Differences Between Meta-analyses on Breastfeeding and Obesity Support Causality of the Association: In Reply
Christopher G. Owen, PhD
Peter H. Whincup, FFPH
Derek G. Cook, PhD
Division of Community Health Sciences
St George's, University of London
University of London
London SW17 0RE, United Kingdom
Richard M. Martin, MFPH
George Davey Smith, FRCP
Department of Social Medicine
University of Bristol
Bristol BS8 1TH, United Kingdom
In Reply.—
We are grateful to Harder et al for drawing attention to the discrepancy between the results of their systematic review1 of the relations between breastfeeding and obesity prevalence, which reported a considerably stronger inverse association (pooled odds ratio [OR]: 0.75; 95% confidence interval [CI]: 0.69–0.82)1 than we observed in our recent report (pooled OR: 0.87; 95% CI: 0.85–0.89).2 They propose that the reason for the discrepancy is our inclusion of studies in which the formula-fed subjects included breastfed subjects, thereby reducing the strength of the association.
We do not believe that this is the correct explanation for the different findings of the 2 reviews. We have examined the effect of excluding 6 studies in which the formula-feeding group was not exclusive3–8; this exclusion did not make any material difference to the results of our analysis (pooled OR: 0.88; 95% CI: 0.85–0.90). We believe that the crucial difference between the 2 reviews was that we included a report by Grummer-Strawn and Mei9 (based on a very large study of 177304 American children aged 4 years), which was not included in the Plagemann and Harder review.1 As we stated in our article, exclusion of this very large study (which accounted for 73% of total weight in our analysis and showed an OR of 0.92 [95% CI: 0.90–0.95]) strengthened the relation between breastfeeding and obesity prevalence so that the effect estimate (OR: 0.73; 95% CI: 0.70–0.77) was in close agreement with that of Plagemann and Harder. Including the Grummer-Strawn and Mei study (which met the entry criteria of Plagemann and Harder, particularly the requirement for exclusivity of the formula-feeding group) strengthened the case for small-study bias in our study, leading us to use a fixed-effects analysis, which is less susceptible to this form of bias. Had the Grummer-Strawn and Mei report been included in the Plagemann and Harder review, we believe its findings would have become very similar to our own.
We agree with Harder et al that we need to address dose-response relationships as well as overall estimates in studying the relationship between breastfeeding and obesity prevalence. However, we believe that it is also very important to address the issue of confounding, particularly for social circumstances and maternal factors. Our more recent review of the relationship between breastfeeding and mean BMI showed that adjustment for confounding markedly attenuated both the strength of overall association and the evidence of a relationship between breastfeeding duration and BMI.10 The importance of confounding has also been highlighted by Nelson et al,11 who showed that the association between infant feeding and overweight observed in a large cohort of 11998 American adolescents was lost in a sibling-pair analysis.
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