PEDIATRICS Vol. 115 No. 5 May 2005, pp. 1367-1377 (doi:10.1542/peds.2004-1176)
REVIEW ARTICLE |
Effect of Infant Feeding on the Risk of Obesity Across the Life Course: A Quantitative Review of Published Evidence


* Department of Community Health Sciences, St George's Hospital Medical School, London, United Kingdom
Department of Social Medicine, University of Bristol, Bristol, United Kingdom
| ABSTRACT |
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Objective. To examine the influence of initial infant feeding on obesity in later life.
Methods. A systematic review of published studies investigating the association between infant feeding and a measure of obesity was performed with Medline (1966 onward) and Embase (1980 onward) databases, supplemented with manual searches. Data extraction was conducted by 2 authors. Analyses were based on odds ratios of obesity among initially breastfed subjects, compared with formula-fed subjects, pooled with fixed-effects models.
Results. Sixty-one studies reported on the relationship of infant feeding to a measure of obesity in later life; of these, 28 (298900 subjects) provided odds ratio estimates. In these studies, breastfeeding was associated with a reduced risk of obesity, compared with formula feeding (odds ratio: 0.87; 95% confidence interval [CI]: 0.850.89). The inverse association between breastfeeding and obesity was particularly strong in 11 small studies of <500 subjects (odds ratio: 0.43; 95% CI: 0.330.55) but was still apparent in larger studies of
500 subjects (odds ratio: 0.88; 95% CI: 0.850.90). In 6 studies that adjusted for all 3 major potential confounding factors (parental obesity, maternal smoking, and social class), the inverse association was reduced markedly (from an odds ratio of 0.86 to 0.93) but not abolished. A sensitivity analysis examining the potential impact of the results of 33 published studies (12505 subjects) that did not provide odds ratios (mostly reporting no relationship between breastfeeding and obesity) showed little effect on the results.
Conclusions. Initial breastfeeding protects against obesity in later life. However, a further review including large unpublished studies exploring the effect of confounding factors in more detail is needed.
Key Words: infant feeding obesity systematic review
Abbreviations: CI, confidence interval
Obesity represents a major public health problem in both developed and developing countries, which has increased rapidly in prevalence in the past 2 decades.1,2 After the suggestion that nutrition in early life might influence the risk of subsequent obesity,3 some reports suggested that initial breastfeeding might protect against obesity in later life,46 whereas others failed to confirm the association.7,8 Inconsistency in results could reflect variation in the statistical power of different studies or differences in the extent of adjustment for potential confounding factors, particularly maternal obesity, smoking, and socioeconomic background.5,8 Differences in the age of outcome assessment, calendar year of infant feeding, country, and method of assessment of infant feeding could also be important. Selective reporting or publication, particularly of small studies with extreme results, could also be an important factor. In an attempt to establish the extent to which infant feeding influences obesity, we reviewed the published literature on the relationship between infant feeding and obesity, to examine the overall consistency of reported associations, the extent of potential publication and reporting biases, and the potential contributions of confounding factors.
| METHODS |
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Systematic Review Process
The data retrieved for this review were based on a larger, inclusive, systematic search of all published articles, letters, abstracts, and review articles on infant feeding and cardiovascular disease, cardiovascular disease risk factors, and growth in the Medline and Embase bibliographic databases (Table 1). In addition, the reference lists of all studies that fulfilled our eligibility criteria and those of 3 relevant reviews were examined.911 The review was restricted to studies conducted with human subjects.
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The electronic search (completed in September 2003) yielded 3600 unduplicated references. Three additional articles with relevant data that were published recently were also included.7,8,12 One reviewer (R.M.M.) completed the literature search. Abstract review suggested that 97 articles were potentially relevant, and 2 authors (C.G.O. and R.M.M.) extracted data from these studies, with total agreement. Thirty-six articles were excluded; 14 studies duplicated data in other reports and 22 did not compare obesity among formula-fed and breastfed subjects. A list of excluded studies is available from the authors. Therefore, 61 studies that compared a measure of obesity (quantitatively or narratively) among breastfed and formula-fed subjects were considered. Mean BMI differences between breastfed and formula-fed subjects were available for 8 studies,6,1218 4 of which also provided odds of obesity.6,12,13,15 Studies that defined the odds of obesity or being overweight for breastfed and formula-fed subjects were reported more often and were included in a meta-analysis; 28 studies with 29 estimates (1 study reported results for 2 populations)19 met this inclusion criterion (Table 2). The definitions of obesity differed among studies (Table 2). However, most studies used a percentile cutoff based on BMI, describing subjects at the tail of the distribution. The 95th or 97th percentile was used most often, although some studies used cutoff values as low as the 85th percentile. A smaller number of studies used absolute BMI values15,20,21 or cutoff values based on standardized weight22,23 or weight for height.19,24,25 Studies involving infants used definitions based on percentiles of weight for length2527 or percentiles of weight only.23 Initial feeding status was ascertained through maternal recall at the time of infant feeding or
3 years after birth. Comparisons were based on breastfed and formula-fed groups.
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The World Health Organization defines exclusive breastfeeding as "breastfeeding or formula feeding while giving no other food or liquid, not even water."28 However, few studies report this definition, and exclusive breastfeeding is rarely maintained for the first 4 months and if possible 6 months of life, as advised by the World Health Organization. Therefore, the exclusiveness of infant feeding was based on the classification given in each article, as listed in Table 2. The feeding groups were defined as being mutually exclusive in 4 studies,5,2931 the breastfed group included mixed feeders in 7 studies,6,15,19,23,27,32,33 and the formula-fed group included mixed feeders in 7 studies.6,13,26,3336 In 2 studies in which infants were breastfed exclusively, the exclusiveness of formula feeding could not be gauged.4,37 The exclusiveness of initial feeding was unclear in 10 additional studies.8,12,2022,24,25,3840 No studies reported the use of nonstandard commercial formulas. Among studies that reported odds ratios (including 4 studies that reported both odds ratios and mean differences in BMI), 8 studies were based on populations from North America, 15 from Western Europe, 3 from Eastern Europe, 2 from Australasia, and 1 from China.
Statistical Analyses
The odds ratio of being defined as obese (or overweight) among initially breastfed subjects, compared with formula-fed subjects, was used as the principal outcome, with its variance. In many studies, the odds ratios were provided directly. For other studies, we calculated the odds ratios from reported prevalence rates of obesity in different feeding groups or from combinations of odds ratios given for different durations of breastfeeding with fixed-effects models, with formula-fed subjects as the reference group. In 2 studies, data for male and female subjects were combined.15,38 The main analysis was based on odds ratios that were unadjusted or adjusted for current age and gender and in some cases ethnic group.5,30 Results from fixed-effects models are reported throughout, because these reflect only the random error within each study, are more conservative because they are less affected by results of smaller studies that show stronger associations, and make no assumptions about the representativeness of the available studies. Because heterogeneity across studies was marked, possible sources of heterogeneity were examined. Funnel plots were used to assess whether small studies yielded larger effect estimates than larger studies, raising the possibility of publication bias.41,42 Tests described by Begg and Mazumdar43 and Egger et al42 for publication bias and funnel plot asymmetry, respectively, were also performed. Meta-regression was used to examine the influence of the following factors (defined a priori) with a test for trend: study size (<500, 5002500, or >2500 subjects), age group at outcome measurement (infants
1 year of age, young children >1 to 9 years of age, older children 10 to <16 years of age, or adults
16 years of age), year of birth, and response rates (analyzed as a continuous variable). The effects of adjustment for factors such as parental body size (mostly BMI), socioeconomic status, and maternal smoking were examined in 6 studies that provided data before and after adjustment for all 3 of these factors. The effects of study methods, particularly the method of ascertainment of infant feeding status (whether contemporary or recalled over a period of
3 years), study response rate, and definition of obesity (equivalent to <95th percentile, 95th to <97th percentile, or
97th percentile of BMI), were examined with meta-regression and sensitivity analyses.
Assessment of Reporting Biases
To establish the likelihood of reporting bias, the directions of reported associations were compared among studies that did or did not provide a quantitative estimate of the relative risk of obesity associated with breastfeeding. A sensitivity analysis examining the potential impact of studies not providing quantitative estimates was then conducted with meta-analyses providing an estimate of the pooled odds ratio, weighting each study estimate by the total number of subjects in that study. This was conducted first for studies providing published estimates and then for all studies. Unpublished odds ratios were derived from information on the direction of effect provided in the article. In all except 2 cases, this was reported to be a null effect and the odds ratio was assumed to be 1 (Table 3). The derivation of an odds ratio in the 2 studies that reported a direction of effect is outlined in a footnote to Table 3.44,45
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| RESULTS |
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Among 61 observational studies that reported on the effects of infant feeding on a measure of adiposity in later life, 28 studies (298900 subjects) provided 29 unadjusted odds ratios relating the initial infant feeding method and obesity (Table 2). Four observations were for infants, 23 for children, and 2 for adults (Table 2). Twenty-eight of 29 estimates related breastfeeding to a lower risk of obesity. There was evidence of marked heterogeneity among studies (
282 = 111, P < .001). In a fixed-effects model including all studies, breastfed subjects were less likely to be defined as obese than were formula-fed subjects (odds ratio: 0.87; 95% confidence interval [CI]: 0.850.89) (Fig 1 and Table 2). This estimate was unaltered by exclusion of 4 studies with outcome measurement in infancy. In the fixed-effects model, the statistical weight given to the largest study amounted to 73%.12 Exclusion of this study strengthened the protective effect of breastfeeding on obesity to an odds ratio of 0.73 (95% CI: 0.700.77). Additional exclusion of the next 2 largest studies (accounting for 10% of the statistical weight) had little additional effect.29,33
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Small studies reported the strongest relationships between breastfeeding and reduced risk of obesity (Figs 1 and 2), although the association was still present in larger studies. An odds ratio of 0.43 (95% CI: 0.330.55) was observed in 11 small studies (<500 participants), whereas odds ratios of 0.78 (95% CI: 0.690.89) and 0.88 (95% CI: 0.860.90) were observed in 7 studies of intermediate size (5002500 participants) and in 10 large studies (>2500 participants), respectively. This trend can be seen in the funnel plot (Fig 2); not surprisingly, the results of the Egger test for funnel plot asymmetry were statistically significant (P < .001). The results of the Begg test were not statistically significant (P = .96). There was no clear evidence that the protective effect of breastfeeding altered with increasing age of outcome measurement. Odds ratios of 0.50 (95% CI: 0.260.94) for infants, 0.90 (95% CI: 0.870.92) for young children, 0.66 (95% CI: 0.600.72) for older children, and 0.80 (95% CI: 0.710.91) for adults were observed (test for trend, P = .85, adjusted for study size; P = .99 with the exclusion of infants). The smaller effect with narrow CIs observed for young children is attributable to the inclusion of the largest study with a small effect.12 Year of birth was unrelated to the odds ratio.
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In 6 studies, it was possible to examine the effect of adjustment for the following potentially important confounders: socioeconomic status (based on parental education in 2 studies),12,33 parental BMI, and current maternal smoking33 or maternal smoking in early life.6,8,12,13,15 The pooled odds ratio in these studies was reduced from 0.86 (95% CI: 0.810.91) before adjustment to 0.93 (95% CI: 0.880.99) after combined adjustment. The effect of adjustment for size at birth (based on either birth weight or prevalence of low birth weight) was examined in 10 studies; this had no appreciable effect on the odds ratios.
The protective effect of breastfeeding over obesity was stronger and more homogeneous among 4 studies in which initial feeding groups were exclusive (odds ratio: 0.76; 95% CI: 0.700.83; test for heterogeneity between estimates,
32 = 5.4, P = .143), compared with all other studies.5,2931 In addition, a longer duration of breastfeeding appeared to show a slightly greater protective effect on obesity. In 14 studies with information on breastfeeding duration, the protective effect of breastfeeding over formula feeding was greater among subjects breastfed for
2 months (odds ratio: 0.81; 95% CI: 0.770.84), compared with those breastfed for any duration (odds ratio: 0.89; 95% CI: 0.860.91) in the same studies. The combined odds ratio was little affected by particular obesity cutoff values used in different studies, by whether infant feeding status was recorded in infancy or retrospectively, or by response rate.
Thirty-three studies (12505 participants), although they examined relationships between breastfeeding and obesity, did not provide an estimate of relative risk (Table 3). However, they provided 35 reports of directions of association; of these, breastfeeding was unrelated to risk of obesity in 33, related to a reduced risk in 1, and related to an increased risk in 1. Therefore, studies that did not provide odds ratios were much less likely to report that breastfeeding was associated with a reduced risk of obesity, compared with studies that did provide odds ratios (1 of 35 studies and 18 of 29 studies, respectively;
2 = 26.9, P < .001). However, including these additional studies (which included fewer than one twentieth of the numbers of subjects in the studies that provided odds ratios) appeared to make little difference in the results. In a meta-analysis of the 29 odds ratios from 28 studies with published estimates, weighted according to the total number of subjects in each study, the summary odds ratio was 0.83, close to that reported for the main analysis above. The inclusion of 35 estimates from the 33 studies with no published odds ratio (Table 3) had a minimal effect on the summary estimate (summary odds ratio: 0.84). The difference in the summary estimates was similar when the largest published study, representing nearly three fourths of the combined statistical weight, was excluded from the analyses.12 Studies equivalent in statistical size to this largest study (N = 177304)12 and showing an overall protective effect of formula feeding over breastfeeding on obesity, with an odds ratio of 1.4 (far greater than any effect observed in the current meta-analysis), would be needed to nullify these combined results (ie, to produce an estimated odds ratio of 1).
| DISCUSSION |
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In this overview of published studies relating infant feeding and obesity, studies reporting a quantitative estimate provided consistent evidence of a relationship between breastfeeding and reduced risk of obesity. Although the association was particularly strong among the smallest studies (consistent with the possibility of publication bias), it was also observed among larger studies. The association appeared stronger among prolonged breastfeeders and was unaltered by age at outcome measurement.
An important potential limitation of the evidence presented here is that it is based on observational studies; experimental studies are generally impracticable in this context, except in highly specific circumstances.46 Confounding is therefore an important possibility, and maternal factors are of particular potential importance. Low maternal social class and maternal obesity are related to a tendency to formula feed and to greater risk of obesity among offspring.5,8 Birth size may also be an important confounder, especially because lower mean birth weight may be associated with formula feeding and with an increased risk of later central obesity.5,47 The effect of confounding by maternal factors and birth weight may exaggerate an association between breastfeeding and obesity. In a subset of studies that examined the effect of adjustment for these factors, the association between breastfeeding and reduced risk of obesity was markedly attenuated.6,8,12,13,15,33
The association between breastfeeding and obesity could reflect selective reporting and/or publication. Our results indicated selective reporting of odds ratios by studies that showed a relationship between breastfeeding and reduced risk of obesity. However, because the studies that did not present odds ratios were on average much smaller than those that presented data, their inclusion had a minimal impact on effect estimates. The influence of publication bias is more difficult to assess. The results suggested that there was some selective publication of small studies showing strong associations between breastfeeding and obesity. However, the association remained, although it was weaker, among the larger published studies. It remains possible that, among large unpublished data sources, there is little or no association. However, studies equivalent in statistical size to the largest study (N = 177034)12 would need to show a highly improbable protective effect of formula feeding over breastfeeding to nullify the pooled results presented in this review.
Overall, our results suggest that breastfeeding is protective against obesity, although the precise magnitude of the association remains unclear. Increasing uptake of breastfeeding could form an important part of population strategies to prevent obesity. Several biological mechanisms may explain the association. Breastfeeding affects intakes of calories and protein,48 insulin secretion,49 and modulation of fat deposition and adipocyte development.4 If the effects of breastfeeding are sustained through either habituation or more-complex programming mechanisms, then the association could persist into adult life, as our results suggest. The consistency of the association with increasing age (as observed in the analyses) suggests that the protective effects of early breastfeeding are independent of dietary and physical activity patterns that emerge in later life.
In investigating the presence of a dose-response relationship, it was possible to show, from published data, only that prolonged breastfeeding was associated with an additional reduction in obesity, compared with any breastfeeding in the same studies. Additional data are needed to examine systematically the effects of duration of breastfeeding on obesity in adulthood. Additional studies are also needed to examine the effects of confounding and publication biases in more detail. Additional evidence regarding the effects of confounding factors on the relationship between breastfeeding and obesity, from both published and unpublished studies, is needed. Studies involving populations for which breastfeeding is socially patterned in a way that is different from that for European or North American populations (the predominant source of studies in the present meta-analysis) would be particularly valuable. Follow-up data for participants in randomized, controlled trials of breastfeeding promotion would provide particularly reliable evidence of the association.50 To address the influence of publication biases, additional data on the relationship between breastfeeding and obesity from large unpublished studies are needed, especially for adults. In addition, examination of the relationship of breastfeeding to markers of average adiposity in the comparison groups (for example, mean BMI) would supplement usefully the information on the prevalence of obesity provided in this study. While more data on these issues and on the relationship between duration of breastfeeding and obesity are being obtained, the case for breastfeeding is already strong and well established, based on a combination of other short- and long-term benefits, including improved neural and psychosocial development,51,52 less allergic disease,53 and potentially lower blood cholesterol levels in later life.54
| ACKNOWLEDGMENTS |
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C.G.O. was supported by the British Heart Foundation (grant PG/04/072). R.M.M. was supported by the Wellcome Trust.
| FOOTNOTES |
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Accepted Sep 14, 2004.
Address correspondence to Christopher G. Owen, PhD, Department of Community Health Sciences, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, United Kingdom. E-mail: c.owen{at}sghms.ac.uk
All authors contributed to formulation of the hypothesis. Dr Martin conducted the literature search, Drs Owen and Martin extracted the data, and Dr Owen conducted statistical analyses, drafted the article, to which all authors contributed, and is guarantor. The guarantor accepts full responsibility for the conduct of the study, had access to the data, and controlled the decision to publish.
No conflict of interest declared.
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