- Email: [email protected]
Breastfeeding, atopy, and asthma
CORRESPONDENCE
COMMENTARY
CORRESPONDENCE e-mail submissions to [email protected]
Breastfeeding, atopy, and asthma Sir—Malcolm Sears and colleagues (Sept 21, p 901)1 conclude that breastfeeding could have a role in the development of atopy and asthma. We believe that such a message could have a potential negative public health effect on infant feeding practices, and is not supported by their findings. Such a strong conclusion would require a precise, prospective, and frequent documentation of breastfeeding practices.2 However, in the study, all information on infant feeding during the first 36 months was documented retrospectively by interviewing mothers when the child was 3 years old. A retrospective assessment can yield information biases with regard to exact breastfeeding methods (ie, exclusive, predominant, or mixed) and duration of breastfeeding.2 According to WHO definitions,3 most of the breastfed children included in this study would be neither exclusively, nor predominantly, but mixed breastfed. Thus, the higher risk of atopy and asthma reported in breastfed children might be due to the introduction of complementary foods in mixed breastfed children rather than to breastmilk. In that case, these results would not contradict those of Oddy and colleagues,4 who showed a protective effect of exclusive breastfeeding against asthma and atopy. Consequently, we strongly feel that, instead of pooling non-breastfed children and children breastfed for less than 4 weeks, the authors should have compared children exposed to breastmilk, whatever the duration, with children who were never breastfed. Additionally, further stratified analyses or studies are required to explore the proper effects of exclusive, predominant, and mixed breastfeeding in the development of atopy and asthma. Finally, to suggest that the increase in atopy and asthma in the past three decades would be explained by the increasing prevalence of breastfeeding is confusing. Indeed, because the role of many environmental factors is dominant in the development of asthma,5 their evolution has to be taken into account before reaching that conclusion.
174
Meanwhile, we believe that this study does not provide any convincing evidence leading to reconsideration of the promotion of breastfeeding in developed countries. *Renaud Becquet, Valériane Leroy, L Rachid Salmi Unité INSERM 330, Université Victor Segalen Bordeaux 2, 33076 Bordeaux Cedex, France (e-mail: [email protected]) 1
2
3
4
5
Sears MR, Greene JM, Willan AR, et al. Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Lancet 2002; 360: 901–07. Piwoz EG, Creed de Kanashiro H, Lopez de Romana G, Black RE, Brown KH. Potential for misclassification of infants’ usual feeding practices using 24-hour dietary assessment methods. J Nutr 1995; 125: 57–65. World Health Organization. Indicators for assessing breast-feeding practices: report of an informal meeting. Geneva: World Health Organization, 1991: 14. Oddy WH, Holt PG, Sly PD, et al. Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study. BMJ 1999; 319: 815–19. Sears MR. Epidemiology of childhood asthma. Lancet 1997; 350: 1015–20.
Sir—Malcolm Sears and colleagues1 state that breastfed infants’ exposure to cows’ milk formula in the maternity hospital did not bias their findings of an association between atopy and breastfeeding. I disagree. Exclusive breastfeeding has been shown to have benefits above and beyond those of partial breastfeeding. For example, partial breastfeeding results in increased vertical transmission of HIV from infected mothers compared with exclusive breastfeeding.2 Sears and colleagues did not allow for possible differing results between those who were truly exclusively breastfed and those who were not. This raises the issue of definition. The accepted WHO/UNICEF definition of an exclusively breastfed infant is one who has: “received only milk from a mother or wet nurse, or expressed breastmilk, and no other liquids or solids with the exception of drops or syrups consisting of vitamins, mineral supplements, or medicines”.
The authors cite Kramer’s study,3 and use it to justify their methods. However, one of Kramer’s requirements was for sufficient duration and exclusivity of breastfeeding, a condition which was not met in this study. Consequently, this article adds nothing to current knowledge of the relation between breastfeeding and asthma. Despite the detail of the follow-up investigations on the development of atopy, lack of suitable control groups makes the results irrelevant. Sears and colleagues conclude their article by speculating that “some of the increase in atopy and asthma in the past three decades. . . could be associated with. . . the prevalence of breastfeeding”. Presumably, then, in the era before the advent of formula feeding, when breastfeeding was the norm, there were high rates of asthma which subsequently dropped with widespread use of formula? In conclusion, there is simply not enough evidence to support this claim. A large-scale study conforming to Kramer’s criteria has yet to be done. Eithne Murray National Childbirth Trust, Alexandra House, Oldham Terrace, London W3 6NH, UK (e-mail: [email protected]) 1
Sears MR, Greene JM, Willan AR, et al. Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Lancet 2002; 360: 901–07. 2 Coutsoudis A. Influence of infant feeding patterns on early mother-to-child transmission of HIV-1 in Durban, South Africa. Ann N Y Acad Sci 2000; 918: 136–44. 3 Kramer MS. Does breastfeeding help protect against atopic disease? Biology, methodology and a golden jubilee of controversy. J Pediatr 1988; 112: 181–90.
Sir—Malcolm Sears and colleagues1 report that breastfeeding does not protect children against atopy and asthma, and that breastfed children might even have an increased risk. As mentioned by Sears and colleagues, the hygiene hypothesis is now widely accepted as an explanation for the increased incidence of allergy in recent years. Several studies have shown that high exposure to antigens or allergens is associated with a decreased incidence of allergy and autoimmune
THE LANCET • Vol 361 • January 11, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
CORRESPONDENCE
diseases. Additionally, we know from epidemiological studies that high socioeconomic status correlates with a higher incidence of these inflammatory diseases,2 probably owing to lower antigen exposure. In the study by Sears and colleagues, children were significantly more likely to be breastfed than formula-fed if they were born to parents of higher socioeconomic status. This factor is probably important in the discussion of why breastfed children have a higher incidence of asthma later in life, since one could speculate that antigen exposure is lower in this group. Furthermore, children born into a higher socioeconomic class probably have better access to health-care facilities, resulting in their being prescribed more antibiotics. Prescription of antibiotics in the first year of life is associated with a higher incidence of asthma.3 Sears and colleagues speculate that breastfeeding, which is associated with a Bifidobacterium/Lactobacillus-dominant intestinal flora, might reduce the effect of bacteria and endotoxins on the immune system. However, experimental and clinical studies suggest that such an intestinal flora is associated with reduced incidence of atopy.4 In summary, the higher incidence of asthma in the breastfed group in this population could be associated with lower antigen exposure and increased antibiotic consumption in the higher socioeconomic class. Therefore, it would be interesting to study the differences in antigen exposure and the use of antibiotics in the different socioeconomic classes. Reduced early antigen exposures and alterations in intestinal flora are said to be important environmental factors associated with the steady rise in the incidence of allergic and autoimmune diseases in developed countries. Jaap Jan Boelens Leiden University Medical Center, Department of Paediatrics: J6-Q-208, PO Box 9600, 2300 RC Leiden, Netherlands (e-mail: [email protected]) 1
2
3
4
Sears MR, Greene JM, Willan AR, et al. Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Lancet 2002; 360: 901–07. Stewert AW, Mitchel EA, Pearce N, Strachan DP, Weilandon SK. The relationship of per capita gross national product to the prevalence of symptoms of asthma and other atopic diseases in children (ISAAC). Int J Epidemiol 2001; 30: 173–79. Droste JHJ, Wieringa MH, Weyler JJ, Nelen VJ, Vermeire PA, Van Bever HP. Does the use of antibiotics in early childhood increase the risk of asthma and allergic disease? Clin Exp Allergy 2000; 30: 1547–53. Bjorksten B, Sepp E, Julge K, Voor T,
Mikelsaar M. Allergy development and the intestinal microflora during the first year of life. J Allergy Clin Immunol 2001; 108: 516–20.
Authors’ reply Sir—The duration of breastfeeding was recorded by interviewers when these 1037 children were first recruited into the longitudinal study at age 3 years. At age 9 years, we reviewed books maintained through the New Zealand Plunket Nurse Program in which infants were assessed through regular home and clinic visits through the first year. These recorded the introduction of cows’ milk and complementary feeding, allowing us to analyse the effects of exclusive breastfeeding among the 815 children seen at age 9 years. These were briefly reported in our paper, but more detail is provided below. These analyses confirm more atopy and asthma among breastfed children compared with those not breastfed, but some of the trends are not significant because of smaller numbers. There is no evidence in our study that exclusive breastfeeding, even to 24 weeks, provided protection against atopy and asthma, compared with those not breastfed. We selected a 4-week cutpoint because preliminary analyses in 70 children who discontinued breastfeeding before 4 weeks yielded outcomes very similar to those not breastfed at all, and different to those breastfed for longer than 4 weeks. If we compare outcomes in children breastfed for any duration with those never breastfed, as Renaud Becquet and colleagues request, and as shown in the table below, the findings are essentially unchanged. Exposure to cows’ milk formula in the maternity hospital was almost universal in the 1970s. If exposure A increases risk and exposure B decreases risk, then an admixture of A and B would reduce the effect of either exposure. We have identified an increased risk of atopy and asthma
Cat allergy at 13 years House dust mite allergy at 13 Any atopy at 13 Cat allergy at 21 House dust mite allergy at 21 Any atopy at 21 Asthma ever by 9 Asthma current at 9
in association with exposure to breast milk, and so addition of cows’ milk would reduce the effect of that exposure rather than increase it as the correspondents suggest. We do not state that breastfeeding is contraindicated, and indeed have advocated continuation of breastfeeding for its many benefits. Our study simply removes protection against atopy and asthma from the list of reasons why breastfeeding is beneficial to children, and confirms the findings of another cohort study.1 There is increasing support for the hygiene hypothesis as an explanation for the increase in asthma and allergies in recent decades.2 If increased breastfeeding reduced childhood infections because of better immune protection, deviation of cytokine responses from Th1 dominance to Th2 dominance could explain the increase in allergy and consequently in allergic asthma. Before formula feeding became popular, childhood infection rates were higher than at present, and this might have reduced asthma prevalence rates. Breastfeeding has increased in recent years, but the risk of infections has not, and so a relation between increased breastfeeding and increased allergy seems possible via the hygiene hypothesis. The relation between breastfeeding and atopy or asthma is unlikely to be a direct causal one, because there was no dose-response effect with respect to duration of breastfeeding (see table 3 in the original paper) or duration of exclusive breastfeeding (see current table). *M R Sears, D R Taylor, J M Greene, R Poulton, G P Herbison *Firestone Institute for Respiratory Health, St Joseph’s Healthcare, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada (MRS); Department of Medicine, McMaster University, Hamilton, Ontario, Canada (JMG); and Departments of Medicine (RP), Preventive and Social Medicine (DRT), and Dunedin Multidisciplinary Health and Development Research Unit (GPH), University of Otago, Dunedin, New Zealand (e-mail: [email protected])
Never breastfed
Breastfed exclusively ⭓4 weeks ⭓12 weeks
⭓24 weeks
38/389 (9·8%) 105/389 (27·0%)
51/289 (17·7%)† 98/289 (33·9%)*
10/53 (18·9%)* 16/53 (30·2%)
154/389 (39·6%) 113/464 (24·4%) 242/464 (52·2%)
151/289 (52·3%)† 89/177 (50·3%)* 25/53 (47·2%) 97/306 (31·7%)* 54/192 (28·1%) 13/56 (23·2%) 190/306(62·1%)† 114/192 (59·4%) 34/56 (60·7%)
287/464 (61·9%) 32/457 (7·0%) 24/457 (5·3%)
218/306 (71·2%)† 135/192 (70·3%)* 40/56 (71·4%) 40/338 (11·8%)* 21/212 (9·9%) 8/67 (11·9%) 36/338 (10·7%)† 17/212 (8·0%) 5/67 (7·5%)
28/177 (15·8%)* 58/177 (32·8%)
*p<0·05. †p<0·01.
Prevalence of atopy and asthma in children exclusively breastfed for different durations, compared with those never breastfed
THE LANCET • Vol 361 • January 11, 2003 • www.thelancet.com
175
For personal use. Only reproduce with permission from The Lancet Publishing Group.
COMMENTARY
CORRESPONDENCE e-mail submissions to [email protected]
Breastfeeding, atopy, and asthma Sir—Malcolm Sears and colleagues (Sept 21, p 901)1 conclude that breastfeeding could have a role in the development of atopy and asthma. We believe that such a message could have a potential negative public health effect on infant feeding practices, and is not supported by their findings. Such a strong conclusion would require a precise, prospective, and frequent documentation of breastfeeding practices.2 However, in the study, all information on infant feeding during the first 36 months was documented retrospectively by interviewing mothers when the child was 3 years old. A retrospective assessment can yield information biases with regard to exact breastfeeding methods (ie, exclusive, predominant, or mixed) and duration of breastfeeding.2 According to WHO definitions,3 most of the breastfed children included in this study would be neither exclusively, nor predominantly, but mixed breastfed. Thus, the higher risk of atopy and asthma reported in breastfed children might be due to the introduction of complementary foods in mixed breastfed children rather than to breastmilk. In that case, these results would not contradict those of Oddy and colleagues,4 who showed a protective effect of exclusive breastfeeding against asthma and atopy. Consequently, we strongly feel that, instead of pooling non-breastfed children and children breastfed for less than 4 weeks, the authors should have compared children exposed to breastmilk, whatever the duration, with children who were never breastfed. Additionally, further stratified analyses or studies are required to explore the proper effects of exclusive, predominant, and mixed breastfeeding in the development of atopy and asthma. Finally, to suggest that the increase in atopy and asthma in the past three decades would be explained by the increasing prevalence of breastfeeding is confusing. Indeed, because the role of many environmental factors is dominant in the development of asthma,5 their evolution has to be taken into account before reaching that conclusion.
174
Meanwhile, we believe that this study does not provide any convincing evidence leading to reconsideration of the promotion of breastfeeding in developed countries. *Renaud Becquet, Valériane Leroy, L Rachid Salmi Unité INSERM 330, Université Victor Segalen Bordeaux 2, 33076 Bordeaux Cedex, France (e-mail: [email protected]) 1
2
3
4
5
Sears MR, Greene JM, Willan AR, et al. Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Lancet 2002; 360: 901–07. Piwoz EG, Creed de Kanashiro H, Lopez de Romana G, Black RE, Brown KH. Potential for misclassification of infants’ usual feeding practices using 24-hour dietary assessment methods. J Nutr 1995; 125: 57–65. World Health Organization. Indicators for assessing breast-feeding practices: report of an informal meeting. Geneva: World Health Organization, 1991: 14. Oddy WH, Holt PG, Sly PD, et al. Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study. BMJ 1999; 319: 815–19. Sears MR. Epidemiology of childhood asthma. Lancet 1997; 350: 1015–20.
Sir—Malcolm Sears and colleagues1 state that breastfed infants’ exposure to cows’ milk formula in the maternity hospital did not bias their findings of an association between atopy and breastfeeding. I disagree. Exclusive breastfeeding has been shown to have benefits above and beyond those of partial breastfeeding. For example, partial breastfeeding results in increased vertical transmission of HIV from infected mothers compared with exclusive breastfeeding.2 Sears and colleagues did not allow for possible differing results between those who were truly exclusively breastfed and those who were not. This raises the issue of definition. The accepted WHO/UNICEF definition of an exclusively breastfed infant is one who has: “received only milk from a mother or wet nurse, or expressed breastmilk, and no other liquids or solids with the exception of drops or syrups consisting of vitamins, mineral supplements, or medicines”.
The authors cite Kramer’s study,3 and use it to justify their methods. However, one of Kramer’s requirements was for sufficient duration and exclusivity of breastfeeding, a condition which was not met in this study. Consequently, this article adds nothing to current knowledge of the relation between breastfeeding and asthma. Despite the detail of the follow-up investigations on the development of atopy, lack of suitable control groups makes the results irrelevant. Sears and colleagues conclude their article by speculating that “some of the increase in atopy and asthma in the past three decades. . . could be associated with. . . the prevalence of breastfeeding”. Presumably, then, in the era before the advent of formula feeding, when breastfeeding was the norm, there were high rates of asthma which subsequently dropped with widespread use of formula? In conclusion, there is simply not enough evidence to support this claim. A large-scale study conforming to Kramer’s criteria has yet to be done. Eithne Murray National Childbirth Trust, Alexandra House, Oldham Terrace, London W3 6NH, UK (e-mail: [email protected]) 1
Sears MR, Greene JM, Willan AR, et al. Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Lancet 2002; 360: 901–07. 2 Coutsoudis A. Influence of infant feeding patterns on early mother-to-child transmission of HIV-1 in Durban, South Africa. Ann N Y Acad Sci 2000; 918: 136–44. 3 Kramer MS. Does breastfeeding help protect against atopic disease? Biology, methodology and a golden jubilee of controversy. J Pediatr 1988; 112: 181–90.
Sir—Malcolm Sears and colleagues1 report that breastfeeding does not protect children against atopy and asthma, and that breastfed children might even have an increased risk. As mentioned by Sears and colleagues, the hygiene hypothesis is now widely accepted as an explanation for the increased incidence of allergy in recent years. Several studies have shown that high exposure to antigens or allergens is associated with a decreased incidence of allergy and autoimmune
THE LANCET • Vol 361 • January 11, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
CORRESPONDENCE
diseases. Additionally, we know from epidemiological studies that high socioeconomic status correlates with a higher incidence of these inflammatory diseases,2 probably owing to lower antigen exposure. In the study by Sears and colleagues, children were significantly more likely to be breastfed than formula-fed if they were born to parents of higher socioeconomic status. This factor is probably important in the discussion of why breastfed children have a higher incidence of asthma later in life, since one could speculate that antigen exposure is lower in this group. Furthermore, children born into a higher socioeconomic class probably have better access to health-care facilities, resulting in their being prescribed more antibiotics. Prescription of antibiotics in the first year of life is associated with a higher incidence of asthma.3 Sears and colleagues speculate that breastfeeding, which is associated with a Bifidobacterium/Lactobacillus-dominant intestinal flora, might reduce the effect of bacteria and endotoxins on the immune system. However, experimental and clinical studies suggest that such an intestinal flora is associated with reduced incidence of atopy.4 In summary, the higher incidence of asthma in the breastfed group in this population could be associated with lower antigen exposure and increased antibiotic consumption in the higher socioeconomic class. Therefore, it would be interesting to study the differences in antigen exposure and the use of antibiotics in the different socioeconomic classes. Reduced early antigen exposures and alterations in intestinal flora are said to be important environmental factors associated with the steady rise in the incidence of allergic and autoimmune diseases in developed countries. Jaap Jan Boelens Leiden University Medical Center, Department of Paediatrics: J6-Q-208, PO Box 9600, 2300 RC Leiden, Netherlands (e-mail: [email protected]) 1
2
3
4
Sears MR, Greene JM, Willan AR, et al. Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Lancet 2002; 360: 901–07. Stewert AW, Mitchel EA, Pearce N, Strachan DP, Weilandon SK. The relationship of per capita gross national product to the prevalence of symptoms of asthma and other atopic diseases in children (ISAAC). Int J Epidemiol 2001; 30: 173–79. Droste JHJ, Wieringa MH, Weyler JJ, Nelen VJ, Vermeire PA, Van Bever HP. Does the use of antibiotics in early childhood increase the risk of asthma and allergic disease? Clin Exp Allergy 2000; 30: 1547–53. Bjorksten B, Sepp E, Julge K, Voor T,
Mikelsaar M. Allergy development and the intestinal microflora during the first year of life. J Allergy Clin Immunol 2001; 108: 516–20.
Authors’ reply Sir—The duration of breastfeeding was recorded by interviewers when these 1037 children were first recruited into the longitudinal study at age 3 years. At age 9 years, we reviewed books maintained through the New Zealand Plunket Nurse Program in which infants were assessed through regular home and clinic visits through the first year. These recorded the introduction of cows’ milk and complementary feeding, allowing us to analyse the effects of exclusive breastfeeding among the 815 children seen at age 9 years. These were briefly reported in our paper, but more detail is provided below. These analyses confirm more atopy and asthma among breastfed children compared with those not breastfed, but some of the trends are not significant because of smaller numbers. There is no evidence in our study that exclusive breastfeeding, even to 24 weeks, provided protection against atopy and asthma, compared with those not breastfed. We selected a 4-week cutpoint because preliminary analyses in 70 children who discontinued breastfeeding before 4 weeks yielded outcomes very similar to those not breastfed at all, and different to those breastfed for longer than 4 weeks. If we compare outcomes in children breastfed for any duration with those never breastfed, as Renaud Becquet and colleagues request, and as shown in the table below, the findings are essentially unchanged. Exposure to cows’ milk formula in the maternity hospital was almost universal in the 1970s. If exposure A increases risk and exposure B decreases risk, then an admixture of A and B would reduce the effect of either exposure. We have identified an increased risk of atopy and asthma
Cat allergy at 13 years House dust mite allergy at 13 Any atopy at 13 Cat allergy at 21 House dust mite allergy at 21 Any atopy at 21 Asthma ever by 9 Asthma current at 9
in association with exposure to breast milk, and so addition of cows’ milk would reduce the effect of that exposure rather than increase it as the correspondents suggest. We do not state that breastfeeding is contraindicated, and indeed have advocated continuation of breastfeeding for its many benefits. Our study simply removes protection against atopy and asthma from the list of reasons why breastfeeding is beneficial to children, and confirms the findings of another cohort study.1 There is increasing support for the hygiene hypothesis as an explanation for the increase in asthma and allergies in recent decades.2 If increased breastfeeding reduced childhood infections because of better immune protection, deviation of cytokine responses from Th1 dominance to Th2 dominance could explain the increase in allergy and consequently in allergic asthma. Before formula feeding became popular, childhood infection rates were higher than at present, and this might have reduced asthma prevalence rates. Breastfeeding has increased in recent years, but the risk of infections has not, and so a relation between increased breastfeeding and increased allergy seems possible via the hygiene hypothesis. The relation between breastfeeding and atopy or asthma is unlikely to be a direct causal one, because there was no dose-response effect with respect to duration of breastfeeding (see table 3 in the original paper) or duration of exclusive breastfeeding (see current table). *M R Sears, D R Taylor, J M Greene, R Poulton, G P Herbison *Firestone Institute for Respiratory Health, St Joseph’s Healthcare, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada (MRS); Department of Medicine, McMaster University, Hamilton, Ontario, Canada (JMG); and Departments of Medicine (RP), Preventive and Social Medicine (DRT), and Dunedin Multidisciplinary Health and Development Research Unit (GPH), University of Otago, Dunedin, New Zealand (e-mail: [email protected])
Never breastfed
Breastfed exclusively ⭓4 weeks ⭓12 weeks
⭓24 weeks
38/389 (9·8%) 105/389 (27·0%)
51/289 (17·7%)† 98/289 (33·9%)*
10/53 (18·9%)* 16/53 (30·2%)
154/389 (39·6%) 113/464 (24·4%) 242/464 (52·2%)
151/289 (52·3%)† 89/177 (50·3%)* 25/53 (47·2%) 97/306 (31·7%)* 54/192 (28·1%) 13/56 (23·2%) 190/306(62·1%)† 114/192 (59·4%) 34/56 (60·7%)
287/464 (61·9%) 32/457 (7·0%) 24/457 (5·3%)
218/306 (71·2%)† 135/192 (70·3%)* 40/56 (71·4%) 40/338 (11·8%)* 21/212 (9·9%) 8/67 (11·9%) 36/338 (10·7%)† 17/212 (8·0%) 5/67 (7·5%)
28/177 (15·8%)* 58/177 (32·8%)
*p<0·05. †p<0·01.
Prevalence of atopy and asthma in children exclusively breastfed for different durations, compared with those never breastfed
THE LANCET • Vol 361 • January 11, 2003 • www.thelancet.com
175
For personal use. Only reproduce with permission from The Lancet Publishing Group.