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Differences Between Meta-analyses on Breastfeeding and Obesity Support Causality of the Association

In a recent meta-analysis, Owen et al1 reported that breastfeeding protects against later obesity. Their pooled odds ratio (OR) for risk of obesity after breastfeeding, however, is markedly closer to 1.0 than the pooled OR that we calculated in a meta-analysis on the same topic (0.87 vs 0.75).2 Here, we would like to comment that this difference can be explained easily by methodologic differences between the 2 analyses that thereby provide important additional support for the hypothesis that the association between breastfeeding and risk of later obesity is, in fact, causal. The main methodologic difference between the metaanalysis by Owen et al1 and ours2 concerns the definition of the reference group in the included studies, that is, subjects who received formula. In our analysis, only those studies in which breastfed subjects were compared with exclusively formula-fed probands were included. By contrast, Owen et al also included studies, such as those by Li et al,3 in which formula-fed subjects were allowed to have been breastfed supplementally.1 The consequence of this “exposure contamination” of the reference group, which obviously led to the difference between the resulting ORs in both meta-analyses, can be regarded as further indication of causality of the association under investigation. The relatively lower pooled estimate of studies with an “uncontaminated” reference group (exclusive formula) as compared with the pooled OR of studies with a “contaminated” reference group (formula plus supplementary breastfeeding) supports the impact of different “doses” of breastfeeding exposure on later overweight risk. The existence of a dose-response relationship in general strongly suggests causality of associations, as it also does in epidemiologic studies.4 Interestingly, a recent meta-analysis by our group revealed that the duration of breastfeeding, up to 9 months, is even linearly inversely associated with risk of overweight, thereby showing a dose-response relationship independent of a variety of confounders.5 In summary, both meta-analyses1,2 independently performed support (by indicating a dose-response-relationship) a protective effect of breastfeeding, as compared with formula feeding, on long-term overweight risk in children. Reduction in risk of overweight up to 25%2 is an effect size that is similar to or even larger than most other measures of primary prevention of overweight,6 thereby strongly supporting the public health importance of breastfeeding. It should therefore be recommended rigorously, and efforts should be supported to optimize formula composition in this regard.