vitamin-b-12 and Premature-Birth

Vitamin B12 (hereafter referred to as B12) deficiency in pregnancy is prevalent and has been associated with both lower birth weight (birth weight <2,500 g) and preterm birth (length of gestation <37 weeks). Nevertheless, current evidence is contradictory. We performed a systematic review and a meta-analysis of individual participant data to evaluate the associations of maternal serum or plasma B12 concentrations in pregnancy with offspring birth weight and length of gestation. Twenty-two eligible studies were identified (11,993 observations). Eighteen studies were included in the meta-analysis (11,216 observations). No linear association was observed between maternal B12 levels in pregnancy and birth weight, but B12 deficiency (<148 pmol/L) was associated with a higher risk of low birth weight in newborns (adjusted risk ratio = 1.15, 95% confidence interval (CI): 1.01, 1.31). There was a linear association between maternal levels of B12 and preterm birth (per each 1-standard-deviation increase in B12, adjusted risk ratio = 0.89, 95% CI: 0.82, 0.97). Accordingly, B12 deficiency was associated with a higher risk of preterm birth (adjusted risk ratio = 1.21, 95% CI: 0.99, 1.49). This finding supports the need for randomized controlled trials of vitamin B12 supplementation in pregnancy.

Topics: Birth Weight; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Pregnancy; Pregnancy Complications; Premature Birth; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

Preterm pregnancies account for approximately 10% of the total pregnancies and are associated with low birth weight (LBW) babies. Recent studies have shown that LBW babies are at an increased risk of developing brain disorders such as cognitive dysfunction and psychiatric disorders. Maternal nutrition, particularly, micronutrients involved in one-carbon metabolism (folic acid, vitamin B(12), and docosahexaenoic acid (DHA)) have a major role during pregnancy for developing fetus and are important determinants of epigenesis. A series of our studies in pregnancy complications have well established the importance of omega 3 fatty acids especially DHA. DHA regulates levels of neurotrophins like brain-derived neurotrophic factor and nerve growth factor, which are required for normal neurological development. We have recently described that in one carbon metabolic pathway, membrane phospholipids are major methyl group acceptors and reduced DHA levels may result in diversion of methyl groups toward deoxyribonucleic acid (DNA) ultimately resulting in DNA methylation. In this review, we propose that altered maternal micronutrients (folic acid, vitamin B(12)), increased homocysteine, and oxidative stress levels that cause epigenetic modifications may be one of the mechanisms that contribute to preterm birth and poor fetal outcome, increasing risk for behavioural disorders in children.

Topics: Animals; Epigenesis, Genetic; Fatty Acids, Omega-3; Female; Folic Acid; Humans; Maternal Nutritional Physiological Phenomena; Micronutrients; Models, Biological; Nerve Growth Factors; Oxidative Stress; Pregnancy; Pregnancy Complications; Premature Birth; Vitamin B 12

Folic acid supplementation in those with a low vitamin B-12 intake or status may have adverse effects. These effects are unknown with regard to birth outcome in pregnant Indian women who are routinely supplemented with high doses of folic acid.. The objective was to examine the association of unbalanced vitamin B-12 and total folate (folic acid supplement + dietary folate) intakes during pregnancy with outcomes in small-for-gestational-age (SGA) infants.. This was a prospective observational cohort study of 1838 pregnant women in South India. Low intake of dietary vitamin B-12 in the presence of high total folate intake was examined as the ratio of vitamin B-12 intake to total folate intake.. The inadequacy of vitamin B-12 intake (<1.2 μg/d) assessed by a food-frequency questionnaire in the first, second, and third trimesters of pregnancy was 25%, 11%, and 10%, respectively. Multivariate log binomial regression showed that low vitamin B-12 and folate intakes in the first trimester were independently associated with a higher risk of SGA. In a subgroup of women with high supplemental folic acid intakes in the second trimester, those with the lowest tertile of vitamin B-12:folate ratio had a higher risk of SGA outcome than did those in the highest tertile (adjusted RR: 2.73; 95% CI: 1.17, 6.37). A similar trend was observed in the analysis of blood micronutrient status in a random subset (n = 316) of the sample.. These findings suggest that, in addition to vitamin B-12 and folate deficiencies alone, there may be adverse birth outcomes associated with unbalanced vitamin B-12 and folate intakes or status during pregnancy. These findings have important implications for the antenatal B vitamin supplementation policy in India. This trial was registered at the Clinical Trial Registry of India as 2013/07/005342.

Topics: Adult; Cohort Studies; Diet; Dietary Supplements; Female; Fetal Growth Retardation; Folic Acid; Folic Acid Deficiency; Humans; Incidence; India; Infant, Small for Gestational Age; Male; Maternal Nutritional Physiological Phenomena; Pregnancy; Pregnancy Complications; Premature Birth; Risk; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

To analyse the pregnancy outcome by combining plasma homocysteine with uterine artery Doppler velocimetry at 11 to 14 weeks of gestation.. A prospective cohort study with 103 healthy pregnant women. Uterine artery Doppler velocimetry was performed at between 11 and 14 weeks of gestation. Abnormal blood flow was defined as average pulsatility index >1.5 and presence of unilateral or bilateral diastolic notch. Doppler scores were calculated by a modified scoring method of uterine artery flow velocity waveforms. Serum for measurement of homocysteine, vitamin B(12) and folate levels were collected when the ultrasonographic measurement was performed.. Pre-eclampsia developed in five, gestational hypertension in three, intrauterine growth restriction in two and preterm birth in eight patients. There was a significant difference between mean plasma homocysteine levels at different Doppler scores (p<0.001) and a weak positive correlation between Doppler scores and occurrence of pregnancy complications (r(s) = 0.232, p<0.05). Mean homocysteine level increased with increasing Doppler scores. Any uterine artery abnormality had a sensitivity of 88.9% in predicting obstetric complications. Addition of hyperhomocytenemia to Doppler scores did not change the sensitivity.. Maternal serum homocysteine level is increased in 11 to 14 weeks of gestation that is complicated with pre-eclampsia, gestational hypertension, intrauterine growth restriction and preterm birth. Addition of homocysteine determination to uterine artery Doppler in the first trimester does not add any advantage in predicting adverse perinatal outcome.

Topics: Adult; Biomarkers; Blood Flow Velocity; Female; Fetal Growth Retardation; Folic Acid; Gestational Age; Homocysteine; Humans; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Premature Birth; Prognosis; Prospective Studies; Rheology; Ultrasonography, Prenatal; Uterine Artery; Vitamin B 12

We undertook this study to compare the effectiveness and safety of antenatal daily and weekly supplementation with iron, folic acid, and vitamin B(12) in healthy, pregnant women who were not anemic at gestational week 20.. Women with singleton pregnancies and blood hemoglobin (Hb) >115 g/L at gestational week 20 (equivalent to 105 g/L at sea level) were randomly assigned to two groups, one consuming one tablet containing 60 mg iron, 200 mug folic acid and 1 mug vitamin B(12) daily (DS, n = 56); the other consuming two tablets once weekly (WS, n = 60). Blood Hb and serum ferritin concentrations were measured every 4 weeks from weeks 20 to 36, and pregnancy outcomes were evaluated.. Mild anemia and hypoferritinemia throughout pregnancy occurred less frequently in DS than WS. None of the 116 women had Hb concentrations <103 g/L at any evaluation point. In contrast, hemoconcentration (Hb >145 g/L) from gestational week 28 onwards occurred in 11% in DS and 2% in WS. We observed ex post facto that hemoconcentration at gestational week 28 was associated with a significantly higher relative risk of low birth weight (RR 6.23, 95% CI 1.46-26.57) and premature delivery (RR 7.78, 95% CI 1.45-24.74).. In women who were nonanemic at gestational week 20, both schemes (DS and WS) prevented the occurrence of Hb levels <100 g/L. DS women had a higher incidence of hemoconcentration. Hemoconcentration was associated with increased risk of low birth weight and premature delivery.

Topics: Adult; Anemia; Dietary Supplements; Drug-Related Side Effects and Adverse Reactions; Female; Ferritins; Folic Acid; Gestational Age; Hematinics; Hemoglobins; Humans; Infant, Low Birth Weight; Infant, Newborn; Iron; Pregnancy; Pregnancy Complications, Hematologic; Premature Birth; Risk Factors; Vitamin B 12; Vitamin B Complex

Vitamin B12 and folate deficiency leads to accumulation of homocysteine that increases the risk of adverse pregnancy outcomes like preterm birth and low birth weight (LBW) of the neonate. We explored the association of genetic variants of key vitamin B12 and folate metabolising enzymes (MTHFR C677T and A1298C, MTR A2756G, TCN-2 C776G) with preterm birth and LBW in South Indian women. MTHFR A1298C heterozygotes (AC) were at higher risk for preterm delivery, whereas TCN-2 C776G heterozygotes (CG) were at higher risk for both preterm delivery and LBW. MTHFR C677T, A1298C and MTR A2756G haplotype CAG was protective for preterm delivery (

Topics: Case-Control Studies; Female; Folic Acid; Genotype; Homocysteine; Humans; Infant; Infant, Newborn; Methylenetetrahydrofolate Reductase (NADPH2); Pregnancy; Pregnancy Outcome; Premature Birth; Vitamin B 12

Hyperhomocysteinemia (hypHcy) due to impaired folate metabolism is shown to be a risk factor for preterm birth (PTB) and low birth weight (LBW) in mothers. However, the relationship of fetal hypHcy with adverse pregnancy outcomes is under-represented. The present study aims to investigate the association of fetal hypHcy with oxidative stress and placental inflammation that can contribute to an early breakdown of maternal-fetal tolerance in pre-term birth (PTB).. Cord blood and placenta tissue were collected from PTB and term infant group. Levels of homocysteine, folic acid, vitamin B12 and oxidative stress markers (MDA, T-AOC, 8-OHdG) were measured in cord blood serum using ELISA and respective standard assay kits. Relative expression of candidate genes (TNF-α, IL-6, IL1-β, VEGF-A, MMP2 and MMP9) was also checked using RT-PCR and immunoblotting/immunohistochemistry.. PTB infants showed significantly higher levels of homocysteine (P = .02) and lower levels of vitamin B12 (P = .005) as compared to term infants. We also found that PTB infants with hypHcy had lower T-AOC (P = .003) and higher MDA (P = .04) levels as compared to term infants with normal homocysteine levels. The mRNA and protein levels of TNF-α, VEGF-A, MMP2 and MMP9 were significantly higher in hypHcy PTB infants.. Our results show that fetal hypHcy is associated with oxidative stress and an increase in inflammatory markers in the placenta. Thus, in conclusion, our study demonstrates that fetal hypHcy during pregnancy is a potential risk factor that may initiate an early breakdown of uterine quiescence due to activation of inflammatory processes leading to PTB.

Topics: Biomarkers; Female; Fetal Blood; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Infant; Infant, Newborn; Inflammation; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Placenta; Pregnancy; Premature Birth; Term Birth; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Vitamin B 12

Polymorphisms of genes involved in the metabolism and transport of folate and cobalamin could play relevant roles in pregnancy outcomes. This study assessed the prevalence of genetic polymorphisms of folate and cobalamin metabolism-related genes such as MTHFR, MTR, CUBN, and SLC19A1 in pregnant women of a homogeneous Spanish population according to conception, pregnancy, delivery, and newborns complications. This study was conducted on 149 nulliparous women with singleton pregnancies. Sociodemographic and obstetrics variables were recorded, and all patients were genotyped in the MTHFR, MTR, CUBN, and SLC10A1 polymorphisms. The distribution of genotypes detected in this cohort was similar to the population distribution reported in Europe, highlighting that more than 50% of women were carriers of risk alleles of the studied genes. In women with the MTHFR risk allele, there was a statistically significant higher frequency of assisted fertilisation and a higher frequency of preeclampsia and preterm birth. Moreover, CUBN (rs1801222) polymorphism carriers showed a statistically significantly lower frequency of complications during delivery. In conclusion, the prevalence of genetic variants related to folic acid and vitamin B12 metabolic genes in pregnant women is related to mother and neonatal outcomes. Knowing the prevalence of these polymorphisms may lead to a personalised prescription of vitamin intake.

Topics: Dietary Supplements; Female; Folic Acid; Genotype; Humans; Infant, Newborn; Methylenetetrahydrofolate Reductase (NADPH2); Pregnancy; Pregnant Women; Premature Birth; Vitamin B 12; Vitamins

To determine the occurrence of. 120 consecutive pregnant women who were ≤20 weeks of gestational age from the 82 villages of Kaniyambadi block were recruited. Genomic DNA was isolated from the peripheral blood. PCR amplification was done followed by Sangers sequencing. Maternal and neonatal outcomes were extracted. Data was entered and analysed.. Our study found the occurrence of c.1298A>C variant in homozygous state in 14.2% and c.677C>T heterozygous state in 15%. Sanger sequencing of exon 7 identified another pathogenic variant c.1262G>T in heterozygous state in two of them. Both the mothers who harboured that variant had preterm delivery and one of them gave birth to a low-birth-weight neonate. In the entire cohort, 5% of the mothers had abortion, 4.2% of them had preterm delivery and 8.8% of the neonates had low birth weight. Presence of c.1298A>C or c.677C>T variants were associated with vitamin B12 deficiency [Pearson Chi squared value (χ

Topics: Cross-Sectional Studies; Female; Folic Acid; Genotype; Homocysteine; Humans; India; Infant, Newborn; Longitudinal Studies; Methylenetetrahydrofolate Reductase (NADPH2); Parturition; Polymorphism, Genetic; Pregnancy; Pregnant Women; Premature Birth; Vitamin B 12; Vitamin B 12 Deficiency

Women living with HIV (WLHIV) have a higher prevalence of anemia than women without HIV, possibly related to the effects of HIV and antiretroviral medications.. To estimate the prevalence of anemia in the third trimester of pregnancy and the effect of anemia on preterm births in WLHIV in the longitudinal, US-based Pediatric HIV/AIDS Cohort Study (PHACS).. During the third trimester, we obtained up to three 24-hour dietary recalls to estimate daily intakes of nutrients and measured serum concentrations of iron, vitamin B6, vitamin B12, zinc, folate, ferritin, total iron-binding capacity (TIBC), and high sensitivity C-reactive protein. Third trimester anemia was defined as hemoglobin < 11 g/d and iron-deficiency anemia (IDA) was defined as low ferritin, high TIBC, and low transferrin saturation. A preterm birth was defined as birth at < 37 completed weeks of gestation, regardless of etiology. We fit separate modified Poisson regression models for each outcome (anemia, preterm birth) and each main exposure, adjusted for confounders, and report adjusted prevalence ratios (aPR) and 95% CIs.. Of the 267 WLHIV, 50% were anemic in the third trimester, of whom 43.5% (n = 57/131) had IDA. On average, women with anemia were younger, were more likely to be black, started antiretroviral medications in the second trimester, had a low CD4 count (<200 cells/mm3) early in pregnancy, and were less likely to meet recommended intakes for iron, B6, and folate. The prevalence of anemia was greater in WLHIV with a low CD4 count (aPR = 1.65; 95% CI: 1.20-2.27) and high HIV viral load (>10,000 copies/mL; aPR = 1.38; 95% CI: 1.02-1.87). In total, 16% of women delivered preterm. Anemia was associated with a 2-fold (aPR = 2.04; 95% CI: 1.12-3.71) higher prevalence of preterm births.. Anemia is common in pregnant WLHIV, highlighting the need to address the underlying factors and clinical outcomes of anemia in this population.

Topics: Adult; Anemia; Anemia, Iron-Deficiency; C-Reactive Protein; Female; Ferritins; Folic Acid; HIV; HIV Infections; Humans; Infant, Newborn; Iron; Iron-Binding Proteins; Longitudinal Studies; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Pregnancy Trimester, Third; Premature Birth; Prevalence; United States; Vitamin B 12; Vitamin B 6; Zinc

Vitamin B12 (B12) is a co-enzyme essential for fetal growth and development. Lower maternal B12 status has been associated with preterm birth (<37 gestational weeks) and low birth weight (<2500 g), which are linked to morbidity and mortality across the lifespan. In Canada, 17-25 % of women in early pregnancy had a serum total B12 concentration <148 pmol/l and maternal total B12 concentration decreased throughout pregnancy. This study aimed to determine the association between maternal B12 status and birth outcomes in Canadian mother-newborn dyads. A secondary analysis of 709 mother-newborn dyads in British Columbia (BC), Canada, was conducted. Bio-banked first- (n 656) and second-trimester (n 709) maternal serum samples of apparently healthy South Asian (50 %) and European (50 %) women from the BC Prenatal Genetic Screening Program were quantified for B12 biomarkers (total B12, holotranscobalamin (holoTC), methylmalonic acid (MMA) and total homocysteine (tHcy)). Obstetric history and birth outcome data were obtained from the BC Perinatal Data Registry. All associations were determined using multiple linear regression. Maternal serum total B12, holoTC, MMA and tHcy had a mean weekly decrease of 3·64 pmol/l, 1·04 pmol/l, 1·44 nmol/l and 0·104 μmol/l, respectively (P < 0·001). Despite a total B12 concentration <148 pmol/l among 20-25 % of the women, maternal B12 biomarker concentrations were not associated with birth weight z-score, head circumference z-score and gestational age at birth (P > 0·05). Additional research in women at high risk of adverse birth outcomes and the association between maternal B12 status and functional, for example, cognitive, outcomes is needed.

Topics: Canada; Female; Homocysteine; Humans; Infant, Newborn; Mothers; Pregnancy; Premature Birth; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Hyperhomocysteinemia may be a risk factor for endothelial dysfunction. Folate and vitamin B12 regulate the homocysteine metabolic process. This study aimed to evaluate the associations between subsequent events of adverse pregnancy outcome and early variables of homocysteine, folate, and vitamin B12 in pregnant women.. This multicenter, retrospective, case-control study involved 563 pregnant women with adverse pregnancy outcome and 600 controls. Adverse pregnancy outcomes included one or more of the following events: preeclampsia, preterm birth, low birth weight, and stillbirth. The associations between subsequent events of adverse pregnancy outcome and early variables of homocysteine, folate, and vitamin B12; metabolic parameters; inflammatory markers; anthropometrics; and lifestyle habits at 11-12 weeks of gestation were analyzed using the logistic regression model.. Compared to the lower quartile homocysteine concentrations, the upper quartile homocysteine concentrations were associated with preeclampsia, preterm birth and low birth weight. On the contrary, the lower quartile folate concentrations were associated with preeclampsia, preterm birth and low birth weight compared with the upper quartile folate concentrations. The incidence of adverse pregnancy outcome increased progressively from the first to fourth homocysteine quartiles but decreased progressively from the first to fourth folate quartiles. After adjusting for confounding factors, multivariate logistic regression analysis showed that besides systolic blood pressure, diastolic blood pressure, body mass index and age, homocysteine (IV vs I quartile, aOR 5.89, 95% CI 4.08-8.51, P < 0.001), folate (IV vs I quartile, aOR 0.35, 95% CI 0.25-0.50, P < 0.001), folate supplementation (yes vs no, aOR 0.55, 95% CI 0.35-0.86, P = 0.010) during early pregnancy were independently associated with subsequent events of adverse pregnancy outcome, and vitamin B12 was rejected. Of these, the homocysteine revealed the highest odds ratio in all risk variables, and folate showed the lowest odds ratio in all protective variables.. Higher homocysteine concentration and lower folate level during early pregnancy were associated with adverse pregnancy outcome. However, no association was found between vitamin B12 and adverse pregnancy outcome. Supplementation with folate in early pregnancy may reduce adverse pregnancy outcome.

Topics: Adult; Case-Control Studies; China; Female; Folic Acid; Homocysteine; Humans; Infant, Low Birth Weight; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Premature Birth; Retrospective Studies; Risk Factors; Vitamin B 12

Micronutrients like vitamin B

Topics: Adolescent; Adult; Biomarkers; Birth Weight; Blood Pressure; Case-Control Studies; Female; Fetal Blood; Folic Acid; Gestational Age; Homocysteine; Humans; Infant, Newborn; Infant, Premature; Nutritional Status; Pre-Eclampsia; Pregnancy; Premature Birth; Up-Regulation; Vitamin B 12; Young Adult

Adequate vitamin A is essential for healthy pregnancy, but high levels may be teratogenic. We present a patient who underwent bariatric surgery, prior to child bearing, and suffered maternal and foetal complications during eleven pregnancies, possibly associated with vitamin A deficiency, amongst multiple micronutrient deficiencies and risk factors including smoking and obesity. Maternal complications included visual disturbance, night blindness and recurrent infections. Recurrent foetal pulmonary hypoplasia and microphthalmia led to foetal and neonatal loss, not previously described in the medical literature. Current guidance on vitamin A deficiency in pregnancy is focused on developing countries where aetiology of vitamin A deficiency is different to that of women in developed countries. We describe nutritional management of the micronutritient deficiencies, focusing on vitamin A, during her last pregnancy. The need for specific antenatal nutritional guidance for pregnant women post-bariatric surgery is becoming more urgent as more mothers and offspring will be affected.

Topics: Abortion, Spontaneous; Adult; Anemia, Iron-Deficiency; Biliopancreatic Diversion; Diet; Female; Fetal Diseases; Gestational Age; Humans; Infant, Newborn; Iron; Micronutrients; Obesity; Perinatal Death; Pregnancy; Pregnancy Complications; Premature Birth; Smoking; Vitamin A; Vitamin A Deficiency; Vitamin B 12

Iron (Fe) status of neonates born to women carrying multiple fetuses might be compromised as a consequence of the high prevalence of maternal Fe deficiency and anemia coupled with an increased risk of preterm birth. This study aimed to characterize and identify determinants of anemia in this neonatal population.. Umbilical cord blood obtained from 183 neonates was utilized to assess hemoglobin (Hb), ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, serum Fe, erythropoietin, folate, vitamin B-12, C-reactive protein, and interleukin-6. Associations with maternal Fe status were explored.. Cord Hb or SF did not change significantly as a function of gestational age at birth (25-38 wks). Neonates born to women who were obese prior to pregnancy or smoked cigarettes during pregnancy had a 4-5-fold greater odds of anemia at birth. Cord sTfR was the strongest indicator of cord Hb (P < 0.0001), and it was significantly associated with maternal sTfR at mid-gestation (P = 0.01) and delivery (P = 0.002). Cord Fe indicators were significantly associated with cord hepcidin, but not maternal hepcidin.. Screening for Fe status in neonates born to women carrying multiple fetuses is warranted, especially for those born to smokers or to women who are obese at entry into pregnancy.

Topics: Adult; Anemia; Anemia, Iron-Deficiency; C-Reactive Protein; Cohort Studies; Erythropoietin; Female; Ferritins; Fetal Blood; Folic Acid; Hemoglobins; Hepcidins; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Premature, Diseases; Interleukin-6; Iron; Obesity; Pregnancy; Pregnancy Complications; Pregnancy, Multiple; Premature Birth; Receptors, Transferrin; Smoking; Tobacco Use Disorder; Vitamin B 12; Young Adult

Altered maternal one-carbon metabolism influences placental DNA methylation patterns and 'programs' the fetus for noncommunicable diseases in adult life.. Levels of plasma folate, vitamin B. MTHFR and MTR mRNA levels were higher while protein levels were lower, and MTR CpG sites were hypermethylated in the preterm group, as compared with the term group. Methylated CpG sites were negatively associated with maternal plasma vitamin B. Study suggests a dysregulation of enzyme genes in remethylation arm of the one-carbon metabolism in placenta of women delivering preterm.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Adult; Case-Control Studies; CpG Islands; DNA Methylation; Female; Folic Acid; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Placenta; Placenta Diseases; Pregnancy; Premature Birth; Promoter Regions, Genetic; RNA, Messenger; Vitamin B 12

Folate deficiency during pregnancy has been related to low birth weight, preterm (PT) birth and other health risks in the offspring; however, it is unknown whether prematurity is related to low folate transport through the placenta due to altered expression of specific folate transporters. We determined placental expression (mRNA and protein concentrations by RT-qPCR and WB respectively) of specific folate transporters: RFC, PCFT/HCP1 and FOLR1 in chorionic (fetal) and basal (maternal) plates of placentas of PT pregnancies (PT, 32-36 weeks, n = 51). Term placentas were used as controls (T, 37-41 weeks, n = 47). Folates and vitamin B12 levels were measured by electrochemiluminescence in umbilical cord blood of newborns. FOLR1 mRNA expression was lower and protein concentration higher in PT placentas (both plates) relative to the control group (p <0.05). In addition, gestational age was positively correlated with mRNA expression (Rho = 0.7), and negatively with protein concentration (Rho = -0.7 for chorionic and -0.43 for basal plate). PCFT/HCP1 mRNA was lower in PT placentas, without changes in protein levels. RFC did not differ in PT placentas compared to controls. PT newborns presented higher cord blood folate level (p = 0.049) along with lower vitamin B12 concentration compared to controls (p = 0.037).In conclusion, placental FOLR1 mRNA was positively associated with gestational age. Conversely, FOLR1 protein concentrations along with folate/vitamin B12 ratio in cord blood were negatively associated with gestational age. Placental FOLR1 is likely the main placental folate transporter to the fetus in newborns.

Topics: Adult; Female; Fetal Blood; Folate Receptor 1; Folic Acid; Folic Acid Transporters; Humans; Infant, Newborn; Infant, Premature; Placenta; Pregnancy; Premature Birth; Proton-Coupled Folate Transporter; Reduced Folate Carrier Protein; RNA, Messenger; Term Birth; Vitamin B 12; Young Adult

Maternal folate, vitamin B-12, and vitamin B-6 concentrations during pregnancy have been shown to influence birth outcomes, but the evidence is inconclusive.. We aimed to examine the associations of maternal B-vitamin status with gestational age, birth weight, and length in a birth cohort study in Singapore.. Maternal blood samples (n = 999) collected during weeks 26-28 of gestation were assayed for plasma folate, vitamin B-12, and vitamin B-6 concentrations. Birth weight and gestational age data were obtained from hospital records, and other anthropometric variables were measured within 72 h after birth. Relations between B-vitamin status and birth outcomes were assessed by linear or logistic regression with adjustment for potential confounders.. Median (IQR) plasma concentrations were 34.4 (24.5-44.6) nmol/L for folate, 209 (167-258) pmol/L for vitamin B-12, and 61.8 (25.9-113) nmol/L for vitamin B-6. We found that higher plasma folate concentrations were associated with a longer gestational age (0.12 wk per SD increase in folate; 95% CI: 0.02, 0.21) and tended to be associated with lower risk of all preterm birth (delivery at <37 wk of gestation; OR: 0.79; 95% CI: 0.63, 1.00) and spontaneous preterm birth (OR: 0.76; 95% CI: 0.56, 1.04). Overall, concentrations of maternal folate, vitamin B-12, and vitamin B-6 were not independently associated with birth weight or being born small for gestational age (SGA; birth weight <10th percentile for gestational age).. Higher maternal folate concentrations during late pregnancy were associated with longer gestational age and tended to be associated with a lower risk of preterm birth in this multiethnic Asian population. In contrast, the results of our study suggested little or no benefit of higher folate concentrations for reducing the risk of SGA or of higher vitamin B-6 and vitamin B-12 concentrations for reducing the risk of preterm birth or SGA.

Topics: Adult; Asian People; Birth Weight; Body Height; Cohort Studies; Female; Folic Acid; Gestational Age; Humans; Nutritional Status; Pregnancy; Pregnancy Outcome; Premature Birth; Prospective Studies; Risk Factors; Singapore; Vitamin B 12; Vitamin B 6

Topics: Female; Folic Acid; Homocysteine; Humans; Maternal Nutritional Physiological Phenomena; Pregnancy; Premature Birth; Vitamin B 12; Vitamin B Complex

Maternal nutrition is an important determinant of the duration of pregnancy and fetal growth, and thereby influences pregnancy outcome. Folic acid and vitamin B(12) are involved in one-carbon metabolism and are reported to underlie intrauterine programming of adult diseases.. In the present study, the levels of folate, vitamin B(12) and homocysteine were measured in mothers delivering preterm (PT; gestation <37 weeks; n = 67), those delivering preterm due to preeclampsia (PT-PE; n = 49) and women delivering at term (control group; n = 76).. Increased vitamin B(12) and homocysteine levels (p < 0.05 for both) were seen in the PT-PE and PT groups as compared to the controls. In addition, reduced folate levels (p < 0.05) were observed in the PT group. A negative association of maternal plasma homocysteine with birth weight was seen in the idiopathic preterm group.. Altered maternal micronutrients and resultant increased homocysteine concentrations exist in women delivering preterm. These alterations may also be partly associated with other factors such as undiagnosed inflammatory conditions or inadequate placentation in some women. Since these micronutrients play an important role in epigenetic regulation of vital genes involved in the fetal programming of adult diseases, further studies need to be undertaken to understand their role in preterm deliveries.

Topics: Adult; Birth Weight; Cross-Sectional Studies; Female; Folic Acid; Homocysteine; Humans; Infant, Newborn; Maternal Nutritional Physiological Phenomena; Micronutrients; Nutrition Assessment; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Premature Birth; Vitamin B 12; Vitamin B Complex; Young Adult

In general practice, vitamin B12 levels are measured when searching an origin for an anemic status (usually megaloblastic anemia), for various neurological disorders (usually polyneuropathy) or for neurocognitive disorders. Although the pathologies associated with vitamin B12 deficiency are well known, hypervitaminemic B12 status is often fortuitous and frequent finding. The aim of this article is to present the disease entities associated with hypervitaminemia B12, the clinical implications of this dysvitaminosis and a practical approach when this laboratory abnormality is found.

Topics: Algorithms; Autoimmune Diseases; Female; Hematologic Diseases; Humans; Liver Diseases; Neoplasms; Pregnancy; Premature Birth; Renal Insufficiency; Vitamin B 12

Maternal nutrition is an important determinant of one-carbon metabolism that lies at the heart of intrauterine epigenetic programming. Exchange of nutrients and other vital molecules between the mother and fetus takes place across the placenta and hence may play direct role in fetal programming. Pre-eclampsia (PE) originates in the placenta and altered maternal nutrition may influence epigenetic patterns in the placenta, thereby affecting birth outcome. In the present study, we investigated the global DNA methylation levels in placentas of pre-eclampsia women (i.e., women delivering at term and those delivering preterm) and studied their associations with maternal blood pressure and birth outcome. Increased homocysteine and global DNA methylation levels were seen in the pre-eclampsia group (term and preterm PE) when compared with the normotensive group (p < 0.05). A positive association between global DNA methylation and systolic (p < 0.01) and diastolic (p < 0.05) blood pressure was seen in the term pre-eclampsia group, whereas there was no association with birth outcome. The study for the first time provides evidence for altered global DNA methylation patterns in pre-eclampsia placentas and its association with blood pressure. It is possible that increased homocysteine levels may be related to increased methylation in pre-eclampsia.

Topics: Blood Pressure; DNA Methylation; Female; Folic Acid; Homocysteine; Humans; Hypertension; Infant, Newborn; Mothers; Placenta; Pre-Eclampsia; Pregnancy; Premature Birth; Term Birth; Vitamin B 12

Prematurity and small-for-gestational age (SGA) neonates are at risk for postnatal complications. Concentrations of total homocysteine (tHcy) might be related to neonatal outcome. We hypothesized that concentrations of tHcy are not related to growth restriction in neonates from mothers receiving 5 mg/day folic acid. We studied a total of 133 preterm neonates from normotensive mothers; SGA (n=96) and appropriate-for-gestational age (AGA, n=37).. Concentrations of tHcy, folate and vitamin B12 were measured in venous umbilical cord plasma.. AGA preterm neonates had higher mean birth weight (BW) compared to SGA preterms (2472 g vs. 2007 g; p<0.001) of comparable mean gestational age (GA) (35.1 vs. 35.7 weeks; p=0.059). Concentrations of tHcy (4.86 vs. 4.95 micromol/L), folate (63.3 vs. 55.7 nmol/L), and vitamin B12 (409 vs. 394 pmol/L) were not significantly different between the groups. GA was a strong positive predictor, BW was a significant negative predictor of cord plasma folate. Vitamin B12 concentration was a significant negative predictor of cord tHcy.. Concentrations of tHcy did not differ between SGA and AGA preterm neonates born to mothers supplemented with folic acid. This finding argues against a causal role for folate deficiency or increased tHcy in growth restriction.

Topics: Adult; Birth Weight; Female; Fetal Blood; Fetal Growth Retardation; Folic Acid; Folic Acid Deficiency; Gestational Age; Homocysteine; Humans; Infant, Newborn; Infant, Small for Gestational Age; Mothers; Predictive Value of Tests; Pregnancy; Premature Birth; Vitamin B 12

Topics: Child Abuse; Diagnosis, Differential; Female; Hematoma; Hematoma, Subdural; Homocystinuria; Humans; Hypothermia; Hypovolemia; Infant; Metabolism, Inborn Errors; Methylmalonic Acid; Pregnancy; Premature Birth; Retinal Hemorrhage; Sleep Stages; Vitamin B 12