Vitamin B12 Excess Women Pregnant Journal Article Peer Review

• Loading metrics

Open Access

Peer-reviewed

Enquiry Article

Maternal vitamin B₁₂ deficiency and perinatal outcomes in southern Republic of india

• Julia Fifty. Finkelstein,
• Amy Fothergill,
• Jesse T. Krisher,
• Tinku Thomas,
• Anura 5. Kurpad,
• Pratibha Dwarkanath

x

• Published: April half-dozen, 2021
• https://doi.org/10.1371/journal.pone.0248145

Figures

Abstruse

Background

Vitamin B₁₂ deficiency during pregnancy has been associated with adverse maternal and infant health outcomes. Few prospective studies take investigated vitamin B₁₂ status early on in pregnancy, and its links to infant vitamin B₁₂ status, especially in India where the brunt 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.

Methods

Pregnant women (~12 weeks' gestation) were enrolled in a perinatal cohort study in Bangalore, Bharat. Total vitamin B₁₂, methylmalonic acid (MMA), and homocysteine concentrations were evaluated in maternal samples at enrollment and in neonates at birth using string blood. Linear and binomial regression models were used to evaluate the associations of maternal vitamin B₁₂ biomarkers with neonatal vitamin B₁₂ condition and perinatal outcomes.

Results

A total of 63.ii% of women had vitamin B₁₂ deficiency (<148 pmol/L), 87.2% had vitamin B₁₂ insufficiency (<221 pmol/Fifty), and 47.3% had impaired vitamin B₁₂ condition (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.one% had impaired vitamin B₁₂ status at nativity. Higher maternal vitamin B₁₂ concentrations at enrollment were associated with increased neonatal vitamin B₁₂ concentrations (β(SE): 0.twoscore (0.05); p<0.0001) and lower adventure of neonatal vitamin B₁₂ deficiency (Chance Ratio [RR]: 0.53; 95% CI: [0.43, 0.65]; p<0.0001). Maternal vitamin B₁₂ deficiency (RR: 1.97 [i.43, 2.71]; p<0.001), insufficiency (RR: ii.18 [1.23, 3.85]; p = 0.007), and impaired vitamin B₁₂ condition (RR: 1.49 [1.13, 1.97]; p = 0.005) predicted a 2-fold increase in the gamble of neonatal vitamin B₁₂ deficiency at nascence.

Conclusions

The prevalence of vitamin B₁₂ deficiency was high early in pregnancy and predicted neonatal vitamin B₁₂ status. Time to come 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 wellness.

Citation: Finkelstein JL, Fothergill A, Krisher JT, Thomas T, Kurpad AV, Dwarkanath P (2021) Maternal vitamin B₁₂ deficiency and perinatal outcomes in southern India. PLoS 1 16(4): e0248145. https://doi.org/10.1371/journal.pone.0248145

Editor: Pal Bela Szecsi, Holbaek Sygehus, DENMARK

Received: October 25, 2020; Accepted: February nineteen, 2021; Published: April 6, 2021

Copyright: © 2021 Finkelstein et al. This is an open access commodity distributed under the terms of the Creative Commons Attribution License, which permits unrestricted employ, distribution, and reproduction in whatsoever medium, provided the original author and source are credited.

Data Availability: The data is publicly available at: https://doi.org/x.7910/DVN/HIOUQN (Contact Dr. Pratibha Dwarkanath at: Pratibha@sjri.res.in).

Funding: This enquiry was funded by the Division of Diet, St. John's Research Plant and the Division of Nutritional Sciences, Cornell University. J.L.F. was supported by the ILSI N America Future Leader Award. A.F. was supported by the National Institutes of Health nether accolade 5 T32 HD087137. The content is solely the responsibility of the authors and does non necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health and Human Evolution, or the National Institutes of Wellness. The funders had no role in study design, data drove and analysis, determination to publish, or preparation of the manuscript.

Competing interests: The authors take alleged that no competing interests exist.

Introduction

Vitamin B₁₂ deficiency (vitamin B₁₂ <148 pmol/L) is an important public health trouble worldwide [1–iii]. Although at that place is limited population-level data, vitamin B₁₂ deficiency affects individuals beyond the life cycle, with the highest prevalence in the elderly, meaning women, and young children [1, two, iv–12]. The burden of vitamin B₁₂ deficiency in Bharat is estimated to be amidst the highest in the world [ane, 13–23]. Inadequate vitamin B₁₂ status during pregnancy has been associated with increased hazard of adverse maternal and infant wellness outcomes [1–3, 24, 25], and linked to long-term impairments in child growth and development which may be irreversible [iii, 24, 26–30].

Previous cross-sectional research has noted associations between maternal and infant vitamin B₁₂ status at delivery in studies in Belgium, Canada, Norway, Germany, United Kingdom, Turkey, Serbia, and Brazil [3, 31–40]. Findings from prospective studies have reported significant associations of maternal vitamin B₁₂ status during pregnancy with baby vitamin B₁₂ status at nascency (i.e., in cord claret or serum) [41–46] and at six weeks of age [23], in studies in the Netherlands, Norway, Turkey, Spain, India, and the United States. In dissimilarity, findings regarding the associations of maternal vitamin B₁₂ condition with other child health outcomes or vitamin B₁₂ condition later in childhood have been heterogeneous. Inadequate maternal vitamin B₁₂ status during gestation has too been associated with risk of pregnancy complications, such as spontaneous abortion, preterm delivery, intrauterine growth brake, low nascence weight, and neural tube defects [iii, vii, 47–66]. However, most studies to date have been cross-sectional or case-control in blueprint, constrained by express sample sizes, and relied on a single biomarker of maternal total vitamin B₁₂ concentrations, evaluated at mid-gestation or commitment.

Few prospective studies have been conducted to appointment to examine the impact of maternal vitamin B₁₂ status during pregnancy on vitamin B₁₂ status early in life, or the role of vitamin B₁₂ in the development of agin birth or infant outcomes [iii]. There is limited prospective data, specially early in gestation, and from settings with the highest burden of vitamin B₁₂ deficiency and adverse pregnancy outcomes, such as India. Further inquiry is needed to determine the burden of vitamin B₁₂ deficiency in significant women and their infants in loftier-risk populations, and its implications for maternal and child wellness outcomes.

Nosotros conducted a prospective observational analysis to: 1) make up one's mind the prevalence of vitamin B₁₂ deficiency in meaning women and their infants; 2) examine the associations of maternal vitamin B₁₂ biomarkers with neonatal vitamin B₁₂ status; and 3) examine the associations of maternal vitamin B₁₂ biomarkers with perinatal outcomes, in women participating in a cohort study in Bangalore, Bharat.

Methods

Ethics statement

The inquiry protocol and report procedures were approved by the Institutional Ethical Board of St. John'southward Medical College (Reference number: IEC 42/2001). Written signed informed consent was obtained from all written report participants at enrollment.

Written report population

This report was a prospective observational cohort study of meaning women conducted at St John's Medical College Hospital (SJMCH) in Bangalore, India. St. John's Medical College is a 1350-bed teritary intendance hospital located in Bangalore, Republic of india. Established with a commitment to serve poor and vulnerable populations, its catchment includes a patient population from various social and economic backgrounds. The overall study design of the perinatal cohort and recruitment [67], inclusion criteria, and sampling for the biomarker sub-study [68] have been previously published. Pregnant women were eligible for this study if they were at least 17 years of age, <14 weeks of gestation at enrollment, healthy, and carrying a unmarried fetus. Women who had multiple fetuses (e.g., twins, triplets), reported clinical diagnoses of a chronic condition (e.g., diabetes mellitus, hypertension, cardiovascular disease, thyroid illness), tested positive for HIV, hepatitis B, or syphilis infections, were taking medications, or planned to move outside of Bangalore prior to delivery were excluded from the study. Pregnant women recruited to the perinatal cohort study from 2008 to 2014 who had a venous blood sample collected at enrollment, delivered a live babe at SJCMH, and had cord blood collected at the time of delivery were eligible for this assay (n = 419). A flow chart of report participants is presented in Fig ane.

All women received routine antenatal supplements in accord with the National guidelines of Republic of india. As per standard of care, all women received folic acid at recruitment until the finish of the outset trimester, followed by iron-folic acid and calcium supplementation from the 2nd trimester through commitment. Participants did not have vitamin B₁₂ supplements or multivitamins containing vitamin B₁₂, and no additional supplements or counseling were provided. All study procedures were reviewed and approved by the institutional upstanding review lath at SJCMH, and all participants provided written and signed consent at enrollment.

Information collection

Validated structured questionnaires were administered by trained enquiry staff to collect sociodemographic, clinical, and dietary data, and standardized forms were used to tape anthropometric and biochemical data prospectively starting time at enrollment. Gestational age in weeks was calculated from the day of concluding menstrual period and confirmed through ultrasonographic measurements (GE Volusun 730 Expert, probe 4C-A, Via Del Rio, Yorba Linda, CA, USA) within ii weeks of enrollment; ultrasonographic measurements were collected again before delivery.

At each antenatal visit, maternal weight was recorded to the nearest 100 grams using a digital remainder (Soehnie, Reutilngen, Germany); maternal pinnacle was recorded to the nearest 0.1 centimeter using a stadiometer; mid-upper arm circumference (MUAC; cm) was recorded using a plastic tape; and skinfolds thickness (biceps, triceps, subscapular; mm) were recorded to the nearest 0.two millimeters using Holtain skinfold calipers (Holtain Limited, Crosswell, Wales, UK). Maternal body mass index (BMI) was calculated every bit weight in kilograms divided past height in meters squared (kg/m²). Babe nativity weight was measured on an electronic weighing calibration (Salter Housewares 914 Electronic Baby and Toddler Scale, NY, USA) immediately after birth to the nearest 10 grams. Infant length (cm), circumferences (MUAC, head, chest; cm), and skinfolds (biceps, triceps, subscapular; mm) were measured inside 72 hours of birth.

Laboratory analyses

The laboratory procedures and analyses have been previously described [67, 68]. Briefly, maternal venous whole blood and cord blood samples were collected at enrollment and delivery, respectively, in ethylenediaminetetraacetic acid (EDTA)-coated anticoagulant tubes and plain vacutainers (Becton Dickenson, NJ, U.s.). Maternal venous whole blood and cord blood samples were candy and analyzed in batch, using identical protocols, and instrument specific calibrators were used for all biochemical estimations. Whole blood was treated with 1% ascorbic acid, and hemolysate was stored <–80°C. Plasma, serum, and red blood cells were separated, processed, and stored <–eighty°C until batch assay. A full of 399 participants had blood samples at enrollment available for laboratory analyses.

Hemoglobin and complete blood count (CBC) were analyzed using an automated cyanmethemoglobin technique analyzer (ABX Pentra sixty C+, Horiba ABX Diagnostics, Montpellier, France). The measuring range was betwixt 8 and 18 thousand/dL with a within run precision of <ane.0%. Plasma vitamin B₁₂ concentrations were measured via electrochemiluminescence (Elecsys 2010, Roche Diagnostics Mannheim, United states). Quality-command samples pertaining to low, middle, and high ranges of vitamin B₁₂ were analyzed along with the samples. Intra- and inter-assay CVs were 0.5% and 2.iv%, respectively. Plasma methylmalonic acid (MMA) and total homocysteine (tHcy) concentrations were assessed by gas chromatography-mass spectrometry (GCMS-SQ, 5975, Agilent Technologies, CA, USA) [69].

Definitions of exposures and outcomes

Chief analyses were based on continuous vitamin B₁₂ biomarkers (i.eastward., full vitamin B₁₂, MMA) in pregnant women and neonates (i.east., string blood). We too used conventional cut-offs from adult (non-meaning) populations to describe categorical vitamin B₁₂ variables. Vitamin B₁₂ deficiency and insufficiency were defined as total vitamin B₁₂ concentrations <148 and <221 pmol/L, respectively [7, 70]. Elevated methylmalonic acid concentrations were defined equally MMA >0.26 and >0.37 μmol/50, to reverberate depleted and scarce vitamin B₁₂ status, respectively [seven]. Impaired vitamin B₁₂ status was defined as total vitamin B₁₂ concentrations <148 pmol/L and MMA >0.26 μmol/Fifty. Combined vitamin B₁₂ (cB₁₂), a composite indicator of vitamin B₁₂ condition, modified for iii biomarkers (i.e., vitamin B₁₂, MMA, tHcy), was calculated and defined using the methods adult by Fedosov et al. [71]. Elevated homocysteine concentrations were divers as tHcy >15.0 and >10.0 μmol/50 [7]. Maternal anemia was divers as hemoglobin <11.0 g/dL [72].

Preterm delivery was defined as <37 weeks of completed gestation. Depression nativity weight was defined as birth weight <2,500 grams [73]. Small for gestational age (SGA) was defined equally birth weight <ten^th percentile for gestational age and sex, using the INTERGROWTH reference [73]. Babe ponderal index was defined every bit weight in grams divided past length in centimeters cubed (g/cm³). Earth Health Organisation (WHO) standards were used to summate length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) z-scores. Stunting was defined every bit LAZ <–2, underweight every bit WAZ <–ii, and wasting equally WLZ <–ii [74–76]. Neonatal anemia was defined as hemoglobin <11.0 g/dL [72].

Birth outcomes (east.k., birth weight, low birth weight, gestational age at delivery, preterm delivery); neonatal vitamin B₁₂ condition (eastward.g., vitamin B₁₂ concentrations, MMA concentrations, impaired vitamin B₁₂ status) [77–79]; and neonatal anthropometric outcomes (due east.g., ponderal index, LAZ, WAZ, WLZ, MUAC) were evaluated.

Statistical analyses

Variables were defined using conventional cutoffs wherever bachelor; medians were used to describe variables based on distributions in this population. Not-commonly distributed variables were natural-logarithmically transformed to ensure normality before analysis. Non-transformed data are presented in Tables 1 and ii for interpretation purposes.

Primary analyses were based on continuous vitamin B₁₂ biomarkers (i.e., total vitamin B₁₂, MMA) in significant women and neonates (i.e., string blood). Nosotros also used conventional cut-offs from adult (non-pregnant) populations to ascertain categorical vitamin B₁₂ variables. Linear and binomial regression models were used to evaluate the associations of maternal vitamin B₁₂ biomarkers at enrollment with neonatal vitamin B₁₂ condition and perinatal outcomes, for continuous and categorical outcomes, respectively. Binomial regression models were used to obtain risk ratio estimates for dichotomous variables, and Poisson regression models were used when binomial regression models did non converge [77, 79]. All models were adjusted for gestational age at sample collection, in guild to business relationship for timing of sample drove. In gild to suit for multiple hypothesis testing, significance was evaluated after applying the Bonferroni correction. All p-values presented are the original (unadjusted) p-values for interpretation purposes, and the threshold used to decide statistical significance was α/n, where α is the level of significance (α = 0.05) and n is the number of comparison tests conducted. If the results remained significant afterwards applying the Bonferroni correction, this is reported in the text.

The Rothman and Greenland approach was used to evaluate and adjust for misreckoning, in which all known or suspected take chances factors for the upshot which led to a >10% change-in-estimate were included in the model [59]. Final linear models were assessed for normality, using the Kolmogorov-Smirnoff exam; collinearity, using variance inflation factors; and homoscedasticity, using plots of residuals versus predicted values. Terminal binomial models were examined for goodness of fit, using Hosmer-Lemeshow tests. Statistical analyses were conducted using SAS software, version 9.4 (SAS Institute, Inc., Cary, NC, U.s.a.).

Results

Participant characteristics

A flowchart of participants in this study is presented in Fig ane. The pattern of the perinatal cohort study [67] and inclusion criteria and sampling for the biomarker sub-study [68] have been previously published. Briefly, a total of i,625 meaning women were initially contacted regarding the perinatal accomplice study, of which i,272 provided informed consent. There were a full of 1,059 live births (n = 103 lost to follow-upward; due north = 110 fetal loss), of which 745 participants delivered at the study site, SJCMH. A total of 419 participants were selected for the biomarker sub-report [68]; of these, vitamin B₁₂ status was analyzed in 399 maternal enrollment samples (n = 20 bereft sample/sample book). Nativity outcome information was available for 399 neonates, and 374 string claret samples were available for vitamin B₁₂ analyses.

The characteristics of participants in this study are presented in Table 1. Women selected for the biomarker sub-study (due north = 419) were like compared to women in the overall accomplice (n = 1,272 consented) with respect to baseline characteristics, including historic period, gestational age at enrollment, socioeconomic status (eastward.g., education), parity, and nutritional indicators (e.thousand., weight, hemoglobin). At enrollment, women had a median historic period of 24.0 (IQR: 21.0, 26.0) years, and median gestational historic period of 12.0 (IQR: ix.6, 13.3) weeks; 55.4% were nulliparous and 35.eight% had received a university degree. A total of 82.2% were non-vegetarian (i.eastward., consumed poultry, meat, and/or fish), 17.viii% of women were vegetarian (i.eastward., consumed milk and/or eggs), and 0% were vegan (i.e., no beast source foods); 70.4% of women reported taking prenatal supplements at enrollment. Participants did not take vitamin B₁₂ supplements or multivitamins containing vitamin B₁₂. At delivery, 13.five% of neonates were low birthweight (<2,500 g), 6.0% were preterm (<37 weeks' gestation), and 21.6% were modest for gestational age (Table 1).

Maternal vitamin B₁₂ status

Vitamin B₁₂ status in pregnant women at enrollment is presented in Table 2. At enrollment (median [IQR]: 12.0 [9.6, 13.three] weeks), 63.two% of women had vitamin B₁₂ deficiency (vitamin B₁₂ <148 pmol/L), 87.2% had vitamin B₁₂ insufficiency (vitamin B₁₂ <221 pmol/Fifty), 71.3% had elevated methylmalonic acid (MMA >0.26 μmol/50) levels (MMA >0.37 μmol/L: 51.half dozen%), and 47.3% had impaired vitamin B₁₂ status (vitamin B₁₂ <148 pmol/L and MMA >0.26 μmol/Fifty). Associations between maternal biomarkers of vitamin B₁₂ status (i.e., MMA, tHcy) and maternal vitamin B ₁₂ deficiency are presented in S1 Table. Maternal MMA levels (RR: 1.12; 95% CI: [0.43, 0.65]; p = 0.04) and elevated MMA (>0.26 μmol/L; RR: 1.26 [1.03, one.53]; p = 0.02) were associated with maternal vitamin B₁₂ deficiency.

Neonatal vitamin B₁₂ status

Vitamin B₁₂ status in neonates at nascence is presented in Table 2. A full of 40.viii% of neonates had vitamin B₁₂ deficiency (vitamin B₁₂ <148 pmol/L), 65.six% had vitamin B₁₂ insufficiency (vitamin B₁₂ <221 pmol/L), 95.7% had elevated MMA (MMA >0.26 μmol/50) concentrations (MMA >0.37 μmol/L: 87.4%), and 38.1% had dumb vitamin B₁₂ status (vitamin B₁₂ <148 pmol/L and MMA >0.26 μmol/50) at nativity. Associations between neonatal biomarkers of vitamin B₁₂ condition (i.e., MMA, tHcy) and neonatal vitamin B₁₂ deficiency are presented in S1 Table. Neonatal MMA levels (RR: 1.59 [i.25, ii.02]; p = 0.0001 and tHcy concentrations (RR: 1.37 [1.06, i.76]; p = 0.01) were associated with neonatal vitamin B₁₂ deficiency.

Maternal vitamin B₁₂ status at enrollment and neonatal vitamin B₁₂ condition at nativity

Vitamin B₁₂ status in pregnant women at enrollment and in neonates at birth is shown in Table two. Neonatal vitamin B₁₂ concentrations were significantly higher compared to maternal vitamin B₁₂ concentrations (172.4 [109.7, 265.ane] vs. 127.0 [IQR: 89.6, 172.3]; p<0.0001). However, neonatal MMA (0.63 [IQR: 0.47, 0.86] vs. 0.38 [IQR: 0.24, 0.59]; p<0.0001) and homocysteine (17.vi [IQR: 13.5, 24.viii] vs. 15.7 [IQR: 12.4, 20.7]; p<0.0001) levels were significantly higher in neonates. The prevalence of neonatal vitamin B₁₂ deficiency (xl.8% vs. 63.two%; p<0.0001), vitamin B₁₂ insufficiency (65.6% vs. 87.ii%; p<0.0001), and dumb vitamin B₁₂ status (vitamin B₁₂ <148 pmol/L and MMA >0.26 μmol/L; (38.i% vs. 47.3%; p = 0.01) were lower at delivery compared to significant women at enrollment.

The associations of maternal vitamin B₁₂ biomarkers at enrollment with neonatal vitamin B₁₂ concentrations at delivery are presented in Table 3. College maternal vitamin B₁₂ concentrations were associated with increased neonatal vitamin B₁₂ concentrations at delivery (β [SE]: 0.40 [0.05]; p<0.0001), in multivariate models adjusting for gestational historic period at enrollment, maternal historic period, parity, educational level, and BMI at enrollment. Maternal vitamin B₁₂ deficiency (vitamin B₁₂ <148 pmol/Fifty; β [SE]: -0.xxx [0.07]; p<0.0001) and vitamin B₁₂ insufficiency (vitamin B₁₂ <221 pmol/L; β [SE]: -0.54 [0.ten]; p<0.0001) also predicted significantly lower neonatal vitamin B₁₂ concentrations at delivery. Impaired maternal vitamin B₁₂ status (vitamin B₁₂ <148 pmol/L and MMA >0.26 μmol/L) at enrollment was associated with significantly lower neonatal vitamin B₁₂ concentrations at delivery (β [SE]: –0.21 [0.07]; p<0.002) in multivariate analyses. Higher maternal cB₁₂ was associated with increased neonatal vitamin B₁₂ concentrations (β [SE]: 0.twenty [0.05]; p<0.0001). Findings from these analyses remained statistically significant later correcting for multiple hypothesis testing (p<0.006). All the same, individually, maternal MMA, or homocysteine were not significantly associated with neonatal vitamin B₁₂ concentrations at delivery.

Maternal vitamin B₁₂ biomarkers at enrollment and their associations with chance of neonatal vitamin B₁₂ deficiency (vitamin B₁₂ <148 pmol/L) are presented in Table four. Higher maternal vitamin B₁₂ concentrations predicted lower risk of neonatal vitamin B₁₂ deficiency at birth (RR: 0.53 95% CI: [0.43, 0.65]; p<0.0001), in multivariate models adjusting for gestational age at enrollment, maternal age, parity, educational level, and BMI at enrollment. Impaired maternal vitamin B₁₂ condition (RR: 1.49 95% CI: [1.13, 1.97]; p = 0.005) and maternal vitamin B₁₂ deficiency (RR: ane.97 95% CI: [1.43, ii.71]; p<0.0001) predicted a 1.49 to 1.97-fold higher take chances of neonatal vitamin B₁₂ deficiency at birth. Findings from these analyses remained statistically meaning after correcting for multiple hypothesis testing (p<0.006). All the same, maternal MMA or homocysteine concentrations were not significantly associated with take a chance of neonatal vitamin B₁₂ deficiency.

The associations of maternal vitamin B₁₂ biomarkers at enrollment with neonatal methylmalonic acid concentrations at delivery are shown in Tabular array 5. Maternal vitamin B₁₂ deficiency (β [SE]: 0.16 [0.05]; p = 0.002) at enrollment was associated with increased neonatal MMA concentrations at nascency, in multivariate models adjusting for gestational age at enrollment, maternal historic period, parity, educational level, and BMI at enrollment. However, maternal vitamin B₁₂ concentrations or impaired vitamin B₁₂ status were not significantly associated with neonatal MMA concentrations at nascency, after correcting for multiple hypothesis testing (p<0.006).

The associations of maternal vitamin B₁₂ biomarkers at enrollment with impaired neonatal vitamin B₁₂ status at birth are presented in Table vi. Higher maternal vitamin B₁₂ concentrations were associated with lower adventure of impaired neonatal vitamin B₁₂ status (RR: 0.52 95% CI: [0.42, 0.65]; p<0.0001), in multivariate analyses adjusting for gestational age at enrollment, maternal age, parity, educational level, and BMI at enrollment. Similarly, maternal vitamin B₁₂ deficiency (RR: ii.08 95% CI: [1.46, 2.97]; p<0.0001) and impaired maternal vitamin B₁₂ condition (RR: 1.54 95% CI: [one.fifteen, 2.06]; p = 0.004) predicted increased risk of impaired neonatal vitamin B₁₂ condition. College maternal cB₁₂ (RR: 0.73 95% CI: [0.60, 0.xc]; p = 0.004) was associated with lower take a chance of impaired neonatal vitamin B₁₂ condition at nascence. Findings from these analyses remained statistically significant after correcting for multiple hypothesis testing (p<0.006).

Maternal vitamin B₁₂ status at baseline and its associations with neonatal homocysteine levels at birth are summarized in Table 7. Maternal vitamin B₁₂ insufficiency (vitamin B₁₂ <221 pmol/L) at enrollment was associated with higher neonatal homocysteine concentrations (β [SE]: 0.22 [0.07]; p = 0.003) at birth, in multivariate analyses adjusting for gestational age at enrollment, parity, maternal age, BMI, and educational level at enrollment.

Maternal vitamin B₁₂ status at enrollment and perinatal outcomes

The associations between maternal vitamin B₁₂ biomarkers at enrollment with perinatal outcomes are presented in supplemental tables (S2–S4 Tables). After adjusting for gestational age at enrollment, parity, maternal age, BMI, and educational level at enrollment, maternal vitamin B₁₂ concentrations were not significantly associated with perinatal outcomes (S2 Table). Similarly, maternal MMA concentrations at enrollment were non associated with perinatal outcomes in multivariate analyses (S3 Tabular array). Afterward adjusting for gestational age at enrollment, parity, maternal age, BMI, and highest level of education attained, impaired maternal vitamin B₁₂ status (vitamin B₁₂ <148 pmol/L and MMA >0.26 μmol/L) at enrollment was not associated with any perinatal outcomes (S4 Table). Other maternal vitamin B₁₂ biomarkers were not significantly associated with perinatal outcomes, after correcting for multiple hypothesis testing (p<0.002).

Give-and-take

In this prospective assay amongst pregnant women participating in a cohort study, maternal vitamin B₁₂ deficiency was common early in pregnancy and predicted neonatal vitamin B₁₂ status at birth. Maternal vitamin B₁₂ status at enrollment–including vitamin B₁₂ deficiency (<148 pmol/L), insufficiency (<221 pmol/L), and impaired vitamin B₁₂ status (vitamin B₁₂ <148 pmol/L and MMA >0.26 μmol/50)—predicted chance of neonatal vitamin B₁₂ deficiency. Higher maternal vitamin B₁₂ concentrations at enrollment were associated with increased neonatal vitamin B₁₂ concentrations. Maternal vitamin B₁₂ status at enrollment was non associated with risk of other perinatal outcomes.

This is amidst the largest prospective studies conducted to engagement to examine the burden of vitamin B₁₂ deficiency in pregnancy and its associations with neonatal vitamin B₁₂ status. Vitamin B₁₂ deficiency was common early in pregnancy: 63.2% of women had vitamin B₁₂ concentrations <148 pmol/50, 87.2% had vitamin B₁₂ levels <221 pmol/L, and 47.3% had impaired vitamin B₁₂ status (i.e., vitamin B₁₂ <148 pmol/50 and MMA >0.26 μmol/50) at enrollment. Findings are consistent with previous studies conducted amid pregnant women in India (vitamin B₁₂ <148 pmol/L or <162 pmol/Fifty: 51–73%; ≤18 weeks' gestation) [twenty, 23, 82, 83], and higher than studies in Bangladesh (vitamin B₁₂ <150 pmol/L: 35.4%; <thirteen weeks' gestation), Spain (vitamin B₁₂ <150 pmol/Fifty: 0%; ≤221 pmol/L: 6.3%; <12 weeks' gestation), and Canada (vitamin B₁₂ <148 pmol/L: 17%; 12–16 weeks' gestation) [12, 39, 43, 84, 85].

The prevalence of vitamin B₁₂ deficiency and insufficiency was also loftier in neonates at nascence in this study. A total of 41% of neonates had vitamin B₁₂ deficiency, 66% had vitamin B₁₂ insufficiency, and 38% had impaired vitamin B₁₂ condition at nascence. Findings are consistent with previous studies conducted amidst young infants in India (vitamin B₁₂ <150 pmol/L: 44%, 6 weeks; <150 pmol/50: 62%, 1–3 months of historic period) [23, 86] and higher than in studies conducted in the UK (vitamin B₁₂ <140.9 pmol/L: 29%; cord blood at delivery) and the United states of america (<148 pmol/L: 0%; string blood at delivery) [45]. In the current written report, neonatal vitamin B₁₂ concentrations were 1.3-fold college than maternal vitamin B₁₂ concentrations early in pregnancy. Findings are consistent with previous studies that reported higher vitamin B₁₂ concentrations in infants compared to mothers, ranging from thirteen to 43% at mid-gestation [23, 42, 44, 46, 87, 88] or delivery [31–40, 43, 45, 89] to two-fold higher than maternal vitamin B₁₂ concentrations at delivery [35, 36, 43, 45].

In the current report, maternal vitamin B₁₂ status early in pregnancy–including vitamin B₁₂ concentrations, vitamin B₁₂ deficiency and insufficiency, and impaired vitamin B₁₂ condition–predicted neonatal vitamin B₁₂ condition at birth. For instance, neonates built-in to women who had vitamin B₁₂ deficiency at enrollment had a ii-fold greater risk of vitamin B₁₂ deficiency at birth. Findings are consistent with studies of the associations of maternal vitamin B₁₂ concentrations during gestation [23, 42, 44, 87, 88] and at delivery [31–38, 40, 43, 45, 89] with neonatal vitamin B₁₂ levels at birth and in the first vi weeks of life.

Maternal vitamin B₁₂ deficiency at enrollment likewise predicted neonatal MMA concentrations and elevated neonatal MMA concentrations at nativity. Few studies to date have evaluated MMA concentrations or other functional biomarkers of vitamin B₁₂ status in immature infants, and findings have been divergent. For example, in a study in Ireland, maternal vitamin B₁₂ levels at 8 weeks of gestation were associated with maternal MMA concentrations during labor, but not with MMA levels in cord blood [43]. However, this study was constrained past express range of maternal vitamin B₁₂ status (i.e., no participants had vitamin B₁₂ deficiency or elevated MMA concentrations during pregnancy; and ~26% reported taking cobalamin containing supplements during pregnancy) and smaller sample size (north = 92). In a study in Norway among 169 mother-babe pairs postpartum, maternal vitamin B₁₂ levels were significantly correlated with baby MMA levels (r = -0.38, p<0.001) [90]; however, this report did non study MMA levels during pregnancy to which our findings can be straight compared.

In the electric current study, maternal vitamin B₁₂ status during pregnancy was not significantly associated with risk of agin perinatal outcomes. Findings are in contrast to previous inquiry which identified vitamin B₁₂ as a risk factor for adverse nascency outcomes [3]: inadequate maternal vitamin B₁₂ status in pregnancy has been associated with increased risk of spontaneous abortion or early miscarriage [54, 55, 91, 92], low birth weight (LBW, <2,500 g) [57, 83, 93, 94], intrauterine growth restriction (IUGR) [93], modest for gestational historic period (SGA) [94], and neural tube defects [48–52, 59, 63, 95–97]. Yet, almost of these studies have been case-control (or cantankerous-sectional) in design. In previous prospective analyses in this perinatal cohort, lower maternal vitamin B₁₂ concentrations in pregnancy were associated with increased risk of IUGR [57], and lower tertiles of maternal vitamin B₁₂ levels throughout pregnancy were associated with increased risk of SGA [67], although vitamin B₁₂ deficiency (<148 pmol/L) was not significantly associated with hazard of SGA [58]. Still, these analyses used the previous definition of SGA and IUGR as <10^th percentile of birth weight for gestational age, which constrains comparability of findings. In contrast, other studies take reported that inadequate maternal vitamin B₁₂ status during pregnancy was not associated with risk of adverse birth outcomes, such as gestational age at birth [98–100], nativity weight [12, 28, threescore, 82, 87, 98–111], LBW (<2,500 g) [12, 67], or SGA [60, 98, 105, 106, 109, 111]. In a systematic review and meta-analysis of vitamin B₁₂ in pregnancy and preterm nascence and depression nativity weight, maternal vitamin B₁₂ levels during pregnancy were not significantly associated with birth weight [58]. In overall meta-analyses, vitamin B₁₂ levels were associated with lower run a risk of preterm nativity (ARR 0.89 (95% CI 0.82, 0.97); and low vitamin B₁₂ status (<148 pmol/L) was associated with increased chance of low nascence weight (<2,500; ARR: 1.15, 95% CI: 1.01, 1.31), although these findings were not meaning in the individual studies [58]. Randomized trials are needed to determine the efficacy of vitamin B₁₂ supplementation on nascence outcomes, including preterm birth, depression birth weight, and small-for-gestational historic period.

In this report, maternal vitamin B₁₂ condition was not associated with other neonatal outcomes, including WHO z-scores, ponderal index, mid-upper arm circumference, or head circumference. Although few studies have evaluated the association of vitamin B₁₂ status during pregnancy and babe anthropometric outcomes, well-nigh studies to date accept focused on neonatal head circumference, and findings have been heterogenous [61, 88, 99, 102]. Findings regarding the clan of maternal vitamin B₁₂ status with other infant wellness outcomes have been divergent.

This study is among the largest prospective studies to date to examine the brunt of vitamin B₁₂ deficiency in pregnancy and its associations with neonatal vitamin B₁₂ status and perinatal outcomes. Maternal vitamin B₁₂ biomarkers were evaluated early on in pregnancy (~12 weeks' gestation), and vitamin B₁₂ status was evaluated with both circulating (i.due east., vitamin B₁₂) and functional (i.eastward., MMA, tHcy) biomarkers. We also considered additional indicators of vitamin B₁₂ condition, including cB12 and impaired vitamin B₁₂ status, which combine circulating and functional biomarkers.

This study has several limitations. Maternal and neonatal vitamin B₁₂ status were assessed at a single time point at enrollment and birth, respectively. The cess of maternal vitamin B₁₂ status ~12 weeks of gestation may not reverberate vitamin B₁₂ status periconceptionally or throughout pregnancy. Assessment of neonatal vitamin B₁₂ status using cord blood at nativity is an important report limitation–and limits interpretations of the associations between maternal vitamin B₁₂ and infant status early in life. Participants in this biomarker sub-study were like to the overall perinatal cohort (n = 1,272), in terms of sociodemographic status (due east.g., age, educational level), gestational historic period at enrollment, parity, nutritional variables (e.grand., weight, BMI, hemoglobin), and birth outcomes (due east.g., live birth, preterm delivery, birth weight, LBW, SGA); however, they may differ on other unmeasured variables. In terms of vitamin B₁₂ biomarkers, in improver to total vitamin B₁₂, MMA, and tHcy, inclusion of holo-transcobalamin may be an important circulating biomarker of vitamin B₁₂ status during gestation, although it has not been validated in pregnancy [112]. The role of vitamin B₁₂ needs to be examined in the context of folate-mediated 1-carbon metabolism. Vitamin B₁₂ deficiency may co-occur with other micronutrient deficiencies (e.g., folate) that may influence vitamin B₁₂ status and are contained risk factors for adverse perinatal outcomes. An of import limitation of this study is the employ of vitamin B₁₂ biomarker cut-offs from adult non-meaning populations–these vitamin B₁₂ biomarker cut-offs have non been validated in pregnancy or in infancy. Further research is needed to develop and validate vitamin B₁₂ biomarker cut-offs in significant women and immature infants. Although findings provide evidence of an clan of maternal and neonatal vitamin B₁₂ status, the interpretations of these associations are not causal. Chiefly, our study was not powered to detect differences in birth outcomes, including low nascency weight and minor for gestational age. Randomized trials are needed to examine the furnishings of vitamin B₁₂ (periconceptionally and throughout pregnancy) on the development of maternal and baby health outcomes.

In summary, in this cohort of pregnant women, the prevalence of vitamin B₁₂ deficiency was high early on in pregnancy and predicted risk of baby vitamin B₁₂ deficiency. This is one of the largest studies to date to evaluate the burden of vitamin B₁₂ deficiency in meaning women and their neonates. Findings propose that vitamin B₁₂ deficiency is an important public health problem in this population, and vitamin B₁₂ status early in pregnancy has an important role in determining vitamin B₁₂ status early on in life. Hereafter research, including randomized trials, is needed to decide the independent effects of vitamin B₁₂ on the development of perinatal outcomes, to inform screening and interventions to ameliorate maternal and child wellness.

Supporting information

Acknowledgments

We are grateful to Nancy Nanditha M., Roopashree C., Aruna B.South. and Arogya Mary for their assistance in information drove and Sarita Devi in laboratory analyses. We thank the mothers and children, and field teams, including physicians, nurses, midwives, and inquiry, laboratory and administrative staff who made this study possible; and St. John'south Medical Higher, Bangalore, India, for its institutional support.

References

1. i. Allen LH. How common is vitamin B-12 deficiency? Am J Clin Nutr. 2009;89(2):693S–6S. Epub 2009/01/01. pmid:19116323.
   • View Commodity
   • PubMed/NCBI
   • Google Scholar
2. 2. McLean Due east, Benoist B, Allen L. Review of the magnitude of folate and vitamin B12 deficiencies worldwide. Nutrient and Nutrition Bulletin. 2008;29(two):S38–S51. pmid:18709880
   • View Commodity
   • PubMed/NCBI
   • Google Scholar
3. 3. Finkelstein JL, Layden AJ, Stover PJ. Vitamin B-12 and Perinatal Wellness. Adv Nutr. 2015;half dozen(5):552–63. Epub 2015/09/17. pmid:26374177; PubMed Primal PMCID: PMC4561829.
   • View Article
   • PubMed/NCBI
   • Google Scholar
4. 4. Allen LH, Miller JW, de Groot L, Rosenberg IH, Smith AD, Refsum H, et al. Biomarkers of Nutrition for Evolution (Bond): Vitamin B-12 Review. J Nutr. 2018;148(suppl_4):1995S–2027S. Epub 2018/12/01. pmid:30500928; PubMed Fundamental PMCID: PMC6297555.
   • View Article
   • PubMed/NCBI
   • Google Scholar
5. 5. Allen L, Rosenberg IH, Oakley GP, Omenn GS. Considering the instance for vitamin B12 fortification of flour. Nutrient and Nutrition Message. 2010;31:S36–S46. pmid:20629351
   • View Article
   • PubMed/NCBI
   • Google Scholar
6. 6. Stabler SP, Allen RH. Vitamin B12 deficiency as a worldwide problem. Annu Rev Nutr. 2004;24:299–326. Epub 2004/06/xi. pmid:15189123.
   • View Article
   • PubMed/NCBI
   • Google Scholar
7. 7. Green R, Allen LH, Bjorke-Monsen AL, Brito A, Gueant JL, Miller JW, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3:17040. Epub 2017/07/01. pmid:28660890.
   • View Article
   • PubMed/NCBI
   • Google Scholar
8. 8. Ramirez-Velez R, Correa-Bautista JE, Martinez-Torres J, Meneses-Echavez JF, Lobelo F. Vitamin B12 concentrations in pregnant Colombian women: analysis of nationwide information 2010. BMC Pregnancy Childbirth. 2016;16:26. Epub 2016/02/03. pmid:26832149; PubMed Key PMCID: PMC4736095.
   • View Commodity
   • PubMed/NCBI
   • Google Scholar
9. 9. Baik HW, Russel RM. Vitamin B12 Deficiency in the Elderly. Almanac Review of Nutrition. 1999;xix:357–77. pmid:10448529
   • View Article
   • PubMed/NCBI
   • Google Scholar
10. 10. Stover PJ. Vitamin B12 and older adults. Curr Opin Clin Nutr Metab Care. 2010;13(1):24–7. Epub 2009/11/12. pmid:19904199; PubMed Primal PMCID: PMC5130103.
    • View Article
    • PubMed/NCBI
    • Google Scholar
11. xi. Sukumar Due north, Saravanan P. Investigating vitamin B12 deficiency. BMJ. 2019;365:l1865. Epub 2019/05/12. pmid:31076395.
    • View Article
    • PubMed/NCBI
    • Google Scholar
12. 12. Sukumar N, Rafnsson SB, Kandala NB, Bhopal R, Yajnik CS, Saravanan P. Prevalence of vitamin B-12 insufficiency during pregnancy and its consequence on offspring nativity weight: a systematic review and meta-analysis. Am J Clin Nutr. 2016;103(5):1232–51. Epub 2016/04/xv. pmid:27076577.
    • View Article
    • PubMed/NCBI
    • Google Scholar
13. thirteen. Refsum H, Yajnik C, Milind G, Schneede J, Vollset SE, Orning L, et al. Hyperhomocysteinemia and elevated methylmalonic acid indicate a high prevalence of cobalamin deficiency in Asian Indians. American Journal of Clinical Nutrition. 2001;74:233–41. pmid:11470726
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
14. fourteen. Bhardwaj A, Kumar D, Raina SK, Bansal P, Bhushan Southward, Chander V. Rapid Assessment for Coexistence of Vitamin B12 and Fe Deficiency Anemia among Adolescent Males and Females in Northern Himalayan Country of India. Anemia. 2013;2013:959605. Epub 2013/08/24. pmid:23970962; PubMed Central PMCID: PMC3736489.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
15. 15. Taneja S, Bhandari North, Strand TA, Sommerfelt H, Refsum H, Ueland PM, et al. Cobalamin and folate condition in infants and young children in a low-to-centre income customs in Bharat. Am J Clin Nutr. 2007;86:1302–ix. pmid:17991639
    • View Article
    • PubMed/NCBI
    • Google Scholar
16. 16. Naik South, Mahalle N, Bhide 5. Identification of vitamin B12 deficiency in vegetarian Indians. Br J Nutr. 2018;119(six):629–35. Epub 2018/02/16. pmid:29446340.
    • View Article
    • PubMed/NCBI
    • Google Scholar
17. 17. Chakraborty S, Chopra Thousand, Mani K, Giri AK, Banerjee P, Sahni NS, et al. Prevalence of vitamin B12 deficiency in healthy Indian school-going adolescents from rural and urban localities and its relationship with various anthropometric indices: a cross-sectional study. J Hum Nutr Diet. 2018;31(4):513–22. Epub 2018/02/23. pmid:29468754.
    • View Article
    • PubMed/NCBI
    • Google Scholar
18. xviii. Singla R, Garg A, Surana 5, Aggarwal S, Gupta G, Singla S. Vitamin B12 Deficiency is Owned in Indian Population: A Perspective from Due north India. Indian J Endocrinol Metab. 2019;23(2):211–four. Epub 2019/06/05. pmid:31161105; PubMed Central PMCID: PMC6540890.
    • View Article
    • PubMed/NCBI
    • Google Scholar
19. xix. Duggan C, Srinivasan One thousand, Thomas T, Samuel T, Rajendran R, Muthayya S, et al. Vitamin B-12 supplementation during pregnancy and early lactation increases maternal, breast milk, and infant measures of vitamin B-12 status. J Nutr. 2014;144(5):758–64. Epub 2014/03/07. pmid:24598885; PubMed Central PMCID: PMC3985831.
    • View Article
    • PubMed/NCBI
    • Google Scholar
20. 20. Katre P, Bhat D, Lubree H, Otiv S, Joshi S, Joglekar C, et al. Vitamin B 12 and folic acid supplementation and plasma total homocysteine concentrations in pregnant Indian women with low B12 and high folate condition. Asia Pac J Clinical Diet. 2010;19(3):335–43.
    • View Commodity
    • Google Scholar
21. 21. Pathak P, Kapil U, Yajnik C, Kapoor S, Dwivedi S, Singh R. Iron, folate, and vitamin B12 stores amidst pregnant women in a rural expanse of Haryana State, Bharat. Food and Nutrition Bulletin. 2007;28(4):435–eight. pmid:18274171
    • View Article
    • PubMed/NCBI
    • Google Scholar
22. 22. Samuel TM, Duggan C, Thomas T, Bosch R, Rajendran R, Virtanen SM, et al. Vitamin B(12) intake and condition in early pregnancy among urban South Indian women. Ann Nutr Metab. 2013;62(ii):113–22. Epub 2013/01/25. pmid:23344013; PubMed Fundamental PMCID: PMC4742783.
    • View Article
    • PubMed/NCBI
    • Google Scholar
23. 23. Finkelstein JL, Kurpad AV, Thomas T, Srinivasan K, Duggan C. Vitamin B12 status in pregnant women and their infants in S India. Eur J Clin Nutr. 2017. pmid:28402324.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
24. 24. Black M. Effects of vitamin B12 and folate deficiency on brain development in children. Food and Diet Bulletin. 2008;29. pmid:18709887
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
25. 25. Molloy AM, Kirke PN, Brody LC, Scott JM, Mills JL. Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, baby, and kid development. Food Nutr Balderdash. 2008;29(2 Suppl):S101–eleven; discussion S12-5. Epub 2008/08/20. pmid:18709885.
    • View Article
    • PubMed/NCBI
    • Google Scholar
26. 26. Venkatramanan Due south, Armata IE, Strupp BJ, Finkelstein JL. Vitamin B-12 and Knowledge in Children. Advances in Nutrition. 2016;vii. pmid:27633104
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
27. 27. Pepper MR, Black MM. B12 in fetal development. Semin Cell Dev Biol. 2011;22(half-dozen):619–23. Epub 2011/06/15. pmid:21664980.
    • View Article
    • PubMed/NCBI
    • Google Scholar
28. 28. Bhate VK, Joshi SM, Ladkat RS, Deshmukh US, Lubree HG, Katre PA, et al. Vitamin B12 and folate during pregnancy and offspring motor, mental and social evolution at 2 years of historic period. J Dev Orig Health Dis. 2012;3(ii):123–xxx. Epub 2012/04/01. pmid:25101923.
    • View Article
    • PubMed/NCBI
    • Google Scholar
29. 29. Lai JS, Mohamad Ayob MN, Cai S, Quah PL, Gluckman PD, Shek LP, et al. Maternal plasma vitamin B12 concentrations during pregnancy and baby cerebral outcomes at 2 years of age. Br J Nutr. 2019;121(11):1303–12. Epub 2019/04/03. pmid:30935438; PubMed Central PMCID: PMC6660314.
    • View Article
    • PubMed/NCBI
    • Google Scholar
30. 30. Thomas S, Thomas T, Bosch RJ, Ramthal A, Bellinger DC, Kurpad AV, et al. Outcome of Maternal Vitamin B12 Supplementation on Cognitive Outcomes in South Indian Children: A Randomized Controlled Clinical Trial. Matern Child Health J. 2018. Epub 2018/07/fourteen. pmid:30003521.
    • View Article
    • PubMed/NCBI
    • Google Scholar
31. 31. Obeid R, Morkbak AL, Munz West, Nexo E, Herrmann W. The cobalamin-binding proteins transcobalamin and haptocorrin in maternal and string blood sera at nascence. Clin Chem. 2006;52(2):263–ix. Epub 2005/12/31. pmid:16384893.
    • View Article
    • PubMed/NCBI
    • Google Scholar
32. 32. Balci YI, Ergin A, Karabulut A, Polat A, Dogan M, Kucuktasci K. Serum vitamin B12 and folate concentrations and the effect of the Mediterranean diet on vulnerable populations. Pediatr Hematol Oncol. 2014;31(1):62–7. Epub 2013/x/04. pmid:24088029.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
33. 33. Radunovic North, Lockwood CJ, Stanojlovic O, Steric M, Kontic-Vucinic O, Sulovic N, et al. Fetal and maternal plasma homocysteine levels during the second half of uncomplicated pregnancy. J Matern Fetal Neonatal Med. 2014;28(xi):1244–9. Epub 2014/08/28. pmid:25162468.
    • View Article
    • PubMed/NCBI
    • Google Scholar
34. 34. Guerra-Shinohara EM, Paiva A, Rondo P, Yamasaki K, Terzi C, D'Almeida V. Relationship between total homocysteine and folate levels in pregnant women and their newborn babies according to maternal serum levels of vitamin B12. BJOG. 2002;109:784–91. pmid:12135215
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
35. 35. Koc A, Kocyigit A, Soran M, Demir Northward, Sevinc East, Erel O, et al. High frequency of maternal vitamin B12 deficiency as an of import cause of infantile vitamin B12 deficiency in Sanliurfa province of Turkey. Eur J Nutr. 2006;45(5):291–7. Epub 2006/04/08. pmid:16601915.
    • View Article
    • PubMed/NCBI
    • Google Scholar
36. 36. Lindblad B, Zaman S, Malik A, Martin H, Ekstrom AM, Amu S, et al. Folate, vitamin B12, and homocysteine levels in South Asian women with growth-retarded fetuses. Acta Obstet Gynecol Scand. 2005;84:1055–61. pmid:16232172
    • View Article
    • PubMed/NCBI
    • Google Scholar
37. 37. Frery N, Huel G, Leroy M, Moreau T, Savard R, Blot P, et al. Vitamin B12 amid parturients and their newborns and its relationship with birthweight. European Journal of Obstetrics and Gynecology. 1992;42:155–63. pmid:1511760
    • View Article
    • PubMed/NCBI
    • Google Scholar
38. 38. Adaikalakoteswari A, Vatish G, Lawson A, Wood C, Sivakumar K, McTernan PG, et al. Depression maternal vitamin B12 condition is associated with lower cord claret HDL cholesterol in white Caucasians living in the UK. Nutrients. 2015;vii(4):2401–14. Epub 2015/04/08. pmid:25849948; PubMed Fundamental PMCID: PMC4425151.
    • View Article
    • PubMed/NCBI
    • Google Scholar
39. 39. Visentin CE, Masih SP, Plumptre L, Schroder Th, Sohn KJ, Ly A, et al. Depression Serum Vitamin B-12 Concentrations Are Prevalent in a Accomplice of Pregnant Canadian Women. J Nutr. 2016;146(5):1035–42. Epub 2016/04/15. pmid:27075906.
    • View Article
    • PubMed/NCBI
    • Google Scholar
40. 40. Jacquemyn Y, Alaji K, Karepouan North, Jacquemyn N, Van Sande H. Vitamin B12 and folic acid status of term significant women and newborns in the Antwerp region, Belgium. Clin Exp Obstet Gynecol. 2014;2:141–3. pmid:24779238
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
41. 41. Relton CL, Pearce MS, Parker L. The influence of erythrocyte folate and serum vitamin B12 status on nativity weight. British Journal of Nutrition. 2007;93(05). pmid:15975157
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
42. 42. Muthayya Due south, Dwarkanath P, Mhaskar M, Mhaskar R, Thomas A, Duggan C, et al. The relationship of neonatal serum vitamin B12 status with nascency weight. Asia Pac J Clinical Nutrition. 2006;15:538–43. pmid:17077072
    • View Article
    • PubMed/NCBI
    • Google Scholar
43. 43. Spud MM, Molloy AM, Ueland PM, Fernandez-Ballart J, Schneede J, Arija V, et al. Longitudinal Written report of the Effect of Pregnancy on Maternal and Fetal Cobalamin Status in Salubrious Women and Their Offspring. Journal of Nutrition. 2007.
    • View Article
    • Google Scholar
44. 44. Kalay Z, Islek A, Parlak Grand, Kirecci A, Guney O, Koklu E, et al. Reliable and powerful laboratory markers of cobalamin deficiency in the newborn: plasma and urinary methylmalonic acid. J Matern Fetal Neonatal Med. 2014;29(1):60–3. Epub 2014/xi/12. pmid:25385266.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
45. 45. Finkelstein JL, Guillet R, Pressman EK, Fothergill A, Guetterman HM, Kent TR, et al. Vitamin B12 Status in Pregnant Adolescents and Their Infants. Nutrients. 2019;11(two). Epub 2019/02/20. pmid:30781902; PubMed Central PMCID: PMC6413223.
    • View Article
    • PubMed/NCBI
    • Google Scholar
46. 46. Bergen NE, Schalekamp-Timmermans S, Jaddoe VW, Hofman A, Lindemans J, Russcher H, et al. Maternal and Neonatal Markers of the Homocysteine Pathway and Fetal Growth: The Generation R Study. Paediatr Perinat Epidemiol. 2016;30(iv):386–96. Epub 2016/06/09. pmid:27271101.
    • View Article
    • PubMed/NCBI
    • Google Scholar
47. 47. Molloy AM. Should vitamin B12 status be considered in assessing risk of neural tube defects? Ann N Y Acad Sci. 2018;1414(1):109–25. Epub 2018/01/30. pmid:29377209; PubMed Central PMCID: PMC5887889.
    • View Article
    • PubMed/NCBI
    • Google Scholar
48. 48. Molloy AM, Kirke PN, Troendle JF, Burke H, Sutton K, Brody LC, et al. Maternal vitamin B12 condition and hazard of neural tube defects in a population with loftier neural tube defect prevalence and no folic Acid fortification. Pediatrics. 2009;123(iii):917–23. Epub 2009/03/04. pmid:19255021; PubMed Cardinal PMCID: PMC4161975.
    • View Article
    • PubMed/NCBI
    • Google Scholar
49. 49. Ratan SK, Rattan KN, Pandey RM, Singhal S, Kharab South, Bala M, et al. Evaluation of the levels of folate, vitamin B12, homocysteine and fluoride in the parents and the affected neonates with neural tube defect and their matched controls. Pediatr Surg Int. 2008;24(7):803–viii. Epub 2008/05/09. pmid:18463884.
    • View Article
    • PubMed/NCBI
    • Google Scholar
50. 50. Wilson A, Platt R, Wu Q, Leclerc D, Christensen B, Yang H, et al. A common variant in methionine synthase reductase combined with low cobalamin (Vitamin B12) increases risk for spina. Molecular Genetics and Metabolism. 1999;67(4). pmid:10444342
    • View Article
    • PubMed/NCBI
    • Google Scholar
51. 51. Gu Q, Li Y, Cui ZL, Luo XP. Homocysteine, folate, vitamin B12 and B6 in mothers of children with neural tube defects in Xinjiang, China. Acta Paediatr. 2012;101(11):e486–ninety. Epub 2012/08/07. pmid:22860981.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
52. 52. Ray JG, Wyatt PR, Thompson MD, Vermeulen MJ, Meier C, Wong P-Y, et al. Vitamin B12 and the Risk of Neural Tube Defects in a Folic-Acid-Fortified Population. Epidemiology. 2007;18(three):362–6. pmid:17474166
    • View Article
    • PubMed/NCBI
    • Google Scholar
53. 53. Rowland AS, Baird DD, Shore DL, Weinberg CR, Savitz DA, Wilcox AJ. Nitrous oxide and spontaneous abortion in female dental assistants. American Periodical of Epidemiology. 1995;141(6). pmid:7900720
    • View Article
    • PubMed/NCBI
    • Google Scholar
54. 54. Hubner U, Alwan A, Jouma M, Tabbaa M, Schorr H, Herrmann Due west. Low serum vitamin B12 is associated with recurrent pregnancy loss in Syrian women. Clin Chem Lab Med. 2008;46(9):1265–ix. Epub 2008/07/xix. pmid:18636794.
    • View Article
    • PubMed/NCBI
    • Google Scholar
55. 55. Reznikoff-Etievant MF, Zittoun J, Vaylet C, Pernet P, Milliez J. Low Vitamin B12level equally a risk factor for very early recurrent abortion. European Periodical of Obstetrics, Gynecology, & Reproductive Biological science. 2002;104(2). pmid:12206930
    • View Article
    • PubMed/NCBI
    • Google Scholar
56. 56. Hogeveen M, Blom HJ, den Heijer M. Maternal homocysteine and small-for-gestational-age offspring: systematic review and meta-assay. Am J Clin Nutr. 2012;95(1):130–6. Epub 2011/12/16. pmid:22170376.
    • View Article
    • PubMed/NCBI
    • Google Scholar
57. 57. Muthayya S, Kurpad AV, Duggan CP, Bosch RJ, Dwarkanath P, Mhaskar A, et al. Low maternal vitamin B12 status is associated with intrauterine growth retardation in urban Southward Indians. Eur J Clin Nutr. 2006;threescore(6):791–801. Epub 2006/01/13. pmid:16404414.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
58. 58. Rogne T, Tielemans MJ, Chong MF, Yajnik CS, Krishnaveni GV, Poston L, et al. Associations of Maternal Vitamin B12 Concentration in Pregnancy With the Risks of Preterm Birth and Low Nascency Weight: A Systematic Review and Meta-Assay of Private Participant Information. Am J Epidemiol. 2017;185(3):212–23. Epub 2017/01/22. pmid:28108470; PubMed Central PMCID: PMC5390862.
    • View Article
    • PubMed/NCBI
    • Google Scholar
59. 59. Senousy SM, Farag MK, Gouda As, El Noury MA, Dabbous OA, Gaber KR. Association between biomarkers of vitamin B12 status and the take a chance of neural tube defects. J Obstet Gynaecol Res. 2018;44(10):1902–eight. Epub 2018/07/26. pmid:30043514.
    • View Article
    • PubMed/NCBI
    • Google Scholar
60. threescore. Sukumar N, Venkataraman H, Wilson Southward, Goljan I, Selvamoni S, Patel V, et al. Vitamin B12 Condition amongst Pregnant Women in the UK and Its Association with Obesity and Gestational Diabetes. Nutrients. 2016;8(12). Epub 2016/12/06. pmid:27916927; PubMed Cardinal PMCID: PMC5188423.
    • View Article
    • PubMed/NCBI
    • Google Scholar
61. 61. Jiang HL, Cao LQ, Chen HY. Blood folic acid, vitamin B12, and homocysteine levels in pregnant women with fetal growth restriction. Genet Mol Res. 2016;15(4). Epub 2016/12/22. pmid:28002587.
    • View Article
    • PubMed/NCBI
    • Google Scholar
62. 62. Thompson MD, Cole DE, Ray JG. Vitamin B-12 and neural tube defects: the Canadian feel. Am J Clin Nutr. 2009;89(2):697S–701S. Epub 2009/01/01. pmid:19116334.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
63. 63. Nasri 1000, Ben Fradj MK, Touati A, Aloui G, Ben Jemaa Due north, Masmoudi A, et al. Clan of maternal homocysteine and vitamins condition with the gamble of neural tube defects in Tunisia: A case-control study. Birth Defects Res A Clin Mol Teratol. 2015;103(12):1011–20. Epub 2015/09/20. pmid:26386249.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
64. 64. Fofou-Caillierez MB, Gueant-Rodriguez RM, Alberto JM, Chery C, Josse T, Gerard P, et al. Vitamin B-12 and liver activity and expression of methionine synthase are decreased in fetuses with neural tube defects. Am J Clin Nutr. 2019;109(three):674–83. Epub 2019/03/09. pmid:30848279.
    • View Article
    • PubMed/NCBI
    • Google Scholar
65. 65. Kouroglou Eastward, Anagnostis P, Daponte A, Bargiota A. Vitamin B12 insufficiency is associated with increased adventure of gestational diabetes mellitus: a systematic review and meta-analysis. Endocrine. 2019;66(ii):149–56. Epub 2019/08/xxx. pmid:31463884.
    • View Article
    • PubMed/NCBI
    • Google Scholar
66. 66. Peker Eastward, Demir Northward, Tuncer O, Ustyol Fifty, Balahoroglu R, Kaba S, et al. The levels of vitamin B12, folate and homocysteine in mothers and their babies with neural tube defects. J Matern Fetal Neonatal Med. 2016;29(18):2944–8. Epub 2015/10/20. pmid:26479326.
    • View Article
    • PubMed/NCBI
    • Google Scholar
67. 67. Dwarkanath P, Barzilay J. R., Thomas T., Thomas A., Bhat Southward., & Kurpad A. 5. Loftier folate and low vitamin B12 intakes uring pregnancy are associated with small-for-gestational historic period infants in Due south Indian women: a prospective observational cohort written report. American Journal of Clinical Diet. 2013. pmid:24108785
    • View Article
    • PubMed/NCBI
    • Google Scholar
68. 68. Dwarkanath P, Vinotha P, Thomas T, Joseph S, Thomas A, Shirley Yard, et al. Relationship of Early Vitamin D Concentrations and Gestational Diabetes Mellitus in Indian Pregnant Women. Front end Nutr. 2019;6:116. Epub 2019/08/27. pmid:31448279; PubMed Central PMCID: PMC6691186.
    • View Article
    • PubMed/NCBI
    • Google Scholar
69. 69. Windelberg A, Arseth O, Kvalheim Chiliad, Ueland PM. Automated assay for the determination of methylmalonic acid, full homocysteine, and related amino acids in human serum or plasma past means of methylchloroformate derivatization and gas chromatography-mass spectrometry. Clin Chem. 2005;51(eleven):2103–9. Epub 2005/08/27. pmid:16123148.
    • View Article
    • PubMed/NCBI
    • Google Scholar
70. seventy. Yetley EA, Pfeiffer CM, Phinney KW, Bailey RL, Blackmore South, Bock JL, et al. Biomarkers of vitamin B-12 status in NHANES: a roundtable summary. Am J Clin Nutr. 2011;94(ane):313S–21S. Epub 2011/05/twenty. pmid:21593512; PubMed Cardinal PMCID: PMC3127527.
    • View Article
    • PubMed/NCBI
    • Google Scholar
71. 71. Fedosov SN, Brito A, Miller JW, Green R, Allen LH. Combined indicator of vitamin B12 condition: modification for missing biomarkers and folate status and recommendations for revised cut-points. Clin Chem Lab Med. 2015;53(eight):1215–25. pmid:25720072.
    • View Article
    • PubMed/NCBI
    • Google Scholar
72. 72. WHO. Iron deficiency anemia: assessment, prevention and control: a guide for programme managers. Geneva, Switzerland: UNICEF, United Nations Academy, WHO, 2001.
73. 73. Villar J, Cheikh Ismail L, Victora CG, Ohuma EO, Bertino East, Altman DG, et al. International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Projection. Lancet. 2014;384(9946):857–68. pmid:25209487.
    • View Article
    • PubMed/NCBI
    • Google Scholar
74. 74. Organization WH. WHO Anthro for Personal Computers; Software for assessing growth and development of the world'd children. In: Development DoNfHa, editor. Geneva: World Health Arrangement; 2011.
75. 75. Group WMGRS. WHO Kid Growth Standards: growth velocity based on weight, length and caput circumference: methods and development. Geneva2009.
76. 76. Group WMGRS. WHO Kid Growth Standards: methods and development: length/acme-forage, weight-for-age, weight-for-length, weight-for-height and body mass index-for-historic period. Geneva: Earth Health Organization; 2006.
77. 77. Spiegelman D, Hertzmark E. Like shooting fish in a barrel SAS calculations for gamble or prevalence ratios and differences. Am J Epidemiol. 2005;162(3):199–200. Epub 2005/07/01. pmid:15987728.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
78. 78. Wacholder S. Binomial regression in GLIM: estimating take chances ratios and take chances differences. Am J Epidemiol. 1986;123(1):174–84. pmid:3509965.
    • View Article
    • PubMed/NCBI
    • Google Scholar
79. 79. Zou 1000. A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol. 2004;159(vii):702–6. pmid:15033648.
    • View Article
    • PubMed/NCBI
    • Google Scholar
80. 80. Report WHOT. Obesity: preventing and managing the global epidemic. Written report of a WHO consultation. 2000.
81. 81. Consultation We. Appropriate trunk-mass alphabetize for Asian populations and its implications for policy and intervention strategies. Lancet. 2004. pmid:14726171
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
82. 82. Yajnik CS, Deshpande SS, Jackson AA, Refsum H, Rao South, Fisher DJ, et al. Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study. Diabetologia. 2008;51(i):29–38. Epub 2007/09/14. pmid:17851649; PubMed Cardinal PMCID: PMC2100429.
    • View Article
    • PubMed/NCBI
    • Google Scholar
83. 83. Mishra J, Tomar A, Puri M, Jain A, Saraswathy KN. Trends of folate, vitamin B12, and homocysteine levels in unlike trimesters of pregnancy and pregnancy outcomes. Am J Hum Biol. 2020:e23388. Epub 2020/01/04. pmid:31898383.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
84. 84. Schulze KJ, Mehra South, Shaikh Southward, Ali H, Shamim AA, Wu LS, et al. Antenatal Multiple Micronutrient Supplementation Compared to Iron-Folic Acrid Affects Micronutrient Status but Does Non Eliminate Deficiencies in a Randomized Controlled Trial Amidst Meaning Women of Rural Bangladesh. J Nutr. 2019;149(vii):1260–lxx. Epub 2019/04/23. pmid:31006806; PubMed Central PMCID: PMC6602890.
    • View Article
    • PubMed/NCBI
    • Google Scholar
85. 85. Sole-Navais P, Salat-Batlle J, Cavalle-Busquets P, Fernandez-Ballart J, Ueland PM, Ballesteros G, et al. Early pregnancy folate-cobalamin interactions and their effects on cobalamin condition and hematologic variables throughout pregnancy. Am J Clin Nutr. 2018;107(ii):173–82. Epub 2018/03/xiii. pmid:29529156.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
86. 86. Mittal Thousand, Bansal V, Jain R, Dabla PK. Perturbing Status of Vitamin B12 in Indian Infants and Their Mothers. Food Nutr Bull. 2017;38(2):209–15. Epub 2017/05/xviii. pmid:28513265.
    • View Article
    • PubMed/NCBI
    • Google Scholar
87. 87. Hay G, Clausen T, Whitelaw A, Trygg G, Johnston C, Henriksen T, et al. Maternal folate and cobalamin condition predicts vitamin condition in newborns and six-month-former infants. J Nutr. 2010;140(three):557–64. Epub 2010/01/xv. pmid:20071650.
    • View Article
    • PubMed/NCBI
    • Google Scholar
88. 88. Youssry MA, Radwan AM, Gebreel MA, Patel TA. The Touch of Third Trimester Maternal Serum Vitamin B12 and Folate Status on Fetal Nativity Weight. Is Maternal Serum Homocysteine a Predictor of Low Nascence Weight Infants? Open Journal of Obstetrics and Gynecology. 2017;07(11):1102–15.
    • View Article
    • Google Scholar
89. 89. Pisal H, Dangat K, Randhir Yard, Khaire A, Mehendale S, Joshi S. Higher maternal plasma folate, vitamin B12 and homocysteine levels in women with preeclampsia. J Hum Hypertens. 2019;33(5):393–9. Epub 2019/01/17. pmid:30647465.
    • View Article
    • PubMed/NCBI
    • Google Scholar
90. 90. Bjorke Monsen AL, Ueland PM, Vollset SE, Guttormsen AB, Markestad T, Solheim E, et al. Determinants of Cobalamin Status in Newborns. Pediatrics. 2001;108:624–30. pmid:11533328
    • View Article
    • PubMed/NCBI
    • Google Scholar
91. 91. Rowland Equally, Baird DD, Shore DL, Weinberg CR, Savitz DA, Wilcox AJ. Nitrous oxide and spontaneous abortion in female dental assistants. American journal of epidemiology. 1995;141(vi):531–8. pmid:7900720.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
92. 92. Reznikoff-Etievant MF, Zittoun J, Vaylet C, Pernet P, Milliez J. Low Vitamin B(12) level as a run a risk factor for very early on recurrent abortion. Eur J Obstet Gynecol Reprod Biol. 2002;104(2):156–9. Epub 2002/09/11. pmid:12206930.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
93. 93. Muthayya South, Kurpad AV, Duggan CP, Bosch RJ, Dwarkanath P, Mhaskar A, et al. Low maternal vitamin B12 status is associated with intrauterine growth retardation in urban South Indians. European periodical of clinical diet. 2006;60(half-dozen):791–801. Epub 2006/01/13. pmid:16404414.
    • View Article
    • PubMed/NCBI
    • Google Scholar
94. 94. Hogeveen M, Blom HJ, den Heijer M. Maternal homocysteine and small-for-gestational-age offspring: systematic review and meta-analysis. The American journal of clinical diet. 2012;95(one):130–6. Epub 2011/12/16. pmid:22170376.
    • View Article
    • PubMed/NCBI
    • Google Scholar
95. 95. Adams MJ Jr., Khoury MJ, Scanlon KS, Stevenson RE, Knight GJ, Haddow JE, et al. Elevated midtrimester serum methylmalonic acid levels equally a risk gene for neural tube defects. Teratology. 1995;51(five):311–7. pmid:7482352.
    • View Article
    • PubMed/NCBI
    • Google Scholar
96. 96. Wilson A, Platt R, Wu Q, Leclerc D, Christensen B, Yang H, et al. A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida. Molecular genetics and metabolism. 1999;67(iv):317–23. pmid:10444342.
    • View Article
    • PubMed/NCBI
    • Google Scholar
97. 97. Ray JG, Wyatt PR, Thompson Doc, Vermeulen MJ, Meier C, Wong PY, et al. Vitamin B12 and the risk of neural tube defects in a folic-acrid-fortified population. Epidemiology (Cambridge, Mass). 2007;18(3):362–vi. Epub 2007/05/03. pmid:17474166.
    • View Article
    • PubMed/NCBI
    • Google Scholar
98. 98. Chen LW, Lim AL, Colega M, Tint MT, Aris IM, Tan CS, et al. Maternal folate status, but not that of vitamins B-12 or B-6, is associated with gestational historic period and preterm birth risk in a multiethnic Asian population. J Nutr. 2015;145(1):113–20. Epub 2014/12/21. pmid:25527665.
    • View Article
    • PubMed/NCBI
    • Google Scholar
99. 99. Yang T, Gu Y, Wei X, Liang X, Chen J, Liu Y, et al. Periconceptional folic acid supplementation and vitamin B 12 status in a cohort of Chinese early pregnancy women with the chance of adverse pregnancy outcomes. 2017;lx(ii):136–42.
    • View Article
    • Google Scholar
100. 100. Krikke GG, Grooten IJ, Vrijkotte TG, van Eijsden M, Roseboom TJ, Painter RC. Vitamin B12 and folate status in early pregnancy and cardiometabolic risk factors in the offspring at historic period 5–6 years: findings from the ABCD multi-ethnic birth accomplice. BJOG. 2016;123(3):384–92. Epub 2016/01/27. pmid:26810674.
     • View Commodity
     • PubMed/NCBI
     • Google Scholar
101. 101. Zhu Ten, Wei L, Cao D, Liu C, Tian J, Long Y, et al. Low serum folate status in the second trimester increase the risk of low birthweight in Chinese women. J Obstet Gynaecol Res. 2018;44(eleven):2037–44. Epub 2018/07/19. pmid:30019799.
     • View Article
     • PubMed/NCBI
     • Google Scholar
102. 102. Halicioglu O, Sutcuoglu South, Koc F, Ozturk C, Albudak E, Colak A, et al. Vitamin B12 and folate statuses are associated with nutrition in pregnant women, only not with anthropometric measurements in term newborns. J Matern Fetal Neonatal Med. 2012;25(9):1618–21. Epub 2011/12/22. pmid:22185230.
     • View Article
     • PubMed/NCBI
     • Google Scholar
103. 103. Riaz One thousand, Shaikh F, Fawwad A, Hakeem R, Shera AS, Hitman GA, et al. Maternal Nutrition during Early Pregnancy and Cardiometabolic Status of Neonates at Birth. J Diabetes Res. 2018;2018:7382946. Epub 2018/06/01. pmid:29850608; PubMed Fundamental PMCID: PMC5941780.
     • View Article
     • PubMed/NCBI
     • Google Scholar
104. 104. McCullough LE, Miller EE, Mendez MA, Murtha AP, Murphy SK, Hoyo C. Maternal B vitamins: furnishings on offspring weight and DNA methylation at genomically imprinted domains. Clin Epigenetics. 2016;8:8. Epub 2016/01/26. pmid:26807160; PubMed Central PMCID: PMC4722751.
     • View Article
     • PubMed/NCBI
     • Google Scholar
105. 105. Baker PN, Wheeler SJ, Sanders TA, Thomas JE, Hutchinson CJ, Clarke G, et al. A prospective written report of micronutrient status in boyish pregnancy. Am J Clin Nutr. 2009;89(4):1114–24. Epub 2009/02/27. pmid:19244368.
     • View Article
     • PubMed/NCBI
     • Google Scholar
106. 106. Bergen NE, Jaddoe VW, Timmermans South, Hofman A, Lindemans J, Russcher H, et al. Homocysteine and folate concentrations in early pregnancy and the risk of adverse pregnancy outcomes: the Generation R Study. BJOG. 2012;119(6):739–51. Epub 2012/04/12. pmid:22489763.
     • View Article
     • PubMed/NCBI
     • Google Scholar
107. 107. Kaymaz C, Demir A, Bige O, Cagliyan East, Cimrin D, Demir N. Analysis of perinatal outcome by combination of commencement trimester maternal plasma homocysteine with uterine avenue Doppler velocimetry. Prenat Diagn. 2011;31(13):1246–50. Epub 2011/11/29. pmid:22120509.
     • View Article
     • PubMed/NCBI
     • Google Scholar
108. 108. Takimoto H, Mito N, Umegaki Grand, Ishiwaki A, Kusama K, Abe South, et al. Relationship between dietary folate intakes, maternal plasma total homocysteine and B-vitamins during pregnancy and fetal growth in Nippon. Eur J Nutr. 2007;46(5):300–half-dozen. Epub 2007/07/12. pmid:17623226.
     • View Article
     • PubMed/NCBI
     • Google Scholar
109. 109. Sukumar N, Bawazeer Due north, Patel V, Saravanan P. Depression B12 level is associated with maternal obesity and college birthweight in gestational diabetes. Journal of Developmental Origins of Wellness and Illness. 2011;2:128–nine.
     • View Article
     • Google Scholar
110. 110. Dayaldasani A, Ruiz-Escalera J, Rodriguez-Espinona M, Rueda I, Perez-Valero V, Yahyaoui R. Serum Vitamin B12 Levels During the Starting time Trimester of Pregnancy Correlate with Newborn Screening Markers of Vitamin B12 Deficiency. International Journal for vitamin and diet research. 2014;84:92–vii. pmid:25835239
     • View Article
     • PubMed/NCBI
     • Google Scholar
111. 111. Krishnaveni GV, Veena SR, Karat SC, Yajnik CS, Fall CH. Clan between maternal folate concentrations during pregnancy and insulin resistance in Indian children. Diabetologia. 2014;57(1):110–21. Epub 2013/x/29. pmid:24162586; PubMed Cardinal PMCID: PMC3855580.
     • View Article
     • PubMed/NCBI
     • Google Scholar
112. 112. Nexo East, Hoffmann-Lucke E. Holotranscobalamin, a marker of vitamin B-12 status: belittling aspects and clinical utility. Am J Clin Nutr. 2011;94(1):359S–65S. Epub 2011/05/20. pmid:21593496; PubMed Central PMCID: PMC3127504.
     • View Article
     • PubMed/NCBI
     • Google Scholar

crabtreedris1938.blogspot.com

Source: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248145

Share this post