Vitamin D Insufficiency Is Associated With Challenge-Proven Food Allergy in

Infants
Elizabeth J. Feuille and Anna H. Nowak-Wegrzyn
Pediatrics 2013;132;S7
DOI: 10.1542/peds.2013-2294I

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/132/Supplement_1/S7.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2013 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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between 18 and 35 years, and had lived in northern

Manhattan or the South Bronx for at least 1 year.
METHODS. Urine BPA concentrations were measured in
spot urine samples collected from mothers during the
third trimester and from children at ages 3, 5, and 7 years.
During visits at ages 5, 6, and 7 years, questionnaires were
used to assess for wheeze in the preceding 12 months.
Asthma diagnosis was determined once between ages 5
and 12 years by a physician by using history and physical
as well as pre- and postbronchodilator testing. At 7- and
11-year visits, fraction of exhaled nitric oxide values were
measured. At the 7-year visit, sero-atopy was determined
by measuring specic IgE levels to aeroallergens, with
sero-atopy dened as a specic IgE level .0.35. Odds
ratios (ORs) for development of wheeze, asthma, and
allergic sensitization were determined by using logistic
and linear regression models.
RESULTS. BPA concentrations at ages 3, 5, and 7 years were
associated with a diagnosis of asthma at ages 5 to 12 years
(ORs were 1.5, 1.4, and 1.5 and P values were .005, .03, and
.04, respectively). Urinary BPA concentration at age 3 years
was associated with wheeze at age 5 years (OR: 1.4; P 5
.02) and 6 years (OR: 1.4; P 5 .02). BPA concentration at
age 7 years was positively associated with wheeze at age 7
years (OR: 1.4; P 5 .04) and fraction of exhaled nitric oxide
values (b 50.1, P 5 .02). Contrary to the authors hypothesis, prenatal urinary BPA concentrations were inversely associated with wheeze at age 5 years (OR: 0.7; P 5
.02). BPA concentrations measured at ages 3, 5, and 7 years
were not associated with sero-atopy at age 7 years (P 5 .8).
CONCLUSIONS. Results of this study suggest that BPA exposure

increases risk of airway hyperresponsiveness in children.

REVIEWER COMMENTS. This is the rst study to report an association between urinary BPA concentrations and asthma
in children. This study is limited by use of spot urine
samples to assess exposure to BPA, which has a half-life of
6 hours. Further studies may use more rigorous methods
of assessing BPA exposure and additionally explore the
role of BPA exposure in development of other atopic
diseases such as food allergy and atopic dermatitis.
URL: www.pediatrics.org/cgi/doi/10.1542/peds.20132294H

Elizabeth J. Feuille, MD
Anna H. Nowak-We grzyn, MD
New York, NY

who reside farther from the equator, investigators sought

to determine the association between vitamin D and food
allergy.
STUDY POPULATION. From 2007 to August 2011, a total of

7134 infants between 11 and 15 months of age (inclusive)

were approached during immunization visits at 120
locations throughout Australia.
METHODS. A total of 5120 infants underwent skin-prick
testing (SPT) to peanut, egg, sesame, and cows milk or
shrimp. Infants with a detectable wheal $1 mm as well
as a random sample of infants with negative SPT were
referred to a food allergy center for oral food challenge
and repeat SPT using an extended panel of foods. Infants
were deemed food allergic if they had both positive food
challenge by objective criteria and an SPT wheal size $2
mm or a specic IgE $0.35 kUA/L. For foods on the
extended spectrum SPT, a wheal size $8 mm was
considered indicative of food allergy. Infants were
labeled food-sensitized tolerant if they had negative
oral food challenge despite a wheal size $2 mm or a
specic IgE $0.35 kUA/L. Blood samples were obtained
for measurement of 25-hydroxyvitamin D3 levels and
were seasonally adjusted. Vitamin D deciency was
dened as a serum level #25 nmol/L (,10 ng/mL),
insufciency as 25 to 50 nmol/L (1020 ng/mL), and
sufciency as .50 nmol/L (equivalent to 20 ng/mL).
Associations between vitamin D and food allergy were
analyzed by using multiple logistic regression, adjusting
for potential risk factors and confounding variables.
RESULTS. A total of 928 (85%) of the infants with positive
SPT test and 197 (20%) controls visited the food allergy
referral center. Complete data were available for a total of
481 infants. Among those classied as food sensitized
(361), infants with vitamin D insufciency were 3 times
more likely to have food allergy than to be food-sensitized
tolerant. For infants of Australian-born parents (271),
vitamin Dinsufcient infants were 3 times more likely
to have any food allergy (P 5 .032), 10 times more likely
to have multiple food allergies ($2) (P 5 .014), 11 times
more likely to have peanut allergy (P 5 .006), and 3
times more likely to have egg allergy (P 5 .025). The
relationship between vitamin D status and food allergy
was not signicant for infants of foreign-born parents.
Vitamin D insufciency did not increase odds of the
infant having eczema.
CONCLUSIONS. This is the rst study to demonstrate an as-

Vitamin D Insufciency Is Associated With

Challenge-Proven Food Allergy in Infants
Allen KJ, Koplin JJ, Ponsonby AL, et al. J Allergy Clin
Immunol. 2013;131(4):11091116, e1e6
PURPOSE OF THE STUDY. In light of epidemiologic studies that
show increased prevalence of food allergy in populations

sociation between challenge-proven food allergy and

vitamin D levels at 12 months, particularly among
infants with allergic sensitization.
REVIEWER COMMENTS. This study provides supporting evidence for the hypothesis that vitamin D insufciency is
a risk factor for development of food allergy. It adds to the
growing body of literature suggesting that vitamin D

PEDIATRICS Volume 132, Supplement 1, October 2013

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S7

modies risk of allergic diseases such as asthma, allergic

rhinitis, and food allergy, although, notably, the investigators did not nd an association between vitamin D
levels and eczema. Further study is needed to determine
whether correction of vitamin D insufciency would
result in decreased food allergy and increased tolerance
among those sensitized.
URL: www.pediatrics.org/cgi/doi/10.1542/peds.20132294I

Elizabeth J. Feuille, MD
Anna H. Nowak-We grzyn, MD
New York, NY

Maternal and Newborn Vitamin D Status and Its

Impact on Food Allergy Development in the
German LINA Cohort Study
Weisse K, Winkler S, Hirche F, et al. Maternal and
newborn vitamin D status and its impact on food allergy
development in the German LINA cohort study. Allergy.
2013;68(2):220228
PURPOSE OF THE STUDY. To investigate the relationship of

maternal and cord blood vitamin D levels on atopic

outcomes in early childhood.

to food allergens (aOR: 1.59; 95% CI: 1.042.45) in the

second year of life. Cord blood 25(OH)D3 levels were
associated with diagnosis of food allergy in the second
year of life (aOR: 4.65; 95% CI: 1.5014.48) and negatively
correlated with regulatory T-cell numbers (R 5 20.168,
P 5 .031).
CONCLUSIONS. Higher vitamin D levels in pregnancy and at

birth were associated with a higher risk of food allergy

and lower numbers of regulatory T cells.
REVIEWER COMMENTS. The role of vitamin D in the development of atopic disease remains unclear. Whereas some
previous studies have suggested that maternal vitamin D
deciency may increase the risk of developing allergy,
and may even be a key reason behind the rapidly rising
prevalence of food allergy, this study suggests the complete opposite. Although vitamin D supplementation may
be advised for many reasons, the prevention of allergy is
not yet one of them.
URL: www.pediatrics.org/cgi/doi/10.1542/peds.20132294J

Karen A. Robbins, MD
Robert A. Wood, MD
Baltimore, MD

STUDY POPULATION. A total of 378 mother-infant pairs from

Leipzig, Germany, a subgroup of the LINA (Lifestyle and

environmental factors and their Inuence on Newborns
Allergy risk) cohort study, were included. Mothers with
immune or infectious disease concerns during the
pregnancy were excluded.

Environmental and Demographic Risk Factors

for Egg Allergy in a Population-Based Study of
Infants
Koplin JJ, Dharmage SC, Ponsonby A-L, et al; HealthNuts
Investigators. Allergy. 2012;67(11):14151422

METHODS. Blood samples were collected from expectant

mothers at the 34th week of gestation and from infant cord
blood at delivery for measurement of vitamin D (25[OH]D3).
Regulatory T cells were also quantied from cord blood
samples. Total IgE and allergen-specic IgE measurements
were determined at birth (cord blood) and at 1 and 2 years
of age in participating children. During pregnancy and at
the childrens rst and second birthdays, parents completed questionnaires regarding family history of atopy,
housing and environmental conditions, and atopic outcomes of their children (doctor-diagnosed atopic dermatitis and/or food allergy or parental report of symptoms
consistent with atopic dermatitis).

PURPOSE OF THE STUDY. To determine the inuence of a variety

of environmental and demographic factors on the development of challenge-conrmed egg allergy in infants.

RESULTS. A high correlation was observed between maternal and cord blood 25(OH)D3 levels (R 5 0.812, P #
.001). Most pregnant women included in the study were
either 25(OH)D3 decient (,20 ng/mL; 44%) or insufcient (2029.9 ng/mL; 25.7%), and few received vitamin D supplementation during pregnancy. Maternal
25(OH)D3 levels were positively associated with childrens risk of diagnosis of food allergy (adjusted odds ratio
[aOR]: 3.66; 95% condence interval [CI]: 1.369.87) in
the second year of life or within the 2-year lifetime period
(aOR: 1.91; 95% CI: 1.093.37), and with sensitization

S8

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STUDY POPULATION. The study included 5276 infants pre-

senting for their 12-month immunizations in Melbourne,

Australia, with a focus on 453 infants with egg allergy
conrmed by oral food challenge.
METHODS. At the time of initial testing, parents completed
a questionnaire regarding a variety of environmental exposures and demographic factors. Infants underwent skinprick testing (SPT) to egg regardless of history of reaction.
Infants with a positive SPT then underwent additional
testing, including allergen-specic immunoglobulin E
testing by ImmunoCAP and an oral food challenge to
egg. Infants with SPT .2 mm and positive challenge
were deemed egg allergic. Multivariable logistic regression
was used to determine factors associated with challengeconrmed egg allergy. Adjustment was made for multiple
confounding variables.
RESULTS. Factors that demonstrated a low risk for the development of egg allergy included having older siblings
and having a dog in the house. Having siblings ,6 years
of age and having multiple siblings showed an even

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on November 13, 2014

Vitamin D Insufficiency Is Associated With Challenge-Proven Food Allergy in

Infants
Elizabeth J. Feuille and Anna H. Nowak-Wegrzyn
Pediatrics 2013;132;S7
DOI: 10.1542/peds.2013-2294I
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright 2013 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on November 13, 2014