Cobalamin Status and Its Biochemical Markers Methylmalonic Acid and Homocysteine in Different Age Groups from 4 Days to 19 Years

Abstract

Background: Recent data indicate that cobalamin and folate status, including the metabolic markers methylmalonic acid (MMA) and total homocysteine (tHcy), undergo marked changes during childhood, particularly during the first year. Methods: Serum cobalamin, serum and whole-blood folate, and plasma MMA and tHcy were determined in a cross-sectional study of 700 children, ages 4 days to 19 years. Results: During the first 6 months, serum cobalamin was lower than and plasma MMA, tHcy, and serum folate were higher than the concentrations detected in the other age groups. In infants 6 weeks to 6 months of age, median MMA and tHcy concentrations were >0.78 and >75 mol/L, respectively. In older children (>6 months), serum cobalamin peaked at 3-7 years and then decreased, median plasma MMA remained low (<0.26 mol/L), median plasma tHcy was low (<6 mol/L) and increased from the age of 7 years on, and serum folate gradually decreased. Plasma MMA was inversely associated with cobalamin (r ‫؍‬ ؊0.4) in both age groups, but across the whole range of cobalamin concentrations, MMA was markedly higher in infants (<6 months) than in older children. Plasma tHcy showed a strong negative correlation to cobalamin (r ‫؍‬ ؊0.52) but not to serum folate in infants <6 months. In older children, tHcy showed the expected association with both cobalamin (r ‫؍‬ ؊0.48) and folate (r ‫؍‬ ؊0.51).

Marked Biological Variance in Endocrine and Biochemical Markers in Childhood: Establishment of Pediatric Reference Intervals Using Healthy Community Children from the CALIPER Cohort

“…This result differs from those in previous reports indicating low (approximately 270 pg/mL) cobalamin concentrations until 1 year of life, a peak concentration occurring between 5 and 7 years of age, and a subsequent decline to approximately 540 pg/mL into adolescence (25 ). The reason for this discrepancy is unclear but is likely related to dietary factors as well as cobalamin supplementation during pregnancy and fetal transfer (24 ).…”

“…The reason for this discrepancy is unclear but is likely related to dietary factors as well as cobalamin supplementation during pregnancy and fetal transfer (24 ). For both cobalmin and folate, significantly higher RIs were reported across all ages compared with previous studies (25 ), likely reflecting maternal supplementation and folate fortification programs.…”

Screening for Serum Total Homocysteine in Newborn Children

“…In the first weeks after birth, plasma concentrations of tHcy and folate are relatively stable (17 ), whereas MMA increases dramatically (14 ), sometimes leading to a benign or transient methylmalonic acidemia (44 ). The changes in MMA are only partly explained by changes in B 12 concentrations (14 ).…”

“…1) at birth. They continue to have a low B 12 status during infancy, particularly if the baby is exclusively breastfed (13,17,18 ). B 12 deficiency may lead to failure to thrive and developmental delay in infancy and lower cognitive function later in childhood (16 ).…”

Association between vitamin B12intake and EURRECA's prioritized biomarkers of vitamin B12in young populations: a systematic review

“…In that study, the dose-response association between injected vitamin B 12 and levels of biomarkers was not estimated. (58) Only data on biomarkers Monsen et al (2006) (59) Does not address any relationships of interest Casanueva et al (2006) (60) Type of intervention: multivitamin supplement Choudhry et al (1972) (61) Study design: intervention but not RCT Cikot et al (2001) (62) Only data on biomarkers Couto et al (2007) (63) Only data on biomarkers Cornel et al (2005) (64) Irrelevant micronutrient Czeizel and Dudas (1992) (65) Type of intervention: multi-vitamin supplement Czeizel and Medveczky (2003) (66) Does not address any relationships of interest Dagnelie et al (1989) (67) Does not address any relationships of interest Dawson et al (2000) (68) Study design: intervention but not RCT van Dusseldorp et al (1999) (69) Study design: case-control study Eilander et al (2010) (70) Study design: cross-sectional study investigating S-H relationship Gomber et al (2003) (71) Study design: cross-sectional study investigating S-H relationship Gomber et al (1998) (72) Study design: cross-sectional study investigating S-H relationship Gordon and Carson (1976) (73) Study design: case report Graham et al (1992) (74) Population group: infants did not meet the inclusion criteria (unhealthy) Haggarty et al (2006) (75) Irrelevant health outcome (76) Type of intervention: multi-vitamin supplement …”