Cow’s milk challenge through human milk evokes immune responses in infants with cow’s milk allergy

doi:10.1016/S0022-3476(99)70175-7

The Journal of Pediatrics

Volume 135, Issue 4, October 1999, Pages 506-512

https://doi.org/10.1016/S0022-3476(99)70175-7 Get rights and content

Abstract

Objectives: In order to measure the immune response evoked in breast-fed infants with cow’s milk allergy (CMA) by cow’s milk challenge through human milk, mothers were given increasing doses of cow’s milk after they had been on a cow’s milk elimination diet. Another objective was to study the secretion of β-lactoglobulin (BLG) into human milk before and during milk challenge in relation to the appearance of symptoms in infants. Study design: Seventeen asymptomatic mothers who had infants with challenge-proven CMA and 10 asymptomatic mothers who had healthy infants were recruited. Infants ranged in age from 1.8 to 9.4 months. A solid-phase enzyme-linked immunoassay (ELISPOT) was used to assess the total number of immunoglobulin-secreting and specific antibody-secreting cells. Flow cytometry was used to enumerate different lymphocyte subpopulations among peripheral blood lymphocytes primed during provocation by cow’s milk antigens. BLG levels were assessed in human milk before the challenge and 1, 2, 3, and 4 hours after the commencement of the challenge. Results: All but one of the infants with CMA showed symptoms of CMA during cow’s milk challenge through human milk. There was a significant rise in the total number of immunoglobulin-secreting cells in the IgA and IgG classes associated with a positive cow’s milk challenge response, but the proportions of peripheral blood B cells bearing CD19, CD23, CD19 and 23, CD5, or CD19 and CD5 were comparable. BLG levels were comparable in both study groups. Conclusions: Most of the infants with CMA reacted to cow’s milk challenge through human milk. Hypersensitivity reactions to food antigens through human milk may be more common than previously thought. (J Pediatr 1999;135:506-12)

Section snippets

Study Population

Twenty-seven infants and their breast-feeding mothers were studied; the mothers gave written informed consent to participate in the study. Of the infants, 19 were prospectively followed up from birth. At the time of the challenge through human milk, the infants ranged in age from 1.8 to 9.4 months. The atopic mothers did not have symptoms of hay fever, eczema, urticaria, or asthma at the time of the study. All the infants and their mothers were on elimination diets for 2 to 4 weeks before the

Clinical Characteristics of Study Patients

Seventeen mothers had an infant with CMA, proven by clinical cow’s milk challenge as described elsewhere,¹² and 10 mothers had a healthy infant with a negative response to cow’s milk provocation. Of the mothers who had an infant with CMA, 11 of 17 (65%) were atopic, and of the mothers who had a healthy infant, 5 of 10 (50%) were atopic. The geometric mean ages of the infants with CMA, 5.4 months (95% CI, 4.4 to 6.7), and of healthy infants, 5.1 months (95% CI, 3.6 to 7.2), were comparable. The

DISCUSSION

In this study we have demonstrated that cow’s milk given to the nursing mother evokes clinical symptoms of CMA, as well as abnormal immune responses, in the breast-fed infant with CMA. We have further shown that allergic reactions to cow’s milk proteins can occur also through human milk without any cow’s milk being given directly to the infant.

Human postnatal sensitization to cow’s milk through human milk of presumably exclusively breast-fed infants has been suggested but not conclusively

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Cited by (100)

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines update – X – Breastfeeding a baby with cow's milk allergy
2023, World Allergy Organization Journal
Cow's milk allergy is rare in exclusively breastfed infants. To support the continuation of breastfeeding an infant after diagnosis with a cow's milk allergy, it is critical to examine the evidence for and against any form of cow's milk elimination diet for lactating mothers. In this narrative review, we highlight the lack of high-quality evidence, hence subsequent controversy, regarding whether the minuscule quantities of cow's milk proteins detectable in human milk cause infant cow's milk allergy symptoms. Current clinical practice recommendations advise a 2–4 week trial of maternal cow's milk dietary elimination for: a) IgE-mediated cow's milk allergy only if the infant is symptomatic on breastfeeding alone; b) non-IgE-mediated associated symptoms only if the history and examination strongly suggest cow's milk allergy; and c) infants with moderate to severe eczema/atopic dermatitis, unresponsive to topical steroids and sensitized to cow's milk protein. There should be a clear plan for home reintroduction of cow's milk into the maternal diet for a period of 1 week to determine that the cow's milk elimination is responsible for resolution of symptoms, and then subsequent reoccurrence of infant symptoms upon maternal cow's milk reintroduction. The evidence base to support the use of maternal cow's milk avoidance for the treatment of a breastfed infant with cow's milk allergy is of limited strength due to a lack of high-quality, adequately powered, randomised controlled trials. It is important to consider the consequences of maternal cow's milk avoidance on reducing immune enhancing factors in breast milk, as well as the potential nutritional and quality of life impacts on the mother. Referral to a dietitian is advised for dietary education, along with calcium and vitamin D supplementation according to local recommendations, and a maternal substitute milk should be advised. However, for most breastfed infants with cow's milk allergy maternal cow's milk dietary elimination will not be required, and active support of the mother to continue breastfeeding is essential.
Food Proteins in Human Breast Milk and Probability of IgE-Mediated Allergic Reaction in Children During Breastfeeding: A Systematic Review
2022, Journal of Allergy and Clinical Immunology: In Practice
Citation Excerpt :
Thirty-two studies included in this systematic review were published between 1983 and 2020 and can be grouped into 2 main categories in accordance with the study design: (a) interventional12-33 and (b) observational.16,17,19,34-43 All included interventional studies administered either single12-15,18-21,23-43 or multiple16,17,22 foods for various durations during lactation. Fourteen studies investigated cow’s milk proteins (β-lactoglobulin [BLG] and casein),13,18-20,23,24,26,31,34,36-38,41,42 9 measured egg proteins (ovalbumin [OVA]14,21,25,27,28,39,40,43 and ovomucoid [OM]35), 4 assessed peanut proteins (Ara h 2 and Ara h 6),12,29,30,33 and 2 looked at wheat protein (gliadin).15,32
Previous reports suggested that food proteins present in human milk (HM) may trigger symptoms in allergic children during breastfeeding, but existing evidence has never been reviewed systematically.
To assess the probability of food proteins in HM to trigger allergic reactions in infants with IgE-mediated food allergy.
Electronic bibliographic databases (MEDLINE, EMBASE) were systematically searched from inception to November 3, 2021. The data regarding the levels of food proteins detected in HM were extracted and compared with data from the Voluntary Incidental Trace Allergen Labelling (VITAL 3.0) guide to assess the probability of food-allergic individuals to experience immediate type allergic reactions on ingesting HM.
A total of 32 studies were identified. Fourteen studies assessed excretion of cow’s milk proteins into HM, 9 egg, 4 peanut, and 2 wheat; 3 measured levels of cow’s milk and egg proteins simultaneously. We found that levels of all food proteins across the studies were much lower than the eliciting dose for 1% of allergic individuals (ED01) in most of the samples. The probability of an IgE-mediated allergic reaction in a food-allergic infant breastfed by a woman consuming the relevant food can be estimated as ≤1:1000 for cow’s milk, egg, peanut, and wheat.
To our knowledge, this is the first systematic review that assesses and summarizes evidence on food proteins in HM and potential for IgE-mediated allergic reactions. Our data suggest that the probability of IgE-mediated allergic reactions to food proteins in HM is low.
Atopic dermatitis and nutrition
2022, Clinics in Dermatology
Atopic dermatitis, a common chronic and pruritic inflammatory skin disorder, can create significant disruptions in sleep and quality of life. Atopic dermatitis is especially common in infants and children; therefore, safe and natural therapeutic options have considerable appeal. Over the past several decades, there has been an increase in the prevalence of atopic dermatitis in industrialized nations. Also, there is variability in the prevalence of atopic dermatitis in the United States, both across and within states. Environmental factors including diet are believed to be associated with this increased risk. Dietary interventions continue to be an area of keen interest and have been studied extensively, albeit with variable results. Maternal dietary restrictions during pregnancy and lactation, hydrolyzed or partially hydrolyzed formulas, delaying the introduction of solid foods, and omega-3 or omega-6 fatty acids supplementation do not appear to have a beneficial effect on the treatment and prevention of atopic dermatitis. Exclusive breastfeeding for 3 to 4 months, a diet high in fruits and vegetables, and prebiotics might have a beneficial effect. Because environmental triggers, including dietary exposures, are thought to play a role in the pathogenesis of atopic dermatitis, we herein review the current literature on the role of dietary habits, vitamin and mineral supplementation, and probiotics on the treatment and prevention of atopic dermatitis.
Epidemiological study and diet difficulties of cow's milk allergy in the Northern east of Algeria
2021, Cahiers de Nutrition et de Dietetique
L’APLV est une pathologie lourde de conséquences sur la santé des patients et de leur entourage par sa symptomatologie variée et sa prise en charge difficile. Cette étude est une contribution à une meilleure connaissance de la situation de cette pathologie en Algérie. Ce travail est une étude épidémiologique de l’APLV dans neuf wilayas du Nord Est algérien avec un échantillon de 9305 enfants âgés de 0 à 3 ans. L’étude a fait ressortir une prévalence assez élevée qui atteint 3,17 % des enfants âgés de moins de trois ans. L’unique traitement à cette pathologie est l’éviction totale de toutes les protéines du lait bovin et l’administration de substituts adaptés, basés le plus souvent sur des hydrolysats plus ou moins poussés de protéines de diverses origines.
Cow's milk protein allergy (CMPA) is a disease with serious consequences on the health of patients and their families through its various symptoms and its difficult managements. This study is a contribution to a better understanding of the situation of this disease in Algeria. This work is devoted to an epidemiological study of CMPA and involved 9305 children from 0 to 3 years of age in nine north eastern Algerian wilayate. The study showed a high prevalence of CMPA reaching 3.17% of children aged less than three years. The only treatment for this pathology is the total eviction of all the proteins of bovine milk and administration of adapted substitute based on protein hydrolysates or proteins of various origins.
Provider recommendations and maternal practices when providing breast milk to children with immunoglobulin E–mediated food allergy
2021, Annals of Allergy, Asthma and Immunology
There is limited research investigating maternal dietary practices and health care provider recommendations when providing breast milk (BM) to children with immunoglobulin (Ig) E–mediated food allergy.
To explore health care provider recommendations and maternal practices when providing BM to children with IgE-mediated food allergy and to assess for possible IgE-mediated reactions to BM while the mother consumed the food to which her child has allergy.
A web-based survey was distributed to breastfeeding (BF) mothers of children with IgE-mediated food allergies. Reported reactions to BM were scored by an allergist, provided only with the details of the possible reaction and not the suspect allergen or route of exposure, as to the likelihood that the reaction was IgE mediated.
A total of 133 mothers completed the survey. After food allergy diagnosis, 47.4% (n = 63) of the mothers reported that they were advised by their health care provider to continue BF without dietary restriction, 17.3% (n = 23) were advised to avoid eating the food(s) their child has allergy to while BF, and in 28.6% (n = 38), this concern was not addressed. A few of the mothers (12%, 16/133) reported that their child experienced an allergic reaction to BM. An allergist evaluated most of these reactions (75%, 12/16) as not likely IgE mediated.
This study exposed inconsistent recommendations for mothers providing BM to children with IgE-mediated food allergies. Most mothers were able to consume the food their child has allergy to without adverse sequelae. Standardized, evidence-based recommendations would enhance the well-being of these mother-infant dyads.
Immunologic components in human milk and allergic diseases with focus on food allergy
2021, Seminars in Perinatology
Citation Excerpt :
We measured BLG in 16 mothers of infants with challenge-proven CMA seen in a tertiary referral center and 10 mothers of healthy infants.53 After a 2-4 week maternal elimination diet, mothers consumed CM and all but one of the infants with CMA had clinical manifestations of an immune response with eczema being the most common reaction.53 BLG was not detected in almost half of the milk samples at the time of symptoms, however not all CM proteins such as caseins were measured.53
Human milk contains a wide range of immunomodulatory factors, including immunoglobulins, human milk oligosaccharides, cytokines, microbiome, innate factors and food antigens. Maternal diet can influence the content of human milk as it is well-established that dietary antigens can be secreted in human milk after maternal consumption, but whether these dietary antigens promote tolerance or sensitization in the infant is a subject of debate. This review summarizes the current literature on these immunologically active factors in human milk, including the microbiome, innate factors, and maternal diet-derived dietary antigens in the context of development of allergic diseases, with the focus on food allergy.

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^☆: Supported (personal grant) by The Finnish Society of Allergology and Immunology and The Allergy Research Foundation in Finland (K.-M.J.).

^☆☆: Reprint requests: Hanna Suomalainen, MD, PhD, Helsinki University Central Hospital, Skin and Allergy Hospital/Department of Dermatology, PO Box 160, FIN-00029 HUCH, Helsinki, Finland.

^★: 0022-3476/99/$8.00 + 0 9/21/100848

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Cow’s milk challenge through human milk evokes immune responses in infants with cow’s milk allergy☆,☆☆,★

Abstract

Section snippets

Study Population

Clinical Characteristics of Study Patients

DISCUSSION

Lancet

J Allergy Clin Immunol

J Pediatr

J Pediatr

J Allergy Clin Immunol

J Allergy Clin Immunol

Lancet

Diagnostic criteria for food allergy with predominantly intestinal symptoms

J Pediatr Gastroenterol Nutr

Cow’s milk allergy in breast-fed infants: the role of allergen and maternal secretory IgA antibody

J Allergy Clin Immunol

Allergies in breast-fed babies to ingredients in breast milk

Ann Allergy

Antigen absorption in the gut [editorial]

Lancet

Passage of cow’s milk protein in breast milk

Clin Allergy

The passage of maternal dietary proteins into human breast milk

Int Arch Allergy Appl Immunol

Cow’s milk provocation induces an immune response to unrelated dietary antigens

Gut

Large number of CD19+/CD23+ B cells and small number of CD8+ T cells as early markers for cow’s milk allergy (CMA)

Pediatr Allergy Immunol