Maternal Vitamin B12 Concentrations Research Articles

Vitamin B12 supplementation during pregnancy for maternal and child health outcomes.

Vitamin B12 deficiency is a major public health problem worldwide, with the highest burden in elderly people, pregnant women, and young children. Due to its role in DNA synthesis and methylation, folate metabolism, and erythropoiesis, vitamin B12 supplementation during pregnancy may confer longer-term benefits to maternal and child health outcomes. To evaluate the benefits and harms of oral vitamin B12 supplementation during pregnancy on maternal and child health outcomes. We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) on 2 June 2023, and reference lists of retrieved studies. Randomised controlled trials (RCTs), quasi-RCTs, or cluster-RCTs evaluating the effects of oral vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation during pregnancy. We used standard Cochrane methods. Four review authors independently assessed trial eligibility. Two review authors independently extracted data from included studies and conducted checks for accuracy. Three review authors independently assessed the risk of bias of the included studies using the Cochrane RoB 1 tool. We used GRADE to evaluate the certainty of evidence for primary outcomes. The review included five trials with 984 pregnant women. All trials were conducted in low- and middle-income countries, including India, Bangladesh, South Africa, and Croatia. At enrolment, 26% to 51% of pregnant women had vitamin B12 deficiency (less than 150 pmol/L), and the prevalence of anaemia (haemoglobin less than 11.0 g/dL) ranged from 30% to 46%. The dosage of vitamin B12 supplementation varied from 5 μg/day to 250 μg/day, with administration beginning at 8 to 28 weeks' gestation through to delivery or three months' postpartum, and the duration of supplementation ranged from 8 to 16 weeks to 32 to 38 weeks. Three trials, involving 609 pregnant women, contributed data for meta-analyses of the effects of vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation. Maternal anaemia: there may be little to no difference for maternal anaemia by intervention group, but the evidence is very uncertain (70.9% versus 65.0%; risk ratio (RR) 1.08, 95% confidence interval (CI) 0.93 to 1.26; 2 trials, 284 women; very low-certainty evidence). Maternal vitamin B12 status: vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain (25.9% versus 67.9%; RR 0.38, 95% CI 0.28 to 0.51; 2 trials, 272 women; very low-certainty evidence). Women who received vitamin B12 supplements during pregnancy may have higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (mean difference (MD) 60.89 pmol/L, 95% CI 40.86 to 80.92; 3 trials, 412 women). However, there was substantial heterogeneity (I2 = 85%). Adverse pregnancy outcomes: the evidence is uncertain about the effect on adverse pregnancy outcomes, including preterm birth (RR 0.97, 95% CI 0.55 to 1.74; 2 trials, 340 women; low-certainty evidence), and low birthweight (RR 1.50, 95% CI 0.93 to 2.43; 2 trials, 344 women; low-certainty evidence). Two trials reported data on spontaneous abortion (or miscarriage); however, the trials did not report quantitative data for meta-analysis and there was no clear definition of spontaneous abortion in the study reports. No trials evaluated the effects of vitamin B12 supplementation during pregnancy on neural tube defects. Infant vitamin B12 status: children born to women who received vitamin B12 supplementation had higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (MD 71.89 pmol/L, 95% CI 20.23 to 123.54; 2 trials, 144 children). Child cognitive outcomes: three ancillary analyses of one trial reported child cognitive outcomes; however, data were not reported in a format that could be included in quantitative meta-analyses. In one study, maternal vitamin B12 supplementation did not improve neurodevelopment status (e.g. cognitive, language (receptive and expressive), motor (fine and gross), social-emotional, or adaptive (conceptual, social, practical) domains) in children compared to placebo (9 months, Bayley Scales of Infant and Toddler Development Third Edition (BSID-III); 1 trial; low-certainty evidence) or neurophysiological outcomes (72 months, event-related potential measures; 1 trial; low-certainty evidence), though children born to women who received vitamin B12 supplementation had improved expressive language domain compared to placebo (30 months, BSID-III; 1 trial; low-certainty evidence). Oral vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency and may improve maternal vitamin B12 concentrations during pregnancy or postpartum compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain. The effects of vitamin B12 supplementation on other primary outcomes assessed in this review were not reported, or were not reported in a format for inclusion in quantitative analyses. Vitamin B12 supplementation during pregnancy may improve maternal and infant vitamin B12 status, but the potential impact on longer-term clinical and functional maternal and child health outcomes has not yet been established.

Prenatal vitamin B12 status and cognitive functioning in children at 4 years of age: The ECLIPSES Study.

Maternal vitamin B12 deficiency has been associated with disturbed cognitive functioning in offspring at different ages during childhood. However, this association has not been explored in pre-school-age children. The objective of this study was to examine the association between maternal vitamin B12 levels at the beginning and end of pregnancy and cognitive functioning in their children at 4 years of age. This longitudinal prospective study included a subsample of pregnant women and their children aged 4 years (n = 249) who participated in the ECLIPSES Study conducted in the province of Tarragona, Spain, from 2013 to 2017. Maternal vitamin B12 concentrations were determined in the first and third trimesters, and sociodemographic, nutritional and psychological data were collected. The children's cognitive functioning was assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) and subtests of the Neuropsychological Assessment of Development (NEPSY-II). The multivariable models showed a significant relationship between vitamin B12 and the working memory index in the first trimester of the pregnancy but not in the third trimester. Children of mothers in the second vitamin B12 level tertile (314-413 pg/mL) (β = 6.468, 95% confidence interval [CI]: = 2.054, 10.882, p = 0.004) and third vitamin B12 level tertile (≥414 pg/mL) (β = 4.703, 95% CI: = 0.292, 9.114, p = 0.037) scored higher in the working memory index of the WPPSI-IV than the children of mothers with vitamin B12 levels in the first tertile (<314 pg/mL). Maintaining an adequate level of maternal vitamin B12 during early pregnancy contributes to improved performance in childhood working memory at 4 years of age.

Maternal Vitamin B12 Status during Pregnancy and Early Infant Neurodevelopment: The ECLIPSES Study

In this prospective cohort study of 434 mother-infant pairs from the ECLIPSES study, we examine the association between maternal vitamin B12 status at the beginning and end of pregnancy and the neurodevelopmental outcomes of infants 40 days after birth in a pregnant population from a Mediterranean region of northern Spain. Maternal vitamin B12 concentrations were determined in the first and third trimesters, and sociodemographic, nutritional, and psychological data were collected. At 40 days postpartum, the Bayley Scales of Infant Development-III (BSID-III, cognitive, language, and motor skills) were administered to the infants and several obstetrical data were recorded. In the multivariable models, medium maternal first-trimester vitamin B12 levels (312 to 408 pg/mL, tertile 2) were associated with better neonatal performance in the motor, gross motor, language, and cognitive skills with respect to tertile 1 (<312 pg/mL). The probability of obtaining a neonatal motor, gross motor, and receptive language score >75th percentile was significantly higher also in the tertile 2 group. In summary, good maternal vitamin B12 status in the early stage of pregnancy appears to be associated with better infant motor, language, and cognitive performance at 40 days postpartum.

Maternal vitamin B12 deficiency and perinatal outcomes in southern India.

BackgroundVitamin B12 deficiency during pregnancy has been associated with adverse maternal and infant health outcomes. Few prospective studies have investigated vitamin B12 status early in pregnancy, and its links to infant vitamin B12 status, particularly in India where the burden of vitamin B12 deficiency is estimated to be the highest globally. The objective of this study was to examine the associations of maternal vitamin B12 biomarkers with neonatal vitamin B12 status.MethodsPregnant women (~12 weeks’ gestation) were enrolled in a perinatal cohort study in Bangalore, India. Total vitamin B12, methylmalonic acid (MMA), and homocysteine concentrations were evaluated in maternal samples at enrollment and in neonates at birth using cord blood. Linear and binomial regression models were used to evaluate the associations of maternal vitamin B12 biomarkers with neonatal vitamin B12 status and perinatal outcomes.ResultsA total of 63.2% of women had vitamin B12 deficiency (<148 pmol/L), 87.2% had vitamin B12 insufficiency (<221 pmol/L), and 47.3% had impaired vitamin B12 status (vitamin B12<148 pmol/L and MMA>0.26μmol/L) at enrollment; 40.8% of neonates had vitamin B12 deficiency, 65.6% were insufficiency, and 38.1% had impaired vitamin B12 status at birth. Higher maternal vitamin B12 concentrations at enrollment were associated with increased neonatal vitamin B12 concentrations (β(SE): 0.40 (0.05); p<0.0001) and lower risk of neonatal vitamin B12 deficiency (Risk Ratio [RR]: 0.53; 95% CI: [0.43, 0.65]; p<0.0001). Maternal vitamin B12 deficiency (RR: 1.97 [1.43, 2.71]; p<0.001), insufficiency (RR: 2.18 [1.23, 3.85]; p = 0.007), and impaired vitamin B12 status (RR: 1.49 [1.13, 1.97]; p = 0.005) predicted a two-fold increase in the risk of neonatal vitamin B12 deficiency at birth.ConclusionsThe prevalence of vitamin B12 deficiency was high early in pregnancy and predicted neonatal vitamin B12 status. Future research is needed to determine the role of vitamin B12 in the development of pregnancy and infant outcomes, and to inform screening and interventions to improve maternal and child health.

Vitamin B12 Status in Pregnant Adolescents and Their Infants.

Vitamin B12 deficiency has been associated with increased risk of adverse pregnancy outcomes. Few prospective studies have investigated the burden or determinants of vitamin B12 deficiency early in life, particularly among pregnant adolescents and their children. The objectives of this study were to determine the prevalence of vitamin B12 deficiency and to examine associations between maternal and neonatal vitamin B12 status in a cohort study of healthy pregnant adolescents. Serum vitamin B12 and folate concentrations were measured in adolescents at mid-gestation (n = 124; 26.4 ± 3.5 weeks) and delivery (n = 131; 40.0 ± 1.3 weeks), and in neonates at birth using cord blood. Linear regression was used to examine associations between maternal and neonatal vitamin B12 status. Although the prevalence of vitamin B12 deficiency (<148.0 pmol/L; 1.6%) in adolescents was low during pregnancy, 22.6% of adolescents were vitamin B12 insufficient (<221.0 pmol/L; 22.6%) at mid-gestation. Maternal vitamin B12 concentrations significantly decreased from mid-gestation to delivery (p < 0.0001), and 53.4% had insufficient vitamin B12 status at delivery. Maternal vitamin B12 concentrations (p < 0.001) and vitamin B12 deficiency (p = 0.002) at delivery were significantly associated with infant vitamin B12 concentrations in multivariate analyses, adjusting for gestational age, maternal age, parity, smoking status, relationship status, prenatal supplement use, pre-pregnancy body mass index, race, and intake of vitamin B12 and folate. Maternal vitamin B12 concentrations significantly decreased during pregnancy and predicted neonatal vitamin B12 status in a cohort of healthy pregnant adolescents.

Association of pre-eclampsia risk with maternal levels of folate, homocysteine and vitamin B12 in Colombia: A case-control study.

BackgroundMaternal serum concentrations of folate, homocysteine, and vitamin B12 have been associated with pre-eclampsia. Nevertheless, reported studies involve limited number of cases to reliably assess the nature of these associations. Our aim was to examine the relation of these three biomarkers with pre-eclampsia risk in a large Colombian population.Materials and methodsDesign: A case-control study.Setting: Cases of pre-eclampsia and healthy pregnant controls were recruited at the time of delivery from eight different Colombian cities between 2000 and 2012.Population or Sample: 2978 cases and 4096 controls were studied. Maternal serum concentrations of folate, homocysteine, and vitamin B12 were determined in 1148 (43.6%) cases and 1300 (31.7%) controls. Also, self-reported folic acid supplementation was recorded for 2563 (84%) cases and 3155 (84%) controls.Analysis: Adjusted odds ratios (OR) for pre-eclampsia were estimated for one standard deviation (1SD) increase in log-transformed biomarkers. Furthermore, we conducted analyses to compare women that reported taking folic acid supplementation for different periods during pregnancy.Main Outcomes Measures: Odds ratio for pre-eclampsia.ResultsAfter adjusting for potential confounders in logistic regression models, the OR for pre-eclampsia was 0.80 (95% CI: 0.72, 0.90) for 1SD increase in log-folate, 1.16 (95%CI: 1.05, 1.27) for 1SD increase in log-homocysteine, and 1.10 (95%CI: 0.99, 1.22) for 1SD increase in log-vitamin B12. No interactions among the biomarkers were identified. Women who self-reported consumption of folic acid (1 mg/day) throughout their pregnancy had an adjusted OR for pre-eclampsia of 0.86 (95%CI: 0.67, 1.09) compared to women that reported no consumption of folic acid at any point during pregnancy.ConclusionsMaternal serum concentrations of folate were associated as a protective factor for pre-eclampsia while concentrations of homocysteine were associated as a risk factor. No association between maternal vitamin B12 concentrations and preeclampsia was found.

Maternal and Fetal Folate, Vitamin B12, and Homocysteine Concentrations and Childhood Kidney Outcomes

BackgroundFolate, vitamin B12 and homocysteine concentrations during pregnancy are important factors for early development and may persistently influence kidney function in the offspring. We examined the associations of folate, vitamin B12, and homocysteine concentrations during pregnancy with kidney outcomes in school-aged children.Study designPopulation-based prospective cohort study from fetal life onwards.Settings & participantsThis study was performed among 4,226 pregnant women and their children.PredictorsFolate, vitamin B12 and homocysteine blood concentrations measured in early pregnancy (median gestational age 13.2 weeks (25th to 75th percentiles 12.2, 14.8) and at birth (cord blood).Outcomes & measurementsAt the median age of 6.0 years (25th to 75th percentiles 5.9, 6.3) we measured combined kidney volume with ultrasound, estimated glomerular filtration rate based on creatinine (eGFRcreat) and cystatin C (eGFRcystC) concentrations and microalbuminuria.ResultsWe observed that higher maternal folate concentrations were associated with larger childhood combined kidney volume, whereas higher maternal vitamin B12 concentrations were associated with higher childhood eGFRcystC (p-values <0.05). These associations were independent of homocysteine concentrations. Higher maternal homocysteine concentrations were associated with smaller combined kidney volume and lower childhood eGFRcystC (p-values <0.05). The association of maternal homocysteine concentrations with childhood eGFRcystC was largely explained by combined kidney volume. Higher cord blood homocysteine concentrations were associated with larger combined kidney volume and lower eGFRcystC (p-values <0.05). Folate, vitamin B12 or homocysteine concentrations were not associated microalbuminuria.LimitationsObservational study, so causality cannot be established.ConclusionOur findings suggest that folate, vitamin B12 and homocysteine concentrations during fetal life are associated with offspring kidney development. However, the effect sizes are small. Further studies are needed to replicate these findings and assess the causality and consequences for kidney health in later life.

Vitamin B12 and Folate Status in Pregnant Adolescents and Their Infants

ObjectiveTo determine the prevalence of vitamin B12 deficiency and examine the associations between maternal and infant vitamin B12 and folate status in a cohort of healthy pregnant adolescents.DesignSerum vitamin B12 and folate concentrations were measured in pregnant adolescents at mid‐gestation, delivery, and in cord blood. Linear and binomial regression models were used to examine the associations between maternal and infant vitamin B12 and folate status.ResultsSerum vitamin B12 concentrations decreased significantly during pregnancy (p&lt;0.0001) resulting in an increased prevalence of vitamin B12 deficiency (&lt;148 pmol/L) from mid‐gestation (1.6%) to delivery (15.3%). At delivery, an additional 46.6% of mothers were vitamin B12 insufficient (&lt;200 pmol/L). Maternal vitamin B12 concentrations (p&lt;0.001) and vitamin B12 deficiency (p&lt;0.001) at delivery were associated with infant B12 concentrations, with 1% of infants being vitamin B12 deficient at birth. Similarly, maternal folate concentrations at delivery (p&lt;0.001) were associated with infant folate concentrations.ConclusionsMaternal vitamin B12 and folate status at delivery predicted infant vitamin B12 and folate status in healthy pregnant adolescents.Support or Funding InformationSupported by grants from the United States Department of Agriculture (USDA): USDA 2005‐35200‐15218 and USDA 2010‐34324‐20769; and the Division of Nutritional Sciences, Cornell University

Vitamin B12 and folate status in early pregnancy and cardiometabolic risk factors in the offspring at age 5-6 years: findings from the ABCD multi-ethnic birth cohort.

To explore whether maternal vitamin B12 and folate status during early pregnancy are associated with cardiometabolic risk factors in the offspring at age 5-6. Prospective multi-ethnic birth cohort, the Amsterdam Born Children and their Development study (ABCD). 12,373 pregnant women living in Amsterdam were approached between 2003 and 2004 for participation in the study. Mother-child pairs for whom information on maternal vitamin B12 or folate status in early gestation and health at age 5-6 years was available (n = 1950). Vitamin B12 and folate concentrations were determined in maternal serum at intake in early pregnancy (median 13 weeks' gestation). Anthropometric measurements, blood pressure and fasting blood samples were collected during a health check of children aged 5-6 years. Multiple linear regression was performed to investigate the association between maternal serum concentrations and children's outcomes, corrected for confounders. Gestational age at birth, birthweight, body mass index (BMI), glucose levels, triglyceride levels, blood pressure and heart rate of the offspring at age 5-6. Low maternal folate levels during early pregnancy were associated with slightly higher BMI in the offspring [decrease per 10 units: β 0.07 kg/m(2), 95% confidence interval (CI) 0.01, 0.13]. Low maternal vitamin B12 concentrations were associated with higher heart rates (decrease per 100 units: β 0.49 beats/min, 95% CI 0.11, 0.87). This study provides further evidence that maternal nutrition in early pregnancy may possibly program cardiometabolic health of the offspring. Low folate and vitamin B12 levels during pregnancy are associated with higher BMI and heart rate in offspring.

Vitamin B12 status in pregnant women and their children in India (135.6)

Objective: To examine the prevalence and determinants of poor infant vitamin B12 status at birth, and determine the associations between maternal and infant vitamin B12 status.Methods: 366 pregnant women participating in a vitamin B12 supplementation trial in India were monitored to assess maternal vitamin B12 status in pregnancy and its association with infant vitamin B12 status at 6 weeks of age. Binomial and linear regression were used to evaluate the associations between maternal and infant vitamin B12 status.Results: 51% of mothers were vitamin B12 deficient (&lt;150pmol/L) at baseline, and 47% of infants were vitamin B12 deficient at 6 weeks of age. Maternal vitamin B12 concentrations during 3 trimesters (T) were significantly correlated with infant vitamin B12 status (T1: r=0.19, p=0.10; T2: r=0.39, p&lt;0.01; T3: r=0.56, p&lt;0.0001); with stronger correlations in B12‐supplemented women (T1: r=0.42, p&lt;0.01; T2: r=0.55, p&lt;0.001; T3: r=0.55, p=0.001). After adjusting for vitamin B12 supplementation, higher maternal B12 concentrations at baseline predicted increased infant vitamin B12 levels (p=0.06), and infants born to vitamin B12‐deficient mothers were 1.6 times more likely to be vitamin B12 deficient (p=0.05).Conclusions: Inadequate maternal vitamin B12 status during pregnancy predicted increased risk of infant vitamin B12 deficiency.Grant Funding Source: Supported by: NICHD, ICMR

Association between maternal folate concentrations during pregnancy and insulin resistance in Indian children

Aims/hypothesisIn an Indian birth cohort, higher maternal homocysteine concentration in pregnancy was associated with lower birthweight of the offspring. Lower maternal vitamin B12 and higher folate concentrations were associated with higher offspring insulin resistance. Disordered one-carbon metabolism during early development may increase later metabolic risk. We explored these associations in another birth cohort in India at three age points.MethodsWe measured plasma vitamin B12, folate and homocysteine concentrations at 30 ± 2 weeks’ gestation in 654 women who delivered at one hospital. Neonatal anthropometry was recorded, and the children’s glucose and insulin concentrations were measured at 5, 9.5 and 13.5 years of age. Insulin resistance was estimated using HOMA of insulin resistance (HOMA-IR).ResultsMaternal homocysteine concentrations were inversely associated with all neonatal anthropometric measurements (p < 0.05), and positively associated with glucose concentrations in the children at 5 (30 min; p = 0.007) and 9.5 years of age (120 min; p = 0.02). Higher maternal folate concentrations were associated with higher HOMA-IR in the children at 9.5 (p = 0.03) and 13.5 years of age (p = 0.03). Maternal vitamin B12 concentrations were unrelated to offspring outcomes.Conclusions/interpretationMaternal vitamin B12 status did not predict insulin resistance in our cohort. However, associations of maternal homocysteine and folate concentrations with birth size, and with childhood insulin resistance and glycaemia in the offspring, suggest a role for nutritionally driven disturbances in one-carbon metabolism in fetal programming of diabetes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-013-3086-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Maternal first-trimester dietary intake and childhood blood pressure: the Generation R Study

Suboptimal maternal dietary intake during pregnancy might lead to fetal cardiovascular adaptations and higher blood pressure in the offspring. The aim of the present study was to investigate the associations of maternal first-trimester dietary intake with blood pressure in children at the age of 6 years. We assessed first-trimester maternal daily dietary intake by a FFQ and measured folate, homocysteine and vitamin B₁₂ concentrations in the blood, in a population-based prospective cohort study among 2863 mothers and children. Childhood systolic and diastolic blood pressure was measured using a validated automatic sphygmomanometer. First-trimester maternal daily intake of energy, fat, protein and carbohydrate was not associated with childhood blood pressure. Furthermore, maternal intake of micronutrients was not associated with childhood blood pressure. Also, higher maternal vitamin B₁₂ concentrations were associated with a higher diastolic blood pressure (0·31 mmHg per standard deviation increase in vitamin B₁₂ (95% CI 0·06, 0·56)). After taking into account multiple testing, none of the associations was statistically significant. Maternal first-trimester folate and homocysteine concentrations were not associated with childhood blood pressure. The results from the present study suggest that maternal Fe intake and vitamin B₁₂ concentrations during the first trimester of pregnancy might affect childhood blood pressure, although the effect estimates were small and were not significant after correction for multiple testing. Further studies are needed to replicate these findings, to elucidate the underlying mechanisms and to assess whether these differences in blood pressure persist in later life.

Vitamin B12 in pregnancy: Maternal and fetal/neonatal effects—A review

Vitamin B12 maintains normal folate metabolism which is essential for cell multiplication during pregnancy. No good data are available on what constitutes vitamin B12 deficiency in pregnancy, nevertheless vitamin B12 deficiency is frequently reported in pregnancy due to inadequate dietary intake of vitamin B12 and a physiological decline of maternal vitamin B12 concentrations. This decline can be explained by the increased maternal metabolic rate and active transport by the placenta to the fetus. If the mother is deficient during pregnancy, the baby may have low serum vitamin B12 concentrations at birth [1]. Vitamin B12 deficiency during pregnancy is associated with preeclampsia, fetal growth restriction, preterm labor, neural tube defects, neonatal megaloblastic anemia and neonatal neurological symptoms. It has been suggested to improve vitamin B12 status of women in the periconceptional period by supplementation of vitamin B12, but no randomized studies on the outcome of such supplementation have been published.