Maternal and neonatal vitamin B12 deficiency detected through expanded newborn screening--United States, 2003-2007.
ABSTRACT The incidence of neonatal vitamin B12 (cobalamin) deficiency because of maternal deficiency was determined by surveying state newborn screening programs. Thirty-two infants with nutritional vitamin B12 deficiency were identified (0.88/100,000 newborns). Pregnant women should be assessed for their risk of inadequate intake/malabsorption of vitamin B12.
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ABSTRACT: Low vitamin B12 and folate levels in expectant mothers may lead to low stores in babies. The aim of this study was to determine the frequencies of vitamin B12 and folate deficiencies in pregnant women and neonates, and to assess the effect of maternal vitamin status on babies' vitamin levels in the Aegean region of Turkey, where the Mediterranean diet (mainly fresh fruits and vegetables) is adopted. We studied 72 pregnant women and their singleton-term babies. Venous blood samples of expectant mothers were collected 1 h before delivery and cord blood of babies were obtained at birth. The mean vitamin B12 in maternal and cord blood serum was 163.1 ± 72.0 pg/mL and 146.2 ± 102.5 pg/mL, and the mean folate, 9.8 ± 4.8 ng/mL and 15.8 ± 3.8 ng/mL, respectively. There were statistically significant correlation between maternal and cord blood serum vitamin B12 (r = 0.61, P = .04) and folate levels (r = 0.65, P < .001). 70.8% of the mothers and 83.9% of the babies were vitamin B12 deficient (<200 pg/mL). Neither group showed folate deficiency. The mean level of vitamin B12 in mothers significantly varied by the type of diet (241.6 (72.1) pg/mL versus 155.9 (68.2) pg/mL; P = .012). Vitamin B12 deficiency in pregnant women and neonates may be a public health problem in our community. The Mediterranean diet in these vulnerable groups may be an aggravating factor for vitamin B12 deficiency. Prenatal screening of all expectant mothers, prenatal supplementation of vitamin B12, and an increase in animal-source food intake may improve expectant mother's vitamin B12 level.Pediatric Hematology and Oncology 10/2013; · 0.90 Impact Factor
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ABSTRACT: Objectives Besides the inherited form, vitamin B12 deficiency may be due to diet restrictions or abnormal absorption. The spread of newborn screening programs worldwide has pointed out that non inherited conditions are mainly secondary to a maternal deficiency. Aim of our work was to study seven cases of acquired vitamin B12 deficiency detected during our newborn screening project. Moreover, we aimed to evaluate vitamin B12 and related biochemical parameters status on delivering female to verify the consequences on newborns of eventually altered parameters. Design & Methods 35000 newborns were screened; those showing altered propionyl carnitine (C3) underwent second-tier test for methylmalonic acid (MMA) on dried blood spot (DBS). Subsequently, newborns positive to the presence of MMA on DBS and their respective mothers underwent further tests: serum vitamin B12, holo-transcobalamin (Holo-TC), folate and homocysteine; newborns were also tested for urinary MMA content. A control study was conducted on 203 female that were tested for the same parameters when admitted to hospital for delivery. Results Approximately 10 % of the examined newborns showed altered C3. Among these, seven cases of acquired vitamin B12 deficiency were identified (70 % of the MMA-positive cases). Moreover, our data show an high frequency of vitamin B12 deficiency in delivering female (approximately 48 % of examined pregnants). Conclusions We suggest to monitor vitamin B12 and Holo-TC until delivery and to reconsider the reference interval of vitamin B12 for a better identification of cases at risk. Finally, newborns from mothers with low or borderline levels of vitamin B12 should undergo second-tier test for MMA; in the presence of MMA they should be supplemented with vitamin B12 to prevent adverse effects related to vitamin B12 deficiency.Clinical Biochemistry 09/2014; · 2.23 Impact Factor
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ABSTRACT: Abstract Inborn errors of metabolism (IEM) are a phenotypically and genetically heterogeneous group of disorders caused by a defect in a metabolic pathway, leading to malfunctioning metabolism and/or the accumulation of toxic intermediate metabolites. To date, more than 1000 different IEM have been identified. While individually rare, the cumulative incidence has been shown to be upwards of 1 in 800. Clinical presentations are protean, complicating diagnostic pathways. IEM are present in all ethnic groups and across every age. Some IEM are amenable to treatment, with promising outcomes. However, high clinical suspicion alone is not sufficient to reduce morbidities and mortalities. In the last decade, due to the advent of tandem mass spectrometry, expanded newborn screening (NBS) has become a mandatory public health strategy in most developed and developing countries. The technology allows inexpensive simultaneous detection of more than 30 different metabolic disorders in one single blood spot specimen at a cost of about USD 10 per baby, with commendable analytical accuracy and precision. The sensitivity and specificity of this method can be up to 99% and 99.995%, respectively, for most amino acid disorders, organic acidemias, and fatty acid oxidation defects. Cost-effectiveness studies have confirmed that the savings achieved through the use of expanded NBS programs are significantly greater than the costs of implementation. The adverse effects of false positive results are negligible in view of the economic health benefits generated by expanded NBS and these could be minimized through increased education, better communication, and improved technologies. Local screening agencies should be given the autonomy to develop their screening programs in order to keep pace with international advancements. The development of biochemical genetics is closely linked with expanded NBS. With ongoing advancements in nanotechnology and molecular genomics, the field of biochemical genetics is still expanding rapidly. The potential of tandem mass spectrometry is extending to cover more disorders. Indeed, the use of genetic markers in T-cell receptor excision circles for severe combined immunodeficiency is one promising example. NBS represents the highest volume of genetic testing. It is more than a test and it warrants systematic healthcare service delivery across the pre-analytical, analytical, and post-analytical phases. There should be a comprehensive reporting system entailing genetic counselling as well as short-term and long-term follow-up. It is essential to integrate existing clinical IEM services with the expanded NBS program to enable close communication between the laboratory, clinicians, and allied health parties. In this review, we will discuss the history of IEM, its clinical presentations in children and adult patients, and its incidence among different ethnicities; the history and recent expansion of NBS, its cost-effectiveness, associated pros and cons, and the ethical issues that can arise; the analytical aspects of tandem mass spectrometry and post-analytical perspectives regarding result interpretation.Critical Reviews in Clinical Laboratory Sciences 11/2013; 50(6):142-62. · 3.78 Impact Factor
Newborn Screening—United States, 2003–2007
Cynthia F. Hinton, PhD, MS, MPH, Jelili A. Ojodu, MPH, Paul M. Fernhoff, MD, Sonja A. Rasmussen, MD, MS,
Kelley S. Scanlon, PhD, and W. Harry Hannon, PhD
The incidence of neonatal vitamin B12(cobalamin) deficiency because of maternal deficiency was determined by
surveying state newborn screening programs. Thirty-two infants with nutritional vitamin B12deficiency were iden-
tified (0.88/100 000 newborns). Pregnant women should be assessed for their risk of inadequate intake/malabsorp-
tion of vitamin B12. (J Pediatr 2010;157:162-3)
gastric bypass.1Unrecognized neonatal vitamin B12 defi-
ciency worsens if the infant is breastfed without vitamin B12
supplementation. Clinical presentation of vitamin B12defi-
ciency is often nonspecific (eg, developmental delay and fail-
ure to thrive), which can lead to a delay in diagnosis and
treatment.1,2Irreversible neurologic damage results from
gree of disability depends on the severity and duration of the
deficiency.1Thus early detection and intervention is critical.
In newborn screening (NBS), tandem mass spectrometry
(MS/MS) detects many metabolic disorders including those
that result in methylmalonic acidemia (indicated by eleva-
tions of the acylcarnitines, propionylcarnitine [C3] or meth-
ylmalonylcarnitine [C4DC]).3All 50 states and the District of
to identify vitamin B12deficiency, an important and treatable
condition.5,6NBS programs refer newborns with elevated
levels of C3 or C4DC to a metabolic center for testing and
malonic acid, a sensitive and specific indicator of infant B12
deficiency. Infants subsequently diagnosed with nutritional
vitamin B12deficiency are not routinely recorded in NBS
records. Therefore the incidence of neonatal vitamin B12
deficiency resulting from maternal deficiency is unknown.1,7
auses of maternal vitamin B12deficiency include ad-
of animal products, pernicious anemia, and previous
A 10-question survey was distributed to each NBS follow-up
program in 50 states and 2 territories. Respondents replied
through a web-based survey collection tool. Reminder
e-mails were sent to nonresponders at 3 and 6 weeks after
the survey was launched in September 2008. Calls were
made when no response was received. Programs were asked
about their use of MS/MS during the study period (January
levels of C3 or C4DC acylcarnitines, and whether newborns
with increased levels had been identified during this time pe-
riod. The survey also collected information on confirmation
of nutritional vitamin B12deficiency among the infants with
increased levels of C3 or C4DC and whether the mothers of
infants with nutritional deficiency adhered toa strict vegetar-
ian (vegan) diet, had undergone gastric bypass surgery, had
autoimmune pernicious anemia, or had nutritional defi-
ciency resulting from an unknown, or other, cause. Informa-
tion on how cases were confirmed was beyond the scope of
Thirty-one programs responded. This represents a response
rate of 67% among the 46 programs that used MS/MS during
all or at least part of the study period.3Of these, 12 state pro-
grams were able to provide data on detection of nutritional
vitamin B12deficiency among newborns. In these 12 states,
32 newborns with increased levels of C3 or C4DC acylcarni-
tines because of nutritional vitamin B12deficiency were de-
tected. Seven infants were born to women who adhered to
a vegan or strict vegetarian diet, 3 were born to women
who previously had undergone gastric bypass, and 3 were
born to women identified with autoimmune pernicious ane-
mia. Nineteen cases were identified as nutritional in origin
From the National Center on Birth Defects and Developmental Disabilities (C.H.,
S.R.), the National Center for Environmental Health (P.F., W.H.), and the National
Center for Chronic Disease Prevention and Health Promotion (K.S.), Centers for
Human Genetics, Emory University School of Medicine (P.F.), Atlanta, GA; and the
Association of Public Health Laboratories (J.O.), Silver Spring, MD
The findings and conclusions in this report are those of the authors and do not
necessarily represent the official position of the Centers for Disease Control and
Prevention. The authors declare no conflicts of interest.
0022-3476/$ - see front matter. Copyright ª 2010 Mosby Inc.
All rights reserved. 10.1016/j.jpeds.2010.03.006
Tandem mass spectrometry
but of unknown cause. To estimate the rate of nutritional vi-
tamin B12deficiency from 2003–2007, the number of live
births was obtained for the reporting 12 states for the study
period.8Confidence intervals were calculated with a Poisson
distribution. The rate of nutritional vitamin B12deficiency
was 0.88/100 000 births (95% CI = 0.60-1.26).
Identification of newborns with nutritional vitamin B12defi-
ciency is an additional benefit of NBS programs. However,
the finding that several states were unable to provide details
that feedback to state NBS programs about these conditions
lonic acidemia to be ‘‘false-positive’’ results or outside the
realm of their program’s intent. Timely detection of nutri-
tional vitamin B12deficiency and intervention can reduce
or prevent morbidity and mortality rates associated with
This study is subject to several limitations. Not all state
NBS programs responded to the survey or to the question re-
lated to detection of acylcarnitines. Programs that did not re-
spond might have been less likely to detect infants with this
deficiency, resulting in an overestimate of the incidence.
The sensitivity of MS/MS for NBS screening nutritional vita-
min B12deficiency is unknown6; these results could be over-
estimates or underestimates. We lack information on how
maternal conditions were determined, which might affect
the number of cases of unknown nutritional cause. The use
of live births as the denominator assumes that 100% of new-
borns were screened, but the actual number of screened new-
borns may be slightly less. This limitation is unlikely to have
a significant effect on our estimated incidence.
Vitamin B12deficiency should be considered in infants
who exhibit failure to thrive, developmental delay, neuro-
logic or behavioral disorders, and who were born to mothers
at risk for this deficiency.1NBS programs should consider
newborns diagnosed with confirmed nutritional vitamin
B12deficiency to be true-positive, not false-positive, cases.9
Future improvements inthefeedback frommetabolic centers
to NBS follow-up programs will result in a better estimate of
the incidence of this preventable nutritional disorder.
Finally, health-care providers should ask pregnant and lac-
tating women about their diet and medical history to identify
those who are at risk for an inadequate intake or malabsorp-
tion of vitamin B12. Providers should not rely solely on mea-
surement of serum vitamin B12levels but should measure
plasma methylmalonic acid and total homocysteine to diag-
nose vitamin B12deficiency in at-risk women.9If a deficiency
is suspected, then both the mother and the infant should be
promptly evaluated for vitamin B12deficiency.1n
Submitted for publication Oct 6, 2009; last revision received Dec 23, 2009;
accepted Mar 9, 2010.
Reprint requests: Cynthia F. Hinton, PhD, MS, MPH, Centers for Disease
Control and Prevention, 1600 Clifton Rd, NE, MS E-86, Atlanta, GA 30333. E-
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syndrome of infantile cobalamin deficiency: developmental regression
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4. National Newborn Screening Information Center. Available from: http://
www2.uthscsa.edu/nnsis/. [cited January 7, 2009].
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