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Background:
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.
Study des...
Contexts in source publication
Context 1
... Folate is an essential B-vitamin, important for cell growth and replication and is together with vitamin B 12 , an important methyl donor in many reactions, including the production of thymidine for DNA synthesis, polyamine synthesis and biosynthesis of methionine from homocysteine.7-9 Folate and vitamin B 12 contribute to lowering homocysteine concentrations ( Figure 1).10 Animal studies indicate that elevated homocysteine concentrations may lead to glomerular damage, and folic acid supplementation lowers creatinine concentration and urinary albumin excretion induced by hyperhomocysteinemia.11 Also, studies in adults have shown associations of elevated homocysteine concentrations with an accelerated decline in kidney function.12 ...
Citations
... According to the literature 13,14,20 and the characteristics of this study, the covariates considered in the study were sociodemographic characteristics including maternal residence, maternal age, maternal educational level, neonatal gender, gestational age, and parity and maternal health-related factors from 3 months before pregnancy to delivery covering passive smoking, having had a cold, and folic acid supplementation. Gestational age was calculated based on the date of last menstruation and the date of delivery. ...
... 25 Lower maternal vitamin B 12 and folate could increase the concentration of homocysteine, which may be related to NTDs, cardiovascular diseases, kidney diseases, and other diseases. 8,20,26 The symptoms due to vitamin B 12 deficiency were largely similar to those of folate deficiency, and increased folic acid intake could interfere with the clinical diagnosis of vitamin B 12 deficiency, 6 which means that folic acid supplementation may cover up the lack of vitamin B 12 , so it is suggested that attention should also be paid to replenishment of vitamin B 12 in the practice of maternal folic acid supplementation. Socio-demographic factors could affect dietary intake of micronutrients, among them residence, age, and educational level of women could be key variables. ...
Purpose
There remains a data gap on vitamin B12 and folate level in maternal and child populations. This study aimed to assess the status of vitamin B12 and folate in maternal serum (MS) and umbilical cord serum (UCS).
Materials and Methods
This was a planned secondary analysis of a case-control study. A total of 858 pregnant women during late pregnancy and their newborns in the hospitals of China were included. Maternal peripheral venous blood and neonatal umbilical cord blood were collected to determine serum vitamin B12 and folate concentration. Relationship of vitamin B12 or folate concentration between MS and UCS was assessed by a quantile regression model and the non-linear relationship between them was examined.
Results
Nutritional status of serum folate was better than that of vitamin B12. Prevalence of deficiency in MS vitamin B12 and folate was 73.4% and 14.2%, respectively and these figures were about 17.8% and 0.1% in UCS. Both vitamin B12 and folate levels in UCS were significantly higher than those in MS (vitamin B12: 321.0 pg/mL vs 158.3 pg/mL, folate: 16.5 ng/mL vs 7.0 ng/mL, P <0.001). The median UCS-MS ratio of vitamin B12 and folate was 2.0 (95% CI: 1.94–2.06) and 2.4 (95% CI: 2.30–2.53), respectively. The levels of folate and vitamin B12 in UCS increased nonlinearly with their increase in MS which presented an inverted U-shaped curve.
Conclusion
Deficiency in vitamin B12 and folate in the women during late pregnancy in China is prevalent. Nutritional status of the two vitamins in umbilical cord serum is correlated nonlinearly with that in maternal serum. Folic acid supplementation may be accompanied with vitamin B12 to improve status of vitamin B12 and folate during pregnancy.
... 63 Albeit FA has not reverted some disorders associated with nephrogenesis, it is suggested that folate deficiency might impact this process through epigenetic modulation. 43 There are hypotheses that little availability of folate, B12 vitamin, and other nutrients affects the volume of the kidneys and decreases the nephrons number of the offspring, predisposing to chronic renal disease in adulthood, 45,64 it reinforcing the concept of fetal programming. ...
Unlabelled:
Supplementation with folic acid (FA) during gestation has been recommended by medical society all over the world, but some studies have shown that intake of high folic acid diet may unleash damages to the descendants.
Objectives:
Describing the effects of maternal supplementation with FA during gestation on offspring's kidney at late life stages.
Data source:
It is a systematic review by which were consulted the following databases: Medline, through Pubmed, Lilacs, and SciELO. The research was performed using the keywords "Folic acid", "Gestation" and "Kidney".
Study selection:
Eight studies were regarded for this systematic review.
Data collection:
Only studies that evaluated folic acid consumption during gestation and its effects exclusively on descendants' kidney at several phases of life were regarded.
Results:
Gestational FA intake did not change the renal volume, glomerular filtration rate and the expression of some essential genes in the kidney of puppies whose dams were supplemented with FA. Maternal consumption of double FA plus selenium diet was effective in preserving antioxidant enzymes activity in the kidney of descendants from mothers exposed to alcohol. FA supplementation decreased some gross anomalies in the puppies caused by teratogenic drug despite of had not been effective in preventing some renal architectural damages.
Conclusion:
FA supplementation did not cause renal toxicity; it exerted an antioxidant protective effect and mitigated some renal disorders caused by severe aggressions.
... Vitamin B12 (cobalamin) is an essential nutrient for humans and can be obtained from meat, fish, dairy, eggs, and liver [1]. Lower maternal circulating vitamin B12 concentrations during pregnancy have been associated with adverse health outcomes in the offspring, including higher risk of low birth weight and preterm birth, suboptimal cardiometabolic outcomes, and lower kidney function [2][3][4][5][6][7]. Vitamin B12 concentrations typically decline during pregnancy, but a clinical cut-off for deficiency in pregnancy has not been established [8,9]. ...
... Vitamin B12 is involved in one-carbon metabolism, which supplies the methyl groups for DNA methylation by guaranteeing the availability of methionine [8]. Differential foetal DNA methylation may underlie the known associations of circulating vitamin B12 concentrations during foetal development with childhood health [2][3][4][5]8]. Previously, circulating vitamin B12 concentrations during pregnancy have been associated with global and gene-specific, but not epigenome-wide cord blood DNA methylation [10,11]. ...
... For the hypothesized inverse association with neural tube defects, vitamin B12 status during early pregnancy seems more relevant than during late pregnancy [41]. Also, inconsistent associations with child cardiometabolic outcomes have been previously reported for maternal versus newborn circulating vitamin B12 concentrations [2,44]. Finally, the different findings for maternal and newborn meta-analyses may be explained by differences between the cohorts included in both meta-analyses, such as vitamin B12 intake from diet or multivitamins, which might be used less frequently in late pregnancy, as compared to early pregnancy. ...
Circulating vitamin B12 concentrations during pregnancy are associated with offspring health. Foetal DNA methylation changes could underlie these associations. Within the Pregnancy And Childhood Epigenetics Consortium, we meta-analysed epigenome-wide associations of circulating vitamin B12 concentrations in mothers during pregnancy (n = 2,420) or cord blood (n = 1,029), with cord blood DNA methylation. Maternal and newborn vitamin B12 concentrations were associated with DNA methylation at 109 and 7 CpGs, respectively (False Discovery Rate P-value <0.05). Persistent associations with DNA methylation in the peripheral blood of up to 482 children aged 4–10 y were observed for 40.7% of CpGs associated with maternal vitamin B12 and 57.1% of CpGs associated with newborn vitamin B12. Of the CpGs identified in the maternal meta-analyses, 4.6% were associated with either birth weight or gestational age in a previous work. For the newborn meta-analysis, this was the case for 14.3% of the identified CpGs. Also, of the CpGs identified in the newborn meta-analysis, 14.3% and 28.6%, respectively, were associated with childhood cognitive skills and nonverbal IQ. Of the 109 CpGs associated with maternal vitamin B12, 18.3% were associated with nearby gene expression. In this study, we showed that maternal and newborn vitamin B12 concentrations are associated with DNA methylation at multiple CpGs in offspring blood (PFDR<0.05). Whether this differential DNA methylation underlies associations of vitamin B12 concentrations with child health outcomes, such as birth weight, gestational age, and childhood cognition, should be further examined in future studies.
... The association between PMPCs and several markers such as low-molecular-weight heparin (LMWH), antiphospholipid antibody (APLA), serum folic acid levels, and serum vitamin B12 levels have been studied in the past, but the findings are still conflicting [2][3][4]. Recent research has suggested that serum 1 1 2 1 1 1 homocysteine (Hct) levels may be linked to several pregnancy-related complications, but the degree to which maternal hyperhomocysteinemia (HHct) increases the risk of PMPCs is yet to be studied in detail [5]. ...
Background
Placenta-mediated pregnancy complications (PMPCs) are a significant contributor to adverse maternal and fetal outcomes. Though the exact cause of the array of pregnancy-related vascular disorders is still unknown, increased maternal serum homocysteine (Hct) levels have been linked to the pathophysiology. Hyperhomocysteinemia (HHct) has been strongly linked with the risk of developing PMPCs such as preeclampsia (PE), fetal growth restriction (FGR), intrauterine fetal death (IUFD), preterm births and placental abruption.
Methodology
The present observational study was carried out on 810 low-risk antenatal women in their early second trimester (13-20 weeks gestation age) in the department of obstetrics and gynecology of a tertiary care rural hospital to identify the significance of abnormally raised maternal serum Hct level in developing PMPCs.
Results
Of the 810 participants studied, 224 (27.65%) had raised Hct levels whereas the rest of the 586 (72.35%) participants had normal Hct levels. The mean Hct level of raised homocysteine group (18.59 ± 2.46 micromol/L) was substantially raised than the normal Hct group (8.64 ± 3.1 micromol/L). It was observed that women with elevated serum Hct levels developed PMPCs significantly more than women with normal serum Hct levels (p-value <0.05). Among HHct subjects, 65.18% developed PE, 34.38% had FGR, 28.13% had a preterm delivery, 4.02% had abruptio placentae and 3.57% had IUFD.
Conclusions
The focus of the current study is on an easy and quick intervention such as assessing the often-ignored levels of Hct during pregnancy that can help predict and prevent PMPCs. It also highlights the necessity for well-thought-out large-scale studies and trials to further examine the phenomena, as pregnancy may be the only time when rural women will have the opportunity to receive advice and to be tested for HHct.
... In adults, elevated tHcy was associated with microalbuminuria, however in the birth cohort they did not find the same association, suggesting that microalbuminuria might not be detectable during childhood. In the same study they also found that higher maternal folate status was associated with larger kidney volume of the children, and similarly, higher maternal cobalamin status was associated with higher estimated glomerular filtration rate based on cystatin C in the children (Miliku et al., 2017). In the first formal definition of the metabolic syndrome, microalbuminuria was one of components proposed by WHO, as explained in the metabolic syndrome section of this thesis. ...
http://hdl.handle.net/10803/687506
Inadequate pregnancy cobalamin status has been associated with adverse offspring health in Asia but there are few studies in countries with low prevalence of cobalamin deficiency. Less is known regarding the association between the betaine-dimethylglycine pathway during pregnancy, foetal growth and mid-childhood health. The associations between pregnancy fasting plasma total homocysteine (tHcy), cobalamin status (cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA)) and mid-childhood (6-8y) metabolic score (MetSco) (including fat mass index, homeostatic model assessment of insulin resistance and dyslipidemia) were studied in a prospective study of 293 mother–child dyads. Associations between pregnancy fasting plasma betaine, dimethylglycine (DMG)/betaine, c.716G>A BHMT genotype and foetal growth were investigated in a prospective study of 748 mother–neonate dyads. The association between pregnancy fasting plasma betaine and mid-childhood (7.5 y) MetSco was investigated in 213 mother–child dyads. Child plasma metabolite status was studied according to pregnancy 1C metabolism status and bivariate correlations between child plasma metabolites and anthropometric measurements in 238 children were studied to identify potential biomarkers associated with the metabolic syndrome. Moderately elevated pregnancy tHcy, low holoTC and high MMA were associated with increased mid-childhood MetSco in boys. Cord plasma betaine was inversely associated with foetal growth. Babies born to mothers with the BHMT c.716 AA genotype had a higher risk of small for gestational age (SGA) compared to GG, and GA+GG genotypes. The pregnancy betaine-DMG pathway was not associated with child MetSco. Plasma betaine was higher in children born to mothers in the lowest tertile of pregnancy plasma cobalamin compared to the mid-high tertiles, while plasma tryptophan was lowest in those born to mothers in the highest vs low-mid maternal pregnancy plasma tHcy tertiles. Child plasma betaine, cysteine, 3-hydroxyanthranilic acid, kynurenic acid, histidine and asymmetric dimethylarginine were positively correlated with adiposity while picolinic acid, trigonelline and neopterin were negatively associated.
... Serum Hct was substantially linked with glucose levels measured after two hours in GDM patients [47]. Serum Hct levels in GDM patients were higher than in healthy pregnant women between weeks 24 and 28 of pregnancy [48]. Sixty people with GDM and 19 healthy pregnant women were studied for a Polish study that examined their serum Hct levels. ...
The most extremely unfavourable outcome of pregnancy is the death of the mother and newborn. Negative outcomes for mothers or babies can occur as a result of complications or issues during pregnancy, birth or the post-partum period. Early elevated maternal homocysteine (Hct) levels during pregnancy have been linked to altered placental development. There is evidence that suggests an elevated maternal blood Hct level is the new obstetrical risk factor, and the association between hyperhomocysteinemia (HHct) and numerous obstetrical problems was recently recognised.
Hct is an essential amino acid, which contains sulphur and is formed from the metabolism of methionine. HHct has several known aetiologies, including genetic anomalies; a deficiency in folic acid, vitamin B6 and vitamin B12; hypothyroidism; old age; and renal illnesses. Vascular problems, coronary artery disease, atherosclerosis and embolic illnesses can all occur as a result of high blood levels of Hct. Hct levels are lower in normal pregnancies than it is in women who are not pregnant. Many pregnancy-related problems, including pre-eclampsia (PE), recurrent pregnancy loss (RPL), placental abruption, premature delivery and foetal growth restriction (FGR) have been connected to HHct in recent research.
We looked for pertinent literature using a thorough and systematic search from PubMed, Medline, Embase, Cochrane Library, Google, etc., and articles that were published before August 2022 based on serum Hct levels and various placenta-mediated complications for this review.
In this review, we described the synthesis and metabolism of Hct in humans, Hct levels at various phases of normal pregnancy and the association between Hct and placenta-mediated pregnancy complications.
The outcomes discovered can help obstetricians increase the likelihood of a successful pregnancy in cases where placenta-mediated issues are present. Lowering Hct levels with a high dose of folic acid tablets during the subsequent pregnancy may be useful for women who experienced these difficulties in prior pregnancies as a result of HHct.
... For example, maternal obesity and diabetes are correlated with an increased risk of kidney disease in adulthood [39,40]. Additionally, deficiencies in maternal total energy [41], folate [42], and vitamin A [43] during pregnancy were associated with detrimental influence on kidney structure and function. Epidemiological studies also showed that maternal exposure to polycyclic aromatic hydrocarbon, per-and polyfluoroalkyl substances, and polycyclic aromatic hydrocarbon, as well as air pollution associated with premature birth and LBW [44][45][46][47], are both risk factors for low nephron number. ...
The gut–kidney interaction implicating chronic kidney disease (CKD) has been the focus of increasing interest in recent years. Gut microbiota-targeted therapies could prevent CKD and its comorbidities. Considering that CKD can originate in early life, its treatment and prevention should start in childhood or even earlier in fetal life. Therefore, a better understanding of how the early-life gut microbiome impacts CKD in later life and how to develop ideal early interventions are unmet needs to reduce CKD. The purpose of the current review is to summarize (1) the current evidence on the gut microbiota dysbiosis implicated in pediatric CKD; (2) current knowledge supporting the impact of the gut–kidney axis in CKD, including inflammation, immune response, alterations of microbiota compositions, short-chain fatty acids, and uremic toxins; and (3) an overview of the studies documenting early gut microbiota-targeted interventions in animal models of CKD of developmental origins. Treatment options include prebiotics, probiotics, postbiotics, etc. To accelerate the transition of gut microbiota-based therapies for early prevention of CKD, an extended comprehension of gut microbiota dysbiosis implicated in renal programming is needed, as well as a greater focus on pediatric CKD for further clinical translation.
... A total of 34 children (9 girls, 25 boys) with vitamin B12 deficiency and 36 healthy controls (17 girls, 19 boys) were analysed in the study. There was no difference between the groups in terms of median age [13 (range, 4-17) vs. 12.5 (range, [5][6][7][8][9][10][11][12][13][14][15][16][17]]. Physical examination was unremarkable in all subjects participated in ...
... Urinary neutrophil gelatinaseassociated lipocalin (uNGAL) is a biomarker reflecting renal tubular damage, and it has been shown to be increased urinary excretion in renal damage (5). Although there are many studies in the literature on the neurological and hematological effects of vitamin B12 deficiency, there are scarce data investigating the effect on renal functions (6)(7)(8). ...
... Miliku et al. (8) also investigated the effects of maternal and fetal B12 and homocysteine levels on the renal function of children, they observed high GFR values in those with high fetal B12 values. It has been concluded that those with higher levels of homocysteine may also have smaller kidney sizes and decreased GFR values. ...
... Subtle differences in circulating maternal folate, vitamin B12 and homocysteine concentrations during pregnancy have been associated with offspring health outcomes [1][2][3][4][5]. DNA methylation may be a mechanism underlying these associations [6][7][8][9]. ...
... Previous studies have reported associations of these micronutrients in blood with newborn DNA methylation [10][11][12][13]. Altered epigenetic aging in response to the environment in utero, resulting in gestational age acceleration, might be an underlying mechanism for the associations of circulating folate, vitamin B12 and homocysteine concentrations during pregnancy and health outcomes in children [2,3,5,9,20]. We hypothesized that subtle differences in Table 4 Associations of circulating folate, vitamin B12 and homocysteine concentrations with gestational age acceleration (subgroup analysis) *This association at nominal significance did remain if we applied a Bonferroni correction, adjusting for four exposures (0.05/4) ...
... These findings are in line with our hypothesis. Previous work from birth cohorts reported associations of lower circulating homocysteine concentrations but higher circulating vitamin B12 concentrations during fetal development with beneficial health outcomes from birth onwards [2,3,5]. Changes in epigenetic gestational age may be an underlying mechanism. ...
Background
Circulating 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.
Results
Up 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.
Conclusions
We 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.
... In adults, hyperhomocysteinemia is associated with endothelial dysfunction and increased cardiovascular risk (13)(14)(15). Previous prospective birth cohorts, including the cohort in which the current study was embedded, have suggested associations of not taking folic acid supplements and of suboptimal maternal folate, vitamin B-12, and homocysteine blood concentrations in pregnancy with lower uteroplacental vascular resistance, lower offspring birth weight, higher BMI, higher heart rate, and lower kidney function in offspring at school age (4,(16)(17)(18)(19)(20)(21). No previous studies have assessed associations of multiple 1-carbon metabolism markers, measured at 2 time points in pregnancy, with a wide range of detailed cardiometabolic outcomes in childhood. ...
... Active B-12 was analyzed in stored serum samples only and therefore available in a smaller subgroup. We also dichotomized maternal and cord blood folate (≥8 and <8 nmol/L, respectively), total B-12 (≥145 and <145 pmol/L, respectively), active B-12 (≥21 and <21 pmol/L, respectively), and homocysteine (<19 and ≥19 μmol/L, respectively) concentrations into normal and low according to the 95% reference interval for healthy adults (4,6,24,25). To explore whether an imbalance of circulating maternal high folate status and low vitamin B-12 status is associated with detrimental cardiometabolic outcomes in childhood (12,22), we categorized mothers based on their combined circulating folate/total B-12 status and similarly based on their combined circulating folate/active B-12 status. ...
... Main models were also adjusted for maternal age, education, prepregnancy BMI, smoking and alcohol consumption, parity, and child ethnicity. To compare effect estimates, exposures and outcomes were analyzed in SDSs after natural log transformation of FMI, android fat mass percentage, android-togynoid fat ratio, and insulin and triglyceride concentrations, which all had skewed distributions (4,33). As a sensitivity analysis, we assessed whether effect estimates of the associations were similar in an ethnic homogeneous Dutch subgroup. ...
Background
Higher circulating folate and vitamin B-12 concentrations and lower circulating homocysteine concentrations during pregnancy seem to be associated with fetal development. These micronutrients may also be associated with cardiometabolic health.
Objective
We examined the associations of circulating folate, vitamin B-12, and homocysteine concentrations during pregnancy and in neonates with childhood cardiometabolic outcomes.
Methods
This study was embedded in the Generation R Study, a population-based prospective cohort study from early pregnancy onward. We sampled blood in early pregnancy and cord blood. We measured cardiometabolic outcomes in the children at school age. Among 4449 children aged 10 y (median: 9.7; 95% range: 9.3, 10.7), we examined associations of plasma folate, serum vitamin B-12, and plasma homocysteine concentrations in early pregnancy and at birth with BMI, body fat distribution, heart rate, blood pressure, and insulin, glucose, and lipid concentrations, using linear regression models. Using logistic models, we examined the associations of these micronutrients with risks of overweight/obesity and clustering of cardiovascular risk factors.
Results
One standard deviation score (SDS) higher maternal plasma folate concentration was associated with lower BMI (−0.04 SDS; 95% CI: −0.08, −0.01), android-to-gynoid fat ratio (−0.04 SDS; 95% CI: −0.07, −0.01), systolic blood pressure (−0.06 SDS; 95% CI: −0.10, −0.03), risk of overweight (OR: 0.87; 95% CI: 0.78, 0.96), and clustering of cardiovascular risk factors (OR: 0.79; 95% CI: 0.68, 0.91). One SDS higher maternal serum total B-12 concentration was associated with lower glucose (−0.06 SDS; 95% CI: −0.10, −0.02) and higher HDL cholesterol concentrations (0.04 SDS; 95% CI: 0.00, 0.08). Cord blood folate, vitamin B-12, and homocysteine concentrations were not consistently associated with cardiometabolic outcomes.
Conclusions
Subtle differences in circulating folate and vitamin B-12 concentrations in early pregnancy may be associated with child cardiometabolic health at age 10 y. The causality and mechanisms underlying these associations need further study.
