High incidence of maternal vitamin B12 deficiency detected by newborn screening: first results from a study for the evaluation of 26 additional target disorders for the German newborn screening panel

Gramer, Gwendolyn; Fang-Hoffmann, Junmin; Feyh, Patrik; Klinke, Glynis; Peter, Markus; Okun, Jürgen G.; Hoffmann, Georg F.

doi:10.1007/s12519-018-0159-1

Cited by 20 publications

(26 citation statements)

References 45 publications

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“…In our data, there was a wide, overlapping range of C3 concentrations in both genetic and acquired vitamin B12 deficiency cases, with some of the highest values found in newborns determined to be unaffected. Two recent papers substantiate our finding that C3 is not a specific marker for disorders of propionate metabolism [13,33]. Within our data, there was also significant overlap in the C3/C2 values between IEM and false positive cases, which differed from the findings of other groups, who have suggested that C3/C2 provides better sensitivity and is more frequently high in genetic rather than acquired conditions [33,34].…”

Section: Discussionsupporting

confidence: 86%

“…The screening algorithm was later modified to include the ratio of propionylcarnitine to acetylcarnitine (C3/C2) as a primary biomarker. In 2013, Wisconsin lowered the cutoff value for C3 from <6.92 µM to <5.0 µM and implemented second-tier testing for methylmalonic acid (MMA) and methylcitric acid (MCA) to maximize the sensitivity and specificity of the screen, as shown by other published studies [ 8 , 9 , 10 , 11 , 12 , 13 ]. It is widely accepted that early ascertainment of MMA, MCA, and total homocysteine levels through second-tier testing aids in classification of the disease and its severity.…”

Section: Introductionmentioning

confidence: 99%

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Screening for Methylmalonic and Propionic Acidemia: Clinical Outcomes and Follow-Up Recommendations

Held

Singh

Schwoerer

2022

IJNS

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Wisconsin’s newborn screening program implemented second-tier testing on specimens with elevated propionylcarnitine (C3) to aid in the identification of newborns with propionic and methylmalonic acidemias. The differential diagnosis for elevated C3 also includes acquired vitamin B12 deficiency, which is currently categorized as a false positive screen. The goal of this study was to summarize screening data and evaluate their effectiveness at establishing diagnoses and categorizing false positive cases. All Wisconsin newborns born between 2013 and 2019 with a positive first-tier screen for C3 were included in this study. For each case the first- and second-tier newborn screening data and confirmatory test results were compiled. The clinical determination for each case was reviewed and categorized into groups: inborn error of metabolism, maternal B12 deficiency, infant B12 deficiency, and false positive. A review of the screening data showed a significant overlap in the concentration of biomarkers for newborns with genetic versus acquired disease. Additionally, a review of confirmatory test results showed incomplete ascertainment of maternal vitamin B12 status. The Wisconsin newborn screening program recommended a confirmatory testing algorithm to aid in the diagnosis of inborn errors of metabolism and acquired vitamin B12 deficiency.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Screening for Methylmalonic and Propionic Acidemia: Clinical Outcomes and Follow-Up Recommendations

Held

Singh

Schwoerer

2022

IJNS

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“…Maternal B12 deficiency was also the most common finding in newborn screening results published recently from Germany. 34…”

Section: Discussionmentioning

confidence: 99%

Compromised Vitamin B12 Status of Indian Infants and Toddlers

Mittal

Jain

2020

Food Nutr Bull

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Background: Vitamin B12 deficiency is prevalent worldwide especially in vegetarian communities. Its deficiency in early childhood may result in serious neurological and cognitive deficits. It is important to know the prevalence among our infants and toddlers so that nutritional policy changes could be suggested in this regard. Objective: To evaluate the vitamin B12 status of apparently healthy Indian children between 6 and 23 months of age. Methods: Apparently healthy Indian children (n = 210), of age 6 to 23 months, attending pediatric outpatient department were recruited and samples obtained to evaluate their hemogram and levels of vitamin B12, folate, and ferritin. Data were analyzed to obtain the mean levels and the proportion of participants deficient in vitamin B12. The dietary habits of the children were also analyzed and correlated with their vitamin B12 status. Results: Vitamin B12 deficiency was observed in 37.6% of the participants. Conclusions: There is a high prevalence of vitamin B12 deficiency in our infants and toddlers, and there is need to initiate supplement to prevent any possible neurological consequences. Early initiation of animal milk had a positive effect on the vitamin B12 status of the child though it was not significant.

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“…Therefore, based on published data [ 3 , 10 ], we developed a decision algorithm based on C3 and methionine and distinct ratios of these markers to select samples for measurement of tHCy as a second-tier marker ( Figure 1 ). Following a recent publication [ 12 ] and simultaneous with a change of the analytic instrument after 8 months of screening for suspected B12D, we adjusted the selection algorithm towards a higher number of samples selected via low methionine as well as a stronger emphasis on the C3/Met ratio ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Figure 1 shows the percentiles and absolute values (in µM) for the different cutoff values used for the two observation periods. Of note, referring to a recent publication [ 12 ], in the second period the selection scheme was modified to select more cases via the methionine- and less via the C3-dependent criteria with an emphasis on the C3/Met ratio ( Figure 1 ).…”

Section: Methodsmentioning

confidence: 99%

Elevated Homocysteine after Elevated Propionylcarnitine or Low Methionine in Newborn Screening Is Highly Predictive for Low Vitamin B12 and Holo-Transcobalamin Levels in Newborns

et al. 2020

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Early diagnostics and treatment of vitamin B12 deficiency (B12D) in infants, mainly maternally conditioned, is crucial in preventing possible developmental delay and neurological deficits. Currently, B12D is rarely listed in regular newborn screening panels and mostly regarded as an incidental finding. The aim of this study was to evaluate a targeted newborn screening strategy for detection of suspected B12D. A decision strategy based on the primary parameters propionylcarnitine and methionine for selection of samples to be analyzed for total homocysteine by mass spectrometry was established. Therefore, 93,116 newborns were initially screened. Concentrations of vitamin B12 and holotranscobalamin in serum were obtained from clinical follow-up analyses of recalled newborns. Moreover, an extremely sensitive mass spectrometric method to quantify methylmalonic acid from the dried blood spots was developed. Overall, 0.15% of newborns were screened positive for suspected B12D, of which 64% had vitamin B12 concentrations below 148 pM. We also determined a cutoff value for methylmalonic acid in dried blood spots indicative for B12D in infants. Overall, we calculated a prevalence of 92/100,000 for suspected B12D in the Austrian newborns. In conclusion, we present a screening algorithm including second-tier measurement of total homocysteine that allows detection of low B12 serum concentrations with a high detection rate and low false-positive rate.

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High incidence of maternal vitamin B12 deficiency detected by newborn screening: first results from a study for the evaluation of 26 additional target disorders for the German newborn screening panel

Cited by 20 publications

References 45 publications

Screening for Methylmalonic and Propionic Acidemia: Clinical Outcomes and Follow-Up Recommendations

Screening for Methylmalonic and Propionic Acidemia: Clinical Outcomes and Follow-Up Recommendations

Compromised Vitamin B12 Status of Indian Infants and Toddlers

Elevated Homocysteine after Elevated Propionylcarnitine or Low Methionine in Newborn Screening Is Highly Predictive for Low Vitamin B12 and Holo-Transcobalamin Levels in Newborns

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