Folate and vitamin B12 levels in early pregnancy and maternal obesity

O’Malley, Eimer G.; Reynolds, Ciara; Cawley, S.; Woodside, Jayne V.; Molloy, Anne M.; Turner, Michael J.

doi:10.1016/j.ejogrb.2018.10.001

Cited by 30 publications

(29 citation statements)

References 25 publications

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“…The regression analysis in cohort 1, after correcting for multiple confounders, we found that B12 is independently associated with BMI whereas in cohort 2, in addition to B12, social deprivation was also associated with BMI. The association between BMI and B12 has been shown in other studies in pregnant women 15,16,17 but also in adolescents 14 and in women of childbearing age 28 . In addition, B12 deficiency may be causally related to dysglycaemia 9 .…”

Section: Discussionsupporting

confidence: 53%

“…In children and adolescents, increase in BMI 13 and IR 14 have been associated with low B12 levels. Furthermore, studies in early pregnancy have focussed on association between lower maternal micronutrient status (B12, folate, iron) with pre-pregnancy overweight and obesity in mothers 15,16,17 , with lower micronutrients in low-birth weight infants 18 and with higher BMI and heart rate in children at age 5-6 19 . Our in vitro studies have shown that B12 deficiency in adipocytes altered DNA methylation levels 2 of the transcription factors of lipid regulation 2 and the adipose derived miRNAs targeting IR 3 thereby suggesting that B12 deficiency dysregulates epigenetic mechanisms.…”

Section: Sdmentioning

confidence: 99%

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Vitamin B12 deficiency and altered one-carbon metabolites in early pregnancy is associated with maternal obesity and dyslipidaemia

Adaikalakoteswari

Wood

Mina

et al. 2020

Sci Rep

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Vitamin B12 (B12) is a micronutrient essential for one-carbon (1C) metabolism. B12 deficiency disturbs the 1C cycle and alters DNA methylation which is vital for most metabolic processes. Studies show that B12 deficiency may be associated with obesity, insulin resistance and gestational diabetes; and with obesity in child-bearing women. We therefore hypothesised that the associations between B12 deficiency, BMI and the metabolic risk could be mediated through altered 1C metabolites in early pregnancy. We explored these associations in two different early pregnancy cohorts in the UK (cohort 1; n = 244 and cohort 2; n = 60) with anthropometric data at 10-12 weeks and plasma/serum sampling at 16-18 weeks. B12, folate, total homocysteine (tHcy), methionine, MMA, metabolites of 1C metabolism (SAM, SAH) and anthropometry were measured. B12 deficiency (< 150 pmol/l) in early pregnancy was 23% in cohort 1 and 18% in cohort 2. Regression analysis after adjusting for likely confounders showed that B12 was independently and negatively associated with BMI (Cohort 1: β = − 0.260, 95% CI (− 0.440, − 0.079), p = 0.005, Cohort 2: (β = − 0.220, 95% CI (− 0.424, − 0.016), p = 0.036) and positively with HDL cholesterol (HDL-C) (β = 0.442, 95% CI (0.011,0.873), p = 0.045). We found that methionine (β = − 0.656, 95% CI (− 0.900, − 0.412), p < 0.0001) and SAH (β = 0.371, 95% CI (0.071, 0.672), p = 0.017) were independently associated with triglycerides. Low B12 status and alteration in metabolites in 1C metabolism are common in UK women in early pregnancy and are independently associated with maternal obesity and dyslipidaemia. Therefore, we suggest B12 monitoring in women during peri-conceptional period and future studies on the pathophysiological relationship between changes in 1C metabolites and its association with maternal and fetal outcomes on larger cohorts. This in turn may offer potential to reduce the metabolic risk in pregnant women and their offspring. Abbreviations 1CM One-carbon metabolism B12 Vitamin B12 GDM Gestational diabetes tHcy Total homocysteine IR Insulin resistance MMA Methylmalonic acid

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Section: Discussionsupporting

confidence: 53%

Section: Sdmentioning

confidence: 99%

Vitamin B12 deficiency and altered one-carbon metabolites in early pregnancy is associated with maternal obesity and dyslipidaemia

Adaikalakoteswari

Wood

Mina

et al. 2020

Sci Rep

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“…Periconceptional folic acid supplementation reduces the incidence of neural tube defects across resource settings 58 . While there are some differences within published guidelines, FIGO’s advice is that all women of childbearing age should consume at least 0.4 mg (400 μg) supplementary folic acid a day for at least 1 month before conception, continuing until at least the end of the first trimester of pregnancy, to reduce the risk of neutral tube defects 33,44,59 . Consideration should be given to the potential use of a higher dose (5 mg/d) for women with obesity, for example in those who may have other additional risk factors for neural tube defects, for example pregestational diabetes or family history, in line with local and national guidelines and resources 37,60,61 .…”

Section: Figo Guidance For Prepregnancy Obesitymentioning

confidence: 99%

Management of prepregnancy, pregnancy, and postpartum obesity from the FIGO Pregnancy and Non‐Communicable Diseases Committee: A FIGO (International Federation of Gynecology and Obstetrics) guideline

McAuliffe

Killeen

Jacob

et al. 2020

Intl J Gynecology & Obste

114

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Obstetricians and gynecologists are well positioned to influence population health through maternity and women's health services. Obesity is common in women of reproductive age and the prevalence is rising in both low-/middle-income and high-income countries 1. Obesity affects requirements for assessment, monitoring, and intervention and can impact maternal and child outcomes. Obstetricians and gynecologists require guidance on the care of women of reproductive age with obesity at all time points related to pregnancy, including how to address modifiable risk factors such as diet and physical activity. Many guidelines have been developed to date, although they vary in scope, methodology, and individual recommendations. FIGO's Committee Guideline for the Management of Prepregnancy, Pregnancy, and Postpartum Obesity (Table 1) reviews good clinical practice recommendations (Table 2-4) from previously published international documents. It serves as a practical resource to support obstetricians and gynecologists in the management of This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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“…Additionally, a high proportion of the cohort was obese, which may be associated with altered pharmacokinetics of folic acid and may have affected the trends seen among the mothers in this cohort [37,38]. However, controversy exists whether changes seen in folate metabolism among obese women has to do with total body weight or lean body mass [39] and whether observed differences warrant additional supplementation with folic acid and/or vitamin B12 [40]. Also, an initial assessment of our data found no correlation between BMI and folate concentrations, with no significant differences seen between mean 5MTHF concentrations between obese (BMI !…”

Section: Discussionmentioning

confidence: 99%

The effect of race and supplementation on maternal and umbilical cord plasma folates

Maulik

Haandel

Allsworth

et al. 2019

The Journal of Maternal-Fetal & Neonatal Medicine

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Objective: The purpose of this study is to test the hypothesis that race and supplementation affect the concentration and correlation of various folate species in maternal and umbilical cord blood. Methods: This is a single-center, prospective, cross-sectional cohort of cord blood samples obtained from 40 uncomplicated term pregnancies as a pilot study, following a protocol approved by the Institutional Review Board. High performance liquid chromatography mass spectrometry quantitated the following concentrations in extracted plasma samples: 5-methyltetrahydrofolate (5MTHF), 5,10-methenyl-tetrahydrofolate (5,10-MeTHF), tetrahydrofolate (THF), and unmetabolized folic acid. Results: Folate concentrations in the umbilical cord plasma were consistently higher than maternal samples for 5MTHF (p < .001), 5,10-MeTHF (p < .001), and THF (p < .001); cord blood folic acid levels, however, were lower than maternal samples (p < .03). While 5MTHF was the most prevalent folate, ratios comparing cord blood to maternal blood folates suggests a fourfold preponderance of THF in cord blood folate signature, a trend unchanged by supplementation. Prenatal supplementation increased the concentrations of 5MTHF, for both maternal (p < .01) and cord blood samples (p < .005). In comparison to the other two racial groups, African American 5MTHF concentration demonstrated a lower total folate concentration in both maternal samples and cord blood samples, in addition to a relatively blunted response to supplementation. A significantly positive correlation between maternal and cord blood 5MTHF concentration was noted in all three racial groups. Supplementation resulted in a positive correlation between maternal and cord blood 5MTHF concentrations (r ¼ 0.85, p < .0001). Conclusions: 5MTHF is the most prevalent folate in both cord and maternal plasma, and race and supplementation primarily affect variations in maternal and fetal 5MTHF concentrations and their correlation with each other. However, the greater concentration of THF in cord blood relative to maternal blood offers preliminary insight into the importance of how folate metabolism differs in the specific context of fetal development and physiology, with greater emphasis on DNA synthesis and stability. Furthermore, supplementation appeared to not have as great an impact on African American maternal or cord blood folates, suggesting a variable benefit of current repletion strategies to certain subsets of the population. Future studies that further elucidate these differences and their impact on birth outcomes may help inform supplementation protocols that are more personalized, with greater efficacy in promoting positive perinatal outcomes. ARTICLE HISTORY

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Folate and vitamin B12 levels in early pregnancy and maternal obesity

Cited by 30 publications

References 25 publications

Vitamin B12 deficiency and altered one-carbon metabolites in early pregnancy is associated with maternal obesity and dyslipidaemia

Vitamin B12 deficiency and altered one-carbon metabolites in early pregnancy is associated with maternal obesity and dyslipidaemia

Management of prepregnancy, pregnancy, and postpartum obesity from the FIGO Pregnancy and Non‐Communicable Diseases Committee: A FIGO (International Federation of Gynecology and Obstetrics) guideline

The effect of race and supplementation on maternal and umbilical cord plasma folates

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