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Maternal plasma vitamin B12 concentrations during pregnancy and infant cognitive outcomes at 2 years of age.

ABSTRACT: Evidence on long-term influences of maternal vitamin B12 deficiency or concentrations on infant cognition is limited. We examined associations between maternal plasma vitamin B12 and cognitive development in 24-month-old infants. Maternal plasma vitamin B12 concentrations were measured at 26-28 weeks' gestation; infant cognitive development was assessed with the Bayley Scales of Infant and Toddler Development-III at 24 months, for 443 mother-infant pairs from the Growing Up in Singapore Towards Healthy Outcomes cohort. Linear regressions adjusted for key confounders examined associations of maternal vitamin B12 with cognitive, receptive and expressive language, fine and gross motor subscales. Co-occurrence of maternal vitamin B12 with folate or vitamin B6 insufficiencies on child's cognition was explored. Average maternal plasma vitamin B12 concentrations was 220·5 ± 80·5 pmol/l; 15 % and 41 % of mothers were vitamin B12 deficient (<148 pmol/l) and insufficient (148-220·9 pmol/l), respectively. Infants of mothers with vitamin B12 deficiency had 0·42 (95 % CI -0·70, -0·14) sd lower cognitive scores, compared with infants of mothers with sufficient vitamin B12. Co-occurrence of maternal vitamins B12 and B6 insufficiencies was associated with 0·37 (95 % CI -0·69, -0·06) sd lower cognitive scores in infants compared with infants of mothers sufficient in both vitamins. No significant associations were observed with other subscales. Study findings suggest the possible need to ensure adequate vitamin B12 during pregnancy. The impact of co-occurrence of maternal B-vitamins insufficiencies on early cognitive development warrants further investigation.

SUBMITTER: Lai JS

PROVIDER: S-EPMC6660314 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Maternal plasma vitamin B12 concentrations during pregnancy and infant cognitive outcomes at 2 years of age.

Lai Jun S JS Mohamad Ayob M Na'im MN Cai Shirong S Quah Phaik Ling PL Gluckman Peter D PD Shek Lynette P LP Yap Fabian F Tan Kok Hian KH Chong Yap Seng YS Godfrey Keith M KM Meaney Michael J MJ Broekman Birit F P BFP Rifkin-Graboi Anne A Chong Mary F F MFF

The British journal of nutrition 20190402 11

Evidence on long-term influences of maternal vitamin B12 deficiency or concentrations on infant cognition is limited. We examined associations between maternal plasma vitamin B12 and cognitive development in 24-month-old infants. Maternal plasma vitamin B12 concentrations were measured at 26-28 weeks' gestation; infant cognitive development was assessed with the Bayley Scales of Infant and Toddler Development-III at 24 months, for 443 mother-infant pairs from the Growing Up in Singapore Towards ...[more]

PMID: 30935438

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Project description:Background & aimsSuboptimal circulating vitamin B12, folate and homocysteine concentrations during fetal life seem to be associated with cardiometabolic health at school-age. We examined whether fetal exposure to lower circulating vitamin B12 and folate concentrations and higher circulating homocysteine concentrations is also associated with early signs of atherosclerosis at school-age.MethodsThis study among 3826 school-age children and their mothers was embedded in the Generation R Study, a population-based prospective cohort study from early pregnancy onwards. We examined the associations of early-pregnancy and cord blood serum total and active B12 and plasma folate and homocysteine concentrations with common carotid artery intima-media thickness and distensibility in the children aged ten years.ResultsAs compared to normal early-pregnancy serum total B12 concentrations (≥145 pmol/L), low serum total B12 concentrations (<145 pmol/L) were associated with higher carotid intima-media thickness in the children at school-age (difference 0.09 standard deviations score (SDS); 95% confidence interval (CI): 0.01, 0.16). As compared to normal early-pregnancy plasma folate concentrations (≥8 nmol/L), low plasma folate concentrations (<8 nmol/L) were associated with lower carotid distensibility in the children at school-age (difference -0.16 SDS; 95% CI: -0.28, -0.04). Early-pregnancy circulating total and active B12, folate and homocysteine concentrations measured continuously were not associated with carotid intima-media thickness or carotid distensibility in the children at school-age. One SDS higher plasma homocysteine concentrations measured in cord blood at birth was associated with a -0.05 SDS (95% CI: -0.09, -0.02) lower carotid distensibility at school-age. Cord blood total and active B12 and folate concentrations were not associated with carotid intima-media thickness or carotid distensibility at school-age.ConclusionsCirculating total B12, folate and homocysteine concentrations during fetal life seem to be associated with markers of subclinical atherosclerosis at school-age. Further studies need to examine the causality and mechanisms underlying these associations.

Project description:Folate, 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.Population-based prospective cohort study from fetal life onward.This study was performed among 4,226 pregnant women and their children.Folate, vitamin B12, and homocysteine blood concentrations measured in early pregnancy (median gestational age, 13.2 [IQR, 12.2-14.8] weeks) and at birth (cord blood).At the median age of 6.0 (IQR, 5.9-6.3) years, we measured combined kidney volume with ultrasound, estimated glomerular filtration rate based on creatinine (eGFRcr) and cystatin C (eGFRcys) concentrations, and microalbuminuria.We 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 eGFRcys (P for both <0.05). These associations were independent of homocysteine concentrations. Higher maternal homocysteine concentrations were associated with smaller combined kidney volume and lower childhood eGFRcys (P for both < 0.05). The association of maternal homocysteine concentrations with childhood eGFRcys was largely explained by combined kidney volume. Higher cord blood homocysteine concentrations were associated with larger combined kidney volume and lower eGFRcys (P for both < 0.05). Folate, vitamin B12, or homocysteine concentrations were not associated with microalbuminuria.Observational study, so causality cannot be established.Our findings suggest that folate, vitamin B12, and homocysteine concentrations during fetal life are associated with offspring kidney development. However, effect sizes are small. Further studies to replicate these findings and assess the causality and consequences for kidney health in later life are needed.

Project description:Maternal nutritional status during pregnancy impacts fetal brain development. Vitamin B12 plays a vital role in neuronal development. However, findings from studies on the association between maternal B12 status and child cognitive functions have been inconsistent. We performed a randomized, placebo-controlled clinical trial of oral B12 supplementation (50?µg) beginning at <14?weeks of gestation through a 6-week post-partum. In the present study, we report the effects of maternal B12 supplementation on cognitive development in infants at 9?months of age on Bayley Scales of Infant Development-III (BSID-III). One hundred eighty-three pregnant women received vitamin B12, and 183 received placebo. Nine-month BSID-III development score was available in 178 infants. There were no significant differences in maternal sociodemographic characteristics and baseline biochemical measures between infants who underwent BSID-III evaluation and infants who were not evaluated. There were no significant differences in any of the subscales of BSID-III between infants born to mothers who received B12 supplementation (n?=?78) vs. placebo (n?=?100). On multiple regression analysis, elevated maternal total homocysteine (tHcy) levels adjusted for treatment group, birthweight, parity, income and home environment at second trimester of pregnancy were significantly negatively associated with expressive language (??=?3.13 points, P?<?0.001), and in third trimester of pregnancy with expressive language (??=?-2.29 points, P?<?0.001) and fine motor (??=?-1.41 points, P?=?0.005) domains of BSID-III. While no significant effects of maternal B12 supplementation were seen on cognitive development in infants at 9?months of age, elevated maternal tHcy levels were associated with poorer cognitive performance in some of the subdomains of BSID-III. In pregnant women with elevated tHcy levels and or B12 deficiencies, it may be worthwhile to study the impact of longer term maternal supplementation on infant cognitive outcomes.

Project description:BackgroundCirculating folate, vitamin B12 and homocysteine concentrations during fetal development have been associated with health outcomes in childhood. Changes in fetal DNA methylation may be an underlying mechanism. This may be reflected in altered epigenetic aging of the fetus, as compared to chronological aging. The difference between gestational age derived in clinical practice and gestational age predicted from neonatal DNA methylation data is referred to as gestational age acceleration. Differences in circulating folate, vitamin B12 and homocysteine concentrations during fetal development may be associated with gestational age acceleration.ResultsUp to 1346 newborns participating in the Generation R Study, a population-based prospective cohort study, had both cord blood DNA methylation data available and information on plasma folate, serum total and active B12 and plasma homocysteine concentrations, measured in early pregnancy and/or in cord blood. A subgroup of 380 newborns had mothers with optimal pregnancy dating based on a regular menstrual cycle and a known date of last menstrual period. For comparison, gestational age acceleration was calculated based the method of both Bohlin and Knight. In the total study population, which was more similar to Bohlin's training population, one standard deviation score (SDS) higher maternal plasma homocysteine concentrations was nominally associated with positive gestational age acceleration [0.07 weeks, 95% confidence interval (CI) 0.02, 0.13] by Bohlin's method. In the subgroup with pregnancy dating based on last menstrual period, the method that was also used in Knight's training population, one SDS higher cord serum total and active B12 concentrations were nominally associated with negative gestational age acceleration [(- 0.16 weeks, 95% CI - 0.30, - 0.02) and (- 0.15 weeks, 95% CI - 0.29, - 0.01), respectively] by Knight's method.ConclusionsWe found some evidence to support associations of higher maternal plasma homocysteine concentrations with positive gestational age acceleration, suggesting faster epigenetic than clinical gestational aging. Cord serum vitamin B12 concentrations may be associated with negative gestational age acceleration, indicating slower epigenetic than clinical gestational aging. Future studies could examine whether altered fetal epigenetic aging underlies the associations of circulating homocysteine and vitamin B12 blood concentrations during fetal development with long-term health outcomes.

Dataset Information

Maternal plasma vitamin B12 concentrations during pregnancy and infant cognitive outcomes at 2 years of age.

Publications

Maternal plasma vitamin B12 concentrations during pregnancy and infant cognitive outcomes at 2 years of age.

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