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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 17  |  Issue : 1  |  Page : 86-95

Frequency of cow milk protein allergy in children during the first 2 years of life in Damietta Governorate


1 Department of Pediatrics, Al-Azhar University, Damietta, Egypt
2 Department of Chest, Al-Azhar University, Damietta, Egypt
3 Department of Clinical Pathology, New Damietta Faculty of Medicine, Al-Azhar University, Damietta, Egypt
4 Pediatrics Department Alazhar University Damietta, Alexandria University, Alexandria, Egypt

Date of Submission15-Feb-2019
Date of Acceptance07-May-2019
Date of Web Publication12-Sep-2019

Correspondence Address:
Eman Abd A.M Elmahdy
Shabas Emir, Kalin, Kafer El Sheikh 33722
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AZMJ.AZMJ_29_19

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  Abstract 


Background Many research studies have been done to explore the prevalence of cow milk allergy.
Aim of the work The aim of this study is to determine the frequency of cow’s milk protein allergy (CMPA) among children of Damietta Governorate during the first 2 years of life.
Patients and methods A cross-sectional study with nonsystemic random sampling was conducted on 1000 children in the first 2 years of age, comprising 512 male and 488 female exposed to cow milk or its products either directly or indirectly, attending outpatient clinics of Al Azhar University Hospital in New Damietta. Each included infant was subjected to history taking and clinical examination, and suspected cases from history and examination were subjected to skin prick test, specific immunoglobulin E (IgE) for cow’s milk protein, oral food challenge, and food elimination tests.
Results In the present work, there was a male predominance among the suspected group (58.5% males and 41.5% females). We found that infants from urban regions were more affected than those from rural regions (61.76% of the confirmed cases were from urban areas and 38.24% from rural regions). We found that the risk of CMPA declined in exclusively breast-fed infants. The clinical manifestations in infants with suspected CMPA were variable, and the main presenting feature was gastrointestinal tract manifestations (84% of the cases) (P<0.001).
Conclusion This study showed that the frequancy of CMPA in infants in the first 2 years of life in Demietta Governrate was 3.4%, as confirmed by positive food elimination and oral food challenge tests, and the IgE-mediated CMPA was more common, as 67.6% of cases had IgE-mediated CMPA.

Keywords: cow′s milk protein allergy, food elimination and challenge test, skin prick test


How to cite this article:
Maksoud HA, Al Seheimy LF, Hassan KG, Salem MF, Elmahdy EA. Frequency of cow milk protein allergy in children during the first 2 years of life in Damietta Governorate. Al-Azhar Assiut Med J 2019;17:86-95

How to cite this URL:
Maksoud HA, Al Seheimy LF, Hassan KG, Salem MF, Elmahdy EA. Frequency of cow milk protein allergy in children during the first 2 years of life in Damietta Governorate. Al-Azhar Assiut Med J [serial online] 2019 [cited 2019 Oct 20];17:86-95. Available from: http://www.azmj.eg.net/text.asp?2019/17/1/86/266735




  Introduction Top


Exclusive breastfeeding from birth until 6 months of life, with continuation of breastfeeding for the first 2 years of life, is perceived as the gold standard for infant feeding [1],[2]. In contrast to infant formula, which has very narrow range of composition, composition of breast milk is dynamic and fluctuates within a feeding and between mothers and populations. This compositional difference is owing to maternal and environmental factors and the expression and management of milk. Furthermore, some bioactive components found in breast milk are being created and tried for possible medical importance as prophylactic or therapeutic agents [3]. Early introduction of cow’s milk is implicated as a major environmental factor in the development of cow’s milk protein allergy (CMPA) which is considered the first allergic disease in the ‘atopic march,’ as cow’s milk proteins (CMP) are the first foreign agent experienced by an infant [4]. Exclusive breastfeeding decreases the incidence of CMPA compared with formula feeding or mixed feeding [5]. Of exclusively breast-fed infants, only 0.5% show clinical reactions to CMP, and most of these are mild to moderate [6]. This is caused by the low level of CMP in breast milk, which is 100 000 times less than that in cow’s milk [7],[8]. In Egypt, in specific regions and subsequently to social and financial reasons, cow’s raw milk is introduced to the infants very early from the age of 2 months or even since birth [9]. The recommedations about the age of introduction of cow milk should be based on the traditional and feeding habits in the different nations [10]. Numerous parents presume that their children have CMPA if they have skin eruption, difficulty in sleeping, persistent nasal obstruction, and seborrheic dermatitis of unknown causes. Owing to diagnostic burdens, as the diagnosis needs elimination of cow’s milk followed by challenge, children should undergo tests to prove diagnosis [11]. The number of children diagnosed as having CMPA is probably two to three times more than justified [12],[13]. CMPA can be presented by a wide range of signs and symptoms affecting different systems in the form of either acute or late-onset manifestations. The symptoms among breast-fed infants are similar to formula-fed infants. Gastrointestinal symptoms are particularly challenging owing to their nonspecificity and wide differential diagnosis, but CMPA should always be suspected [14]. The initial step to diagnose CMPA is a thorough medical history and physical examination. If any of the features occur in an infant or a child and cannot be explained by another cause, CMPA may be considered a potential diagnosis. In most cases with suspected CMPA, the diagnosis needs to be confirmed or excluded by an elimination and challenge procedure. This can be performed as an open, single-blind or double-blind challenge, depending on clinical findings, history, and age of the child; however, there are conditions under which physicians may cancel a challenge procedure because either the diagnosis of CMPA is extremely high or the challenge procedure would be very risky if there is a history of anaphylaxis in a sensitized child [15]. For clinical practice, the determination of specific immunoglobulin E (IgE) in a blood sample and the skin prick test (SPT) are useful diagnostic tests at any age, but it is not necessary to do the two tests for the diagnostic workup [15]. The presence of CMP-specific IgE and/or a positive SPT to cow’s milk means sensitization to CMP and presence of IgE-mediated immunological process; however, physicians must decipher these results through medical history and food challenge procedure [15]. Quantification of both of these test results allows prediction of the occurrence of a further reaction and so it is useful for prognostic purposes. The higher the antibody titer and the larger the diameter of the SPT reaction, the greater is the possibility of having a reaction to CMP and allergy persistence. However, an oral challenge test is necessary in most cases to confirm an adverse reaction to CMP. Children with gastrointestinal manifestations of CMPA are more likely to have negative specific IgE test results compared with patients with skin manifestations, but a negative test result does not exclude CMPA. Children with positive test result for specific IgE at the time of diagnosis have a longer period of intolerance as compared with those children who have negative test results [15],[16]. Food elimination and challenge test is the only method to confirm CMPA diagnosis [13]. Oral food challenge (OFC) is the ‘gold standard’ to confirm children suspected of food hypersensitivity [17].


  Aim of the work Top


The aim of this study is to determine the frequency of CMPA among children of Damietta Governorate during the first 2 years of life.


  Patients and methods Top


A cross-sectional study with nonsystemic random sampling was conducted on 1000 child in the first 2 years of age, comprising 512 male and 488 female, exposed to cow milk or its products either directly (720 infants) or indirectly through the maternal feeding during lactation or other sources (280 infants), attending outpatient clinics of Al Azhar University Hospital in New Damietta during the period from September 2017 to July 2018. The aim of this study was explained to the parents of all including infants and their permission to participate in the study was taken. Each included infant was subjected to history taking and complete clinical examination, and suspected cases from history and examination were subjected to the following: SPT, specific IgE for CMP, food elimination test, and OFC test.

Inclusion criteria

Children aged 24 months or less of both sexes were included.

Exclusion criteria

Infants with chronic illness and inborn errors of metabolism, and infants with apparent major congenital anomalies such as congenital heart diseases and neurological disorders were excluded. The following procedures were carried out for all children included in the study: verbal consent of the mother or the caregiver to participate in the study; full history taking with stress on dietetic history regarding type of milk taken, complementary feeding, maternal cow milk ingestion, history of manifestation suggesting food allergy such as vomiting, diarrhea, colic, overcrying, refusal of feeding, and cough, and family history of food allergy; and thorough clinical examination using a special examination sheet with stress on allergic manifestation such as gastrointestinal tract (GIT) manifestation (diarrhea, vomiting, colic, stomatitis, refusal of feeding, and constipation), respiratory manifestation (cough, runny nose, and snorting), skin manifestation (skin allergy, skin rash, and napkin dermatitis), and systemic manifestation (overcrying, anorexia, and irritability). Suspected cases from history and examination were subjected to the following: SPT, specific IgE for CMP, food elimination test, and OFC test. SPT was conducted on the symptomatic children with cow’s milk SPT solution [18]. Histamine dihydrochloride was used as positive and negative controls. One drop of each solution was injected in the forearm, and then after 10–20 min, interpretation of the test was done using specific roller. Estimation of serum specific IgE for CMP using enzyme-linked immunosorbent assay technique was done. Food elimination test and OFC test were performed as follows: cow’s milk and cow milk products were strictly eliminated from the diet of the mother and the child for a period of 2–4 weeks before the OFC test. OFC was carried out in the form of open challenge for cases with suspected allergic response to CMP with follow-up for 1 month after the therapeutic trial. Initially, one drop of cow’s milk was applied to the perioral region and lips, and then 15 min later, 10 ml of cow’s raw milk was administered. The dose was increased and administered at regular intervals of 15–30 min, and the infants were re-examined before each dose. The total volume given for each infant was 100 ml of cow’s raw milk. The infants were kept under close observation throughout the OFC, which continued for at least 2 h following OFC. At the first symptom or sign of an allergic reaction (irritability, crying, vomiting), the OFC was stopped, vital signs were evaluated, and inspections of the skin, oropharynx, and chest auscultation were performed immediately.

Statistical analysis of data

Data were collected, coded, revised, and entered to the Statistical Package for the Social Science (IBM SPSS, USA), version 20. The data were presented as numbers and percentages for the qualitative data; mean, SDs, and ranges for the quantitative data with parametric distribution; and median with interquartile range for the quantitative data with nonparametric distribution. The confidence interval was set to 95%, and the margin of error accepted was set to 5%. So, the P value was considered significant as the following: P value more than 0.05: nonsignificant, P value less than 0.05: significant, and P value less than 0.01: highly significant.


  Results Top


The results of this study are demonstrated in tables.

In the present work, the age of the study infants ranged from 0 to 24 months (mean±SD 12.06±7.60 months), where 28.9% of the infants aged from 0 to less than 6 months, 32.5% of the infants aged from more than 6 to 12 months, and 38.6% of the infants aged from more than 12 to 24 months. There is an evident male predominance in the present study; male percentage was 51.2%, whereas female percentage was 48.8% ([Table 1]). The suspected infants having CMPA were 10% (n=100) ([Table 2]).
Table 1 Demographic data of the studied infants (N=1000)

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Table 2 Frequency of suspected infants for cow milk protein allergy

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There was a male predominance among both suspected group (58.5% males vs. 41.5% females) and confirmed group (79.4% males vs. 20.6% females). We found that infants from urban regions [21 (61.76%) infants] were more affected than those from rural regions [13 (38.24%) infants] among the confirmed cases. We found that exclusive breastfeeding decreases the risk of CMPA [exclusive breastfed infants with maternal exposure (13 (2.5%) of 510 breastfed infants were the least suspected infants, whereas only one (2.9%) case was confirmed to have CMPA (P<0.001)]. The formula-fed infants were the most suspected infants (61.4%), where 19 (55.88%) cases of them were confirmed to have CMPA (P<0.001); then infants who consumed cow milk and its products (14.28%), where five (14.71%) cases were confirmed to have CMPA (P=0.086); then breast-fed and formula-fed infants (12.5%), where four (11.7%) cases of them were confirmed to have CMPA (P=0.051); then formula-fed and cow’s raw milk or its products (6.6%), where three (8.82%) cases of them were confirmed to have CMPA (P=0.501); and then breast-fed and cow’s raw milk or its products (6.25%), where two (5.88%) cases of them were confirmed to have CMPA (P=0.358) ([Table 3] and [Table 4]). We found that positive family history of allergy is a risk factor for CMPA, where 37% (37 of 100 infants suspected for CMPA) had a positive family history of allergy (evaluated based on self-reporting only); 29 infants of 34 infants who were diagnosed as having CMPA had positive family history of allergy (representing 85% of confirmed cases having positive family history of allergy). We found that the early introduction of cow milk and its products before 6 months of age increases the risk of developing CMPA, as of 57 infants of the suspected group (100 infants) who introduced CM before 6 months, 20 (58.82%) infants of them were confirmed to have CMPA, and 41.17% (14 infants) of confirmed cases were exposed to cow milk and its products after 6 months of age. Of 900 infants of the nonsuspected group, 415 infants take cow milk and its products before 6 months of age (P=0.038) ([Table 5]). We found that the clinical manifestations in infants with suspected CMPA were variable. GIT manifestations were found to be the main presenting feature (84% of the cases) (P<0.001), followed by skin manifestations (44%) (P=0.049), respiratory manifestations (31%) (P<0.001), and pallor (11%) (P=0.001). Overall, 97.05% (33 infants) of the confirmed infants had GIT manifestations, 52.94% had skin manifestations, 47.06% had respiratory manifestations, 38.24% had systemic manifestation, and 26.47% had pallor. We found that 67.65% of confirmed cases of CMPA had more than one system affected, whereas 32.35% of them had only one system affected. We found that 77% of the suspected infants had negative SPT, 13% had positive SPT with range of more than or equal to 3 to less than 6 mm, 6% had positive SPT with range of 6 to less than 9 mm, and 4% had positive SPT with range of 9–12 mm. Overall, 37% of children had positive food elimination test result, and 34.6% had positive challenge test result ([Table 6]). We found that the SPT in suspected infants was positive in 23% (n=23), with mean±SD of 2.86±1.90 and weal range of 1–9 mm. We found that specific IgE for CMP in suspected infants was 15.5% (14 of 90 infants, as 10 samples were discarded) with mean±SD of 358.90±421.73. Moreover, there is a positive correlation between specific IgE for CMP and SPT (r=0.512, P<0.001). Oral challenge test was positive in 34.6% (34 infants) of suspected infants (n=98 infants, as two infants did not complete the challenge). In addition, food elimination test was positive in 37% (37 infants) of suspected infants. There was a positive correlation between food elemination test and both spesific IgE for CMPA and SPT (P<0.001), and a positive correlation between OFC test and both SPT and spesific IgE (P<0.001). We also found the sensitivity of 41.18% and specificity of 100% of specific IgE in OFC test, as well as positive predictive value of 100% and the negative predictive value of 73% and cutoff point of more than 342 ng/ml, and area under the curve (AUC) of 0.638. We found that the sensitivity of SPT in OFC test was 45.95%, the specificity was 90.48%, the positive predictive value was 73.9%, the negative predictive value was 74%, and cutoff point was more than 2 mm, with AUC of 0.678 ([Table 7] and [Figure 1] and [Figure 2]). We found that 67.65% of confirmed cases had positive SPT result, 41.18% of confirmed cases had positive specific IgE, and 100% of confirmed cases had positive food elimination test and challenge test ([Table 8]).
Table 4 Type of feeding in the confirmed cases (N=34)

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Table 5 Comparison between suspected group (group2) (N=100) and nonsuspected group (group 1) (N=900) regarding age of introduction of cow milk and its products

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Table 6 Frequency of cases positive for skin prick test, food elimination test, and challenge test among suspected group (N=100)

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Table 7 Cutoff point, sensitivity, and specificity of specific immunoglobulin E and skin prick test in positive challenge test

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Figure 1 Cutoff point, sensitivity, and specificity of specific IgE in positive challenge test. IgE, immunoglobulin E.

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Figure 2 Cutoff point, sensitivity, and specificity of skin prick test in positive challenge test.

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Table 8 Skin prick test, specific immunoglobulin E, food elimination test, and challenge test in confirmed cases (N=34)

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  Discussion Top


Cow’s milk is considered one of the most frequent causes of food allergy in the first years of life [19]. Cow’s milk allergy (CMA) is considered as a significant cause of illness in infancy and childhood [20]. It is characterized by various reactions to CMP, affecting the skin, intestinal, and respiratory systems [21]. Many studies estimated the incidence of CMPA to be between 2 and 3% in infants and decline in older children. The percentage of children who were considered to have CMA or other food allergy is between 5 and 20% [22]. Many physicians refer children for suspected CMPA based on parent perception, unspecific symptoms, and/or positive results to unspecific investigations. Owing to diagnostic burdens, as cow’s milk elimination followed by food challenge is required to confirm the diagnosis, children are considered CMPA without proven diagnosis [23]. This makes the number of children treated for CMA two to three times higher than justified [24]. In addition, those children are suspected to unnecessary dietary limitations without a sufficient medical and dietary supervision. These inappropriate dietary restrictions may provoke nutritional imbalances, particularly in the first year of life.

It is also important to know that here in Egypt in certain areas and because of cultural and financial reasons, cow’s milk and its products is introduced to the infants very early from the age of 2 months or even immediately after birth, owing to the low cost of these products and the wide availability that motivate their use [9]. This study comprised 1000 children (512 males and 488 females) who were subdivided into two groups: suspected (100 infants) and nonsuspected (900 infants) groups. The age of the study population ranged from 1 to 24 months, which represented the common age of CMPA, with a mean±SD of 11.46±7.21 months for the suspected group and a mean±SD of 12.12±7.64 months for the nonsuspected group, and the age of confirmed children ranged from 1 to 24 months, with mean±SD of 8.22±5.66 years, for the confirmed cases. Many studies have demonstrated the common age of CMPA in the first 2 years of life, such as Schoemaker et al. [16], who conducted a study in Europe on 12 094 infants in the first 2 years of age, with the age of the suspected group [median (range) being 7 (1–24) months and the age of nonsuspected group being 14 (2–24) months], which is slightly near our results [16], and Vierra and colleagues [25],[26],[27],[28], who explained that this age is the common age of CMPA. In this study, 43% were females and 57% were males for the suspected group and 48.2% were females and 51.8% were males for the nonsuspected group. Schoemaker et al. [16] conducted a study on 12 094 children in the first 2 years of age in Europe and found that 41.5% were females and 58.5% were males of the suspected group and 48.6% were females and 51.4% were males of the nonsuspected group, which is near to our results. Pegah et al. [29] in Iran found that of 49 patients, male to female ratio was 59.2–40.8%, respectively, in the suspected group, which is slightly near our results. Moreover, Kelly and Gangur [30] conducted a screening study for published studies of the PubMed database and stated that among children, males were more affected with allergy, whereas among adults, females are more frequently affected. In our study, we found also 27 (79.4%) of the infants who were confirmed to have CMPA were males and only seven (20.6%) infants were females. Schoemaker et al. [16] also found that 56.4% of confirmed cases were males and 43.6% were females, which means that males are more affected than females. Liu et al. [31] in US conducted the study on 8203 children in the first 5 years of life and also reported male sex as a risk factor for food allergy development. So males appear to be more affected, which may be owing to higher exposure because of the Egyptian cultural view concerned with preference to male sex (sex discrimination). Genetic predisposition may be another cause and also the sexual genotype (XX in females and XY in males) is the basis of sex differences, and an X-linked recessive trait associated with allergic disease would be un-masked in males and could explain the male predominance of food allergies at young age. In this study, we found that exclusively breast-fed infants with maternal exposure [13 (2.5%) of 510 breast-fed infants] were the least suspected infants, and only one (2.9%) case was confirmed to have CMPA (P<0.001). The formula-fed infants were the most suspected infants (61.4%), where 19 (55.88%) cases of them were confirmed to have CMPA (P<0.001), followed by infants who consume cow milk and its products (14.28%), where five (14.71%) cases were confirmed to have CMPA (P=0.086); then breast- and formula-fed infants (12.5%), where four (11.7%) cases of them were confirmed to have CMPA, (P=0.051); then formula-fed and cow’s raw milk or its products (6.6%), where three (8.82%) cases of them were confirmed to have CMPA (P=0.501); and then breast-fed and cow’s raw milk or its products (6.25%), where two (5.88%) cases of them were confirmed to have CMPA (P=0.358). There is evidence that exclusive breastfeeding for at least 4 months compared with feeding with CMP formula decreases the incidence of atopic eczema and CMA in the first 2 years of life.

Anca and colleagues, had opposite results to our study, as they found that 70% of the exclusively breast-fed infants had symptoms before 2 years age (45 children out of 64). Hochwallner et al. [32] stated that breastfeeding decreases the risk of CMPA. Yvan et al. [28] conducted a study on 170 infants in the age range 2–11 months and found that only ∼0.5% of exclusively breastfed infants show reproducible clinical reactions to CMP, and most of these are mild to moderate. This is owing to the low level of CMP present in breast milk, which is 100.000 times lower than that in cow’s milk, in addition to immune-modulators present in breast milk and differences in the gut flora in both breast-fed and formula-fed infants [28].

Some studies, such as Jing et al. [33], and Thijs et al. [34], demonstrated a protective effect by introduction of CMP in the infant’s diet with breast milk, as breast milk may help development of oral tolerance because of its immunologic factors. In this study, we found that the early introduction of cow milk and its products before 6 months of age increases the risk of developing CMPA, as of 57 infants of 100 infants of the suspected group, 58.82% (20 infants) of them were confirmed to have CMPA, and 41.17% (14 infants) of confirmed cases were exposed to cow milk and its products after 6 months of age. Of 900 infants of the nonsuspected group, 415 infants take cow milk and its products before 6 months of age (P=0.038). In addition, Saarinen and Savilahti [4] conducted a study on 622 infants in the age range of 18–34 months and found that the early exposure to cow’s milk for an average of 2 days after birth increased the risk of occurrence of CMA, owing to the immaturity of the infants’ GIT, for its permeability is highest during the first few days of life, which is in agreement with our results. Katz et al. [35] conducted a stud on the UK cohort of the EuroPrevall project of 1140 infants from 2006 to 2008 and found that infants who were introduced to complementary foods at less than or equal to 16 weeks were more allergic than control infants (35 vs. 14%; P=0.011), which supports our results. In contrary to our results, Katz et al. [36] found that infants whose regular exposure to CMP was postponed till the age of 4–6 months were at the highest risk for IgE-CMA. In their study, almost half of the newborns were exposed to CMP in the first 2 weeks, and the incidence of IgE-CMA among these infants was extremely low. In this study, we found that the clinical manifestations in infants with suspected CMPA were variable; they were grouped as follows: systemic, gastrointestinal, cutaneous, and respiratory. GIT manifestations were found to be the main presenting feature (84% of the cases) (P<0.001), where diarrhea was the main symptom (36%), followed by colic (33%) and then vomiting (9%). This was followed by skin manifestations (44%) (P=0.049), with napkin dermatitis being the main symptom (18%). Respiratory manifestations were reported in 31% (P<0.001) followed by pallor (11%) (P=0.001) followed by irritability (9%) and refusal of feeding (7%) (P=0.001).

Moreover, we found that 97.05% (33 infants) of confirmed infants had GIT manifestations, where 50% had diarrhea, 5.88% had vomiting, 26.5% had colic, 8.82% had abdominal distention, 5.88% had constipation, and 0% had stomatitis, followed by 52.94% (18 infants) had skin manifestation, where 14.71% had urticarial rash and 52.94% had napkin dermatitis, followed by 47.06% (16 infants) had respiratory manifestations, followed by 38.24% had systemic manifestation, and 26.47% had pallor. Høst [37] reported that the manifestations mainly occur at the level of the digestive tract in 50% of cases, followed by the skin, and the respiratory tract (20%). Moreover, Anca [38] conducted a study in Romania on 64 infants and found that gastrointestinal manifestations were the main presenting symptoms in 62.5% of suspected cases followed by failure to thrive in 60.94% of suspected infants followed by skin manifestation in 40%. In this study, vomiting was present in 9% of suspected infants, whereas Vieirra et al. [47], who performed a study on 9478 patients with gastrointestinal symptoms and suspected for CMPA with age less than 24 months, found that vomiting was present in 53.5% of suspected infant. The difference can be explained by the difference of subject selection, as we included any child suspected for CMPA, whereas Vieirra et al. included only those with gastrointestinal symptoms. In this study, we found that the SPT in suspected infants (n=100) was positive in 23% (23 infants) of suspected infants and negative in 77% (77 infants) of suspected cases with mean±SD of 2.86±1.90, and weal range of 1–9 mm. Schoemaker et al. [16] found that of the suspected 358 infants for CMPA, 23.7% (85 infants) of them had positive SPT, which was near to our study results. Moreover, Mehl et al. [39] conducted a study on 395 children suspected for CMPA aged from 3 months to 13 years of life and found that 57% of them had positive SPT result, with median weal diameter of SPTs of 4.5 mm with a range of 0–20 mm. This difference may be owing to the difference in age range between this study and our study. In this study, we found that specific IgE for CMP in suspected infants (n=100) was 15.5% (14 of 90 infants, 10 samples were discarded) with mean±SD of 358.90±421.73. Schoemaker et al. [16] found that 35.4% of suspected infants (127 infants) had positive results of specific IgE for CMP. This difference may be owing to the discarded samples in our study. In addition, Mehl et al. [39] found that 70% of suspected children had positive values of specific IgE for CMP. This difference may be owing to the age difference between this study (3 months to 13 years) and ours; this wide age range may be the cause of this difference. Moreover, Saarinen and Savilahti [4] found 31% (75 infants) of suspected infants had positive specific IgE for CMP. This difference may be owing to the discarded samples in our study.

In our study, we found a positive correlation between specific IgE for CMP and SPT (r=0.512, P<0.001). Mehl et al. [39] conducted a study on 395 children suspected for CMPA aged from 3 months to 13 years of life and found such a correlation ((r=0.55, P<0.001). Vanto et al. [40] conducted a study on 301 infants in the first year of age and also found such a correlation (r=0.78, P<0.001). The difference may be owing to the time difference between this study and our study.

In this study, 37% of infants (with suspected CMPA) who were subjected to food elimination and challenge test have positive food elimination test result and 34.6% of them have positive challenge test result (n=98 infants, as two infants did not complete the challenge). Schoemaker et al. [16] conducted the food elimination test on 316 infants and found that 60 infants (24% of 248) of them had positive elimination results, and 248 infants complete the challenge and found that 55 infants had positive challenge test result (22%) (eight infants were placebo reactors and six were inconclusive). This difference may be owing to the difference in the challenge test as we conducted open challenge test, but Schoemaker et al. [16] conducted double-blind placebo challenge test (DBPCFC). Mauro et al. [41] conducted a study on 104 children in the first year of life (60 infants suspected to have CMPA and 44 infants included to confirm the diagnosis of CMPA) and conducted an open challenge test on 70 infants and found 30% of them were positive. This result is slightly near our results. They conducted DBPCFC on 34 infants and found that 20.6% were positive. Mehl et al. [39] conducted a study on 395 children suspected for CMPA aged from 3 months to 13 years of life and found that 52% (205 children) were positive for the challenge test. This difference may be owing to the age range difference between this study and our study. In this study, we found a positive correlation between food elemination test and both spesific IgE for CMP and SPT (P<0.001). We also find a positive correlation between OFC test and both SPT and spesific IgE (P<0.001). Kido et al. [42] conducted a study on 135 children with suspected CMA and found a positive correlation between oral food provocation tests and both SPT and spesific IgE (P<0.001). Petersen et al. [43] conducted a study on 78 children referred to the allergy center during a 13-year period and found a positive correlation between food elemination test and both spesific IgE for CMP and SPT (P<0.001). These results are similar to our result. In our study, we found the sensitivity of 41.18% and specificity of 100% of specific IgE in OFC test, as well as positive predictive value of 100%, negative predictive value of 73%, and cut-off point of more than 342 ng/ml, with AUC of 0.638. Moreover, we found the sensitivity of 45.95% and specificity of 90.48% of SPT in OFC test and positive predictive value of 73.9% and the negative predictive value of 74%, and cutoff point of more than 2 mm, with AUC of 0.678. Franco et al. [44] conducted a study on 122 childern and found that sensitivity of 67% and specificity of 39% of specific IgE in OFC test and positive predictive value of 63% and the negative predictive value of 43% and cutoff point of 0.35 kUA/l. The difference between this study and our study may be owing to the difference of the method, as Franco et al. [44] estimated specific IgE for each component of cow milk and found the sensitivity of 45% and specificity of 90% of SPT in OFC test and positive predictive value of 88% and the negative predictive value of 51%), and cut-off point of 5.17 mm.

The confirmed cases of CMPA in our study was 34 infants out of 1000 infants (3.4%). These cases were confirmed with positive elemination and OFC tests (23 cases have positive SPT result and 14 cases have positive specific IgE). From these results, we found 23 cases had IgE-mediated CMA (67.6%) and 11 cases had non-IgE-mediated CMA (32.3%), which confirmed that IgE-mediated CMPA is more common. Schoemaker et al. [16] found that the incidence of CMA in the first 2 years of life was less than 1% in Europe (ranging from 0 to 1.3%) and IgE-associated CMA is more preavelent. This difference may be owing to the difference in nutritional habits and the traditional weaning methods in our country. Sanz et al. [45] conducted a review of 229 PubMed articles on CMA for the years 1967 through 2001 and found that the incidence of CMPA in infancy is ∼2–3% in developed countries. Martorell-Aragonés et al. [46] stated that the estimated prevalence of CMPA in the first year of life is 1.6–3%, and decreases to less than 1% in children aged 6 years or older. Saarinen and Savilhti [4] conducted a study on 118 childern with CMA in the age 6–8 years and found that 86 (73%) childern had IgE-mediated CMA, and this result is slightly near to our results. In contrary to our study, Katz et al. [36] conducted a prospective study of the feeding history of 13 019 infants and found that the cumulative incidence for IgE-mediated CMA was 0.5% (66/13 019 patients), and so it stated that IgE-mediated CMA is less common than generally estimated. Moreover, Schoemaker et al. [16] found that most affected infants had IgE-associated CMA, which was in agreement with our study. Vieira et al. [47] conducted a study on 9478 consultations in the pediatric age range and found that the prevalence of confirmed CMA in the study population was 5.4% (513/9478), and the incidence was 2.2% (211/9478), and they stated that non-IgE-mediated allergy is more common, which was against our study.


  Conclusion Top


This study shows that the frequancy of CMPA in Demietta Governrate in infants in the first two years of life is 3.4%, and the IgE-mediated CMPA is more common, as 67.6% of cases had IgE-mediated CMA and 32.3% of cases had non-IgE-mediated CMA.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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