2 tables omitted
During 2001, neurologic impairment resulting from cobalamin (vitamin
B12) deficiency was diagnosed in two children in Georgia. The children
were breastfed by mothers who followed vegetarian diets.* This report summarizes
the two cases and provides guidance for health-care providers on identifying
and preventing cobalamin deficiency among breastfed infants of vegetarian
During August 2001, a girl aged 15 months was hospitalized for lethargy
and failure to thrive. She was born after a full-term pregnancy complicated
by prolonged nausea and vomiting. She was breastfed for 8 months, but the
extent (exclusivity) of breast milk consumed relative to other food was unknown.
Her mother reported following a vegan diet during the preceding 7 years and
took nutritional and vitamin supplements. The cobalamin content of the supplements
was unknown. When the child was aged approximately 8 months, organic whole-grain
cereals and fruit shakes were introduced, but she had a poor appetite and
vomited regularly. Her parents became concerned about her growth and development,
and she was evaluated by a pediatrician at age 15 months. The pediatrician
diagnosed failure to thrive, developmental delay, and severe macrocytic anemia.
The child was hospitalized, and cobalamin deficiency was diagnosed (marked
elevation [not quantified] of urine methylmalonic acid; serum B12:100
pg/mL [normal range: 210-911 pg/mL]).
The child received supplementary food by mouth and by nasogastric tube.
She also received 2 mg of cyanocobalamin and 3 mg of hydroxocobalamin intramuscularly
(IM) over 3 days. Three days later, she had partial complex seizures, which
stopped without anticonvulsants. A brain MRI indicated global cerebral atrophy.
The mother was treated with 1 mg of cobalamin IM.
At age 16 months, the child was seen in a genetics clinic to eliminate
possible genetic causes of her neurologic deficiency. At age 28 months, her
developmental skills ranged from 9 months for fine motor skills to 18 months
for gross motor skills. Her expressive language was at 10 months, and her
receptive language was at 12 months. At age 32 months, she had made developmental
progress but continued to have developmental delays, especially in speech
and language. She was prescribed daily sublingual cobalamin supplements.
During March 2001, a boy aged 30 months with failure to thrive and mild
global developmental delays was taken to a genetics clinic. He was born after
a full-term pregnancy and breastfed exclusively until age 9 months. The mother
reported following a vegetarian diet during the preceding 20 years, with negligible
amounts of meat, fish, and dairy products. She reported intermittent intake
of a vitamin supplement (TwinLab® Stress B Complex Caps, containing 250
mcg of "cobalamin concentrate," according to the label). When the boy was
age 9 months, the health-care provider and his parents became concerned about
the child's growth and development. His diet was supplemented with fruit and
dry cereals to improve growth. When this was unsuccessful, he underwent a
frenectomy at age 11 months to free tongue movements and improve coordination
of swallowing and chewing. Despite this intervention, growth was inadequate.
His diet was supplemented with soy- and cow's milk–based formulas. He
tolerated neither and started a multigrain nondairy formula (Multigrain Milk®)
in addition to fruit, vegetables, chicken, an unknown vitamin supplement,
and a product called Greens Plus® (no cobalamin content listed on label).
Because of poor motor and speech development at age 11 months, the child was
evaluated by a developmental pediatrician, who ordered genetic and metabolic
studies and prescribed speech, occupational, and physical therapies. The child
had persistent elevation of urine methylmalonic acid on three occasions but
received no treatment for cobalamin deficiency until after the third measurement,
which was ordered for a genetics clinic evaluation.
After diagnosis of cobalamin deficiency was confirmed at the genetics
clinic (moderate peak [not quantified] of urine methylmalonic acid; serum
B12: 149 pg/mL), the child was treated with 1 mg of hydroxocobalamin
IM (2 weeks apart) and 1 mg sublingual doses daily. The mother also was treated
with 1 mg of oral cobalamin daily. At the genetics clinic visit, the child
had no frank neurologic signs but exhibited delays in speech. He experienced
catch-up development in motor skills and completed physical therapy but continued
speech, language, and occupational therapies. Approximately 6 months after
beginning treatment, the child exhibited slight speech and fine motor skill
delays but had age-appropriate gross motor skills. The parents reported that
the child was administered a 1 mg cobalamin sublingual preparation every other
R Muhammad, MD, P Fernhoff, MD, Dept of Pediatrics, Emory Univ, Atlanta,
Georgia. S Rasmussen, MD, Div of Birth Defects and Developmental Disabilities;
B Bowman, PhD, Div of Diabetes Translation; K Scanlon, PhD, L Grummer-Strawn,
PhD, L Kettel Khan, PhD, Div of Nutrition and Physical Activity, National
Center for Chronic Disease Prevention and Health Promotion; M Jefferds, PhD,
EIS Officer, CDC.
The most common cause of cobalamin deficiency in infants and young children
is maternal dietary deficiency,2 which generally
manifests in breastfed infants at age 4-8 months.3 This
deficiency is difficult to diagnose because of nonspecific symptoms.4 The two children described in this report had cobalamin
deficiency and manifested multiple symptoms of undernutrition, particularly
growth failure. After treatment for cobalamin deficiency, both children showed
marked improvement in cobalamin status and development. In some cases, irreversible
neurologic damage results from prolonged cobalamin deficiency, but the extent
and degree of disability depends on the deficiency severity and duration.4 Seizures after treatment have been reported previously
in children with cobalamin deficiency, although whether these are secondary
to the treatment or to the underlying condition is unknown.5
The prevalence of cobalamin deficiency is unknown for children aged
<4 years. No clinical practice guidelines exist for diagnosing cobalamin
deficiency in young children. Methylmalonic acid is a sensitive and specific
indicator of cobalamin deficiency; holotranscobalamin II, total homocysteine,
and serum B12 also are useful indicators.2,4,6 Macrocytic
anemia and other hematologic indices are not appropriate screening tools.4
Persons who follow vegetarian diets should ensure adequate cobalamin
intake. The only reliable unfortified sources are animal products, including
meat, dairy products, and eggs. Most naturally occurring plant sources of
cobalamin are not bioavailable; however, plant foods fortified with cobalamin,
such as some cereals, meat analogs, soy or rice beverages, and nutritional
yeast,7 can be reliable and regular sources.
The content of fortified food is usually listed on the food label and ingredient
list. Fortified food and supplements made from cobalamin (e.g., cyanocobalamin)
provide cobalamin that is physiologically active in humans.6 Products
whose labels do not specify cobalamin and list only vitamin B12 might
include nonbioavailable sources. Vegetarians, particularly women during pregnancy
and lactation, should be knowledgeable about the cobalamin content of their
food or seek nutritional advice. Few of the common infant-toddler cereals
are fortified with cobalamin.8 Breast milk
from mothers with adequate nutritional status, infant formula, cow's milk,
or a cobalamin-fortified soy or rice beverage provide a cobalamin source for
infants and children. If it is not possible to acquire the recommended dietary
intake of cobalamin through food, a daily supplement should be taken that
contains at least the recommended dietary intake of cobalamin from a reliable
Health-care providers should be vigilant about the potential for cobalamin
deficiency in breastfed children of vegetarian mothers. Potential cobalamin
deficiency should be included in the differential diagnosis when assessing
young children of vegetarian mothers who have symptoms consistent with cobalamin
deficiency, including failure to thrive, developmental delay, neurologic/psychiatric
manifestations, and hematologic abnormalities.4
Health-care providers who care for mothers in the preconceptional, prenatal,
and postpartum periods and their young children should ask pregnant and lactating
mothers about their diets to identify those who are vegetarians. Pregnant
and lactating women should eat foods rich in cobalamin or take a daily supplement
containing at least the recommended dietary intake of cobalamin. For those
eating no or very limited food of animal origin or a known cobalamin source,
a cobalamin assessment is indicated. If lactating mothers are cobalamin deficient,
their infants should be evaluated for cobalamin deficiency and treated appropriately.
*Vegetarian diets vary. For example, vegan diets generally do not include
food of animal origin, whereas lacto-ovovegetarian diets include dairy products
and eggs. In this report, the term "vegetarian" refers to all diets that limit
food of animal origin.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 6
Customize your page view by dragging & repositioning the boxes below.
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.