Paediatrica Indonesiana

VOLUME 52 NUMBER 2 March 2O12

Original Article
Paediatr Indones, Vol. 52, No. 2, March 2012 67
IgE-mediated soy protein sensitization in children
with cows milk allergy
Agustina Santi, Mohammad Juffrie, Sumadiono
Abstract
Background Sov-based formula as an alternative to cow's milk
formula is preferable to extensivelv hvdrolvzed protein formula
because of the lower cost and more acceptable taste. However,
cow's milk aller,v patients can subsequentlv develop a sensitivitv
to sov protein.
Objective 1o compare sov protein sensitization in children with
and without an aller,v to cow's milk.
Methods 1his studv was conducted in Yo,vakarta from September
2OO7 until March 2OOo. Subjects were children a,ed below 1
vears with an atopic historv. Subjects were divided into 2 ,roups:
those with a positive skin prick test to cow's milk and those
with a ne,ative skin prick test to cow's milk (control ,roup).
Both ,roups were ,iven sov formula and tested at 6 weeks for
sensitization to sov.
Results 1here were 15 children in each ,roup. A,e, sex, and
atopic historv were similar in both ,roups. We found no sov
protein sensitization (ne,ative skin prick results) in all subjects
from both ,roups.
Conclusion Risk of immuno,lobulin l-mediated sensitization
to sov protein was not proven in children with cow's milk aller,v.
[Paediatr Indones. 2012;52:67-71].
Keywords: cows milk allergy, immunoglobulin
E-mediated sensitization to soy protein
lrom the Department of Child Health, Oadjah Mada Universitv Medical
School, Yo,vakarta, lndonesia.
Reprint requests to: A,ustina Santi, MD, Department of Child
Health, Oadjah Mada Universitv, Sardjito Hospital, Jl. Kesehatan No 1,
Yo,vakarta, lndonesia. 1el. 62-271-561616. lax: 62-271-5o3715. l-mail:
agustina_santi@yahoo.com
A
ller,ies in children can start in infancv and
continue into adulthood. An aller,v is a
condition characterized bv the occurrence
of an overreaction of the immune svstem
to usuallv harmless environmental substances.
Aller,ies mav occur earlv in life due to children's
immature immune status and hi,h ,astrointestinal
mucous permeabilitv.
1
lf a child has an atopic historv
he mav become easilv sensitized, and develop aller,ies
to aller,ens such as food and airborne particles.
2
lor non-breastfed infants, cow's milk formula
contains the manv of the first forei,n proteins ,iven
to an infant. Aller,v to cow's milk has become more
common todav, as an increasin, number of parents
,ive cow's milk formula to their infants. Aller,v
to cow's milk is often the first atopic disease in
children.
3
1he incidence of cow's milk aller,v has been
estimated at 2-7.5' in formula-fed infants and O.5'
in exclusivelv breastfed infants, ,enerallv occurrin,
within the first six months of life.
1
A studv from Cipto
Man,unkusumo Hospital, showed approximatelv 2.1'
of children were aller,ic to cow's milk.
5
ln Yo,vakarta,
an estimated 3O,OOO children suffer from cow's milk
Agustina Santi et al: l,l-mediated sov protein sensitization in children with cow's milk aller,v
68 Paediatr Indones, Vol. 52, No. 2, March 2012
aller,v.
6
Mana,ement of cow's milk aller,v involves
substitutin, the formula with a non-cow's milk base
until tolerance to cow's milk is developed. Substitutes
for cow's milk formula include extensivelv hvdrolvzed
protein formula, amino acid formula, and sov-based
formula. Sov-based formula is recommended because
it is hvpoaller,enic, lower cost, has an acceptable taste
and has adequate nutrition to meet the ,rowth needs
in children.
7
Sovbean-based foods are verv popular in
lndonesia, includin, sov milk, tempeh, tofu, and sov
sauce. But some children with cow's milk aller,v can
be subsequentlv sensitized and develop a sov milk
aller,v. 1his mav be caused bv cross-reaction between
the sov protein B3 polvpeptide and 11S ,lobulin
protein casein from cow's milk.
9
Sensitization to sov
and sov milk aller,v in cow's milk aller,v patients
remain to be a health problem in various re,ions
of the world, with a reported prevalence of o to
11'. However, severe anaphvlactic reactions rarelv
occur.
1O
Ahn KM et al reported a prevalence of 17'
in Ban,kok and 1o.3' in Korea of sov aller,v in
cow's milk aller,ic children.
11
A studv in lndonesia
reported incidence of sensitization to sov milk of
17.5'.
12
1he time required for sensitization to sov milk bv
oral administration has not been reported in humans.
However, Mclau,hlan et al reported that in ,uinea
pi,s sensitization to cow's milk protein or sov milk
occurred at dav 37 of feedin,.
13
Similarlv, a studv bv
Villoslada et al showed that sensitization took six weeks
of exposure to cow's or ,oat's milk proteins in mice.
11
Accordin, to Vandenplas, sensitization takes one to
six weeks,
15
while accordin, to We,rzvn, sensitization
occurs within one to two weeks.
16
Sensitization can
also occur within a few davs or even three or four
weeks after consumin, sov milk.
17
lnspite of varvin,
opinions on sov milk sensitization, substitution with
sov milk is still lar,elv recommended.
1he aim of this studv was to determine whether
cow's milk aller,v is a risk factor for sov protein
sensitization in children.
Methods
1his studv was conducted at Bhakti lbu Hospital,
Yo,vakarta from September 2OO7 until March 2OOo.
Subjects were children a,ed less than 1 vears with
atopic historv. lnclusion criteria were children who
had not consumed sov formula and had ne,ative skin
prick tests to sov milk. We excluded children with
con,enital abnormalities and severe aller,ic reactions
(anaphvlaxis or severe atopic dermatitis). Subjects
were divided into 2 ,roups based on their skin prick
test results to cow's milk. We calculated the need
for 15 subjects per ,roup, takin, into account the
relative risk,
1o
and the percenta,e of sov-sensitive
children with aller,v to cow milk's (17.5'
12
) and
those without aller,v to cow's milk (1.1'
31
). We
selected for controls with a,e matchin, within
6 months. lnformed consent was obtained from
parents. 1his studv was approved bv the Research
lthics Committee, Oadjah Mada Universitv Medical
School /Sardjito Hospital.
All subjects were ,iven sov protein isolate milk
for 6 weeks, after which we conducted blinded sov
protein skin prick tests. Sov protein skin prick tests
were performed usin, rea,ents from Alvostal prick test
(Staller,enes SA-lrance) 1OOO lC/ml. 1est rea,ents,
positive control and ne,ative control were placed
on the volar forearm area 2 cm awav from the elbow
fold or wrist. Care was taken to use area without skin
rash. liquids were pricked into the skin usin, lancets/
needles at an an,le of 3O - 15
o
to the skin surface.
After 15 minutes, liquid residue was removed with
tissue paper, and results of the examination were read.
All data was processed bv SPSS for Windows. We
calculated relative risk (RR) to compare skin prick
results between ,roups.
Table 1. Basic characteristics of subjects
Allergy to cow's
milk
(n=45)
No allergy to
cow's milk
(n=45)
Age, months
<12
>12-24
>24-36
>36-48
Mean age, months (SD)
Sex (male)
Atopic history
Mother
Father
Father and mother
Sibling
21
14
5
5
18.0 (11.3)
18
45
16
12
1
16
22
17
3
3
16.7 (10.1)
25
45
19
13
0
13
Agustina Santi et al: l,l-mediated sov protein sensitization in children with cow's milk aller,v
Paediatr Indones, Vol. 52, No. 2, March 2012 69
Results
1here were 9O subjects enrolled in this studv, divided
into two ,roups. A,e, sex, and atopic historv were
similar in the two ,roups (Table 1).
Figure 1 shows that aller,ic reactions to
cow's milk were mostlv manifested as dermatitis (21
subjects), rhinitis (9 subjects) and constipation (6
subjects).
After 6 weeks follow-up, we found no cases of sov
protein sensitization (all ne,ative skin prick results)
in all subjects from both ,roups.
Discussion
ln this studv, cow's milk aller,v occurred mostlv in
children a,ed less than 12 months (1o.O SD 11.3).
1his findin, is in a,reement with other studies
that reported cow's milk aller,v occurred in under
four vear-olds, particularlv in the first 12 months
of life and decreasin, with a,e.
19-21
A studv bv
Zeiger et al found that of subjects with cow's milk
aller,v, 2O.1' were a,ed O-12 months and 5o.1'
were a,ed 12-21 months, with a mean a,e of 19.1
months.
1O
Aller,v to cow's milk mav be related
to the immaturitv of the ,astrointestinal barrier
and immune svstem in infants and children.
19-21
ln earlv life, the mucosal epithelial laver has low
levels of mucin and sl,A, thus resultin, in reduced
,astrointestinal tract barrier function, in terms of
abilitv to prevent attachment of anti,en to mucosal
surfaces and anti,en clearin,. Production of ,astric
acid and protease enzvmes mav also decrease. 1his
condition mav be accompanied bv hi,h permeabilitv
of ,astrointestinal mucosa resultin, in a hi,h
incidence of aller,ic reactions.
2O,22
Clinical manifestations of cow's milk aller,v
mostlv occurred in the inte,umentarv svstem
(53.1'), followed bv respiratorv (2o.o') and
,astrointestinal (17.7') svstems. ur findin,s
were similar to those of zei,er et al,
1O
Muktiarti et
al,
12
and Host et al
23
ln contrast, Hill et al reported
,astrointestinal svmptoms to be the most common
clinical manifestation
.21
We found no sensitization to sov protein in anv of
our subjects, possiblv due to earlier tolerance to sovbean
protein if the subjects had consumed sov protein-based
foods (such as tempeh, tofu, sov sauce, oncom, and
tauco). lndonesians consume manv forms of sov protein-
based foods at levels of 1o.6 k,/capita/vear in cities, and
13.9 k,/capita/vear in villa,es.
25,26
1empeh is often used
as nutritional therapv for acute diarrhea treatment in
children. Darwin
27
and Mien
2o
showed that sovbean
protein formula can shorten hospitalization duration for
diarrhea compared to rice formula. lt can also improve
wei,ht ,ain in children with chronic diarrhea. Soenarto
et al showed that acute diarrhea in children improved
with sov formula, with shorter duration of illness and
increased wei,ht ,ain.
29
Another possible explanation for our results is our
use sov protein isolate, which is less aller,enic. 1sumura
et al reported aller,enicitv to sov milk protein isolates
(E-con,lvcinin which is a fraction of the 7s ,lobulin
and P31) was diminished bv the presence of enzvmes
hvdrolvzin, Proleather FG-F, an alkaline protease from
B. subtilis.
3O
1hese aller,ens are different from those
reported to cause cross-reactions in cow's milk aller,v
patients, namelv the B3 polvpeptide, a fraction of the
11S ,lobulin.
9
1he aller,ens we used for skin prick test
were in accordance with 1sumura's research. A studv
bv Ra,no et al of 2O cow's milk aller,v patients used sov
milk as a placebo.
32
None of those patients developed
sensitization to sov protein.
ln conclusion, cow's milk aller,v does not
increase the risk of immuno,lobulin l-mediated
sensitization to sov protein in children.
Acknowledgments
We thank Kristia Hermawan, Windi Saufia, and Aprivanti
Handavani for their technical assistance.
Figure 1. Clinical manifestations of cows milk allergy
Agustina Santi et al: l,l-mediated sov protein sensitization in children with cow's milk aller,v
70 Paediatr Indones, Vol. 52, No. 2, March 2012
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