OH-dG, an oxidative stress marker) and proinflammatory cytokine levels, and examine associations between maternal plasma, breastmilk and infant B12 status as well as immune function markers.MethodIn a blinded, placebo-controlled trial, Bangladeshi women (n = 68, 18–35 years, hemoglobin < 11 g/dL, gestational weeks 11–14) received either 250 μg/day B12 or placebo throughout pregnancy up to 3-months postpartum. Samples were collected from mothers at baseline and 3-months postpartum and from infants at 3-months to measure B12 status indicators, 8-OH-dG and proinflammatory cytokines.ResultsMaternal postpartum B12 was positively associated with infant plasma B12. Higher milk B12 concentrations were associated with increased infant B12 (beta (β) = 277, 95% confidence interval (CI) = (132, 423), p<0.001) and lower total homocysteine (β = -7.63, 95% CI = (-12.40, -2.86), p = 0.002) levels. Maternal B12 supplementation reduced plasma 8-OH-dG concentrations among postpartum mothers and infants compared to the placebo group. Supplementation increased plasma TNF-α and IL-6 levels among mothers and IL-10 and IFN-γ levels among infants.ConclusionMilk and maternal plasma B12 at 3 months were associated with infant B12. Maternal B12 supplementation modulates 8-OH-dG and several cytokines which may protect against immune response-induced oxidative stress.Trial registration(clinicaltrials.gov: NCT01795131- 1st posted on 20/02/2013).

One-carbon metabolite supplementation increases vitamin B12, folate, and methionine cycle metabolites in beef heifers and fetuses in an energy dependent manner at day 63 of gestation.

One-carbon metabolites (OCM) are metabolites and cofactors which include folate, vitamin B12, methionine, and choline that support methylation reactions. The objectives of this study were to investigate the effects of moderate changes in maternal body weight gain in combination with OCM supplementation during the first 63 d of gestation in beef cattle on (1) B12 and folate concentrations in maternal serum (2) folate cycle intermediates in maternal and fetal liver, allantoic fluid (ALF), and amniotic fluid (AMF) and (3) metabolites involved in one-carbon metabolism and related metabolic pathways in maternal and fetal liver. Heifers were either intake restricted (RES) and fed to lose 0.23 kg/d, or fed to gain 0.60 kg/d (CON). Supplemented (+ OCM) heifers were given B12 and folate injections weekly and fed rumen-protected methionine and choline daily, while non-supplemented (-OCM) heifers were given weekly saline injections. These two treatments were combined in a 2 × 2 factorial arrangement resulting in 4 treatments: CON-OCM, CON + OCM, RES-OCM, and RES + OCM. Samples of maternal serum, maternal and fetal liver, ALF, and AMF were collected at slaughter on day 63 of gestation. Restricted maternal nutrition most notably increased (./ ≤ 0.05) the concentration of vitamin B12 in maternal serum, 5,10-methylenetetrahydrofolate and 5,10-methenyltetrahydrofolate in maternal liver, and cystathionine in the fetal liver; conversely, maternal restriction decreased (P = 0.05) 5,10-methylenetetrahydrofolate concentration in fetal liver. Supplementing OCM increased (P ≤ 0.05) the concentrations of maternal serum B12, folate, and folate intermediates, ALF and AMF 5-methyltetrahydrofolate concentration, and altered (P ≤ 0.02) other maternal liver intermediates including S-adenosylmethionine, dimethylglycine, cystathionine Glutathione reduced, glutathione oxidized, taurine, serine, sarcosine, and pyridoxine. These data demonstrate that OCM supplementation was effective at increasing maternal OCM status. Furthermore, these data are similar to previously published literature where restricted maternal nutrition also affected maternal OCM status. Altering OCM status in both the dam and fetus could impact fetal developmental outcomes and production efficiencies. Lastly, these data demonstrate that fetal metabolite abundance is highly regulated, although the changes required to maintain homeostasis may program altered metabolism postnatally.

Status of Vitamin B12 Deficiency among Lactating Mothers at Six Weeks Postpartum at a Tertiary Care Hospital, West Bengal, India

Introduction: Vitamin B12 (vit B12) deficiency is a preventable disorder and has dire consequences on the neurological development of the infant. The only source of vit B12 for exclusively breastfed newborns is their mother’s milk. So, determining the status of maternal vit B12 levels during early lactation is vital. In India, very few studies have documented vit B12 deficiency among lactating mothers, especially eastern region remains unexplored. Aim: To estimate the prevalence of vit B12 deficiency among healthy lactating mothers attending the postpartum clinic at six weeks at a Tertiary Care Hospital of West Bengal, India and also to compare the haematological values between vit B12 deficient and sufficient groups among the lactating mothers. Materials and Methods: An observational cross-sectional study was conducted in the Department of Biochemistry in collaboration with postpartum clinic of Calcutta National Medical College, West Bengal, India. The study was carried out over a period of two months, from July 2022 to August 2022. Serum vit B12, serum ferritin and haematological parameters {Haemoglobin (Hb), Mean Corpuscular Haemoglobin (MCH), Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin Concentration (MCHC)} were measured in 121 apparently healthy lactating women attending the postpartum clinic for a regular check-up at six weeks. Detailed socioclinical history and dietary history was taken from each participant and these variables were compared between vit B12 deficient and sufficient groups. Pearson’s Chi-square test, Fisher’s-exact test, Mann-Whitney U test were applied to analyse the data. Results: The total study population comprised of 121 mothers with an average age of 25.65±3.71 years and 75% of them consumed non vegetarian diet. A prevalence of 19 (15.7%) deficiency of vit B12 was found among the lactating mothers at six weeks postpartum. Mothers who were vegetarian, multigravida and with complaints of paraesthesia were more associated to cobalamin deficiency. The vit B12 deficient mothers had significantly higher erythrocyte indices than the sufficient group but none of the values were in the megaloblastic range. Conclusion: The vit B12 deficiency was prevalent during early lactation in 19 (15.7%) lactating mothers. The first postnatal visit at six weeks might be the most feasible period to screen and supplement these women to prevent long term sequelae in both mother and child. Haematological parameters were of limited use in identifying vit B12 deficiency during lactation.

The Association Of Adiponectin, Homocysteine, B 12 And Folic Acid In Iraqi Women With Preeclampsia And Its Severity

Background: preeclampsia is a common obstetric disorder that remains a leading cause of maternal and perinatal mortality and morbidity. Maternal serum concentrations of adiponectin, folate, homocysteine, and vitamin B12 have been found to be associated with pre-eclampsia. Nevertheless, reported studies involved still not clear with variable reliably. The aim of the present study is to examine the relationship between these biomarkers and pre-eclampsia and its severity in Iraqi population. Aims: The study aims to evaluate the association between maternal serum adiponectin, homocysteine, B12 and Folic acid and preeclampsia and its severity. Study design and setting: A case control study carried out in Al-Zahraa Maternity and Pediatric Teaching Hospital in Najaf city/ Iraq from the 1st of December 2019 to the 1st of December 2020. Patient and Methods: The study included 50 pregnant women with preeclampsia and a comparative control group of 50 normotensive pregnant women. Preeclamptic women were further subdivided into 14 women with severe preeclampsia and 36 women with mild preeclampsia. Serum Adiponectin, Homocysteine, B 12, and Folic acid were measured by using special ELIZA (Enzyme linked immunosorbent assay) technique. Results: There was a significant increment in the level of Adiponectin and Homocysteine while vitamin B12 and Folic acid were significantly decreased in preeclamptic pregnant women in comparison to the control group. On the other hand, there was no significant relation between the severity of preeclampsia and the level of Adiponectin, Homocysteine, Vitamin B 12, and Folic acid. Conclusion: Women with preeclampsia had significantly lower vitamin B12 and folic acid and significantly higher concentrations of adiponectin and homocysteine than normotensive pregnant women, but no relation with its severity.

Biochemical, Nutritional, and Clinical Parameters of Vitamin B12 Deficiency in Infants: A Systematic Review and Analysis of 292 Cases Published between 1962 and 2022

Pooled data from published reports on infants with clinically diagnosed vitamin B12 (B12) deficiency were analyzed with the purpose of describing the presentation, diagnostic approaches, and risk factors for the condition to inform prevention strategies. An electronic (PubMed database) and manual literature search following the PRISMA approach was conducted (preregistration with the Open Science Framework, accessed on 15 February 2023). Data were described and analyzed using correlation analyses, Chi-square tests, ANOVAs, and regression analyses, and 102 publications (292 cases) were analyzed. The mean age at first symptoms (anemia, various neurological symptoms) was four months; the mean time to diagnosis was 2.6 months. Maternal B12 at diagnosis, exclusive breastfeeding, and a maternal diet low in B12 predicted infant B12, methylmalonic acid, and total homocysteine. Infant B12 deficiency is still not easily diagnosed. Methylmalonic acid and total homocysteine are useful diagnostic parameters in addition to B12 levels. Since maternal B12 status predicts infant B12 status, it would probably be advantageous to target women in early pregnancy or even preconceptionally to prevent infant B12 deficiency, rather than to rely on newborn screening that often does not reliably identify high-risk children.

Examining the relationship between autism spectrum disorder and neural tube defects.

Folate and vitamin B12 deficiencies have been strongly associated with neural tube defects, preliminary research suggests folate and B12 deficiency may also be associated with autism spectrum disorder (ASD). We examined the association between neural tube defects and ASD as a further avenue to examine the hypothesis that ASD is related to maternal folate and B12 deficiency during pregnancy. A retrospective case-control study was performed using the Military Health System Data Repository. Cases and matched controls were followed from birth until at least 6 months after their first autism diagnosis. International Classification of Diseases, 9th Revision, codes were used to identify neural tube defects in the health records. A total of 8760 cases between the ages of 2 and 18 years were identified. The prevalence of any neural tube defect was 0.11% in children without ASD and 0.64% in children with ASD. Children with autism were over 6 times as likely to have a neural tube defect. The increased odds of neural tube defect in children diagnosed with ASD, found through our methodology, supports prior studies. Although additional studies are needed to elucidate the relationship between ASD and maternal folate and vitamin B12 deficiency during pregnancy this study supports their use during pregnancy.

Association of maternal folate and B12 vitamin status with gestational diabetes mellitus: Still an open issue

ObjectivesThere is conflicting evidence about the role of folate and B12in gestational diabetes mellitus (GDM) onset. The association of vitamin status with GDM was therefore revalued, also measuring the B12active form holotranscobalamin. Methods677 women were evaluated at 24–28 weeks of gestation when OGTT was carried out. The ‘one-step’ strategy was employed for GDM diagnosis. Odds ratio (OR) of having GDM was estimated to quantify the association with vitamin levels. Results180 women (26.6%) had GDM. They were older (median, 34.6 vs. 33.3 years, p = 0.019) and had higher body mass index (BMI) (25.8 vs. 24.1 kg/m2, p < 0.001). Multiparous women had lower levels of all evaluated micronutrients, while overweight lowered both folate and total B12, but not holotranscobalamin. Lower total B12(270 vs. 290 ng/L, p = 0.005), but not holotranscobalamin, was observed in GDM, being weakly negatively correlated with fasting glycemia (r = −0.11, p = 0.005) and 1-h OGTT serum insulin (r = −0.09, p = 0.014). At multivariate analysis, age, BMI and multiparity remained the strongest GDM predictors, while total B12(but not holotranscobalamin and folate) showed a slight protective effect (OR = 0.996, p = 0.038). ConclusionsA weak association between total B12 levels and GDM risk was shown, but it was not confirmed when holotranscobalamin was measured.

Vitamin B12 status in term pregnant women and the cord blood samples of their newborns: A cross-sectional study.

Background and aim: In India, total vitamin B12 (Vit B12) and its active form (active B12) have not been studied in mother's blood and cord blood. We hypothesized that total and active B12 levels are sufficiently maintained in cord blood despite low levels in mothers. Methods: Two hundred term pregnant mother's blood and cord blood was collected and analyzed for total Vit B12 (radioimmunoassay method) and active B12 levels (enzyme-linked immunosorbent assay). Mean values of constant or continuous variables (hemoglobin (Hb), packed cell volume (PCV), mean corpuscular volume (MCV), white blood cells (WBC), and Vit B12) were compared in mother's blood and newborn cord blood using Student's t-test and multiple comparisons within the groups were carried out with ANOVA. Spearman's correlation (Vit B12) and multivariable backward regression analyses (height, weight, education, body mass index (BMI) and Hb, PCV, MCV, WBC, and Vit B12 levels) were also performed. Results: Total Vit 12 deficiency was highly prevalent at 89% and active B12 deficiency was 36.7% in mothers. Cord blood showed total Vit B12 deficiency prevalence of 53% and active B12 deficiency being 9.3%. Total Vit B12 (p<0.001) and active B12 (p<0.001) levels were significantly higher in cord blood when compared to mother's blood. In multivariate analysis, higher total and active B12 levels in mother's blood predicted higher levels of total and active B12 levels in cord blood. Conclusion: Our study showed higher prevalence of total and active Vit B12 deficiency in mothers compared to cord blood thus indicating their transfer to fetus irrespective of mother's status. Maternal Vit B12 levels affected cord blood Vit B12 levels.

A Treatable Cause of Neuroregression

We report the case of a 13-month-old girl with neuroregression over 3 months and encephalopathy at presentation. Marked skin hyperpigmentation and being exclusively breastfed gave the clue to B12 deficiency secondary to maternal B12 deficiency as the possible etiology which was confirmed on investigation. Upon treatment with parenteral B12 therapy she demonstrated dramatic improvement at follow-up. Nutritional B12 deficiency is an imminently treatable cause of neurocognitive dysfunction. Better awareness, healthy complementary feeding practices in infancy and perhaps maternal B12 supplementation can help prevent this disorder.

Evaluating Deficiency of Vitamin B12 and Risk Factors in Healthy Infants

Background: The deficiency of vitamin b12 is highly extensive within the developed countries and is often found to remain undiagnosed within these populations. the main feature within infants suffering from vitamin b12 deficiency is altered neurological development and generalized growth. Effects of vitamin b12 deficiency on the brain can be prevented. To avoid these morbidities and mortality associated with vitamin b12 deficiency it is pivotal for clinicians to understand what other risk factors are associated with a deficiency within the infant population of developing countries. Materials and methods: This cross-sectional study was conducted on 82 healthy infants for the assessment of Vitamin B12 at Pediatric Department of LGH, Lahore from March 2021 to August 2021. Participants were selected who were healthy. After recruitment, participants underwent hematological and biochemical indices analysis. Hemoglobin, serum vitamin b12, homocysteine and methylmalonic acid were different parameters measured. Maternal vitamin b12 deficiency was investigated along with risk factor vitamin b12 deficiency in healthy infants. Results: A total of 82 recruited participants were selected after screening and meeting the recruitment criteria. After assessment of hematological data, anemia was diagnosed in 67.82% of infants (n=56). The breakdown of the anemic population showed that the male population was predominant with 58.2% affected males and 41.8% affected females. Decreased levels of plasma vitamin b12 concentration were documented in 22% of the population with a total number of 18 participants (male: 11, female: 7). Increased levels of homocysteinemia were documented in 49.1% of infants with n=40. Increased levels of methylmalonic acid were appreciated in all infants. As defined by previous criteria, the diagnosis of vitamin b12 deficiency was appreciated in 30 infants with a percentage of 38%. Furthermore, an assessment of folate deficiency showed that 8 out of 82 participants had concurrent folate deficiency in red cells with a percentile prevalence of 9.7%. maternal vitamin b12 deficiency was considered as risk factor for infant vitamin b12 deficiency Conclusion: The prevalence of vitamin b12 deficiency in healthy infants is significantly high in developing and underdeveloped countries. Vitamin b12 deficiency cooccurs with anemia and other variation of biological markers. The study concluded that among the various risk factors that may predispose an infant to vitamin b12 deficiency, maternal b12 deficiency remains the highest appreciated risk factor. Keywords: Vitamin B12, Risk Factors, Vitamin B12 deficiency, Maternal B12

Screening for Methylmalonic and Propionic Acidemia: Clinical Outcomes and Follow-Up Recommendations.

Wisconsin’s newborn screening program implemented second-tier testing on specimens with elevated propionylcarnitine (C3) to aid in the identification of newborns with propionic and methylmalonic acidemias. The differential diagnosis for elevated C3 also includes acquired vitamin B12 deficiency, which is currently categorized as a false positive screen. The goal of this study was to summarize screening data and evaluate their effectiveness at establishing diagnoses and categorizing false positive cases. All Wisconsin newborns born between 2013 and 2019 with a positive first-tier screen for C3 were included in this study. For each case the first- and second-tier newborn screening data and confirmatory test results were compiled. The clinical determination for each case was reviewed and categorized into groups: inborn error of metabolism, maternal B12 deficiency, infant B12 deficiency, and false positive. A review of the screening data showed a significant overlap in the concentration of biomarkers for newborns with genetic versus acquired disease. Additionally, a review of confirmatory test results showed incomplete ascertainment of maternal vitamin B12 status. The Wisconsin newborn screening program recommended a confirmatory testing algorithm to aid in the diagnosis of inborn errors of metabolism and acquired vitamin B12 deficiency.

B12 deficiency in breastfed infants due to maternal B12 deficiency: A case series

B12 deficiency in breastfed infants due to maternal B12 deficiency: A case series

Imbalanced Folate and Vitamin B12 in the Third Trimester of Pregnancy and its Association with Birthweight and Child Growth up to 2 Years.

Folic acid supplementation during pregnancy may lead to an imbalance when vitamin B12 intake is low (folate trap) and may affect child's growth. The authors study the association between third trimester maternal intakes of folate and B12 and birthweight and postnatal growth of 2632 infants from the KOALA Birth Cohort Study. Plasma vitamin biomarkers are measured in 1219 women. Imbalanced total intakes (folate >430µg day-1 combined with B12 <5.5µg day-1 ) are not associated with birthweight [β adj (95% CI) = -14.87 (-68.87, 39.13)]compared with high intakes of both.Imbalanced intake is associated with a lower z score of weight at 1-2 years [β adj = -0.14 (-0.25, -0.03)].Having red blood cell folate >745nmol L-1 and plasma B12 <172pmol L-1 is not associated with birthweight [β adj = -7.10 (-97.90, 83.71) g].Maternal dietary B12 intake[β adj = -9.5 (-15.6, -3.3)] and plasma methylmalonic acid [β adj = 234 (43, 426)] are associated with birthweight. Low maternal dietary B12 intake and elevated methylmalonic acid rather than imbalanced vitamins are associated with higher birthweight, suggesting thatlow maternal B12 can predispose the infants for later obesity.

Pre-conceptional Maternal Vitamin B12 Supplementation Improves Offspring Neurodevelopment at 2 Years of Age: PRIYA Trial.

Background: The first thousand days window does not include the pre-conceptional period. Maternal pre-conceptional health has a profound influence on early embryonic development (implantation, gastrulation, placentation etc). Nutrition provided by B-complex vitamins is important for fetal growth, especially neural development. We report effects of a maternal pre-conceptional vitamin B12 and multi micronutrient (MMN) supplementation on offspring neurodevelopmental performance.Methods: In the Pune Rural Intervention in Young Adolescents trial (PRIYA), adolescents (N = 557, 266 females) were provided with vitamin B12 (2 μg/day) with or without multiple micronutrients, or a placebo, from preconception until delivery. All groups received mandatory iron and folic acid. We used the Bayley's Scale of Infant Development (BSID-III) at 24–42 months of age to investigate effects on offspring neurodevelopment.Results: Participants had similar baseline B12 levels. The levels improved in the B12 supplemented groups during pre-conception and pregnancy (28 weeks gestation), and were reflected in higher cord blood holotranscobalamin (holo-TC) levels compared to the placebo group. Neurodevelopmental outcomes in the B12 alone group (n = 21) were better than the placebo (n = 27) in cognition (p = 0.044) and language (p = 0.020) domains (adjusted for maternal baseline B12 levels). There was no difference in neurodevelopmental outcomes between the B12 + MMN (n = 26) and placebo group. Cord blood Brain Derived Neurotrophic Factor (BDNF) levels were highest in the B12 alone group, though not significant.Conclusion: Pre-conceptional vitamin B12 supplementation improved maternal B12 status and offspring neurodevelopment at 2 years of age. The usefulness of cord BDNF as a marker of brain development needs further investigation. Our results highlight the importance of intervening during pre-conception.

Efficiency of the sublingual route in treating B12 deficiency in infants.

Objective: To evaluate the efficiency of the sublingual route for the treatment of vitamin B12 deficiency in infants. Background: Vitamin B12 deficiency is common in children. In breastfed infants, the main reason is maternal B12 deficiency. Parenteral administration is commonly prescribed. However, patient compliance is not satisfactory due to repeated painful parenteral applications. It is also known that the oral route is efficient in high doses. In recent years, the sublingual route has been tried. This route stands out due to its easy applicability and low cost. However, there are few efficacy studies in infants for the sublingual route. Materials and methods: The study included 49 infants aged 6-12 months. All infants with marginal or deficient B12 levels (<300 pg/mL) were incidentally detected and treated with sublingual methylcobalamin. Each dose was 1000 μg and administered once a day in the first week, every other day in the second week, twice a week in the third week, and once a week in the last week. Serum vitamin B12 levels were measured before and after the treatment. Paired Sample T-Test was used to compare variables. Results: All infants had normal physical development and had no hematological or neurological issues. It was learned from the parents that the infants tolerated treatment well, and no side effects related to the treatment, such as vomiting or rash, were observed. Before and after the treatment, the mean vitamin B12 levels were 199±57 pg/mL and 684±336 pg/ml, respectively. The difference between the means was statistically significant (p<0.001). Conclusion: According to the study, it seems possible to treat vitamin B12 deficiency via a sublingual route in infants. In addition, methylcobalamin can be an alternative to the commonly used cyanocobalamin.

Intrauterine Exposure to Vitamin B12 and Folate Imbalance and Brain Structure in Young Adults of the Pune Maternal Nutrition Study (PMNS) Birth Cohort

ObjectivesIntrauterine nutritional exposures to vitamin B12 and folate are known to influence neurodevelopment. We tested the hypothesis that intrauterine exposure to high folate in presence of low vitamin B12 is associated with poor neurodevelopmental outcomes in young adult offspring. MethodsPMNS is a preconceptional birth cohort in its 24th year of follow up. We examined Intelligence Quotient (IQ) and obtained brain structural MPRAGE T1 sequence on a 3T MRI Scanner [participants selected based on exposure to maternal B12 at 18 wk pregnancy <103 PM(Low maternal B12 group n = 97) and >175 pM (high maternal B12 group, n = 93)]. Brain morphometric measurements (cortical volumes, thickness and subcortical volumes) were performed on Freesurfer software. ResultsThe mean age of participants was 22.3 ± 0.5 years (n = 190, 96 boys). High maternal B12 group showed greater cortical thickness in temporal regions (P < 0.001) and cortical thinning in frontal regions (P < 0.01). Higher maternal folate (median Red Cell Folate at 28 wk pregnancy 420 ng/ml) was associated with greater frontal cortical volumes in the high maternal B12 group but cortical thinning in multiple temporal and parietal cortical areas in the low B12 group(P < 0.05). There was a significant interaction between maternal B12 and folate status in relation to subcortical volumes. Exposure to higher maternal folate was associated with greater subcortical volume in high B12 group but lower volumes in low B12 group (P = 0.02, adjusted for age, education, gender and total intracranial volume). Higher IQ score was associated with larger subcortical brain volume (r = 0.34, P < 0.001) in the offspring. ConclusionsIntrauterine exposure to higher maternal folate in the presence of low vitamin B12 was associated with poorer cortical development in young adult offspring. Higher maternal folate with adequate B12 benefits subcortical brain development which reflects in higher IQ score. Optimizing maternal vitamin B12 and folate concentrations during pregnancy would benefit neurocognitive development in the offspring. Funding SourcesDBT Wellcome India Alliance Clinical and Public Health Intermediate Fellowship.

Maternal Vitamin B12 Status During Pregnancy and Its Association With Outcomes of Pregnancy and Health of the Offspring: A Systematic Review and Implications for Policy in India.

BackgroundVitamins B12 and folate participate in the one-carbon metabolism cycle and hence regulate fetal growth. Though vitamin B12 deficiency is widely prevalent, the current public health policy in India is to supplement only iron and folic acid for the prevention of anaemia. Prompted by our research findings of the importance of maternal vitamin B12 status for a healthy pregnancy, birth and offspring health outcomes, we evaluated available literature evidence using a systematic review approach, to inform policy.MethodsA systematic search was performed for relevant Indian studies in the MEDLINE/PubMed and IndMed databases. We selected studies reporting maternal vitamin B12 status (dietary intake or blood concentrations), and/or metabolic markers of vitamin B12 deficiency (homocysteine, methylmalonic acid) or haematological indices during pregnancy and their associations with outcomes of pregnancy, infancy or in later life. Intervention trials of vitamin B12 during pregnancy were also included. Quality of evidence was assessed on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.ResultsOf the 635 articles identified, 46 studies met the inclusion criteria (cohort studies-26, case-control studies-13, RCT’s -7). There is a high prevalence of vitamin B12 deficiency in Indian women during pregnancy (40-70%) (3 studies). Observational studies support associations (adjusted for potential sociodemographic confounders, maternal body size, postnatal factors) of lower maternal B12, higher homocysteine or an imbalance between vitamin B12-folate status with a higher risk of NTDs (6 studies), pregnancy complications (recurrent pregnancy losses, gestational diabetes, pre-eclampsia) (9 studies), lower birth weight (10 studies) and adverse longer-term health outcomes in the offspring (cognitive functions, adiposity, insulin resistance) (11 studies). Vitamin B12 supplementation (7 RCT’s) in pregnancy showed a beneficial effect on offspring neurocognitive development and an effect on birth weight was inconclusive. There is a high quality evidence to support the role of low maternal vitamin B12 in higher risk for NTD and low birth weight and moderate-quality evidence for higher risk of gestational diabetes and later life adverse health outcomes (cognitive functions, risk for diabetes) in offspring.ConclusionIn the Indian population low maternal vitaminB12 status, is associated with adverse maternal and child health outcomes. The level of evidence supports adding vitamin B12 to existing nutritional programs in India for extended benefits on outcomes in pregnancy and offspring health besides control of anaemia.Systematic Review Registration[website], identifier [registration number]