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Effect of continued feeding of cows' milk on asymptomatic infants with milk protein sensitive enteropathy

Iyngkaran N, Yadav M, Boey CG, Lam KL

Arch Dis Child, 1988 Aug;63(8):911-5.
PMID: 3415326

The clinical response and the histological changes in the mucosa of the small bowel in response to continued feeding with cows' milk protein were assessed over a period of 2-6 weeks in 24 infants who had shown histological changes without immediate clinical symptoms after challenge with a diet containing cows' milk protein. Twenty of the 24 infants (83%) thrived well on cows' milk protein. Jejunal biopsy specimens taken six to eight weeks after the initial biopsy showed histological improvement in all 20 infants compared with biopsy specimens taken soon after the challenge, which had shown mucosal damage. The mucosa had returned to normal in 12, was mildly abnormal in seven, and moderately abnormal in one. Corresponding improvements in the activities of mucosal enzymes were seen. In four of the 24 infants (17%) symptoms developed between three and six weeks. Histological examination of the jejunal biopsy specimens showed that mucosal damage had progressed in two, and remained the same in two; moreover, the disaccharidase activities remained depressed. The present study shows that most infants with enteropathy caused by sensitivity to cows' milk protein but without clinical symptoms develop tolerance to the protein and the mucosa returns to normal despite continued feeding with cows' milk protein.

Matched MeSH terms: Milk Proteins/adverse effects
Fulltext Absence of milk-specific IgE in infants with cow's milk protein-sensitive enteropathy

Yadav M, Iyngkaran N, Seow IKG

Med J Malaysia, 1983 Dec;38(4):266-71.
PMID: 6599980

Infants, one to 56-weeks-old, presenting with persistent diarrhoea were placed on a diet free of cow's milk protein which improved their clinical condition. Six weeks later, 67 infants were challenged with a low-lactose cow's milk formula and jejunal biopsy was taken before and 24-hours after challenge. On the basis of histological changes in the intestinal mucosa and development of clinical symptoms the infants were categorised into three groups: Group 1 (n = 16) with no clinical or mucosal abnormality, Group 2 (n = 20) with mucosal abnormality but lacking clinical symptoms, and Group 3 (n 31) with manifestation of mucosal abnormality and clinical symptoms. In addition to the total IgE the radioallergosorbent test (RAST) was performed on sera from the infants taken before and after milk provocation. The mean total serum IgE level ranged from 288 to 560 IU/ml. In Groups 2 and 3 the prechallenge serum IgE levels were significantly higher than the postchallenge levels but in Group 1 the levels remained unchanged on challenge. A positive RAST to milk proteins was observed in five infants (7.4%), that is, one in Group 2 and four in Group 3, of 67 infants studied. In a survey of 405 consecutive paediatric-age patients admitted for a variety of symptoms, 90 were positive for RAST specific for milk proteins. Interestingly the majority of the patients positive for RAST presented with gastrointestinal ailments. The measurement of specific IgE appears not to be a useful adjunct in the diagnosis of CMPSE in Malaysian children.

Matched MeSH terms: Milk Proteins/adverse effects*
Cow's milk protein sensitive enteropathy (CMPSE): an important cause of protracted diarrhoea in infancy

Iyngkaran N, Robinson MJ, Davis KA, Sumithran E, Kumar MV, Ong TH, et al.

Aust Paediatr J, 1979 Dec;15(4):266-70.
PMID: 546392
Matched MeSH terms: Milk Proteins/adverse effects*
Partially hydrolyzed formula in non-exclusively breastfed infants: A systematic review and expert consensus

Vandenplas Y, Latiff AHA, Fleischer DM, Gutiérrez-Castrellón P, Miqdady MS, Smith PK, et al.

Nutrition, 2019 01;57:268-274.
PMID: 30223233 DOI: 10.1016/j.nut.2018.05.018

OBJECTIVES: Guidance and evidence supporting routine use of partially hydrolyzed formula (pHF) versus intact cows' milk protein (CMP) formula are limited in non-exclusively breastfed infants. The aim of this review was to better clarify issues of routine use of pHF in non-exclusively breastfed infants who are not at risk for allergic disease by using a systematic review and Delphi Panel consensus.
METHODS: A systematic review and Delphi consensus panel (consisting of eight8 international pediatric allergists and gastroenterologists) was conducted to evaluate evidence supporting growth, tolerability, and effectiveness of pHF in non-exclusively breastfed infants.
RESULTS: None of the studies reviewed identified potential harm of pHF use compared with CMP in non-exclusively breastfed infants. There was an expert consensus that pHF use is likely as safe as intact CMP formula, given studies suggesting these have comparable nutritional parameters. No high-quality studies were identified evaluating the use of pHF to prevent allergic disease in non-exclusively breastfed infants who are not at risk for allergic disease (e.g., lacking a parental history of allergy). Limited data suggest that pHF use in non-exclusively breastfed infants may be associated with improved gastric emptying, decreased colic incidence, and other common functional gastrointestinal symptoms compared with CMP. However, because the data are of insufficient quality, the findings from these studies have to be taken with caution. No studies were identified that directly compared the different types of pHF, but there was an expert consensus that growth, allergenicity, tolerability, effectiveness, and clinical role among such pHF products may differ.
CONCLUSIONS: Limited data exist evaluating routine use of pHFs in non-exclusively breastfed infants, with no contraindications identified in the systematic review. An expert consensus considers pHFs for which data were available to be as safe as CMP formula as growth is normal. The preventive effect on allergy of pHF in infants who are not at risk for allergic disease has been poorly studied. Cost of pHF versus starter formula with intact protein differs from country to country. However, further studies in larger populations are needed to clinically confirm the benefits of routine use of pHF in non-exclusively breastfed infants. These studies should also address potential consumer preference bias.

Matched MeSH terms: Milk Proteins/adverse effects
Fulltext Mucosal enterokinase activity in cow's milk protein sensitive enteropathy

Iyngkaran N, Yadav M, Boey CG

Singapore Med J, 1995 Aug;36(4):393-6.
PMID: 8919154

Enterokinase has a critical role in initiating proteolytic digestion by hydrolysing the conversion of pancreatic trypsinogen into trypsin. The enzyme is synthesised by enterocytes of the proximal small intestine and initially incorporated into the brush border from where it is released into the intestinal lumen by the action of pancreatic secretions. The aim of the study was to analyse enterokinase activity in the duodenal mucosa of infants with diarrhoeal disease including cow's milk protein-sensitive enteropathy. Our observations show that the mean depletion of enterokinase was only 17% compared to 60-80% for other brush border enzymes like disaccharidases, peptidases and alkaline phosphatases in infants with diarrhoea. This suggests that enterokinase activity in the small bowel enteropathies may be dependent not only on the degree of mucosal damage specifically but also on the extent of damage to the goblet cell population where the enzyme is synthesised. Thus the enterokinase activity was reduced in acute and chronic diarrhoea with marked mucosal damage where significant reduction of goblet cell population was evident but the enzyme was relatively little affected when the mucosa was damaged mildly.

Matched MeSH terms: Milk Proteins/adverse effects
Causative effect of cow's milk protein and soy protein on progressive small bowel mucosal damage

Iyngkaran N, Yadav M, Boey CG, Kamath KR, Lam KL

J Gastroenterol Hepatol, 1989 3 1;4(2):127-36.
PMID: 2490907

Some infants intolerant to cow's milk protein (CMP) are often also intolerant to other food proteins including soy protein (SP). The effect of CMP and SP in infants recovering from diarrhoeal disease was studied in 22 infants who were maintained on an hypo-allergenic formula for 4-6 weeks. The infants were then challenged successively, initially with SP, followed 24 h later with CMP and then rechallenged with SP 24 h after CMP provocation. Three groups were recognized on the basis of clinical symptoms and mucosal changes following SP challenge. Group 1 comprised four infants who developed clinical and histological reactions on SP challenge. The subsequent CMP challenge, 24 h after the initial SP challenge, resulted in clinical symptoms in three of the four infants, and they developed increased mucosal injury. Rechallenge with SP in the three infants caused development of severe clinical symptoms. Group 2 comprised 12 infants who developed histological reaction but had no clinical symptoms to initial SP challenge. The subsequent CMP challenge caused further progression in mucosal pathology in 11 of the 12 infants and six also had associated clinical symptoms. Rechallenge with SP in the latter six infants resulted in development of clinical symptoms in three and tolerance to SP in three infants. Group 3 comprised six infants who tolerated SP and CMP but one of these infants developed mild histological changes to CMP. The progression of mucosal injury following SP and CMP challenge was associated with a significant decrease in mucosal disaccharidases, alkaline phosphatase levels and presence of reducing sugar in the stools. The 1 h blood xylose level continued to decrease significantly following the pre-SP, post-SP, and post-CMP challenge. It appears that the small bowel mucosa of young infants recovering from diarrhoeal disease remains sensitive not only to CMP but also to SP. The feeding of these proteins in rapid successive sequence to infants with mucosal damage might result in further progression of the mucosal injury. Thus, the exclusion for a variable period of time of antigenic food proteins like CMP and SP from the diet of young infants recovering from diarrhoea might reduce the risk of inducing mucosal sensitivity to these proteins in susceptible infants.

Matched MeSH terms: Milk Proteins/adverse effects*
Severity and extent of upper small bowel mucosal damage in cow's milk protein-sensitive enteropathy

Iyngkaran N, Yadav M, Boey CG, Lam KL

J Pediatr Gastroenterol Nutr, 1988 Sep-Oct;7(5):667-74.
PMID: 3183870

A series of 31 infants, 28 with cow's milk protein sensitive enteropathy (CMPSE) and 3 controls, was studied for severity and extent of mucosal damage of the upper small bowel in relation to the development of clinical symptoms. Following challenge with the offending cow's milk, 18 infants (Group 1) developed severe mucosal changes at both the proximal and distal small bowel mucosa and all of these infants presented with clinical symptoms. The other 10 infants (Group 2) who did not develop clinical symptoms following the challenge had less severe damage to the distal small bowel mucosa as compared to the proximal region. The histological score of both the proximal and distal postchallenge biopsies were significantly lower in Group 2 as compared to Group 1 infants. The mucosal disaccharidase and alkaline phosphatase levels were depleted in both the proximal and distal biopsies following challenge but the depletion was greater in the proximal than the distal biopsies. It is suggested that the extent and severity of mucosal damage to the proximal duodenum and jejunum have a critical bearing on the development of clinical symptoms.

Matched MeSH terms: Milk Proteins/adverse effects*
Intestinal brush border peptidases in cow's milk protein-sensitive enteropathy

Iyngkaran N, Yadav M, Boey CG

Acta Paediatr Scand, 1991 May;80(5):549-50.
PMID: 1678569
Matched MeSH terms: Milk Proteins/adverse effects*