Very early onset perinatal constipation: Can it be cow’s milk protein allergy?

Table 1 Incidences of various diagnoses in infants with very early-onset constipation

Diagnosis	Incidence	Ref.
Hirschsprung’s disease	0.025%	Loening-Baucke and Kimura[2]
Meconium plug syndrome	0.1%-0.2	Loening-Baucke and Kimura[2]
Meconium ileus	0.04	Loening-Baucke and Kimura[2]
Anorectal malformation	0.025%-0.05%	Loening-Baucke and Kimura[2]
CMPA	0.5%-17%	Høst[10], Rona et al[12]

CMPA: Cow’s milk protein allergy.

Table 2 Relative frequencies of Hirschsprung’s disease vs cow’s milk protein allergy in infants with very early-onset constipation

Ref.	HD (%)	CMPA (%)
Burge and Drewett[18]	38.1
Kubota et al[19]	34.6	65.4
Van Leeuwen et al[20]	25.0
Keckler et al[11]	13.0
Cheng et al (unpublished observation)	8.0	92.0

CMPA: Cow’s milk protein allergy; HD: Hirschsprung’s disease.

Table 3 Comparison of atypical vs typical cow’s milk protein allergy

	Atypical CMPA	Typical CMPA
Time of onset	Perinatal period[3]	Early infancy[21,22]
Way of transmission of allergen	Vertically via placenta and amniotic fluid[3]	Vertically via breast feeding
		Horizontally by oral ingestion[21,22]
Typical presentation	Intractable constipation[5,6]	Vomiting and diarrhea, bloody stools[21]
Type of allergy reaction	Non IgE mediated[5]	IgE mediated[5]
Tissues involved	Enteric neurons and smooth muscle[5-8]	Intestinal mucosa[5]
Mechanism involved	Immune mediated neuromuscular dysfunction leading to persistent spasm or failure to relax of the anorectum (HD like changes)[5-8]	Allergic enterocolitis[5]
Diagnosis	CMP avoidance and challenge. Both blood and skin allergy testings are of no diagnostic value[9]	CMP avoidance and challenge with or without blood and skin allergy testing[21]
Treatment	CMP avoidance[9]	CMP avoidance[9]
Awareness to providers	Rarely aware/reported	Well known/reported

CMP: cow’s milk protein; CMPA: cow’s milk protein allergy; HD: Hirschsprung’s disease; IgE: Immunoglobulin E.