versión impresa ISSN 0325-0075
Arch. argent. pediatr. vol.110 no.5 Buenos Aires oct. 2012
Association of dietary patterns and food allergy in infants during the first year of life
Karla Amada Bascuñán Gamboa, MDa, Sergio Gerardo Weisstaub Nuta, MDb, Rodrigo Andrés Chamorro Melo, MDb, María Antonieta Guzmán, MDc and Magdalena Araya Quezada, MDb
a. School of Nutrition
School of Medicine,
b. Institute of Nutrition and Food Technology (Instituto de Nutrición y Tecnología de los Alimentos, INTA), Universidad de Chile.
c. Immunology, HIV and Allergies Division, Department of Medicine, Clinical Hospital, Universidad de Chile. Santiago, Chile.
E-mail: Magdalena Araya, MD: email@example.com
Conflict of interests: None.
Introduction. There is controversy about the effect of dietary patterns during the first year of life
and the occurrence of food allergy. The objective
of this study was to evaluate the association between family history of allergy, allergic manifestations and dietary patterns during the first year
of life in infants with and without food allergy.
Population and methods. We performed a descriptive cross-sectional study in children under 2 years of age (n= 99), sorted in two groups: allergic group (n= 50) and control group (n= 49), matched by socioeconomic status, age and gender. Food allergy was defned by internationally approved clinical criteria, prick and patch tests, and response to diet. Information on diet, clinical data and history of allergy in the parents were collected. The sample size was estimated for logistic regression (Freeman), and Student X2 and Mann-Withney tests were used. The study and consent forms were approved by the Ethics Committee of the Institute of Nutrition and Food Technology (Instituto de Nutrición y Tecnología de los Alimentos, INTA) and the Universidad de Chile.
Results. The allergic group showed a significantly higher prevalence (p <0.0001) of family history of allergy (84%) than the control group (16%). Diarrhea was the symptom most frequently reported by the mothers of allergic infants during the frst year of life. Bottle feeding was introduced earlier in the allergic group than in the control group (3 versus 6 months [p < 0.03]); no differences regarding the start age for supplementary feeding was found. When performing logistic regression, only the family history of allergy was associated with a higher risk of food allergy (OR: 48.2; CI= 14.2-164; p < 0.001).
Conclusions. The early introduction of milk formula could promote the occurrence of food allergy in infants frequently presenting family history of allergy.
Key words: Food allergy; Breastfeeding; Supplementary feeding; Family history; Infants.
Food allergy is a failure of the oral
tolerance phenomenon in genetically-predisposed individuals, a reaction that
may be mediated by antibodies (IgE,
IgG, IgA or IgM) or by cells, with wide
variety of clinical manifestations.1,2
Genetic predisposition is an important risk factor, with allergy being described in up to 70% of the children of allergic parents.3 The genetic base cannot be modified,4 but there are environmental factors to modulate the appearance of food allergy.5 In this context, the role of diet during the first year of life could be a determining factor.6
Food allergies are more frequent in infants, presumably due to the immaturity of immune and non-immune mechanisms that prevent the entry of antigens through the gastrointestinal barrier.7,8 Milk, eggs and peanuts are the most common food allergens in early infancy and childhood. Peanut allergy, though less common than allergy to eggs or milk, is more often associated with serious allergic reactions, including anaphylaxis.9
Recent studies indicate that food allergy prevalence has increased in the US and Europe.10,11 Currently, this condition affects approximately 2% of the general population and close to 4-8% of American children.12 According to a meta-analysis conducted predominantly in European countries, the estimated prevalence of food allergy mediated by IgE ranges between 0-3% for milk, 0-1.7% for egg and 0.2-1.6% for peanut.13
Recently, the American Academy of Pediatrics14 and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition15 published their new guides on nutrition and prevention of allergy in infants and children. Apart from recommending exclusive breastfeeding to 6 months of age, it proposes that supplementary feeding should not be introduced before 17 weeks and all infants should start a solid diet no later than week 26.15 Avoiding or delaying the introduction of potentially allergenic food, such as fish or eggs, is not recommended. Additionally, an elimination diet during pregnancy and breastfeeding is not recommended.16
Dietary practices represent a risk factor potentially modifiable for preventing allergy.17 Factors related to maternal and infant diet, such as placental transfer, breast milk, baby formulas and supplementary feeding, represent the usual way by which infants come into contact with antigens. The possibility of avoiding the incorporation of food allergens through the manipulation of the diet during pregnancy or early childhood remains controversial.16
The objective of this study was to evaluate the association between dietary patterns during the first year of life, the family history of allergy and the risk of developing food allergy in a sample of Chilean infants under two years of age.
POPULATION AND METHODS
The sample studied was made up of infants referred to the Immunology, HIV and Allergies Division of the Department of Medicine, Clinical Hospital
of the Universidad de Chile (HCUCH), and they
were assigned to the allergic group. The sample of infant controls was obtained from Health Centers and
Day Care Centers of Santiago, which were matched
by age (interval of 15 days), sex and socioeconomic status. There were no differences in terms of the
groups' ethnicity, since we worked in the Santiago
district and no infants with parents of Mapuche origin (main national ethnic group) were included.
Inclusion criteria: infants aged 6 to 24 months with a birth weight = 2500 g.
Exclusion criteria: presence of medical conditions such as genetic, autoimmune and metabolic diseases.
Elimination criteria: presence of medical conditions during the study period or parents who rejected to participate after protocol entry.
Collection of information: a semistructured interview was conducted, in which an ad-hoc form was given to the mother. Clinical history, skin tests performed and information needed to confirm the diagnosis by the disappearance of symptoms after the elimination diet were recorded.
Socioeconomic status (SES): categorized by the classification proposed by ESOMAR Chile. This method, originated in Europe, has been previously validated in Chile; it is based on two outcome variables:18 level of education and occupational category of the main supporter of the home. Both outcome variables are combined in a "Socioeconomic classification matrix", to determine the SES of the family
Allergic manifestations were used as dependent variable (see below).
The independent variables were: i) family history (family history of allergy, appearance or absence of allergy history in the father and/or mother and/or sibling(s)); ii) dietary pattern (described as duration of breastfeeding and start age of supplementary feeding, categorized in breastfeeding =4 m and supplementary feeding at =6 m; breastfeeding=4 m and supplementary feeding at <6 m; breastfeeding <4 m and supplementary feeding at =6 m; breastfeeding <4 m and supplementary feeding at<6 m); iii) interaction of outcome variables.
Nutritional status: based on the ministerial technical standard for the assessment of nutritional status in children under 6 years (instrument referring to the growth standards of the World Health Organization [WHO] 2007), we assessed the nutritional status based on the weight for height indicator, according to weight and height for the age.19
Diagnosis of allergy in children: it was based on: i) allergic manifestations described by the primary care physician that referred the infant to the Immunology Service, from where the cases were collected; ii) the positive result of certain foods prick and patch tests; and, iii) the improvement of symptoms after eliminating the allergen.
The clinical diagnosis of allergy required the fulfillment of the three criteria described above and was performed in infants in the allergic group. Infants in the control group were recruited in primary health centers, nurseries and kindergartens of the same geographic area (Metropolitan Area). For control infants, information was obtained from the child's medical record, the health control card and by the survey given during the semistructured interview.
Allergic manifestations: the symptoms that motivated the initial consultation were the cause for a presumptive diagnosis of allergy by the doctor who referred the patient to the specialist. Symptoms were defined operationally: 1) skin: recurrent pruritus, atopy, exanthema or urticaria, eczema, rash; 2) respiratory: wheezing, obstructive signs for more than 24 h responding to bronchodilators, allergic rhinitis; 3) digestive: vomiting, diarrhea, rectal bleeding, moderate to severe esophageal reflux or constipation without proven cause, colic pain making the child cry for more than an hour a day, two or three times per week; 4) others: the child slept less than 6 h a day (greater insomnia and sleep fragmentation has been described in allergic infants).20
Family history: it was considered positive when at least the father/mother and/or a sibling had a history of asthma: when the diagnosis for allergic asthma was performed in a hospital service and/or the family member used bronchodilators.
. Rhinoconjunctivitis: history of one or more of the following symptoms: cluster sneezing, nasal congestion and itching and transparent mucous secretion, along with eye redness, pruritus and tearing, with droopy eyelids.
. Atopic eczema: diagnosed by a doctor, including chronic pruritic dermatitis or chronic relapses; or having a history of eczema with typical occurrence and location (diagnosis conducted by the treating specialists).
. Food allergy: history of pruritus in skin and/or rash and/or lip inflammation and/or lip pain and edematous tongue and/or vomiting and/or diarrhea after eating certain type of food, having had a positive retest (reaction to the consumption of a food antigen).
Taking into consideration feeding, operational
Dietary pattern: the sequence and time for introduction of food to the infant, including the presence and duration of breast or bottle feeding, and the inclusion date of supplementary feeding and its components.
Exclusive breastfeeding: administration of breast milk as the only food to cover the nutritional needs, not requiring any other foods or aggregates.21
Supplementary feeding: administration of any food other than milk.21
Ethical considerations. Prior to the interview, the mother and/or father received detailed information about the study, and those who agreed to participate signed the informed consent. The study and informed consent were evaluated and approved in March 2007 by the Ethics Committee for human research of INTA and HCUCH.
Sample size and statistical analysis. The sample size was calculated according to criteria by Freeman et al.,22 proposing ten events of interest by analyzed outcome variable; considering the variables family history of allergy, dietary pattern, their interaction and allergic manifestation, a sample of 50 children was calculated for each group. Data were validated and normality was evaluated by the Shapiro-Wilk test. We used the Student t test, the chi-square test and the Mann-Withney test for differences between the groups according to their normality and type of variable. Subsequently, to evaluate the risk of allergy we used a logistic regression model that included three independent outcome variables: family history (2 categories), dietary pattern (4 categories) and interaction, being the allergic manifestation (allergic/control group) the dependent variable. A significance level with a p-value <0.05 was used and the data analysis was performed using the software SPSS® v.15.0.
A total of 100 children, 50 cases and 50 consecutive controls were included in this study, collected between May 2007 and February 2008. The final sample analyzed was formed by 99 infants, 50 allergic children and 49 healthy controls; one infant from the control group whose mother decided to withdraw from the study was discontinued. The characteristics of infants are shown in Table 1.
Table1. General characteristics of the sample
Diarrhea was the symptom most frequently reported by mothers of the allergic infants during the first year of life (Figure 1). The frequency of broncho-obstructive syndrome did not differ between both groups.
Figure 1. Clinical characteristics related to allergic symptoms according to the group
In the allergic group, a family history of allergy
was significantly more frequent (84% versus 16%
in controls, p < 0.001) and the current height/age
indicator was significantly lower (71 ± 7.2 versus
74.3 ± 7 cm) in comparison to the control group
(p < 0.03).
We found no differences between dietary patterns of both groups. Almost all children (96%) were breastfed infants and the median (interquartile range) duration of exclusive breastfeeding was of 4 (2-6) and 5 (2.5-6) months in the allergy group and control group, respectively, with no significant differences. Similarly, the median (interquartile range) starting age for supplementary feeding was of 6 (5-6) months in both groups. On the contrary, introduction of bottle feeding occurred earlier in the allergic group: 3 (1.4-16) versus 6 (2.75-12) months, respectively, p < 0.03) as well as the inclusion of foods other than milk before 8 months of age, being earlier in the allergic group (p < 0.02). Finally, there were no differences in the time for inclusion of cereals, fish/shellfish, seeds (peanuts, nuts or almonds), meats (red or white) or legumes during the first year of life.
The univariate logistics regression analysis revealed that family history of allergy (OR: 48.29, [CI: 14.22-164.04], p < 0.001) -not the dietary pattern- determined the greater risk for presenting allergic manifestations. By categorizing the outcome duration of exclusive breastfeeding (=4 months or>4 months) and supplementary feeding (<6 months or =6 months), we found no significant differences between the groups.
This study shows that the presence of allergic
manifestations in infants under 2 years is mainly
associated to the family history of allergy and to
the early incorporation of milk formulas. The frequency of allergy in infants with a family history
of allergy in our sample (84%) is greater than what
was reported for inheritance of atopic syndrome,
since some reports indicate that 66% of newborn
infants with a history of atopy develop the allergic disease.23,24
Our results show that bottle feeding was introduced earlier to the diet of allergic infants, with no differences in the age of introduction or duration of breastfeeding. The first is consistent with studies showing that early introduction of cow milk is associated with greater sensitivity to its protein;25 it is suggested that incorporating a milk formula early in this high risk group would favor the appearance of symptoms in the infants.26 On the other hand, the beneficial effects of breastfeeding have been historically described in children with genetic predisposition to allergy.27 Despite this, the protecting role of breastfeeding has been recently questioned;28 various studies have reported an association between duration of breastfeeding with a greater risk of developing asthma, atopy and atopic dermatitis.29 However, in a critical review of the subject, Muraro et al.30 concluded that exclusive breastfeeding for at least 4 months in infants with a high risk of developing atopic syndrome, is associated with a lower cumulative incidence for developing allergy to cow milk protein at 18 months of age.
Gastrointestinal and skin symptoms turned out to be the most frequent cause that led to suspecting an allergic disorder. Among the first, diarrhea, colic, gastroesophageal reflux, constipation and bloody stools are all frequent symptoms in the evaluated age group. The results are consistent with those reported by Sicherer,31 who reviewed the spectrum of clinical gastrointestinal allergic manifestations in infants and children concluding that these symptoms would be associated to allergic phenomena in the early stages of life.31
It could be suggested that the symptoms described above are as "expected" because they are frequent symptoms in the first year of life, usually explained by the physiological limitations existing at this age; but it should be noted that these patients were referred to the specialty center for a lack of response to the treatment of these symptoms, conducted at primary care level, and this is precisely one of the criteria internationally agreed at present to suspect that the manifestations may be allergic. On the other hand, the skin is one of the target organs more frequently involved in hypersensitivity reactions, with a wide spectrum of symptoms, such as dermatitis, rash and angioedema, all commonly present in food allergy reactions.32 In our sample, atopic dermatitis was mainly reported among allergic infants and was really infrequent in the controls, which is consistent with that published in the literature.
Overall, the results suggest that in the case of symptoms as those described, in a child with a family history of allergy, it would be appropriate to perform a presumptive diagnosis of allergy and refer the patient to a specialist. Given the high frequency of the symptoms described, identifying the family history would represent a useful tool to decide whether the patient should be referred or kept at the local doctor's office.
Our results also show that allergic children present significant differences in relation to their current height compared to the control group; this data can be explained by the late diagnosis. This finding is relevant for the nutritional monitoring conducted by mother and child programs, since it is clear that the referral and diagnosis should be done as early as possible, with a specialized diet treatment.
It is important to note that the control subjects were recruited from different centers of the Metropolitan Area, for which it was not possible to control all the environmental variables that could influence the results of the study. Another limitation is related to recall bias, since it were the mothers who described the chronological order of introduction of food to their children and provided the family history.
On the other hand, the main strength of this study was the possibility of having patients diagnosed at a national referral center for the clinical diagnosis of allergy.
This study shows that, in infants, the early introduction of milk formula is associated with the presence of food allergy and that the most important risk factor for its development is the parents' family history of allergy. It is important to consider these results at the time to indicate the consumption of artificial milk formulas, especially in infants whose parents have a history of allergy.
Specially to the parents of the children who participated in the study, for their support during the development of this paper. To Mrs. Adriana Haberle, nurse; Mrs. Verónica Martínez, paramedic; and Mrs. Pamela Valenzuela, secretary of the Immunology, HIV and Allergies Division; to the School of Nutrition and Dietetics, and to Dr. Hugo Muñoz, all from the Universidad de Chile.
1. Mayer L. Mucosal immunity. Pediatrics 2003;111(6 Pt 3):1595 600.
2. Stanley S. Oral tolerance of food. Curr Allergy Asthma Rep 2002;2(1):73-7.
3. Zeiger RS. Food allergen avoidance in the prevention of food allergy in infants and children. Pediatrics 2003;111(6 Pt 3):1662-71.
4. Sicherer SH, Burks AW. Maternal and infant diets for prevention of allergic diseases: understanding menu changes in 2008. J Allergy Clin Immunol 2008;122(1):29-33.
5. Muche-Borowski C, Kopp R, Reese I, Sitter H, et al. Allergy prevention. Dtsch Arztebl Int 2009;106(39):625-31.
6. Prescott SL, Smith P, Tang M, Palmer DJ, et al. The importance of early complementary feeding in the development of oral tolerance: concerns and controversies. Pediatr Allergy Immunol 2008;19(5):375-80.
7. Sampson HA. Adverse reaction to foods. In: Adkinson NF Jr., et al. Middleton's allergy principles and practice, Mosby: Philadelphia; 2007. Pgs.1619-44.
8. Brandtzaeg P. Mucosal immunity: integration between mother and the breast-fed infant. Vaccine 2003;21(24): 3382-8.
9. Al-Muhsen S, Clarke AE, Kagan RS. Peanut allergy: an overview. CMAJ 2003;168(10):1279-85.
10. Arbes SJ Jr, Gergen PJ, Elliott L, Zeldin DC. Prevalences of positive skin test responses to 10 common allergens in the US population: results from the third National Health and Nutrition Examination Survey. J Allergy Clin Immunol 2005;116(2):377-83.
11. Rona RJ, Keil T, Summers C, Gislason D, et al. The prevalence of food allergy: a meta-analysis. J Allergy Clin Immunol 2007;120(3):638-46.
12. Branum AM, Lukacs SL. Food allergy among U.S. children: trends in prevalence and hospitalizations. NCHS Data Brief 2008;(10): p. 1-8.
13. Grundy J, Matthews S, Bateman B, Dean T, Arshad SH. Rising prevalence of allergy to peanut in children: Data from 2 sequential cohorts. J Allergy Clin Immunol 2002;110(5):784-9.
14. Greer FR, Sicherer SH, Burks AW. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics 2008;121(1):183-91.
15. Agostoni C, Decsi T, Fewtrell M, Goulet O, et al. Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr 2008;46(1):99-110.
16. Joseph CL, Owby DR, Havstad SL, Woodcroft KL, et al. Early complementary feeding and risk of food sensitization in a birth cohort. J Allergy Clin Immunol 2011;127(5):1203-10 e5.
17. Sausenthaler S, Heinrich J, Koletzko S. Early diet and the risk of allergy: what can we learn from the prospective birth cohort studies GINIplus and LISAplus? Am J Clin Nutr 2011;94(6 Suppl):2012S-2017S.
18. European Society for Opinion and Marketing Research. The ESOMAR Standard Demographic Classification. A System of International Socio-Economic Classification of Respondents to Survey Research; Amsterdam; 1997.
19. WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards: Growth velocity based on weight, length and head circumference: Methods and development. Geneva: World Health Organization: 2009; Pg. 242.
20. Kahn A, Rebuffat E, Blum D, Casimir G, et al. Difficulty in initiating and maintaining sleep associated with cow's milk allergy in infants. Sleep 1987;10(2):116-21.
21. Pizarro T. Guía de alimentación del niño menor de dos años. Departamento de nutrición y ciclo vital, división de prevención y control de enfermedades. Santiago: Ministerio de Salud; 2005; Págs. 7-29.
22. Calvo MC. Regresión logística no condicionada y tamaño de muestra: una revisión bibliográfica. Rev Esp Salud Pub 2002;76:85-93.
23. Cogswell JJ. Influence of maternal atopy on atopy in the offspring. Clin Exp Allergy 2000;30(1):1-3.
24. London SJ, James Gauderman W, Avol E, Rappaport EB, Peters JM. Family history and the risk of early-onset persistent, early-onset transient, and late-onset asthma. Epidemiology 2001;12(5):577-83.
25. Host A. Importance of the first meal on the development of cow's milk allergy and intolerance. Allergy Proc 1991;12(4):227-32.
26. Björkstén B. Does breast-feeding prevent the development of allergy? Immunol Today 1983;4:215-17.
27. Kneepkens CM, Brand PL. Clinical practice: Breastfeeding and the prevention of allergy. Eur J Pediatr 2010;169(8):911-7.
28. Ludvigsson JF, Mostrom M, Ludvigsson J, Duchen K. Exclusive breastfeeding and risk of atopic dermatitis in some 8300 infants. Pediatr Allergy Immunol 2005;16(3):201-8.
29. Benn CS, Wohlfahrt J, Aaby P, Westergaard T, et al. Breastfeeding and risk of atopic dermatitis, by parental history of allergy, during the first 18 months of life. Am J Epidemiol 2004;160(3):217-23.
30. Un Muraro A, Dreborg S, Halken S, Host A, et al. Dietary prevention of allergic diseases in infants and small children. Part III: Critical review of published peer-reviewed observational and interventional studies and final recommendations. Pediatr Allergy Immunol 2004;15(4):291-307.
31. Sicherer SH. Clinical aspects of gastrointestinal food allergy in childhood. Pediatrics 2003;111(6 Pt 3):1609-16.
32. Burks W. Skin manifestations of food allergy. Pediatrics 2003;111(6 Pt 3):1617-24.