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- Download full-text
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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