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Keywords:

  • allergy;
  • atopy;
  • breastfeeding;
  • cow's milk;
  • heredity;
  • infant feeding;
  • interaction

Abstract

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Study groups
  5. Methods and data collection
  6. Statistical analyses
  7. Results
  8. Backgrounds of the groups
  9. Interaction between a family history of atopy and breastfeeding
  10. Association between breastfeeding and atopy  – stratified by a family history of atopy
  11. Association between a family history of atopy and atopy in the child – stratified by early feeding pattern
  12. Discussion
  13. Acknowledgments
  14. References

Background: The long-term effect of early feeding on atopic sensitization is still unsolved. The aim of this study was to evaluate the long-term effect of breastfeeding on atopy in groups of 4-year-old children stratified by atopic heredity.

Methods: We collected four groups of 4-year-old children from a birth cohort: two groups with differing backgrounds of atopic heredity, all exclusively breast-fed for at least 3 months; and two groups with differing atopic heredity, but all fed with cow's milk-based formula during their first weeks. The data were collected with a questionnaire, skin prick testing, and measurement of serum total and allergen-specific IgE levels.

Results: Breastfeeding significantly decreased the risk of allergic rhino-conjunctivitis [odds ratio (OR) 0.41, 95% confidence interval (CI) 0.18–0.95] and sensitization to furred pets, as measured by skin prick results, in children with atopic heredity, whereas in children without atopic heredity, breastfeeding was related to an increased risk of symptomatic atopy (OR 2.57, 95% CI 1.16–5.70), and high serum IgE values. A significant interaction was found between heredity and breastfeeding.

Conclusions: The long-term effect of breastfeeding was dual: in children with atopic heredity, breastfeeding protected against atopy, whereas in children without atopic heredity, it increased the risk of atopy.

Prolonged exclusive breastfeeding or feeding with extensively hydrolyzed formula has commonly been associated with a decreased risk of allergic disorders in infancy, at least in infants genetically at high risk of atopy (1–4), although opposite results have also been reported (5). A greater discrepancy relates to the long-term effects of early feeding. Some studies have failed to show any long-term effect (6–8). In one study (9), the beneficial effect of breastfeeding or feeding with hypoallergenic formula, which had been shown in early infancy, was lost later during long-term follow-up. However, in several prospective follow-up studies, the allergy-preventing or asthma-preventing effect of breastfeeding or feeding with hydrolyzed formula has also been found to last for years both in children at high risk of allergy (10–12) and in an unselected population of children (13–15).

The aims of this prospective follow-up study were to evaluate the long-term effects of breastfeeding on atopic sensitization in groups stratified by a family history of atopy, and to compare the effects of atopic heredity on atopy in the child in groups stratified by the type of early milk-feeding.

Study groups

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Study groups
  5. Methods and data collection
  6. Statistical analyses
  7. Results
  8. Backgrounds of the groups
  9. Interaction between a family history of atopy and breastfeeding
  10. Association between breastfeeding and atopy  – stratified by a family history of atopy
  11. Association between a family history of atopy and atopy in the child – stratified by early feeding pattern
  12. Discussion
  13. Acknowledgments
  14. References

We collected four groups of 4-year-old children from an unselected birth cohort of 4674 infants (born between August 1994 and November 1995) who had been followed prospectively during their first year of life during a study of cow's milk allergy (16). The groups were selected according to the early milk-feeding pattern of the child and the presence or absence of a family history of atopy. A positive family history of atopy was defined as asthma or atopic symptoms from two different organs in one or both parents, a negative family history of atopy, respectively, as no atopic symptoms in either parent. The two different early milk-feeding patterns were as follows: exclusive breastfeeding for at least 3 months or feeding with at least 450 ml of cow's milk-based formula during the first 2 weeks of life. Infants of the breastfeeding groups may have been given milk supplement at the maternity hospital, if required, as pasteurized human milk or extensively hydrolyzed whey formula (Pepti-Junior®, Nutricia, The Netherlands) (16). Children whose parent(s) had smoked during pregnancy or during the first year were excluded from the study.

The four study groups constituted a factorial design: group A, a positive family history of atopy and long exclusive breastfeeding; group B, a negative family history of atopy and long exclusive breastfeeding; group C, a positive family history of atopy and early cow's milk-based feeding; and group D, a negative family history of atopy and early cow's milk-based feeding.

The criteria for group A were fulfilled by 116 children. The same number of children were selected for group B, using group matching for sex and for duration of exclusive breastfeeding in blocks of 1 month. For group C, 112 children fulfilled the criteria and the same number of children were selected for group D, using group matching for sex and for the amount of cow's milk (in blocks of 500 ml) during the first 2 weeks of life. The children in groups B and D were selected from the blocks on the basis of computer-generated random numbers. Matching procedures were performed with the SAS software package (SAS Institute, Cary, NC, USA). The percentages of children participating and fulfilling the criteria of each group were 72% in group A (84 of the 116 invited children), 54% in group B (63 of 116), 65% in group C (73 of 112), and 58% in group D (65 of 112).

Methods and data collection

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Study groups
  5. Methods and data collection
  6. Statistical analyses
  7. Results
  8. Backgrounds of the groups
  9. Interaction between a family history of atopy and breastfeeding
  10. Association between breastfeeding and atopy  – stratified by a family history of atopy
  11. Association between a family history of atopy and atopy in the child – stratified by early feeding pattern
  12. Discussion
  13. Acknowledgments
  14. References

Exact data on feeding, atopic symptoms, and infections of the child, mode of day care, number of siblings, atopic symptoms of the other family members, smoking of the parents, and number of furred pets at home were obtained from questionnaires sent to the parents at 0, 2, 6, and 12 months. After 4 years, a new questionnaire was sent to the families, to update the information on atopic symptoms and risk factors for atopy. The children were invited to one visit at the outpatient clinic, where the questionnaire was checked in a structured interview with the parents by one of the authors (M.S.). Physical examination of the children was carried out by the same author. Skin prick testing was performed with a panel of 11 standard Soluprick solutions from ALK (Allergologiska Laboratorium, Copenhagen, Denmark): extracts of birch, alder, timothy, meadow fescue, mugwort, cat, dog, house dust mites Dermatophagoides pteronyssinus and farinae, hen's egg, and fish. Cow's milk testing was performed with pasteurized cow's milk. In the testing, histamine hydrochloride (10 mg/ml) served as a positive control and 50% glycerol solution as a negative control. The reaction was regarded as positive when the wheal diameter was 3 mm or more and the negative control solution caused no reaction.

A blood sample was taken for measurement of serum total and allergen-specific IgE levels (birch, cat, cow's milk, hen's egg, and house dust mite D. pteronyssinus), measured by enzymatic UniCAP fluoroimmunoassay. Serum total IgE levels of over 130 kU/l, and allergen-specific IgE levels of over 0.6 kU/l were considered positive.

The child was diagnosed as having atopic eczema if she or he had a history of chronic or chronically relapsing itching dermatitis with typical morphology and distribution (17). Diagnosis of allergic rhinitis and/or conjunctivitis was based on a history of runny and/or blocked nose and/or itchy, watery eyes with seasonal variation or with animal contacts, and apart from episodes of infection. Recurrent wheezing was confirmed when the child had a history of at least three episodes of wheezing. Asthma was confirmed when diagnosed by a pediatrician (at least three episodes of bronchial obstruction reversed by a bronchodilatator).

If the child had had any of the above-mentioned symptoms, he or she was considered to have symptomatic atopy. When a history of symptomatic atopy was validated by at least one objective finding of an atopic reaction measured in the study (serum total IgE level over 130 kU/l, at least one allergen-specific IgE level over 0.6 kU/l, or at least one positive reaction to skin prick testing), the child was classified as having verified atopy.

Statistical analyses

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Study groups
  5. Methods and data collection
  6. Statistical analyses
  7. Results
  8. Backgrounds of the groups
  9. Interaction between a family history of atopy and breastfeeding
  10. Association between breastfeeding and atopy  – stratified by a family history of atopy
  11. Association between a family history of atopy and atopy in the child – stratified by early feeding pattern
  12. Discussion
  13. Acknowledgments
  14. References

Sample size was calculated with the Medstat statistical program (version 2.12). The procedure was based on an estimate of 15% cumulative incidence of atopy in a group indicating lower risk and 35% in a group indicating higher risk. With at least 82 cases in each group, a difference of 20% could be detected at a 5% level of significance with 80% power (two-sided Fisher's exact test).

Comparisons of the background factors between the groups were performed with the chi-squared test or with Fisher's exact test when the variables were categorical, and with the Kruskal–Wallis and Mann–Whitney tests when the variables were continuous and not normally distributed. The effects of breastfeeding and the effects of a family history of atopy on atopy in the child were analyzed by multivariate stepwise logistic regression analysis with the forward selection method. The effects are given as odds ratios (OR) with 95% confidence intervals (CI). Multivariate models were used to take into account the effect of potential confounding factors. The following independent variables were introduced into the model: breastfeeding or a family history of atopy (according to the groups), sex, season of birth (four categories), number of older siblings (≤1 or >1), parental smoking (yes/no), furred household pets (yes/no), educational level of the mother (two categories), and age at which solid foods were introduced. The interaction between breastfeeding and a family history of atopy was analyzed with logistic regression by applying a factorial design and including an interaction term as an additional predictor variable. Statistical analyses were done using the SPSS software package (Version 8.0 for Windows, Chicago, IL, USA). Statistical significance was interpreted by two-sided α-values of less than 0.05.

The study was approved by the Ethics Committee of the Hospital for Children and Adolescents, University of Helsinki. Written consent was obtained from all the families who participated in the study.

Backgrounds of the groups

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Study groups
  5. Methods and data collection
  6. Statistical analyses
  7. Results
  8. Backgrounds of the groups
  9. Interaction between a family history of atopy and breastfeeding
  10. Association between breastfeeding and atopy  – stratified by a family history of atopy
  11. Association between a family history of atopy and atopy in the child – stratified by early feeding pattern
  12. Discussion
  13. Acknowledgments
  14. References

The mean age of the children was the same in all the groups (Table 1). There were no significant differences between the groups in distributions of sex (Table 1), season of birth, mode of day care, number of respiratory infections, number of older siblings, or type of living area during the first year of life. Smoking of mothers differed significantly between group A and the other groups (Table 1). The socio-economic level of group A also differed significantly from that of the other groups, as judged from the educational levels of the parents: The parents of group A had, on average, a higher education than the parents of the other groups (Table 1). The number of families with furred pets differed significantly between the atopic and nonatopic groups: atopic families (groups A and C) had fewer furred pets than nonatopic families (groups B and D) (Table 1).

Table 1.  Background factors of the groups
 Group A* (n = 84)Group B* (n = 63)Group C* (n = 73)Group D* (n = 65)Difference between the groups (P values)
  1. * Group A = positive family history of atopy and exclusive breastfeeding for at least 3 months; Group B = negative family history of atopy and exclusive breastfeeding for at least 3 months; Group C = positive family history of atopy and cow's milk-based formula feeding during the first 2 weeks of life; Group D = negative family history of atopy and cow's milk-based formula.

  2. † Significant difference between group A and the other groups (A vs B, P = 0.002; A vs C, P < 0.001; A vs D, P < 0.001).

  3. ‡ Significant difference between atopic and nonatopic families (A vs B, P = 0.001; C vs D, P = 0.004; A vs D, P < 0.001). Significant difference between A and C also (P = 0.041).

  4. § Significant difference between group A and C (P = 0.003), and A and D (P = 0.029).

  5. ¶ Significant difference between group A and the other groups (A vs B, P = 0.011, A vs C, P = 0.040, A vs D, P = 0.038).

Child's sex, n (F/M)47/3732/3135/3828/370.462
Mean age, years (SD)4.0 (0.05)4.1 (0.08)4.1 (0.05)4.1 (0.08)0.084
Birth weight, g (SD)3610 (424)3664 (471)3646 (527)3737 (515)0.312
Smoking (after the first year)
 Mother, n (%)07 (11)10 (14)10 (15)0.004†
 Father, n (%)3 (4)6 (10)3 (4)8 (12)0.121
Homes with furred pets
 First year, n (%)6 (7)18 (29)13 (18)26 (40)<0.001‡
Maternal education0.020§
 Higher education, n (%)40 (51)22 (40)18 (27)20 (33) 
 Intermediate or low, n (%)38 (49)33 (60)48 (73)41 (67) 
Paternal education0.040¶
 Higher education, n (%)38 (54)17 (32)23 (36)20 (36) 
 Intermediate or low, n (%)32 (46)37 (68)40 (64)36 (64) 

The mean duration of exclusive breastfeeding was the same, 4.4 months, in both breast milk groups (range 4.0–6.0 in group A and 4.0–6.5 in group B). The mean duration of partial breastfeeding was also the same in these groups, 10.0 months (range 5.0–30.0 in group A and 4.0–36.0 in group B). All the children in groups C and D had been fed with cow's milk-based formula during their first 2 weeks according to the criteria for the groups. In group C, the mean duration of partial breastfeeding was 5.4 months (range 0.5–30.0) and in group D 5.0 months (range 0.8–22.0). The mean age at which solid foods were introduced in group A was 4.5 months (range 3.0–7.0), in group B 4.4 (3.0–8.0), in group C 3.6 (2.0–5.0), and in group D 3.4 (2.5–5.0).

Interaction between a family history of atopy and breastfeeding

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Study groups
  5. Methods and data collection
  6. Statistical analyses
  7. Results
  8. Backgrounds of the groups
  9. Interaction between a family history of atopy and breastfeeding
  10. Association between breastfeeding and atopy  – stratified by a family history of atopy
  11. Association between a family history of atopy and atopy in the child – stratified by early feeding pattern
  12. Discussion
  13. Acknowledgments
  14. References

On applying the factorial design of the study, the logistic regression analyses showed a significant interaction between a family history of atopy and breastfeeding relating to their effect on atopic eczema (P for interaction = 0.022), and on symptomatic atopy (any atopic symptom) (P = 0.006). The interaction between atopic heredity and breastfeeding was not statistically significant in their association with allergic rhino-conjunctivitis (P = 0.056), recurrent wheezing (P = 0.116), asthma (P = 0.611), or verified atopy (P = 0.138). The results provided the basis for further analyses stratified by a family history of atopy or by the breastfeeding pattern.

Association between breastfeeding and atopy  – stratified by a family history of atopy

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Study groups
  5. Methods and data collection
  6. Statistical analyses
  7. Results
  8. Backgrounds of the groups
  9. Interaction between a family history of atopy and breastfeeding
  10. Association between breastfeeding and atopy  – stratified by a family history of atopy
  11. Association between a family history of atopy and atopy in the child – stratified by early feeding pattern
  12. Discussion
  13. Acknowledgments
  14. References

The frequencies of atopic symptoms and the results of IgEs and skin prick tests are presented groupwise in Tables 2 and 3. In a comparison of the atopic findings between the groups with the same background of atopic heredity (group A vs C and group B vs D), a clear association was seen between breastfeeding and atopy. However, the effect was found to be highly dependent on a family history of atopy.

Table 2.  Frequencies of atopic symptoms in the groups (figures represent numbers of cases, percentages in parenthesis)
Symptom/findingGroup A* (n = 84)Group B* (n = 63)Group C* (n = 73)Group D* (n = 65)
  1. * Group A = positive family history of atopy and exclusive breastfeeding for at least 3 months; Group B = negative family history of atopy and exclusive breastfeeding for at least 3 months; Group C = positive family history of atopy and cow's milk-based formula feeding during the first 2 weeks of life; Group D = negative family history of atopy and cow's milk-based formula.

  2. † Difference in multivariate analysis significant between groups A and C.

  3. ‡ Difference in multivariate analysis significant between groups B and D.

  4. § Asthma, allergic rhinitis, allergic conjunctivitis and/or atopic eczema.

  5. ¶ At least one atopic symptom; and serum total IgE > 130 kU/l, or serum allergen-specific IgE > 0.6 kU/l, or at least one positive reaction in SPT.

Recurrent wheezing19 (22.6)10 (15.9)15 (20.5)3 (4.6)
Asthma7 (8.3)4 (6.3)5 (6.8)2 (3.1)
Allergic rhinitis and/or conjunctivitis14 (16.7)8 (12.7)25 (34.2)†6 (9.2)
Atopic eczema44 (52.4)25 (39.7)45 (61.6)15 (23.1)‡
Symptomatic atopy§46 (54.8)30 (47.6)50 (68.5)19 (29.2)‡
Verified atopy¶27 (32.1)11 (17.5)27 (37.0)6 (9.2)
Table 3.  Results of skin prick testing, serum total IgE, and allergen-specific IgEs (figures represent numbers of cases with positive reactions or values, percentages in parentheses)
 Group A*Group B*Group C*Group D*
  1. * Group A = positive family history of atopy and exclusive breastfeeding for at least 3 months; Group B = negative family history of atopy and exclusive breastfeeding for at least 3 months; Group C = positive family history of atopy and cow's milk-based formula feeding during the first 2 weeks of life; Group D = negative family history of atopy and cow's milk-based formula feeding during the first 2 weeks of life.

  2. † Difference in multivariate analysis significant between groups A and C.

  3. ‡ Difference in multivariate analysis significant between groups B and D.

Skin prick test
 Birch14 (16.7)3 (4.8)17 (23.3)2 (3.1)
 Dog3 (3.6)2 (3.2)10 (13.7)†0
 Cat5 (6.0)3 (4.8)12 (16.7)†3 (4.6)
 Dermatophagoides farinae0000
 Dermat. pteronyssinus1 (1.2)000
At least one positive reaction in testing18 (21.4)6 (9.5)24 (32.9)4 (6.2)
Serum total IgE >130 kU/L17 (21.0)17 (27.0)18 (24.7)8 (12.3)‡
Serum specific IgE >0.6 kU/L
 Cat3 (3.7)3 (4.8)12 (16.4)†3 (4.6)
 Birch15 (18.5)5 (7.9)21 (28.8)3 (4.6)
 Dermat. pteronyssinus1 (1.2)001 (1.5)

The children with a positive family history of atopy and long exclusive breastfeeding (group A) were found to have fewer atopic symptoms (except for asthma and recurrent wheezing), fewer positive reactions in skin prick testing, and fewer high serum total and allergen-specific IgE values than the children who had the same positive family history of atopy but who had had early exposure to cow's milk (group C). The difference was significant for the incidence of allergic rhino-conjunctivitis, for the number of cat- and dog-specific reactions in skin prick testing, and for the number of high cat-specific serum IgE values (Table 4).

Table 4.  The effect of breastfeeding vs cow's milk-based formula feeding on atopy in groups stratified by family history of atopy calculated with multivariate logistic regression* (significant differences in boldface)
Atopic findingPositive family history (n = 138)Negative family history (n = 114)
BM vs CM (group A vs C)†BM vs CM (group B vs D)†
OR (95% CI)P-valueOR (95% CI)P-value
  1. * The independent variables used in the model: early milk feeding pattern (cow's milk feeding pattern as a reference category), season of birth, sex, age at starting solid foods, parental smoking, furred pets at home, number of older siblings, and educational level of mother.

  2. † BM = exclusive breastfeeding for at least 3 months; CM = cow's milk-based formula feeding during the first 2 weeks of life.

  3. ‡ OR adjusted.

  4. § Asthma, allergic rhinitis, allergic conjunctivitis and/or atopic eczema.

  5. ¶ At least one atopic symptom; and serum total IgE >130 kU/l, or serum allergen-specific IgE >0.6 kU/l, or at least one positive reaction in skin prick testing.

  6. ** SPT = skin prick testing.

Recurrent wheezing1.39 (0.60–3.21)0.4453.73 (0.95–14.68)0.059
Asthma1.42 (0.40–5.11)0.5871.89 (0.32–10.99)0.481
Allergic rhino-conjunctivitis0.41 (0.18–0.95)0.0371.57 (0.47–5.29)0.462
Atopic eczema0.68 (0.34–1.35)0.2672.37 (1.03–5.48)0.043
Symptomatic atopy§0.56 (0.27–1.14)0.1082.57 (1.16–5.70)0.020
Verified atopy¶0.74 (0.37–1.49)0.4032.40 (0.77–7.53)0.134
At least one positive reaction in SPT**0.59 (0.27–1.32)‡0.2021.87 (0.42–8.21)0.409
Positive reaction to dog in SPT**0.23 (0.06–0.91)0.0360.910
Positive reaction to cat in SPT**0.31 (0.10–0.96)0.0421.44 (0.22–9.29)0.703
Cat-specific IgE level >0.6 kU/l0.19 (0.05–0.72)0.0151.43 (0.22–9.22)0.708
Serum total IgE level >130 kU/l0.66 (0.28–1.55)‡0.3424.19 (1.43–12.27)0.009

In the groups with a negative family history of atopy, the effect of breastfeeding on atopy was found to be opposite to the above-reported results: the children with a negative family history of atopy and long exclusively breastfeeding (group B) were found to have a higher risk of atopy than those with the same negative family history of atopy but early exposure to cow's milk-based formula (group D). For the frequency of atopic eczema and symptomatic atopy and for the number of high serum total IgE values the difference was significant (Table 4).

Association between a family history of atopy and atopy in the child – stratified by early feeding pattern

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Study groups
  5. Methods and data collection
  6. Statistical analyses
  7. Results
  8. Backgrounds of the groups
  9. Interaction between a family history of atopy and breastfeeding
  10. Association between breastfeeding and atopy  – stratified by a family history of atopy
  11. Association between a family history of atopy and atopy in the child – stratified by early feeding pattern
  12. Discussion
  13. Acknowledgments
  14. References

The effect of a family history of atopy on atopy in the child was analyzed between the groups stratified by early milk feeding patterns. The effect was found to be stronger in the children fed with cow's milk-based formula than in those who had received long exclusive breastfeeding: in a comparison of the cow's milk groups (group C vs D), a positive family history of atopy was found to be significantly associated with all the atopic symptoms and findings except asthma, whereas, in a comparison of the breastfeeding groups (group A vs B), a family history of atopy was significantly associated only with skin prick test positivity (Table 5).

Table 5.  The effect of a family history of atopy on atopy of the child between the groups stratified by early milk feeding pattern, calculated with multivariate logistic regression* (significant differences in boldface)
 Exclusive breastfeeding >3 months (n = 132)Early cow's milk-based feeding (n = 120)
FHA+ vs FHA– (group A vs B)†FHA+ vs FHA– (group C vs D)†
OR (95% CI)P-valueOR (95% CI)P-value
  1. * The independent variables used in the model: family history of atopy (negative family history of atopy as a reference category), season of birth, sex, age at starting solid foods, parental smoking, furred pets at home, number of older siblings, and educational level of mother.

  2. † FHA+ = positive family history of atopy; FHA– = negative family history of atopy.

  3. § Asthma, allergic rhinitis, allergic conjunctivitis, and/or atopic eczema.

  4. ¶ At least one atopic symptom; and serum total IgE >130 kU/l, or serum allergen-specific IgE >0.6 kU/l, or at least one positive reaction in SPT.

  5. ‡ OR adjusted.

  6. ** SPT = skin prick testing.

Recurrent wheezing1.05 (0.43–2.58)0.9105.69 (1.46–22.18)0.012
Asthma1.27 (0.35–4.59)0.7102.00 (0.35–11.36)0.434
Allergic rhino-conjunctivitis1.62 (0.60–4.41)‡0.3414.78 (1.63–14.00)0.004
Atopic eczema1.76 (0.87–3.59)‡0.1186.14 (2.71–13.92)<0.0001
Symptomatic atopy§1.38 (0.69–2.77)0.3616.42 (2.90–14.22)<0.0001
Verified atopy¶2.16 (0.94–4.99)0.0707.01 (2.45–20.03)0.0003
At least one positive reaction in SPT**3.05 (1.06–8.81)0.0398.33 (2.29–30.28)0.0013
Positive reaction to dog in SPT**1.07 (0.17–6.65)0.9390.789
Positive reaction to cat in SPT**1.20 (0.27–5.24)0.8116.40 (1.35–30.27)0.019
Cat-specific IgE level >0.6 kU/l0.73 (0.14–3.77)0.7106.27 (1.33–29.65)0.021
Serum IgE level >130 kU/l0.53 (0.22–1.25)‡0.1463.62 (1.18–11.06)0.024

Discussion

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Study groups
  5. Methods and data collection
  6. Statistical analyses
  7. Results
  8. Backgrounds of the groups
  9. Interaction between a family history of atopy and breastfeeding
  10. Association between breastfeeding and atopy  – stratified by a family history of atopy
  11. Association between a family history of atopy and atopy in the child – stratified by early feeding pattern
  12. Discussion
  13. Acknowledgments
  14. References

In children aged 4 years, we found a clear relationship between the early milk-feeding pattern and atopy. An interesting new finding relating to this association was the interaction observed between breastfeeding and a family history of atopy. The effect of breastfeeding was found to be dual, depending strongly on the child's atopic heredity. Long exclusive breastfeeding was shown to decrease the risk of allergic sensitization in children who had a positive family history of atopy. Among them, breast-fed children had significantly less allergic rhino-conjunctivitis and, as measured by skin prick tests, were less sensitized to furred household pets. Similar trends were also seen in all the other indicator variables of atopy, although the differences did not reach statistical significance. This result is consistent with those of previous studies made on children who were genetically at high risk for atopy (10–12).

Several previous studies have also reported corresponding results in unselected populations of children (13–15). In one of these studies (13), the analyses had also been done separately in the subgroups of children with and without atopic heredity, and the preventive effect of prolonged breastfeeding was shown to be significant irrespective of heredity. In the present study, in contrast, the children who had no atopic heredity but who had had long exclusive breastfeeding were found to have a higher risk of atopy than those children who had been fed with cow's milk-based formula. The effects relating to the incidence of atopic eczema, symptomatic atopy, and high serum total IgE values were significant. A parallel trend was found in an earlier study from our clinic (18). In that study, prolonged exclusive breastfeeding was related to an increased risk of atopy in the subgroup of children with no heredity for atopy, but in the children with atopic heredity, long duration of exclusive breastfeeding was not associated with atopy.

The most important solitary predictor variable for atopy, i.e. atopic heredity, was controlled in this study by the grouping procedure. The other important risk factor, i.e. smoking, was an exclusion criteria for entry to the study: children whose parent(s) had smoked during the critical period of pregnancy or during the first year after the birth were excluded. However, in the updated questioning some parents reported to have smoked later. In maternal smoking, the difference between the groups was significant. There was also a significant difference between the groups in number of furred pets, and in social class as judged from the educational level of the parents. The role of furred pets in atopic sensitization is, thus far, ambiguous (19–22), but lower social class has commonly been related to lower incidence of atopy (23, 24). The differences in these background factors in this study related mainly to the breastfeeding group with atopic heredity, higher social class of the groups thus potentially increasing the risk and lower incidence of smoking decreasing the risk of atopy. However, the possible effects of these background factors on atopy of the child were taken into account by performing the analysis with the multivariate logistic regression method and including the factors in the model.

The factorial design of the present study made it possible to investigate the interaction between a family history of atopy and breastfeeding. The interaction between these factors in their effect on atopy was significant, which explains the dual result of this study. The discrepancies between the results of earlier breastfeeding studies may partly be due to the effect of this interaction. The interaction between these factors can also be interpreted to be included in the association between a family history of atopy and atopy of the child: the effect of a family history of atopy appeared far more distinct if the child had been fed early with cow's milk-based formula, whereas exclusive breastfeeding seemed partly to protect the child from the atopy-promoting effect of heredity.

The immunological mechanisms relating to the contrasting role of breastfeeding in the children with and without a heredity predisposing to atopy may partly be explained by the recent finding of a point mutation in proximity to the gene controlling CD14. Individuals homozygous for this point mutation had at the same time a higher concentration of soluble CD14 and a lower serum concentration of IgE (25). CD14 is an important cell-membrane receptor mediating innate immunity against Gram-negative bacteria (26). It is present in soluble form in human breast milk in a high concentration and may be important in initiating the immune responses to bacteria in a newborn infant (27). If, as suggested, the genetic regulation of CD14 and IgE are linked but have opposite effects, the long-standing replenishment of soluble CD14 in breast milk may compensate for the low endogenous CD14 production of individuals with a hereditary predisposition to high IgE production. CD14 in breast milk helps to initiate the immune response to bacteria, which may be decisive in directing the immune response more towards Th1-type responses and inhibiting Th2-type responses. This replenishment may not be important in individuals with high endogenous CD14 production, who are not prone to atopy.

In conclusion, our study showed that the long-term outcome of prolonged exclusive breastfeeding on atopy was dual, being dependent on heredity. Breastfeeding was shown to have beneficial effects on atopy in children genetically at high risk for atopy, but in children with no parental atopy the effect was the opposite. We found a significant interaction between atopic heredity and breastfeeding, which explains the difference in the effect of breastfeeding between the children of non-atopic and atopic parents. Further research is needed to elucidate the mechanisms behind this interaction.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Study groups
  5. Methods and data collection
  6. Statistical analyses
  7. Results
  8. Backgrounds of the groups
  9. Interaction between a family history of atopy and breastfeeding
  10. Association between breastfeeding and atopy  – stratified by a family history of atopy
  11. Association between a family history of atopy and atopy in the child – stratified by early feeding pattern
  12. Discussion
  13. Acknowledgments
  14. References

The study was supported by grants from the Pediatric Research Foundation and the Research Funds of Helsinki University Hospital. We thank Matti Siivola, MSc, for his assistance with the calculation of sample size, and with the selecting and matching procedures at the beginning of the study.

References

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Study groups
  5. Methods and data collection
  6. Statistical analyses
  7. Results
  8. Backgrounds of the groups
  9. Interaction between a family history of atopy and breastfeeding
  10. Association between breastfeeding and atopy  – stratified by a family history of atopy
  11. Association between a family history of atopy and atopy in the child – stratified by early feeding pattern
  12. Discussion
  13. Acknowledgments
  14. References
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