Food allergy is an immunological reaction against specific proteins in particular foods.
Cow's milk protein allergy (CMPA) is a sensitivity reaction cow's milk protein via
immunological pathways. CMPA is the most common food allergy under 3 years of age and its
incidence is increasing in developed and developing countries. The incidence of CMPA in the
first year of life is 2-3%. CMPA can be observed in breast fed, formula fed infants and
infants who have started complementary food. CMPA can be classified as Ig E mediated, non Ig
E mediated and mixed type according to the underlying immunological mechanisms. Basic signs
and symptoms of CMPA involve the skin, gastrointestinal (GI) system and respiratory system.
Ig E mediated CMPA occurs as a result of early over sensitivity to CMP and causes the
clinical symptoms like urticaria, angioedema, atopic dermatitis, asthma and allergic
rhinitis. Gastrointestinal symptoms like regurgitation, vomiting, colic and diarrhea may
accompany. Non Ig E mediated and mixed type CMPA cause different GI signs and symptoms via
inflammation and dismotility. In these groups CMPA symptoms are nonspecific like
gastroesefagial reflux, regurgitation, refusal to feed , vomiting, diarrhea, bloody
defecation and failure to gain weight. This type of CMPA may present as different clinical
entities like protein loosing enteropathy, enterocolitis or eosinophilic eosophagitis. In
some infants the only symptom can be irritability and colic.
The first step in diagnosis is a detailed clinical history and physical examination. Atopy in
the patient and the family should be questioned. There is not a diagnostic test for CMPA.
Serum Ig E and cow's milk specific IgE level can assist in diagnosis of CMPA in Ig E mediated
CMPA however these tests are normal in non IgE mediated CMPA. The diagnosis of CMPA in
suspected patients is based on the recovery of signs and symptoms with elimination of cow
milk from the diet and reappearance of symptoms ad signs after challenge with cow's milk.
Nonspecific symptoms of CMPA such as regurgitation, constipation, diarrhea, and are also
symptoms of functional gastrointestinal diseases in infants which are seen commonly. It has
been observed that at least half of babies under 6 months experience one GI symptom.
Regurgitation, colic and constipation are reported to be very common ( 23.1%, 20.5%,and
17.6%, respectively).
So the pediatricians should be aware of the fact that the symptoms or signs attributed to
functional gastrointestinal diseases in infants may well be due to underlying CMPA. Therefore
developing an awareness tool for pediatricians to distinguish symptoms of CMPA in infants
could be useful in helping to recognize CMPA. Accurate diagnosis in affected infants ensures
that infants are given appropriate diet and thus supports growth and development. On the
contrary, a diet which is given without indication or continuing the diet unnecessarily after
tolerance develops adversely affect growth and disturb the quality of life of the patient and
the family and also cause unnecessary healthcare costs. Therefore proper recommendations and
clear guidelines based on evidence are required.
In September 2014 a workshop was organized by clinicians with expertise in managing children
with GI problems and atopic diseases in Brussels to review the literature and to determine
benefit of a clinical score derived from symptoms associated the ingestion cow's milk
proteins to primary healthcare providers. The cow's milk related symptom score (Comiss) which
considers general manifestations, dermatological, gastrointestinal and respiratory system,
was developed as awareness tool for cow's milk related symptoms.
This awareness tool is based on thegastrointestinal, respiratory system and dermatological
symptoms being together.
This scoring tool is easy, rapid and easy to use awareness tool which pediatricians can use
in determining symptoms of CMPA. It is stated that its usefulness needs to be evaluated by
prospective, randomized studies.
In this prospective and randomized study the investigators aim to evaluate diagnostic
accuracy using CoMISS.
Approaches and Methods to be Applied This study will include infants under 1 year of age who
are admitted to Ankara University School of Medicine, Department of Pediatric
Gastroenterology, Hepatology and Nutrition with GI, respiratory and dermatological symptoms
and who have more than 12 points when evaluated by CoMISS. This study aims to include at
least 120 patients with risk of CMPA.
Complete blood count, peripheral smear, erythrocyte sedimentation rate, albumin level, stool
direct examination, occult blood in stool, Ig E and cow's milk specific IgE will be evaluated
in patients who have more than 12 points according to this scoring system. At admission and
follow up, symptoms and signs, physical examination findings and laboratory findings of the
patients will be recorded with guidance of a form. Elimination diet to infants with a score
of 12 and more will be given (elimination of cow's milk and its products from the diet of the
mother in infants who are only breastfed, switching to extensively hydrolyzed formula in
infants who are fed with standard formula, elimination of cow's milk and its products in
infants who are fed with regular diet) for 2- 4 weeks. At the end of this period,
nonresponsive infants will be switched to an amino acide based formula for 2-4 weeks .
Infants who are nonresponsive to amino acid based formula will be regarded as not having
CMPA. Open cow's milk challenge test will be performed to infants who are responsive to
elimination diet. After 2-4weks f elimination diet an open challenge test will e performed to
infants whose findings have recovered. After this diet alteration we will confirm diagnosis
of CMPA according to response of the diet. The infants in whom findings reappear after the
challenge will be assessed as CMPA (+) ; while those in whom the findings don't reappear will
be assessed as CMPA (-). In patients with IgE mediated CMPA, open challenge test will be
performed under medical supervision in the hospital with infant formula based on cow's milk.
First one drop of the infant formula will be put on infant's lips. If no reaction occurs
after 15 minutes ,the infant formula based on cow's milk will be given 0.5, 1, 3, 10, 30 and
100 ml at 30-minute intervals. If no reaction occurs 2 hours after the last dosage is given,
the formula will be continued at home every day with at least 200ml/day. The parents will be
called by telephone to document any late reactionsIn infants with non IgE mediated CMPA ,
open challenge test will be performed at home Cow's milk containing foods (cake, yogurt,
cheese and milk, respectively ) will be added to the mother's diet with one week intervals in
exclusively breast fed infants. In formula fed infants, standart formula will be added
gradually over days. In infants receiving complementary food, cooked foods containing cow's
milk such as biscuit and cake will be started firstly followed by cow's milk containing foods
like yogurt and cheese with 2-7 days intervals.
Predicted study duration:
- - The study will be finished within 13 months.
Nature of the voluntaries:
2-weeks to 12-months-old infants admitted to outpatient clinics of Department of Pediatrics ,
Department of Social Pediatrics and Child Health , and Department of Gastroenterology with
GI, respiratory system and/or dermatological symptoms and who have more than 12 scores in
CoMİSS will be included.
