Asthma is the most common chronic illness that affects children, with a particularly high prevalence in developed countries (1). Simple, inexpensive interventions during early childhood, such as promotion of breastfeeding, may have an important role if they are shown to be effective in preventing this disease.
Numerous studies have assessed the effect of breastfeeding on the risk of asthma, eczema, or allergic sensitization. During the first few years of life, breastfeeding is generally considered to be protective for wheeze and asthma (2–4). However, the findings in relation to later childhood are varied. Many studies have found no relation between breastfeeding and asthma and allergy (5–7), others have found a protective effect (8–11) and still others have found breastfeeding to be a risk factor (12, 13). It is generally believed by researchers in this area that the diversity of results is because of differences in design of the studies. It has also been argued that apparent adverse associations may be attributable to a form of bias known as reverse causation or disease-related exposure modification (14). Despite improvements in study methodology over the last decade, there remain important design differences, for example, differing definitions for breastfeeding, a lack of consensus for the diagnosis of ‘asthma’, potential for recall bias because of the assessment of breastfeeding practice several years after infancy, and large losses to follow-up leading to possible selection bias. In addition, there may be other, unrecognized and unmeasured confounders such as environmental factors or cultural differences that explain some of the observed heterogeneity.
The heterogeneity among the existing data is typified by two studies conducted on opposite sides of the world, which have recently reported their findings. The Childhood Asthma Prevention Study (CAPS) birth cohort was recruited in Sydney, Australia, to include children whose parent/s or sibling had wheeze or asthma prior to the child’s birth. The infants were enrolled in a randomized, controlled trial testing dietary and house dust mite avoidance interventions in the first 5 yrs of life. In this cohort, duration of breastfeeding was not associated with asthma at 5 yrs of age. However, breastfeeding for 6 months or more was associated with an increased prevalence of sensitization to inhaled and ingested allergens at 5 yrs of age (15). In contrast, the Barn Allergi Miljö Stockholm Epidemiologi (BAMSE) general population birth cohort study conducted in Stockholm, Sweden, found that a longer duration of breastfeeding was protective against the development of asthma and allergen sensitization at 4 and 8 yrs of age (16, 17). There are important differences in the selection criteria for these study populations and some differences in the definition of exposures or outcomes. It is unclear to what extent these divergent findings are attributable to either methodological differences or, alternatively, real environmental or lifestyle differences that alter the impact of breastfeeding.
This study aimed to test the hypothesis that there are not true differences between the CAPS and BAMSE populations in the impact of breastfeeding on the risk of asthma and allergic sensitization and that the observed differences are explained by selection criteria for the cohorts and definitions for exposures and outcomes.
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The study population that met the inclusion criteria and had outcome data available consisted of 419 subjects from CAPS at 5 yrs, 362 subjects from CAPS at 8 yrs, and 463 subjects from BAMSE at 4 and 8 yrs.
Baseline characteristics of the study population, by cohort source, are shown in Table 1. The subjects in the CAPS study, compared with those in the BAMSE study, were more likely to have parents with higher levels of tertiary education; mothers with asthma; and exposure to smoking during pregnancy, the first year of life, and at 4/5 yrs.
Table 1. Baseline characteristics in selected CAPS and BAMSE subjects*. Values are numbers (percentages) unless stated otherwise
|Variable||CAPS (n = 419)||BAMSE (n = 463)|
|Male sex||211 (50.4)||240 (51.8)|
|Mean birth weight (kg)||3.49||3.58|
|Mean gestational age (wks)||39.6||40.1|
|Mean maternal age at delivery (yrs)||28.9||30.0|
|Maternal education||N = 419||N = 459|
| Incomplete secondary||149 (35.6)||169 (36.8)|
| Complete secondary||68 (16.2)||97 (21.1)|
| Tertiary||202 (48.2)||193 (42.1)|
|Paternal education||N = 414||N = 445|
| Incomplete secondary||150 (36.2)||163 (36.7)|
| Complete secondary||79 (19.1)||120 (27.0)|
| Tertiary||185 (44.7)||162 (36.4)|
|Maternal asthma||287 (68.5)||263 (56.8)|
|Paternal asthma||203 (48.6)||231 (50.3)|
|Maternal smoking during pregnancy†||104 (24.8)||57 (12.3)|
|SHS in first year of life†||124 (29.6)||76/452 (16.8)|
|SHS at 4/5 yrs†||109 (26.0)||79/460 (17.2)|
|SHS at 8 yrs†||78/398 (19.6)||85/455 (18.7)|
|Fully breastfed ≥3 months||135/398 (33.9)||367/452 (81.2)|
|Duration of any breast milk (months)||N = 419||N = 452|
| <1||131 (31.3)||10 (2.2)|
| 1–3||68 (16.2)||32 (7.1)|
| 4–6||71 (17.0)||79 (17.5)|
| 7–9||41 (9.8)||150 (33.2)|
| 10–12||27 (6.4)||114 (25.2)|
| ≥13||81 (19.3)||67 (14.8)|
Rates of fully breastfeeding ≥3 months were much higher in BAMSE (81.2%) than in CAPS (33.9%). Similarly, duration of any breastfeeding was longer in Sweden (see Table 1). Only 2.2% of infants in BAMSE were breastfed for less than a month compared with 31.3% of infants in CAPS. The median breastfeeding duration in BAMSE was 8.8 months, whereas in CAPS it was 4.0 months. The decision to fully breastfeed for ≥3 months in CAPS was associated with higher levels of education for both parent and no SHS exposure during the first year of life. In BAMSE, full breastfeeding was associated with a higher birth weight and no smoking by the mother during pregnancy.
Table 2 shows the prevalence of asthma and sensitization in each subgroup used in this study as well as their respective cohorts of origin. At 5 and 8 yrs, the selected subjects from the CAPS cohort had higher rates of wheeze, asthma, and sensitization to local inhaled allergens, whereas the selected BAMSE subjects had significantly higher rates of sensitization to ingested allergens. The disease rates in the selected CAPS subjects were similar to those in the full CAPS cohort (15). This was expected as the selected subgroup represented a large proportion of the original cohort. In contrast, the subjects selected from the BAMSE cohort had disease rates that were almost double those in the full cohort (16, 17). This is because the whole BAMSE cohort had been taken from the general population, whereas the subgroup selected for this analysis consisted of those who had a parental history of asthma, which is a known risk factor for asthma and allergy.
Table 2. Asthma and atopy outcomes in selected CAPS and BAMSE subjects* and whole cohorts. Values are numbers (percentages)
|Variable||CAPS*||CAPS whole cohort||BAMSE*||BAMSE whole cohort|
|4/5 yrs†||(n = 419)||(n = 516)||(n = 463)||(n = 3729)|
| Wheeze in last 12 months||139 (33.2)||165 (32)||109 (23.5)||546 (14.6)|
| Current asthma||96 (22.9)||109 (21.1)||67/461 (14.5)||285 (7.6)|
| Sensitization to ingested allergens‡||24/395 (6.1)||25/488 (5.1)||59/348 (17.0)||332/2616 (12.7)|
| Sensitization to local inhaled allergens‡||151/395 (38.2)||179/488 (36.7)||69/348 (19.8)||382/2616 (14.6)|
|8 yrs||(n = 361)||(n = 450)||(n = 463)||(n = 3417)|
| Wheeze in last 12 months||106 (29.3)||124 (27.6)||91 (19.7)||343 (10)|
| Current asthma||87 (24.1)||103 (22.9)||63 (13.6)||223 (6.5)|
| Sensitization to ingested allergens‡||18/331 (5.4)||22/414 (5.3)||80/350 (22.9)||416/2461 (16.9)|
| Sensitization to local inhaled allergens‡||144/320 (45.0)||178/414 (44.3)||124/350 (35.0)||615//2461 (25.0)|
The effect of fully breastfeeding ≥3 months on risk of current asthma at 4/5 yrs of age differed between the CAPS and BAMSE cohorts (p for interaction = 0.06) (see Table 3). In CAPS, fully breastfeeding ≥3 months made no difference to the asthma outcome at 5 yrs of age, but in BAMSE, fully breastfeeding ≥3 months reduced the risk of having asthma at 4 yrs of age (RR 0.48, 95% CI, 0.31–0.76). The duration of any breastfeeding and its association with asthma at 4/5 yrs of age did not vary significantly between the two cohorts (p for interaction = 0.14), and there was no significant relationship found(see Table 4).
Table 3. Effect of full breastfeeding for ≥3 months on asthma at 4/5 and 8 yrs
| ||Outcome n/N (%)||p Value of interaction*||Adjusted RR (95% CI)|
|CAPS||Crude RR (95% CI)||BAMSE||Crude RR (95% CI)|
| 4/5 yrs†|
| <3 months||57/263 (21.7)||1.00||20/85 (23.5)||1.00||0.06||1.00||1.00|
| ≥3 months||30/135 (22.2)||1.03 (0.69–1.51)||46/367 (12.5)||0.53 (0.33–0.85)||1.06 (0.97–1.56)a CAPS||0.48 (0.31–0.76)b BAMSE|
| 8 yrs|
| <3 months||57/224 (25.4)||1.00||18/85 (21.2)||1.00||0.22||1.00|
| ≥3 months||28/118 (23.7)||0.93 (0.63–1.38)||48/367 (13.1)||0.62 (0.38–1.01)||0.69 (0.52–0.93)c COMBINED|
|Sensitization to ingested allergens|
| 4/5 yrs†|
| <3 months||10/248 (4.0)||1.00||13/63 (20.6)||1.00||0.02||1.00||1.00|
| ≥3 months||14/127 (11.0)||2.73 (1.25–5.98)||44/279 (15.8)||0.76 (0.44–1.33)||2.73 (1.25–5.99)d CAPS||0.76 (0.44–1.33)d BAMSE|
| 8 yrs|
| <3 months||11/206 (5.3)||1.00||15/59 (25.4)||1.00||0.59||1.00|
| ≥3 months||7/106 (6.6)||1.24 (0.49–3.1)||62/283 (21.9)||0.86 (0.53–1.41)||1.81 (1.18–2.76)d COMBINED|
|Sensitization to inhaled allergens|
| 4/5 yrs†|
| <3 months||87/248 (35.1)||1.00||8/63 (12.7)||1.00||0.19||1.00|
| ≥3 months||55/127 (43.3)||1.23 (0.95–1.6)||60/279 (21.5)||1.69 (0.85–3.36)||0.9 (0.71–1.13)e COMBINED|
| 8 yrs|
| <3 months||88/199 (44.2)||1.00||19/58 (32.8)||1.00||0.52||1.00|
| ≥3 months||47/103 (45.6)||1.03 (0.79–1.34)||103/284 (36.3)||1.11 (0.74–1.65)||0.89 (0.73–1.08)f COMBINED|
Table 4. The effect of the duration of any breastfeeding on outcomes at 4/5 and 8 yrs
| ||Current asthma n/N (%)||Sensitization to ingested allergens n/N (%)||Sensitization to inhaled allergens n/N (%)|
|4/5 yrs† duration of breastfeeding|
| <1 month||30/131 (22.9)||1/10 (10)||4/120 (3.3)||2/7 (29)||42/120 (35.0)||1/7 (14.3)|
| ≥1 &<4 months||14/68 (20.6)||11/32 (34.4)||4/66 (6.1)||5/27 (18.5)||18/66 (27.3)||5/27 (18.5)|
| ≥4 & <7 months||17/71 (23.9)||9/79 (11.4)||3/68 (4.4)||11/55 (20.0)||25/68 (36.8)||7/55 (12.7)|
| ≥7 & <10 months||9/41 (22.0)||20/150 (13.3)||4/39 (10.3)||15/115 (13.0)||21/39 (53.9)||21/115 (18.3)|
| ≥10 & <13 months||4/27 (14.8)||17/114 (14.9)||1/27 (3.7)||13/88 (14.8)||10/27 (37.0)||21/88 (23.9)|
| ≥13 months||22/81 (27.2)||8/67 (11.9)||8/75 (10.7)||11/50 (22.0)||35/75 (46.7)||13/50 (26.0)|
| p Value of interaction*||0.14||0.26||0.37|
| Adj p trend||0.7||0.01||0.58|
| RR per Bf duration step||0.97 (0.89–1.05)a||1.19 (1.05–1.34)b||1.01 (0.95–1.08)c|
|8 yrs duration of breastfeeding|
| <1 month||24/109 (22.0)||2/10 (20)||5/98 (5.1)||2/6 (33)||43/95 (45.3)||2/6 (33)|
| ≥1 & <4 months||18/62 (29.0)||9/32 (28.1)||4/57 (7.0)||8/24 (33.3)||22/56 (39.3)||7/24 (29.2)|
| ≥4 & <7 months||14/58 (24.1)||13/79 (16.5)||1/56 (1.8)||12/57 (21.1)||18/52 (34.6)||22/57 (38.6)|
| ≥7 & <10 months||10/32 (31.2)||19/150 (12.7)||1/30 (3.3)||20/117 (17.1)||17/31 (54.8)||36/117 (30.8)|
| ≥10 & <13 months||5/27 (18.5)||16/114 (14.0)||2/24 (8.3)||19/87 (21.8)||9/21 (42.9)||33/87 (37.9)|
| ≥13 months||20/73 (27.4)||7/67 (10.5)||5/66 (7.6)||16/51 (31.4)||35/65 (53.9)||22/51 (43.1)|
| p Value of interaction*||0.03||0.7||0.64|
| Adj p trend||0.6||0.07||0.03||0.91|
| RR per Bf duration step||1.02 (0.95–1.09)d||0.85 (0.72 –1.01)e||1.14 (1.01–1.29)f||1.01 (0.95–1.07)g|
However, the association between fully breastfeeding ≥3 months and asthma at 8 yrs of age did not differ between CAPS and BAMSE cohorts (p for interaction >0.1). Overall, fully breastfeeding ≥3 months was associated with a decreased risk of developing asthma (RR 0.69, 95% CI, 0.52–0.93). The effect of any breastfeeding duration on asthma risk at 8 yrs of age differed between the two studies (p for interaction = 0.03). Table 4 shows duration of any breastfeeding did not have an effect on asthma at 8 yrs of age in CAPS. However, in BAMSE, every 3-month increase in breastfeeding duration was associated with a reduced risk of asthma (RR 0.85 per 3-month period, 95% CI, 0.72–1.01).
Full breastfeeding for more than 3 months was associated with an increased risk of sensitization to ingested allergens (egg, milk, and peanut) in the CAPS study at 4/5 yrs, but not in the BAMSE study (see Table 3). At 8 yrs, the association between full breastfeeding and sensitization to ingested allergens did not differ between the cohorts (p for interaction = 0.59), and the RR was 1.81 (95% CI, 1.18–2.76). Moreover, longer duration of any breastfeeding was associated with an increased risk of sensitization to ingested allergens (egg, milk, and peanut) at 4/5 and 8 yrs in the combined data (see Table 4). Tables 3 and 4 show that there was no association between breastfeeding duration (any or full) and sensitization to local inhaled allergens at 4/5 yrs or at 8 yrs.
Survival analysis (Table 5) found that the presence of early allergic symptoms did not influence mothers to breastfeed their children longer than those who did not exhibit these symptoms; therefore, there is no evidence of reverse causation in these studies. In fact, in this subset of the BAMSE cohort, the presence of wheeze while still breastfeeding was associated with a 39% increase in the risk of ceasing to fully breastfeed. In other words, in this instance, early symptoms reduced, rather than increased, the duration of breastfeeding.
Table 5. Hazard Ratios (HR) for survival analysis
| ||Any breastfeeding*||Full breastfeeding*|
|HR||95% CI||p-Value||HR||95% CI||p-Value|
| Itchy rash||0.85||0.62–1.17||0.31||0.81||0.55–1.18||0.27|
| Eczema diagnosis||0.96||0.67–1.39||0.84||0.91||0.51–1.65||0.76|
| Itchy rash||0.96||0.72–1.27||0.75||0.87||0.60–1.27||0.46|
| Eczema diagnosis||0.94||0.71–1.23||0.64||0.88||0.64–1.23||0.46|
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Our results generally support the hypothesis that, after harmonizing selection criteria by restricting the population to those with a family history of asthma and using common outcome definitions, the effect of breastfeeding on risk of asthma and allergic disease does not differ significantly between the Australian CAPS population and the Swedish BAMSE population. Overall, our study shows that longer duration of breastfeeding has protective effects against asthma and may have adverse effects on the risk of food sensitization. However, the findings are complex and some between study center differences in the observed associations were found despite this harmonization of methods. These may be attributable to unmeasured confounders such as environmental factors or cultural differences between Sweden and Australia.
The major strength of this current analysis was the use of two birth cohort studies from opposite sides of the world with sufficient data in common to allow us to compare and contrast their findings. Access to individual patient data from these two cohorts has allowed us to undertake a metaregression using these data, as opposed to the more conventional random effects meta-analysis based only on summary measures. The use of individual data allowed adjustment for confounding at the level of individual subjects and improved the power of the analysis (25). Although we could apply the same definitions for most of the analysis, there were some features of the data that could not be harmonized.
The first is in the definition for asthma at 4/5 yrs. In both studies, we included children with ‘ever diagnosed asthma’ and ‘wheeze in the last year’. However, we also included subjects without a diagnosis of asthma but with frequent wheeze. In BAMSE, this was measured as ‘wheeze more than four times in the last year’, and in CAPS, it was measured as ‘wheeze for more than 1 wk more than three times in the last year’. This difference may have influenced the findings. However, as most (>80%) of those classified as having current asthma in both cohorts were included based on the common component of the definition (‘ever diagnosed asthma’ and ‘wheeze in the last year’), it is unlikely this difference in selection criteria had a substantial effect.
The second difference is that CAPS children were assessed at 5 yrs of age and BAMSE children at 4 yrs. This age difference may be enough to explain the fact that longer duration of breastfeeding protected against asthma in BAMSE, but not CAPS at this age. Interestingly, at 8 yrs, when the asthma definition and age were the same for both cohorts the study groups were found to be similar, full breastfeeding was shown to be protective for asthma. This finding is supported by several other studies, which measured exclusive breastfeeding for 3 months and asthma in subjects of similar age (5, 17, 26, 27).
A third difference between the two cohorts is that CAPS was a randomized controlled trial and BAMSE was an observational cohort study. It is unlikely that the interventions in CAPS will have influenced the findings in this analysis as they did not affect the study outcomes (19, 28), and also, as the interventions were randomized, they are unlikely to be confounded with breastfeeding status. However, the nature of the trial meant that CAPS participants were followed up at frequent intervals throughout the first year of life, whereas this did not occur in BAMSE. It is possible that this influenced the measurement of breastfeeding status.
The duration of any breastfeeding did not have an effect on asthma prevalence in either cohort or age except in BAMSE at 8 yrs where every 3-month increase in breastfeeding slightly improved the odds of developing asthma.
Until recently, recommendations for infant feeding to decrease the risk of allergy have promoted exclusive breastfeeding for at least 6 months and avoidance of solids until at least 3–6 months (depending on the country) (29). However, recent studies have challenged the validity of these recommendations, and in some countries, they are being re-evaluated (29). For example, some studies have found that increased breastfeeding duration is related to an increased sensitization to food allergens in children with a family history of atopy (30, 31). We have previously shown in the CAPS cohort that early introduction of solid foods was associated with a reduced risk of sensitization (15). The current analysis supports these findings for any breastfeeding and full breastfeeding (except BAMSE at 4 yrs).
Some studies have attempted to adjust for reverse causality by excluding infants who developed eczema or wheeze before breastfeeding ended or before the age of 1 yr (16, 30). The rationale for this restriction is that the mothers of these children may have continued to breastfeed these children longer than planned and this would result in a spurious (reverse causal) association between breastfeeding duration and asthma. The main problem with this method is that if there is a true causal association between longer breastfeeding duration and increased risk of symptoms, this will tend to exclude those who manifest this problem. Hence, this exclusion method will tend to bias results toward the null whether the apparent association is directly causal or reverse causal. The limitation of our study population to those with a family history of asthma will have reduced the potential for bias as a result of reverse causation because all subjects have the same family history. Nevertheless, it is possible that early manifestations of allergic illness might have led to prolonged breastfeeding and hence reverse causation bias. However, the findings of the survival analysis have confirmed that this did not, in fact, occur.
To conclude, longer duration of breastfeeding may protect against asthma in childhood but may also be associated with an increased risk of sensitization to foods in children with a family history of asthma. These effects do not seem to be explained by reverse causation. While we cannot make a recommendation for or against breastfeeding to reduce the risk of allergy-related disorders, we can say that applying the same selection criteria and methods to combined data sets does harmonize the breastfeeding allergy relationships and needs to be attempted using larger sources of data. This will depend on collaboration among researchers on an international scale.
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Barn Allergi Miljo Stockholm has been supported by the Stockholm County Council, the Heart and Lung Foundation, the Swedish Asthma and Allergy Association, the Swedish Research Council and The Centre for Allergy research Karolinska Institutet. CAPS has been supported by the National Health and Medical Research Council of Australia, Cooperative Research Center for Asthma, New South Wales Department of Health, Children’s Hospital at Westmead, University of Sydney, Faculty of Medicine. Dr Almqvist was funded by the Strategic Research Program in Epidemiology at Karolinska Institutet. Dr Bergström was funded by the Swedish Research Council. Contributions of goods and services were made by Allergopharma Joachim Ganzer KG Germany, John Sands Australia, Hasbro, Toll refrigerated, AstraZeneca Australia, and Nu-Mega Ingredients Pty Ltd. Goods were provided at reduced cost by Auspharm, Allersearch and Goodman Fielder Foods. University of Sydney, Faculty of Medicine, Strategic Research Grant 2008.