Clinical, laboratory, and therapeutic differences between immunoglobulin E-mediated and non-immunoglobulin E-mediated cow’s milk protein allergy in children

doi:10.5409/wjcp.v14.i1.100386

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World Journal of Clinical Pediatrics

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Retrospective Cohort Study

World J Clin Pediatr. Mar 9, 2025; 14(1): 100386
Published online Mar 9, 2025. doi: 10.5409/wjcp.v14.i1.100386

Table 1 Demographic data in children with cow’s milk protein allergy, n (%)

Variables	Total, n = 595 (100)	IgE-mediated, n = 135 (22.7)	Non-IgE-mediated, n = 460 (77.3)	P value
Nationality				1.000^a
Bahraini	558 (93.8)	127 (94.1)	431 (93.7)
Non-Bahraini	37 (6.2)	8 (5.9)	29 (6.3)
Governorate
Northern	66 (48.9)	228 (49.6)	294 (49.4)	0.536^b
Capital	39 (28.9)	115 (25.0)	154 (25.9)
Muharraq	18 (13.3)	57 (12.4)	75 (12.6)
Southern	12 (8.9)	60 (13.0)	72 (12.1)
Sex				0.030^a
Male	329 (55.3)	86 (63.7)	243 (52.8)
Female	266 (44.7)	49 (36.3)	217 (47.2)
Gestational age (n = 539)				0.418^a
Full term	445 (82.6)	104 (85.2)	341 (81.8)
Preterm	94 (17.4)	18 (14.8)	76 (18.2)
Delivery (n = 530)				0.914^a
Normal delivery	333 (62.8)	75 (63.6)	258 (62.6)
Cesarean section	197 (37.2)	43 (36.4)	154 (37.4)
Birth weight (kg) (n = 512)	2.9 (2.5-3.3)	2.9 (2.5-3.3)	2.9 (2.5-3.3)	0.626^c
Birth weight group (kg) (n = 512)				0.701^a
< 2.5	111 (21.7)	27 (23.3)	84 (21.2)
≥ 2.5	401 (78.3)	89 (76.7)	312 (78.8)
Age at presentation (months) (n = 589)	3 (2-5)	4 (2-7)	3 (2-5)	0.009^c
Age group (months) (n = 589)				0.031^b
< 6	464 (78.0)	93 (68.9)	371 (80.7)
6-12	102 (17.1)	34 (25.2)	68 (14.8)
13-24	25 (4.2)	7 (5.2)	18 (3.9)
> 24	4 (0.7)	1 (0.7)	3 (0.7)
Associated diseases¹	226 (38.0)	70 (51.9)	156 (33.9)	< 0.001^a
Number of outpatient visits	4 (2-7)	5 (3-7)	4 (2-7)	0.123^c
Follow-up duration (months)	11.8 (5.5-18.2)	13.5 (8.3-21.8)	11.3 (5.0-16.9)	< 0.001^c
Age at last follow-up (years)	1.3 (0.8-1.9)	1.6 (1.1-2.2)	1.2 (0.8-1.8)	< 0.001^c
Age group at last follow-up (years)				< 0.001^b
< 1	25 (18.5)	171 (37.2)	196 (32.9)
1-3	92 (68.1)	254 (55.2)	346 (58.2)
4-6	16 (11.9)	27 (5.9)	43 (7.2)
> 6	2 (1.5)	8 (1.7)	10 (1.7)
FH of allergies²	222 (37.3)	59 (43.7)	163 (35.4)	0.086^a
FH of food allergy	159 (26.7)	41 (69.5)	118 (72.4)	0.737^a
FH of cow’s milk allergy	130 (21.8)	29 (49.2)	101 (62.0)	0.092^a
FH of other allergies³	89 (15.0)	25 (42.4)	64 (39.3)	0.757^a

Data are presented as numbers and percentages or median and interquartile range. Boldface indicates a statistically significant difference with P < 0.05.

^aFisher’s exact test.

^bPearson’s χ² test.

^cMann-Whitney U test.

¹Supplementary Table 1.

²Some patients had more than one type of allergy.

³Bronchial asthma (n = 44), eczema (n = 31), rhinitis (n = 9), atopy (n = 5), drug allergy (n = 3), sinusitis, celiac disease, lactose intolerance, dust allergy (n = 2), powder allergy, psoriasis, allergy, urticaria, pet’s allergy (n = 1).

FH: Family history; IgE: Immunoglobulin E.

Table 2 History and physical examination findings of children with cow’s milk protein allergy, n (%)

History/physical examination¹	Total, n = 595 (100)	IgE-mediated, n = 135 (22.7)	Non-IgE-mediated, n = 460 (77.3)	P value^a
Presenting history
Gastrointestinal manifestations	567 (95.3)	128 (94.8)	439 (95.4)	0.817
Vomiting	282 (47.4)	61 (45.2)	221 (48.0)	0.624
Constipation	200 (33.6)	47 (34.8)	153 (33.3)	0.756
Diarrhea	198 (33.3)	54 (40.0)	144 (31.3)	0.062
Colic	152 (25.5)	32 (23.7)	120 (26.1)	0.654
Blood in the stool	126 (21.2)	22 (16.3)	104 (22.6)	0.121
Failure to thrive	102 (17.1)	33 (24.4)	69 (15.0)	0.013
Mucous in the stool	97 (16.3)	17 (12.6)	80 (17.4)	0.233
Abdominal distention	36 (6.1)	8 (5.9)	28 (6.1)	1.000
Poor appetite	13 (2.2)	4 (3.0)	9 (2.0)	0.505
Gasses	12 (2.0)	2 (1.5)	10 (2.2)	1.000
Regurgitation	8 (1.3)	1 (0.7)	7 (1.5)	0.690
Oily stool	7 (1.2)	3 (2.2)	4 (0.9)	0.196
Change in stool color	6 (1.0)	1 (0.7)	5 (1.1)	1.000
Nausea	1 (0.2)	0 (0.0)	1 (0.2)	1.000
Solid dysphagia	1 (0.2)	0 (0.0)	1 (0.2)	1.000
Pica	1 (0.2)	0 (0.0)	1 (0.2)	1.000
Cutaneous manifestations	278 (46.7)	75 (55.6)	203 (44.1)	0.024
Rash/dry skin	277 (46.6)	74 (54.8)	203 (44.1)	0.031
Facial swelling/angioedema	5 (0.9)	4 (3.0)	0 (0.0)	0.003
Urticaria	2 (0.3)	2 (1.5)	0 (0.0)	0.051
Itching	1 (0.2)	0 (0.0)	1 (0.2)	1.000
Respiratory manifestations	13 (2.2)	8 (5.9)	5 (1.1)	0.003
Cough	7 (1.2)	3 (2.2)	4 (0.9)	0.196
Breathing difficulty	2 (0.3)	2 (1.5)	0 (0.0)	0.051
Rhinitis	3 (0.5)	2 (1.5)	1 (0.2)	0.131
Recurrent aspiration	1 (0.2)	1 (0.7)	0 (0.0)	0.227
Choking episodes	1 (0.2)	1 (0.7)	0 (0.0)	0.227
Other manifestations	29 (4.9)	14 (10.4)	15 (3.3)	0.002
Excessive crying	10 (1.7)	1 (0.7)	9 (2.0)	0.469
Apparent life-threatening event	9 (1.5)	9 (6.7)	0 (0.0)	< 0.001
Irritability	5 (0.8)	2 (1.5)	3 (0.7)	0.318
Sleeping difficulties	5 (0.8)	1 (0.7)	4 (0.9)	1.000
Loss of consciousness	1 (0.2)	1 (0.7)	0 (0.0)	0.227
Positive physical findings	208 (34.9)	63 (46.7)	145 (31.5)	0.002
Eczema	147 (25.0)	46 (34.6)	101 (22.1)	0.004
Abdominal distention	46 (7.8)	9 (6.8)	37 (8.1)	0.715
Hepatomegaly	6 (1.0)	1 (0.8)	5 (1.1)	1.000
Marasmus	6 (1.0)	1 (0.8)	5 (1.1)	1.000
Bowlegs (genu varum)	3 (0.5)	1 (1.8)	2 (0.4)	0.537
Hemangioma	3 (0.5)	1 (1.4)	2 (0.4)	0.129
Wide metaphysis	2 (0.3)	0 (0.0)	2 (0.4)	1.000
Cleft palate	2 (0.3)	0 (0.0)	2 (0.4)	1.000
Colostomy scar	2 (0.3)	0 (0.0)	2 (0.4)	0.401
Wheezy chest	1 (0.2)	1 (0.8)	0 (0.0)	0.266
Other findings²	23 (3.9)	8 (6.0)	15 (3.3)	0.199

Data are presented as numbers and percentages or median and interquartile range. Boldface indicates a statistically significant difference with P < 0.05.

^aFisher’s exact test.

¹Some patients had more than one presenting history or physical finding.

²Hypertonia of upper limbs, erythema and skin peeling of perianal and umbilical area, inguinal hernia, seborrheic dermatitis (n = 2), anal fissure, café au lait spot, hair in the back, hypertonia of lower limbs, hypo and hyperpigmented lesions, hypotonia of upper limbs, ileostomy bag, labial adhesion, umbilical hernia, left hand extra digit, left thoracotomy scar, microcephaly, mild jaundice, swollen face, truncal hypotonia, undescended testis (n = 1 each).

IgE: Immunoglobulin E.

Table 3 Laboratory findings in children with cow’s milk protein allergy, n (%)

Laboratory findings	Result/total tested, n = 595 (100)	IgE-mediated, n = 135 (22.7)	Non-IgE-mediated, n = 460 (77.3)	P value^a
Anemia	424/563 (75.3)	102 (77.3)	322 (74.7)	0.645
Low hematocrit	153/476 (32.1)	31 (26.3)	122 (34.1)	0.139
Low mean corpuscular volume	334/484 (69.0)	89 (73.0)	245 (67.7)	0.309
Low mean corpuscular hemoglobin	376/484 (77.7)	96 (78.7)	280 (77.3)	0.803
Low iron	153/279 (54.8)	42 (48.8)	111 (57.5)	0.194
Low ferritin	29/69 (42.0)	9 (45.0)	20 (40.8)	0.793
Thrombocytosis	229/483 (47.4)	53 (43.4)	176 (48.8)	0.473
Leukocytosis	199/477 (41.7)	46 (39.0)	153 (42.6)	0.520
Vitamin D deficiency	82/271 (30.3)	23 (26.4)	59 (32.1)	0.397
Low albumin	41/223 (18.4)	10 (19.6)	31 (18.0)	0.838
High alkaline phosphatase	49/368 (13.3)	15 (15.8)	34 (12.5)	0.483
Hypocalcemia	19/320 (5.9)	7 (8.0)	12 (5.2)	0.426
Eosinophilia	20/476 (4.2)	5 (4.2)	15 (4.2)	1.000
Hypophosphatemia	5/332 (1.5)	3 (3.1)	2 (0.8)	0.147
High milk-specific IgE	121/240 (50.4)	121 (97.6)	0 (0.0)	< 0.001

Data are presented as numbers and percentages. Boldface indicates a statistically significant difference with P < 0.05.

^aFisher’s exact test.

IgE: Immunoglobulin E.

Table 4 Types of feeding in children with cow’s milk protein allergy, n (%)

Feeding type¹	Total, n = 586 (98.5)	IgE-mediated, n = 135 (23.0)	Non-IgE-mediated, n = 451 (77.0)	P value^a
Exclusive formula feeding	295 (50.3)	70 (51.9)	225 (49.9)	0.696
Both breast and formula-feeding	243 (41.5)	54 (40.0)	189 (41.9)	0.765
Exclusive breastfeeding	48 (8.2)	11 (8.1)	37 (8.2)	1.000
Type of formula used (n = 532)
Amino acid-based formula	322 (60.5)	82 (66.1)	240 (58.8)	0.173
Extensively hydrolyzed formula	300 (56.4)	65 (52.4)	237 (58.1)	0.301
Standard formula	42 (7.9)	8 (6.5)	34 (8.3)	0.573
Partially hydrolyzed formula	31 (5.8)	4 (3.2)	27 (6.6)	0.192
Anti-regurgitation formula	17 (3.2)	6 (4.8)	11 (2.7)	0.247
Plant-based milk formula	15 (2.8)	4 (3.2)	11 (2.7)	0.759
Lactose-free formula	7 (1.3)	3 (2.4)	4 (1.0)	0.208
High energy intake (n = 580)	64 (11.0)	21 (15.6)	43 (7.9)	0.061
Carbohydrate supplement	37 (6.4)	12 (8.9)	25 (5.6)	0.226
High-energy milk formula	35 (6.0)	12 (8.9)	23 (5.2)	0.146

Data are presented as numbers and percentages.

^aFisher’s exact test.

¹Some patients used more than one type of formula.

IgE: Immunoglobulin E.

Citation: Isa HM, Abdulnabi MJ, Naser NS, Lahmda FN, AlAnsari NM, Isa ZH, Mohamed AM. Clinical, laboratory, and therapeutic differences between immunoglobulin E-mediated and non-immunoglobulin E-mediated cow’s milk protein allergy in children. World J Clin Pediatr 2025; 14(1): 100386
URL: https://www.wjgnet.com/2219-2808/full/v14/i1/100386.htm
DOI: https://dx.doi.org/10.5409/wjcp.v14.i1.100386