Reliable and powerful laboratory markers of cobalamin deficiency in the newborn: plasma and urinary methylmalonic acid

Kalay, Zuhal; İşlek, Ali; Parlak, Mesut; Kireçci, Ahmet; Guney, Ozgur; Köklü, Esad; Kalay, Salih

doi:10.3109/14767058.2014.986649

Cited by 16 publications

(7 citation statements)

References 17 publications

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“…There are, however, limited prospective data on maternal vitamin B 12 status during pregnancy and its association with infant vitamin B 12 status—particularly among adolescents—to compare findings. Evidence from studies in adult pregnant women have reported significant correlations between maternal vitamin B 12 status during pregnancy and their infants [19,23,24,26,29]. Few prospective analyses to date have considered potential confounders of these associations in multivariate analyses [25,28].…”

Section: Discussionmentioning

confidence: 99%

“…Maternal vitamin B 12 concentrations during pregnancy are thought to predict fetal [18,19,20,21,22,23,24,25,26] and early infant [25,27,28,29] vitamin B 12 status. Previous cross-sectional studies in Norway, Turkey, Germany, United Kingdom, Serbia, and Brazil have noted a significant correlation between maternal and infant vitamin B 12 status at delivery [18,20,21,22,30,31,32,33]; however, in one study in Belgium, maternal and infant vitamin B 12 concentrations were not significantly correlated [34].…”

Section: Introductionmentioning

confidence: 99%

“…Prospective studies to date in The Netherlands, Norway, Turkey, India, and Spain have reported significant associations [19,23,24,26,29] between maternal vitamin B 12 status during pregnancy and infant vitamin B 12 status in cord blood or serum. In a prospective study in India, maternal vitamin B 12 status during pregnancy was associated with infant vitamin B 12 concentrations at 6 weeks of age [28].…”

Section: Introductionmentioning

confidence: 99%

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Vitamin B12 Status in Pregnant Adolescents and Their Infants

et al. 2019

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Vitamin B12 deficiency has been associated with increased risk of adverse pregnancy outcomes. Few prospective studies have investigated the burden or determinants of vitamin B12 deficiency early in life, particularly among pregnant adolescents and their children. The objectives of this study were to determine the prevalence of vitamin B12 deficiency and to examine associations between maternal and neonatal vitamin B12 status in a cohort study of healthy pregnant adolescents. Serum vitamin B12 and folate concentrations were measured in adolescents at mid-gestation (n = 124; 26.4 ± 3.5 weeks) and delivery (n = 131; 40.0 ± 1.3 weeks), and in neonates at birth using cord blood. Linear regression was used to examine associations between maternal and neonatal vitamin B12 status. Although the prevalence of vitamin B12 deficiency (<148.0 pmol/L; 1.6%) in adolescents was low during pregnancy, 22.6% of adolescents were vitamin B12 insufficient (<221.0 pmol/L; 22.6%) at mid-gestation. Maternal vitamin B12 concentrations significantly decreased from mid-gestation to delivery (p < 0.0001), and 53.4% had insufficient vitamin B12 status at delivery. Maternal vitamin B12 concentrations (p < 0.001) and vitamin B12 deficiency (p = 0.002) at delivery were significantly associated with infant vitamin B12 concentrations in multivariate analyses, adjusting for gestational age, maternal age, parity, smoking status, relationship status, prenatal supplement use, pre-pregnancy body mass index, race, and intake of vitamin B12 and folate. Maternal vitamin B12 concentrations significantly decreased during pregnancy and predicted neonatal vitamin B12 status in a cohort of healthy pregnant adolescents.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Vitamin B12 Status in Pregnant Adolescents and Their Infants

et al. 2019

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“…Because serum B12 assays provide an estimate of total B12 rather than direct evidence of metabolic utilisation, it is not possible to confidently exclude B12 deficiency when results fall in the indeterminate range of 125‐250 pmol/L. Serum concentrations of homocysteine (Hcy) and the cobalamin biomarker, MMA become increased in B12‐deficient subjects and they are, therefore, considered specific markers of B12 deficiency 21 …”

Section: Diagnosismentioning

confidence: 99%

Review of Vitamin B12 deficiency in pregnancy: a diagnosis not to miss as veganism and vegetarianism become more prevalent

Rashid

meier

Patrick

2021

European J of Haematology

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Vegetarianism and veganism are increasingly popular. The Food Standards Agency, biennial Food and You Survey of adults aged 16 years and over living in the UK, found that between 2012 and 2018 the proportion of people who reported never consuming dairy products had increased from 2% to 5%. However, veganism risks development of vitamin B12 deficiency as it is not available from plant sources. Moreover, its impact may be slow to be detected because body stores of vitamin B12 can last years. There is currently no published guidance on antenatal diagnosis and management of vitamin B12 deficiency. This paper reviews the metabolism, diagnosis and treatment of vitamin B12 in pregnancy. It concludes that national screening policymakers should consider introducing screening for B12 deficiency into the Antenatal and Newborn Screening Programmes for mothers and their infants if at risk of vitamin B12 deficiency. In the interim, national policy should be developed for prophylactic vitamin B12 supplementation in high‐risk groups around the time of pregnancy.

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“…Indeed, borderline cobalamin status in pregnant women can be associated with an increased risk of acquired newborn B12 deficiency, and cobalamin alone may not be sufficient to diagnose deficiency among them, which is why MMA tests are required [42]. Last but not least, we are aware that there are more reliable markers of cobalamin deficiency, namely methylmalonic acid (e.g., MMA), which can be used; therefore, further analysis of our group of patients using levels of MMA would be certainly needed and widely beneficial [15,43,44]. The main strength of the study is the relative balance between the study groups, with only a slightly higher number of children aged 0-3 years in the VN group and no significant differences in sex, height, weight, or BMI.…”

Section: Discussionmentioning

confidence: 99%

Cross-Sectional Study of the Prevalence of Cobalamin Deficiency and Vitamin B12 Supplementation Habits among Vegetarian and Vegan Children in the Czech Republic

et al. 2022

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Vegetarian (VG) and vegan (VN) diets in childhood are of growing interest due to their perceived health and environmental benefits. Concerns remain due to the possible disruption of healthy growth and development of children because of the scarcity of evidence-based studies. Among the nutrients of special concern is vitamin B12. Therefore, the Czech Vegan Children Study (CAROTS) decided to examine the relationship between B12 metabolism parameters and B12 intake through diet and supplementation. We analyzed laboratory parameters within n = 79 VG, n = 69 VN, and n = 52 omnivores (OM) children (0–18 years old). There were no significant differences in levels of holotranscobalamin (aB12), folate, homocysteine (hcys), or mean corpuscular volume. However, there was a significant difference in levels of cyanocobalamin (B12) (p = 0.018), even though we identified only n = 1 VG and n = 2 VN children as B12 deficient. On the other hand, we identified n = 35 VG, n = 28 VN, and n = 9 OM children with vitamin B12 hypervitaminosis (p = 0.004). This finding was related to a high prevalence of over-supplementation in the group (mean dose for VG 178.19 ± 238.5 µg per day; VN 278.35 ± 394.63 µg per day). Additionally, we found a significant (p < 0.05) difference between B12, aB12, and hcys levels of supplemented vs. non-supplemented VG/VN children. This can show that the intake of vitamin B12 via diet in the VG group might not be sufficient. Secondly, we analyzed a relation between supplement use in pregnancy and breastfeeding and its impact on vitamin B12 levels of children aged 0–3 years. Out of n = 46 mothers, only n = 3 (e.g., 6.5%) were not supplemented at all. We have not identified any clinical manifestation of B12 deficiency and only n = 1 child with low serum cobalamin, a child who did not receive vitamin B12 supplementation and whose mother took only low doses of vitamin B12 (25/µg/day).To conclude, we did not observe any life-threatening or severe consequences of laboratory-stated vitamin B12 deficiency; thus, our group was well supplemented. On the other hand, we have identified many subjects with vitamin B12 hypervitaminosis of unknown impact on their health. Further research and new guidelines for B12 supplementation among VG and VN children are needed.

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Reliable and powerful laboratory markers of cobalamin deficiency in the newborn: plasma and urinary methylmalonic acid

Abstract: Plasma MMA and urinary MMA B12 are the most robust markers of cobalamin deficiency. As a non-invasive method, urinary MMA is a sensitive method in demonstrating cobalamin deficiency in the newborn.

Cited by 16 publications

References 17 publications

Vitamin B12 Status in Pregnant Adolescents and Their Infants

Vitamin B12 Status in Pregnant Adolescents and Their Infants

Review of Vitamin B12 deficiency in pregnancy: a diagnosis not to miss as veganism and vegetarianism become more prevalent

Cross-Sectional Study of the Prevalence of Cobalamin Deficiency and Vitamin B12 Supplementation Habits among Vegetarian and Vegan Children in the Czech Republic

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