Food, drug, insect sting allergy, and anaphylaxis
Early exposure to cow’s milk protein is protective against
IgE-mediated cow’s milk protein allergy
Yitzhak Katz, MD,a,cNelly Rajuan, MSc,c* Michael R. Goldberg, MD, PhD,aEli Eisenberg, PhD,dEli Heyman, MD,b
Adi Cohen, MD,aand Moshe Leshno, MD, PhDe
Zerifin and Tel Aviv, Israel
Background: The diversity in the perceived prevalence,
recovery, and risk factors for cow’s milk allergy (CMA)
necessitated a large-scale, population-based prospective
Objective: We sought to determine the prevalence,
cross-reactivity with soy allergy, and risk factors for the
development of CMA.
Methods: In a prospective study the feeding history of 13,019
infants was obtained by means of telephone interview (95.8%)
or questionnaire (4.2%). Infants with probable adverse
reactions to milk were examined, skin prick tested, and
Results: Ninety-eight percent of the cohort participated in the
study. The cumulative incidence for IgE-mediated CMA was
0.5% (66/13,019 patients). The mean age of cow’s milk protein
(CMP) introduction was significantly different (P < .001)
between the healthy infants (61.6 6 92.5 days) and those with
IgE-mediated CMA (116.1 6 64.9 days). Only 0.05% of the
infants who were started on regular CMP formula within the
first 14 days versus 1.75% who were started on formula between
the ages of 105 and 194 days had IgE-mediated CMA (P <.001).
The odds ratio was 19.3 (95% CI, 6.0-62.1) for development of
IgE-mediated CMA among infants with exposure to CMP at the
age of 15 days or more (P < .001). Sixty-four patients with
IgE-mediated CMA tolerated soy, and none had a proved
allergy to soy.
Conclusions: IgE-mediated CMA is much less common than
generally reported. Early exposure to CMP as a supplement to
breast-feeding might promote tolerance. Finally, soy is a
reasonable feeding alternative in patients with IgE-mediated
CMA. (J Allergy Clin Immunol 2010;126:77-82.)
Key words: IgE-mediated cow’s milk allergy, soy allergy, breast-
feeding, skin prick test, oral challenge
Cow’s milk protein (CMP) allergy is one of the most common
food allergies and is potentially fatal.1The reported incidence of
CMP allergy is in the range of 2% to 5%, of which only 60% are
IgE mediated.2,3The rate of reported growing out of the allergy
standardized criteria in diagnosing this illness.
The latter source of confusion has been recognized as early as
1957.5It is now well accepted that in patients with IgE-CMA the
minutes, the recommended and practiced time interval in food
reaction.3,10Other immunologically non–IgE-mediated reactions
to food are cell mediated, such as food protein–induced enteroco-
litis syndrome (FPIES) or a mixed IgE-associated and cell-
mediated reaction, such as atopic dermatitis and eosinophilic
esophagitis.10Other clinical entities, including infantile colic,
isolated failure to thrive, or chronic rhinitis and recurrent wheez-
ing, are no longer considered to be in the spectrum of CMA.10
A broad classification for CMA necessitates following a truly
large cohort to obtain meaningful data. Armed with the knowl-
edge of the differing diagnostic criteria used in previous studies,
was exclusively IgE mediated. All newborns (13,234) born over a
Our recruitment of greater than 98% of the cohort allowed for
definitive answers regarding the incidence of IgE-CMA, the
potential for cross-reactivity of IgE-CMA to soy allergy, and
novel conclusions regarding risk factors for the development of
The research protocol was approved by the Helsinki Review Board of the
Assaf Harofeh Medical Center. All newborns (13,234) born from June 10,
2004, to June 30, 2006, at the Assaf-Harofeh Hospital (Zerifin, Israel) were
enrolled. Contact details were verified after the routine anticipatory guidance
session in which breast-feeding was encouraged but other alternative CMP-
based feeding regimens were also discussed. The purpose of the project was
explained, and the mothers were asked to fill out a questionnaire or,
alternatively, to contact the allergy clinic immediately after any adverse
reaction suspected to be related to the initiation of CMP-based feeding or, in
Fromathe Allergy and Immunology Institute andbthe Department of Neonatology, ‘‘As-
saf-Harofeh’’ Medical Center, Zerifin, andcthe Department of Pediatrics, Sackler Fac-
ulty of Medicine,
Astronomy, andethe Faculty of Management and Sackler Faculty of Medicine, Tel
Parts of these data were presented in abstract form at the 2009 American Academy of
Allergy, Asthma & Clinical Immunology meeting in Washington, DC.
Supported by the Israel Dairy Board.
*In partial fulfillment of a PhD thesis at the Sackler School of Medicine, Tel Aviv, Israel.
Israel Dairy Board. The rest of the authors have declared that they have no conflict of
Received for publication January 25, 2010; revised April 21, 2010; accepted for publica-
tion April 21, 2010.
Available online June 11, 2010.
Reprint requests: Yitzhak Katz, MD, Institute of Allergy and Immunology, Assaf Haro-
feh Medical Center, Zerifin, Israel. E-mail: email@example.com.
? 2010 American Academy of Allergy, Asthma & Immunology
dthe Raymond and Beverly Sackler School of Physics and
CMA: Cow’s milk allergy
CMP: Cow’s milk protein
FPIRES: Food protein–induced enterocolitis syndrome
IgE-CMA: IgE-mediated cow’s milk allergy
OFC: Oral food challenge
SPT: Skin prick test
the lack of any unusual event, 14 to 30 days after the initiation of CMP-based
about the project, a prestamped envelope, and a card with contact details. An
explanatory letterabout the projectwas distributed to all healthcare providers
in the region.
If the parents did not contact the clinic by the age of 3 months, a telephone
or mail contact was established, and the questionnaire was provided. The
questionnaire requested demographic details; the length of exclusive breast-
feeding, almost exclusive (including ingestion of water and juice) breast-
feeding, and partial breast-feeding; the age of introduction of CMP-based
formula on a regular basis (at least once daily); and whether any adverse
responses to CMP were noted. If the infant was still breast-fed at the time of
the contact, the mother was encouraged to continue breast-feeding, and
contacts were maintained at 2-month intervals until the infant started to
consume CMP. Any parent noting a possible adverse event related to CMP
(n 5381) was interviewedby oneof the investigators (N.R.),and theirinfants
were invited for an examination. Fifty-two patients refused to have a full
examination. These 52 had a second interview by another investigator (Y.K.)
during which another attempt to recruit the infant for examination was done
and a presumed diagnosis was made. Each final diagnosis was made
independently by 2 investigators (Y.K. and A.C.). Cases of disagreement
(2 cases) were resolved in a conjoint discussion. In the clinic, the patient was
examined and an SPTand an open challenge6were offered, unless clinically
SPTs were done to CMP, soy, a negative control, and histamine (1 mg/mL;
ALK-Abello ´, Port Washington, NY) by using the volar arm and reading the
Challenge to cow’s milk formula was carried out with Materna (Maabarot
Products Ltd,Maabarot,Israel) infant formulaby usingincreasingdoses from
a 1:10 diluted formula of 1.0 mL (2.7 mg of CMP) up to 120 mL (3.24 g of
CMP) every 30 minutes. The challenge was terminated if a cutaneous,
respiratory, gastrointestinal, or systemic response was observed. In case of a
negative challenge result, the infants were observed for 3 hours, and a
subsequent contact was made 2 weeks later inquiring about their infants’
Inc, Chicago, Ill) and MATLAB (Mathworks, Inc, Natick, Mass). The risk
factors that were extracted from the maternity files were entered into the
hospital database, NAMER, an SAP-based system. The data were then trans-
ferred to Microsoft Access and Excel for analysis. Comparisons of risk factor
between-group data for continuous variables were assessed with the use of a t
I). A x2test was used to evaluate categorical variables. A stepwise logistic re-
gression model was used to analyze all potential risk factors for IgE-CMA
(Table II). The entry probability for stepwise analysis was 20%, and the re-
moval probability for stepwise analysis was 25%. The P value of the Hosmer
and Lemeshow test for goodness of fit was .52, supporting the goodness of fit
of the model. To study the dependence of IgE-CMA risk on CMP exposure
age, we classified the cohort into 4 groups according to their age at the first
regular CMP exposure. The fraction of infants with IgE-CMA in the 4 groups
was compared, and significance was assessed by using the Bonferroni-
corrected Fisher exact test for 2 3 2 contingency tables. The relevant raw
data of the cohort are available on request.
Recruitment into the study reached 98.4% (13,019) of our
terview in 12,473 (95.8%) infants and by means of questionnaire
for the remaining 546 (4.2%) infants. The initial information re-
garding CMP-related adverse effects was obtained within
1 week of the event in most of the cases (58%) and in only 25%
of cases in 30 days or longer. In 381 (2.9% of the sample) cases
the parents either complained about adverse effects that they con-
sidered CMP related, or alternatively, these parents avoided CMP
exposure despite having discontinued exclusive or almost exclu-
sive breast-feeding. A causal relationship between the complaint
and CMP was ruled out in 244 cases among these infants. In 71
(0.5%) cases, which will be described separately, a diagnosis of
non–IgE-mediated adverse reaction to CMP was established
(Fig 1). In this latter group 36 patients were given diagnoses of
FPIES and 21 were given diagnoses of proctocolitis; 14 had other
symptoms in which a causative relationship to CMP could not be
Sixty-six infants (0.5% of those studied) were given diagnoses
of IgE-CMA (Fig 1). Forty-eight (72.7%) patients fulfilledall cri-
teria, including a suggestive history of an immediate response, a
positive SPT response, and a positive challenge result to CMP.
Seventeen patients did not perform an oral challenge. In 6
(9.1%) of these infants, an oral challengewas not offered because
of life-threatening responses to CMP exposure. In 11 infants an
oral challenge was not performed because of parental refusal. In
a single case the diagnosis was made by a private allergist, and
by the time the infant was available for examination at the age
symptoms of IgE-CMA were cutaneous reactions (95.5%), in-
this article’s Online Repository at www.jacionline.org).
The distribution of the age of onset of IgE-CMA in this cohort
is presented in Fig 2. In 8 patients the onset of IgE-CMA was
greater than 240 days. These 8 patients were classified as having
secondary IgE-CMA. They were initially given diagnoses of
FPIES because of the delayed clinical response of vomiting and
lethargy, the lack of cutaneous symptoms, and a negative SPTre-
sponse in all but one. However, on a subsequent examination at
the age of 8 to 14 months, after a period of withdrawal of CMP,
their SPTresponses converted to positive, and in 7 of these cases,
an immediate response of 10 minutes or less to small amounts of
peared after 30 minutes. For these 8 patients, it is uncertain
whether the age of onset is the age of the FPIES reaction or
when they had an IgE-CMA reaction. We therefore excluded
them from any analysis in which the age of onset or age of
CMP introduction was involved, unless otherwise specified.
J ALLERGY CLIN IMMUNOL
78 KATZ ET AL
Excluding these patients, the mean age of onset of IgE-CMAwas
3.9 6 2.2 months.
The onset of symptoms started on the first day of consumption
The time from exposure to CMP to the presentation of a clinical
response was measured during the challenge when feasible or
obtained from the parents through history. It was less than 10
minutes in 55 (83%) infants, 10 to 20 minutes in 7 (11%) infants,
and up to 30 minutes in 4 infants.
Risk factors for the development of IgE-CMA
Healthy infants from the cohort (n 5 12,638) were compared
with those given diagnoses ofIgE-CMA (n 5 66) to determine the
risk factors leading to the development of IgE-CMA. All infants
whose parents raised concern about adverse effects but were not
proved to have IgE-CMA were excluded from this analysis (n 5
315). Table I presents the risk factors that were extracted from the
medical chart and from the primary questionnaire obtained from
the parent during the first interview or the first visit. The age of
CMP introduction was significantly different between the healthy
infants and thosewith IgE-CMA (P < .001, Table I). A second sta-
tistically significant difference was noted between the Jewish and
non-Jewishinfants (P < .002, TableI).Ina multivariatelogistic re-
with exposure to CMP in the age range of 15 to 194 days was 19.3
(95% CI, 6.0-62.1) compared with that seen in infants with expo-
sure to CMP before the age of 14 days (Table II). The odds ratio
P < .001). The odds ratio of sex was 1.80 (95% CI, 1.03-3.17).
We next analyzed the risk of IgE-CMA as a function of the age
of regular exposure to CMP (Fig 3). We used the time the mother
discontinued exclusive or almost exclusive breast-feeding and
converted to CMP-containing formula alone or along with
breast-feeding as the age of CMP introduction. One hundred
four infants who were not exposed to CMP during the first year
were not included. There are 3 well-defined periods. IgE-CMA
risk was very low (0.05% [3/6502], group I) in infants introduced
age, peaked at ages 105 to 194 days (1.75% [28/1600], group III),
founders, such as social class, pets, smoking habits, and atopic
background, as risk factors was not studied in the whole cohort.
However, in a subanalysis these confounders were not found to
be significantly different between the control and IgE-CMA
groups. Specifically, parents of the infants with IgE-CMA were
not more atopic, whether evaluated based on self-reporting or ob-
jectively based on SPT positivity to common allergens. Further-
more, in only 4 of the 66 IgE-CMA cases did parents mention
family atopy as a reason for breast-feeding, and this was not sig-
nificantly different from a randomly chosen control group from
the cohort (data not shown).
Breast-feeding and exposure to CMP
In Table III the feeding patterns of Jewish and Muslim mothers
during the first week of life is depicted. There were clear attitudi-
nal differences between them toward exclusive or almost exclu-
sive breast-feeding. Although Arab-Muslim mothers breast-feed
in more than 80% of cases, only 28.3% exclusively breast-fed.
In contrast, Jewish mothers exclusively or almost exclusively
breast-fed 57.5% of the time. These differences result in a higher
exposure to CMP during the first week of life in the offspring of
Arab-Muslim mothers compared with Jewish mothers (71.7%
vs 42.5%; P < .001, Fisher exact test), even though Arab-
Muslim offspring were more likely to be breast-fed compared
with Jewish infants (80.6% vs 75.0%, P < .001). Strikingly,
only a single newborn of 1,806 born to an Arab-Muslim mother
had IgE-CMA, whereas 55 of 10,135 infants born to Jewish
mothers had IgE-CMA (P < .001, Fisher exact test). These data
indicate that breast-feeding by itself was not a risk factor but
rather that exposure to CMP is protective.
Cosensitization and allergy to soy among patients
None of the 66 patients with IgE-CMA had a positive SPT
response to soy. Fifty-nine (89%) patients were on a soy diet on
TABLE I. Characteristics and risk factors of infants with IgE-CMA and healthy infants
IgE-CMA (n 5 66)
(n 5 12,638)P value
Gestational age (wk)
Birth weight (kg)
Maternal age (y)
Type of delivery, PS
Type of delivery, CS
No. of siblings
Dairy product consumption by mother
Age of CMP introduction (d)
39.2 6 1.7
3,255 6 0.42
29.58 6 4.76
2.26 6 1.53
39.15 6 1.9
3,196 6 0.55
29.69 6 5.23
2.35 6 1.53
61.63 6 92.45
116.12 6 64.88 (for 58 patients)
110.09 6 68.82 (for 66 patients?)
156.14 6 133.02 (for 66 patients?)
For the age of CMP introduction, the 58 patients with primary IgE-CMA are first presented. Similar results were obtained when the 8 patients with secondary IgE-CMA were
determined as being exposed to CMP on the day of the onset of FPIES (?) or the day of the diagnosis of IgE-CMA (?).
CS, Cesarean section; PS, Partus spontaneous.
*In Israel a person’s religion is written down in the national identity card unless the citizen specifies ‘‘no religion.’’ The non-Jewish population consists mostly of Arab-Muslim
mothers (62.6%) and Arab-Christian mothers (5.5%), and for the rest, no religion was specified. Those for whom no data were recorded (n 5 371) were excluded.
J ALLERGY CLIN IMMUNOL
VOLUME 126, NUMBER 1
KATZ ET AL 79
the first examination for a period ranging from 16 to 120 days, 6
were fed with extensively hydrolyzed milk (Nutramigen; Mead
Johnson, Glenview, Ill), and 1 consumed an amino acid–based
formula (Neocate; SHS, Liverpool, United Kingdom). After
evaluation, 5 added soy to the diet, and only 1 with a negative
of parental preference. In the 1 patient who consumed Neocate,
the diagnosis of IgE-CMAwas made by a private allergist, and at
the time of evaluation, the challenge result to CMP was negative.
None of the infants had soy allergy during their soy diets. Thus
none in this cohort had a protein allergy to soy, but it could not be
excluded in that last case.
This article presents a large, prospective noninterventional
study in which several fundamental questions regarding milk
allergy were evaluated. To minimize bias, we aimed to reach the
used the least invasive methods for diagnosis, including SPT,
rather than measuring specific IgE cow’s milk antibodies, and a
less demanding open OFC rather than a double-blind placebo-
thermore, our end point to rule out IgE-CMA was regular con-
sumption of CMP, and therefore not even a single case of
clinically relevant milk allergy was missed. In a previous study
designed to examine milk allergy in a similar patient population,
only 41% of the target population was recruited.12Our recruit-
ment of 98.4% of the cohort allowed for definitive answers
regarding the prevalence of IgE-CMA, the potential for cross-
reactivity of IgE-CMA to soy allergy, and novel conclusions re-
garding risk factors for IgE-CMA.
that includes a small fraction of patients with FPIES who later
converted to IgE-CMA, as previously noted,13and 11 patients
who did not have an OFC. The incidence ratewe observed is sim-
ilar to that in an independent cross-sectional study of 9,070
FIG 1. Cohort description. All 381 parents of infants in whom an adverse
reaction to CMP was suspected were interviewed by one of the investiga-
tors (N.R.), and their infants were invited for an examination. Additional
contacts were made as appropriate in these patients, and at the final contact
at the ages of 3 to 5 years, 21 infants were lost to follow-up.
FIG 3. IgE-CMA occurrence as a function of the age of CMP introduction.
The different groups are defined as follows: group I (green), age of CMP ex-
posure of 0 to 14 days; group II (II1II*) (yellow), age of CMP exposure of 15
to 104 days; group III (red), age of CMP exposure of 105 to 194 days; and
group IV (yellow), age of CMP exposure of 195 to 374 days. For statistical
analysis, the second and third bins were combined into one group (group
II, group II*). The error bar represents the statistical error caused by the fi-
nite group size (1 SD). A fraction of infants with IgE-CMA are significantly
(P < .001) different for all pairwise comparisons among the 4 groups, except
for group II versus group IV.
TABLE II. Stepwise multivariate logistic regression analysis of
risk factors for IgE-CMA
OR95% CIP value
No. of siblings
(15-194 d vs < _14 d)
Late exposure was defined as age greater 14 days. Other definitions of late exposure
revealed similar results. For example, when the definition of late exposure was 30
days, the odds ratio for late exposure was 12.2 (95% CI, 5.2-28.6). The odds ratio
remains increased (13.13, P < .001), even when the 11 patients who did not perform an
oral challenge are excluded.
OR, Odds ratio.
FIG 2. Number of patients with IgE-CMA according to their age of onset (in
days). The 8 patients with onset of IgE-CMA at an age of 240 days or greater
were initially given diagnoses of FPIES.
J ALLERGY CLIN IMMUNOL
80 KATZ ET AL
infants, in Israel in which the prevalence of IgE-CMA was esti-
mated to be between 0.3% to 0.4%,14but is significantly lower
than the most widely cited figure of 1.5% for IgE-CMA,3which
is based on observations in other countries. We doubt this low
prevalence reflects genetic or geographic variation because other
prospectivepopulation-based studies from Spain15and Norway16
found a similar cumulative incidence of IgE-CMA. The most ob-
vious explanation for the difference is that other studies included
fulfill the criteria for the diagnosis of IgE-CMA, as definedin this
study. For example, in our study 95% of the patients with IgE-
CMA had immediate cutaneous symptoms, as previously de-
scribed.17-19In many other studies,12,20however, only a fraction
of the patients had immediate cutaneous symptoms, such as urti-
caria or angioedema, and thus only a subset truly had IgE-CMA.
the recent position statement of the American Academy of
with IgE-CMA because of a 10% to 14% reported incidence of
cross-reactivity to soy, none of our patients with IgE-CMA had
soy allergy. The American Academy of Pediatrics statement
was mainly based on 2 prospective randomized trials by Zeiger
et al22and Klemola et al.23In the first study22there were 13 chil-
dren with soy allergy, 12 of whom were recruited from a single
sinophilic esophagitis, another condition in which multiple food
allergies is likely. In the second study23only a single patient
had documented IgE antibodies directed against soy protein. It
tients with IgE-CMA unless the patient has multiple food
The third and perhaps most important finding is the fact that
development of IgE-CMA is influenced by the timing of expo-
sure to CMP. Infants whose regular exposure to CMP was
withheld until the age of 4 to 6 months were at the highest risk for
IgE-CMA. Although the parents did not keep a daily record of
feeding, close telephone contact was maintained with the
parents, and all parents were interviewed in detail on the visit,
allowing for an accurate reported onset of the disease. The
average age of onset of IgE-CMA in this cohort (3.9 months) is in
the range of numerous other reports.12,18,19,24Finally, in the vast
majority of patients of our cohort, the symptoms started on either
the first day of exposure to CMP or during the first 3 days of re-
peated exposure. Similar patterns were noted by other investiga-
tors.15,17-19In our study almost half of the newborns were
exposed to CMP in the first 2 weeks. The incidence of IgE-
CMA among these infants was extremely low. Thus it is likely
that infants exposed regularly to CMP starting from the neonatal
period rarely have IgE-CMA. We do not have data to substantiate
an explanation as to why the risk for IgE-CMA decreased for
those exposed in the oldest age group (group IV) compared
with the prior period (group III).
Three lines of evidence argue against the role of atopy as a risk
factor in our cohort, influencing the choice of feeding, or both.
First, whether evaluated based on self-reporting or objectively
basedonSPTresponsepositivityto commonallergens,parents of
infants with IgE-CMAwere not more atopic. Second, parents of
infants with IgE-CMA did not mention atopy as a reason for
breast-feeding with any significant difference from a randomly
chosen control group from the cohort. Finally, parental atopy was
never shown based on objective criteria to be a significant risk
factor for IgE-CMA. Thus although we cannot completely
exclude reverse causality as an explanation for our findings, we
have no evidence that atopy predisposition in parents or infants
influenced parental feeding decisions.
regimens that are actually practiced globally. The rate of com-
pliance with prolonged and exclusive breast-feeding is low, even
in high-risk infants.25In the Netherlands, for example, only 63%
of mothers expressed intention to breast-feed.26Because an aller-
gic reaction to CMP develops within days15,17-19yet few infants
have IgE-CMA in the first 2 weeks of life,2one must conclude
that there is a protective role for early CMP exposure.
Regular early exposure to CMP might also explain the inter-
esting finding that the risk of IgE-CMA among infants born to
Muslim-Arab women was much lower when compared with the
risk of those born to Jewish women. Despite a higher rate of
intention to breast-feed among Arab women compared with
Jewish women,27the rate of exclusive or almost exclusive breast-
feedingis lower,28resulting ina muchearlier exposureto CMPin
CMP formula in the newborn nursery either forgotten by the
mother or done without her knowledge. However, the role of a
brief intermittent early exposure to milk in the neonatal unit is
sider such intermittent exposures to CMP in this study.
The role of early oral exposure to dietary proteins in rendering
tolerance is gaining recognition.30The exact timing and mecha-
It is possible that different proteins havevarying patterns of toler-
ance versus sensitization and allergenic timing.33Introduction of
tolerance,34whereas in our study milk tolerance appears to be in-
duced by its introduction at an earlier age. A similar idea was re-
ported previously,35but those findings were not integrated into
common practice. The idea of the protective effect of early oral
introduction of protein was suggested more than 25 years ago
by Jarret.36Our study provides large-scale, prospective clinical
evidence to support this hypothesis. Therefore we cannot rule
TABLE III. Feeding pattern during the first week
Exclusively or almost
exclusively breast-fed (%)Partial breast-feeding (%) No breast-feeding (%)Total (%) breast-fedTotal (%) CMP fed
*Christian, atheists, and not known.
J ALLERGY CLIN IMMUNOL
VOLUME 126, NUMBER 1
KATZ ET AL 81
out that some infants with very mild clinical reactions were con-
tinued to be fed CMP and developed tolerance who otherwise
would have eventually had clinically significant IgE-CMA. Fi-
nally, a limitation of this study is the lack of information on the
amount of CMP that has to be introduced to prevent IgE-CMA.
The data should not be interpreted as discouraging breast-
feeding. The great advantages of breast-feeding in providing
essential nutrients and immunomodulatory effects are well
appreciated. Therefore it seems reasonable to consider early
complementary feeding of CMP along with breast-feeding to
promote oral tolerance, especially in high-risk infants.
We thank Regina Zacharov for her help in the newborn nursery. We are
grateful to Michal Mizrahi, Orit Israeli, and Dorit Zilberzvig for the
administration of skin prick testing. We thank Batya Levy for her help in
performing the oral challenges. The work of our clinical coordinator, Hasia
Duani, is highly appreciated. We also thank Stella Adrutin for data manage-
ment entry and R. C. Strunk for helpful discussions.
Clinical implications: Supplementation at birth with CMP
should be recommended to promote its tolerance. For those pa-
tients with IgE-mediated CMP allergy, soy is a reasonable feed-
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J ALLERGY CLIN IMMUNOL
82 KATZ ET AL
FIG E1. Systems affected in patients during IgE-mediated reactions. C, Cutaneous reaction (urticaria, angi-
oedema, and pruritus); GI, gastrointestinal reactions (vomiting and diarrhea); R, respiratory system (sneez-
ing, shortness of breath, coughing, and choking); S, systemic reaction (shock, crying, fainting, and
restlessness). Although we rated pruritis, crying, restlessness, and choking, more objective findings,
such as urticaria, vomiting, shortness of breath, and anaphylaxis, were used to establish the diagnosis.
J ALLERGY CLIN IMMUNOL
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KATZ ET AL 82.e1