Impact of Infant Feeding Practices on Childhood Obesity 1,2

Transcription

1 The Journal of Nutrition Infant Feeding and the Development of Obesity: What Does the Science Tell Us? Impact of Infant Feeding Practices on Childhood Obesity 1,2 Nancy F. Butte* USDA/ARS Children s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas Abstract Childhood obesity is a complex disease influenced by genetic and environmental factors and their interactions. The current surge in childhood obesity in the United States is attributable to an interaction between a genetic predisposition toward obesity and a permissive environment. Several recent systematic reviews and meta-analyses have been published on the association between breast-feeding and childhood obesity. In these analyses, adjustment for confounding factors attenuated or nullified the protective effect of breast-feeding on later obesity. The Viva La Familia Study was designed to identify genetic and environmental factors affecting obesity and its comorbidities in 1030 Hispanic children from 319 families. Odds ratios for potential risk factors associated with childhood overweight were computed using binary logistic regression for panel data. Early infant-feeding practices were not significant. Salient independent risk factors for childhood obesity in this cohort of Hispanic children were age, birth weight, maternal obesity, paternal obesity, number of children in the family, and the percentage of awake time spent in sedentary activity. Breast-feeding may have a small protective effect against childhood obesity, although residual confounding may exist. Human milk is exquisitely fitted for optimal infant growth and development and may uniquely modulate neuroendocrine and immunologic pathways involved in the regulation of body weight. Nevertheless, other genetic and environmental determinants such as socioeconomic status, parental obesity, smoking, birth weight, and rapid infancy weight gain far supersede infant-feeding practices as risk factors for childhood obesity. J. Nutr. 139: 412S 416S, Introduction Childhood obesity is a complex disease influenced by genetic and environmental factors and their interactions. The current surge in childhood obesity in the United States is attributable to an interaction between a genetic predisposition toward obesity and a permissive environment. Epidemiological studies have identified several risk factors for childhood obesity, each with its own genetic and environmental determinants. In this article, the potential effect of early infant feeding on later childhood obesity is evaluated in conjunction with other predictors of childhood obesity. 1 Published as a supplement to The Journal of Nutrition. Presented at the conference Infant Feeding and the Development of Obesity: What Does the Science Tell Us? held in San Diego, CA, April 9, The conference was sponsored by The International Formula Council (IFC), Atlanta, GA. The contents are the sole responsibility of the authors. The articles comprising this supplement were developed independently, and the conclusions drawn do not represent the official views of IFC. The mention of trade names, commercial products, or organizations does not imply endorsement by IFC. The Supplement Coordinator was Heather Gorby, Life Sciences Research Office, Bethesda, MD. Supplement Coordinator disclosure: H. Gorby is an employee of Life Sciences Research Office and received compensation for services performed as Supplement Coordinator. There are no other pending financial interests. 2 Author disclosures: N. Butte, no conflicts of interest. * To whom correspondence should be addressed. nbutte@bcm.edu. Effect of infant feeding practices on childhood obesity Several systematic reviews and meta-analyses have recently been published on the relation between early infant feeding and later development of obesity in childhood, adolescence, and early adulthood (1 5). Inconsistency exists across studies because of variation in study design and subjects, statistical power, definitions of infant feeding and obesity, extent of adjustment for potentially confounding factors, and age of outcome assessment. A systematic review of published studies on early infant feeding and later obesity was performed by Owen et al. (1). The meta-analysis included 28 studies (298,900 subjects). Breastfeeding was associated with a reduced risk of obesity compared with formula feeding. The unadjusted odds ratio (OR) 3 was 0.87 (95% CI: 0.85, 0.89). In 6 studies, adjustment for potential confounders, parental obesity, maternal smoking, and social class, changed the associated risk from 0.86 (95% CI: 0.81, 0.91) to 0.93 (95% CI: 0.88, 0.99). Low maternal social class and maternal obesity are both associated with formula feeding and a greater risk for obesity among offspring. Adjustment for confounders in the 6 studies markedly attenuated the relationship between breast-feeding and later obesity. Owen et al. (2) also conducted a meta-analysis on the effect of breast-feeding on mean BMI later in life to establish whether 3 Abbreviations used: AOR, adjusted odds ratio; FFM, fat-free mass; FM, fat mass; OR, odds ratio; SES, socioeconomic status. 412S /08 $8.00 ª 2009 American Society for Nutrition. First published online December 23, 2008; doi: /jn

2 breast-feeding reduces adiposity. Thirty-six studies (355,301 subjects) were identified. Breast-feeding was associated with slightly lower BMI than formula feeding (20.04; 95% CI: 20.05, 20.02). Adjustment for socioeconomic status (SES), maternal BMI, and maternal smoking in 11 studies abolished the effect of breast-feeding on mean BMI (20.10, 95% CI: 20.14, to 20.01, 95% CI: 20.05, 0.03). In 3 studies, prolonged breast-feeding had a slightly greater protective effect on BMI, but the protective effect was eliminated once data were adjusted for SES, maternal BMI, and maternal smoking in 2 studies. Breast-feeding may be associated with lower prevalence of obesity but not related to mean BMI. The effect of breast-feeding duration on the risk of obesity was explored in a comprehensive meta-analysis of 17 studies by Harder et al. (3). Duration of breast-feeding was negatively associated with the risk of overweight; the crude OR was 0.94 (95% CI: 0.89, 0.98). The OR decreased with the duration of breast-feeding from 0.81 at 1 3 mo, 0.76 at 4 6 mo, 0.67 at 7 9 mo, and 0.68 at.9 mo. The authors argue that it is unlikely that exposure-confounder association would exaggerate the dose-response gradient. However, confounding factors such as the extent of maternal obesity or familial diet and physical activity practices may covary in a graded response with the duration of breast-feeding (6). Quigley (4) suggested that the meta-analysis performed by Harder et al. (3) may have been inappropriate because of the significant heterogeneity among the included studies. Studies included a wide age range (,1 mo to 33 y), variable definitions of overweight, breast-feeding and the comparison non-breast-fed category, and a lack of adjustment for potential confounding factors. Quigley (4) repeated the meta-analysis on the duration of breast-feeding and risk of overweight, adjusting for confounding factors where possible. In 5 studies that used the definition of overweight as BMI percentile $95 or 97, the crude OR was 0.95 (95% CI: 0.92, 0.98). Adjustment for confounders weakened the OR to adjusted odds ratio (AOR) ¼ 0.97 (95% CI: 0.94, 0.99). In 4 studies that used the definition of overweight as BMI percentile $90, the crude OR was 0.94 (95% CI: 0.89, 1.01). Adjustment for confounders weakened the OR to 0.97 (95% CI: 0.93, 1.02). Although the duration of breast-feeding seems to be associated with a reduction in childhood obesity, it is unclear if this is because of residual confounding; for instance, only 3 studies adjusted for maternal BMI. In a systematic review using a priori selection criteria of eligible studies, Arenz et al. (5) identified 9 studies including 69,000 participants to investigate the relationship between breast-feeding and childhood obesity. Inclusion criteria were obesity defined by BMI $90, 95, or 97 kg/m 2, age at follow-up assessment 5 18 y, presentation of a risk estimate, and adjustment of at least 3 relevant confounding factors. The crude OR for breast-feeding and obesity was 0.67 (95% CI: 0.62, 0.73). The AOR was 0.78 (95% CI: 0.71, 0.85). In a meta-analysis, birth weight, maternal overweight, maternal smoking, and SES contributed up to 0.14 to the difference between AOR and crude OR. A dose-dependent effect of breast-feeding duration on the prevalence of obesity was reported in 4 of the studies. Although results were adjusted for at least 3 confounding variables, residual confounding is still possible. Further adjustment for other relevant factors might reduce the effect, but the protective effect would not likely be reduced to zero. Breast-feeding appears to have a small but consistent protective effect against obesity in children. Other early life determinants of childhood obesity In addition to infant feeding practices, epidemiological studies have identified several other risk factors for childhood obesity. In the Avon Longitudinal Study of Parents and Children, early-life risk factors for childhood obesity at age 7 were explored (7). Paternal obesity (AOR ¼ 2.54; 95% CI: 1.72, 3.75), maternal obesity (AOR ¼ 4.25, 95% CI: 2.86, 6.32), very early adiposity rebound (AOR ¼ 15.0, 95% CI: 5.32, 42.3),. 8 h/d TV at age 3 (AOR ¼ 1.55, 95% CI: 1.13, 2.12), catch-up growth (AOR ¼ 2.60, 95% CI: 1.09, 6.16), weight at 8 mo (AOR ¼ 3.13, 95% CI: 1.43, 6.85), weight gain in y 1 of life (AOR ¼ 1.06, 95% CI: 1.02, 1.10), birth weight (AOR ¼ 1.05, 95% CI: 1.03, 1.07), and short sleep duration (AOR ¼ 1.45, 95% CI: 1.10, 1.89) were associated with increased risk of childhood obesity. Sex, breast-feeding, age of introduction of solids, and dietary patterns were not significant predictors. Socioeconomic status. The effect of SES on childhood obesity varies across populations. In Westernized countries and societies in transition, obesity is usually more prevalent in areas of social deprivation and poverty (8). In the United States, the relationship between SES and overweight is weaker and less consistent (9). In the NHANES III data, overweight prevalence among Mexican-American and black children and adolescents was not related to family income; however, an inverse relation was seen for white adolescents. In general, $13 y parental education was associated with the lowest prevalence of childhood overweight. Parental obesity. Parental obesity is a strong predictor of childhood obesity, reflecting both environmental and genetic contributions. Numerous studies have documented the positive influence of maternal and paternal obesity on the risk of obesity in the offspring (10 13). Early-onset obesity (,10 y) has been associated with an increased relative risk of 2.14 (95% CI not reported) for obesity in first-degree relatives, suggesting higher genetic loading and familial aggregation (14). The genetic contribution to the epidemic of childhood obesity may also involve an increase in assortative mating (15). If this is occurring, children born to 2 obese parents would have a substantial chance of inheriting susceptibility gene variants from both parents and of developing severe obesity. Maternal smoking. Maternal smoking during pregnancy has been identified as a positive predictor of childhood obesity despite the well-recognized adverse effect of maternal smoking on birth weight (16). Smoking leads to intrauterine growth retardation and a substantial reduction in birth weight. In a cohort of Swedish men born , maternal BMI (AOR ¼ 1.23, 95% CI: 1.16, 1.30) and smoking (AOR ¼ 1.71, 95% CI: 1.21, 2.43) were the strongest predictors of overweight at age 18 y. A modifying effect of maternal smoking on the association between birth weight and later overweight was seen. Birth weight was positively associated with later obesity only in offspring born to mothers who were nonsmokers (AOR ¼ 1.46, 1.18, 1.81). Birth weight. Early life experiences can impact later childhood obesity. A large number of epidemiological studies have demonstrated a positive relationship between birth weight and BMI attained in childhood and adulthood (17,18). Low birth weight seems to be associated with later risk for central obesity, which also confers increased risk for cardiovascular disease (19), type 2 diabetes (20), and the metabolic syndrome in young adults (21). Rapid infancy weight gain. A systematic review of 18 studies examined the relationship between infant weight or BMI and rapid infancy weight gain on later obesity (22). The OR for infant weight or BMI and obesity at age s 3 35 y ranged from Risk factors for childhood obesity 413S

3 The OR for rapid growth and later obesity ranged from There was no convincing evidence that exposure at a particular time during infancy was more critical than others. Infants defined as obese, at the upper end of distribution for weight or BMI, or who grew rapidly during infancy, were more likely to develop obesity or to remain obese later on. In the National Collaborative Perinatal Project, the crude OR for weight gain during the first 4 mo of life (per 100 g per mo) on overweight status at age 7 y was 1.29 (95% CI: 1.25, 1.33) (23). Adjusted for confounding factors of sex, race, first-born status, birth weight, weight at age 1 y, maternal BMI, and maternal education, the AOR was 1.17 (95% CI: ). In an alternative model, risk of overweight also was associated with weight gain between 4 and 12 mo (OR ¼ 1.60, 95% CI: 1.48, 1.73). Initiation of breast-feeding was not significantly associated with overweight status at age 7 y. The association between rapid infancy weight gain and later obesity appears to be independent of birth weight. No significant interaction between birth weight and rapid infancy weight gain on risk for later obesity was detected (24). Full-term infants who experience catch-up growth after intrauterine growth retardation are not protected against an increased risk of later obesity. Genetics. Classical genetic studies on twins, siblings, nuclear families, and in extended pedigrees have repeatedly shown that the risk of being obese is increased when relatives are also obese. Formalized quantitative genetic analyses of measures of obesityrelated phenotypes have consistently found significant heritabilities, suggesting that there is an additive or oligogenic component to obesity. Estimates of the heritability of BMI generally range from 20% to 60% (25). Based on data from.25,000 twin pairs and 50,000 biological and adoptive family members, the weighted mean heritabilities for BMI were 0.74 for monozygotic twins, 0.32 for dizygotic twins, 0.25 for siblings and 0.19 for parent-offspring pairs (26). Viva La Familia Study: Early life determinants of childhood obesity The Viva La Familia Study was designed to identify genetic and environmental factors affecting obesity and its comorbidities in 1030 Hispanic children from 319 families enrolled between November 2000 and August 2004 in Houston, Texas (27). Family eligibility included an overweight child between ages 4 and 19 y. Here we compute OR for potential risk factors associated with childhood overweight. Binary logistic regression for panel data were used to examine the effect of putative risk factors on childhood obesity (STATA, v 10; STATA Corp, College Station, TX) (Table 1). To account for correlated data within families, family identification number was used as a cluster variable. Childhood overweight was defined according to the Centers for TABLE 1 Early life risk factors for childhood obesity evaluated in the Viva La Familia cohort of Hispanic children and adolescents Risk factors OR 95% CI P-value AOR 95% CI P-value Child characteristics Age, y Gender Tanner stage Child order Birth weight, kg Family characteristics Children in family, n Household income Maternal education, y Paternal education, y Maternal obesity ($30 kg/m 2 ) Paternal obesity ($30 kg/m 2 ) Early infant feeding Exclusive breastfeeding (yes/no) Partial breastfeeding (yes/no) Breastfeeding duration, mo Age introduction of solid food, mo Diet intake Total energy intake, kj/d Diet fat, % energy Diet carbohydrate, % energy Diet protein, % energy Dinner test meal, kj Eating in absence of hunger, kj Physical activity TV, h/wk Sleep time, min Total counts, counts/d Awake sedentary time, % Awake light time, % Awake moderate time, % Awake vigorous time, % S Supplement

4 Disease Control as percentile for BMI $95 and was coded 0 ¼ nonoverweight, 1 ¼ overweight. Risk factors were evaluated individually and then simultaneously to identify statistically independent risk factors for overweight. Family characteristics. A high degree of obesity was present in these families (27). The majority of the parents were either overweight (34%) or obese (57%). Mean BMI of the fathers and mothers was and , respectively. OR for obesity increased significantly if the mother (OR ¼ 1.84; P ¼ 0.001) or father (OR ¼ 1.67; P ¼ 0.001) was obese. Risk decreased with increasing years of paternal education. Risk for obesity increased with the number of children in the family. Child characteristics. Birth weight was higher in overweight than nonoverweight children ( vs kg), controlling for gestational age (28). Birth weights exceeded 4.0 kg in 17.7% of the children. Birth weight, controlled for gestational age, was a significant predictor of current BMI Z-score (adj r 2 ¼ 0.14; P ¼ 0.004), height Z-score (adj r 2 ¼ 0.44; P ¼ 0.001), but not percentage fat mass (FM) (28). Risk of childhood obesity increased significantly with birth weight (P ¼ 0.001). Childhood obesity was shown to be heritable in this cohort of children (28). The heritabilities of body weight, BMI, and FM were 0.36, 0.39, and 0.33, respectively (27). Birth weight was highly heritable (h 2 ¼ 0.92), controlling for gestational age, gestation diabetes, mother s age in pregnancy, birth order, father and mother s education level, family income, and gender. Bivariate genetic analyses between birth weight and later body size and composition were performed (28). Positive genetic correlations between birth weight and childhood height (r ¼ 0.56), weight (r ¼ 0.36), fat-free mass (FFM) (r ¼ 0.59), and FM (r ¼ 0.37) suggest shared genetic determinants of birth weight and later body size. Bivariate linkage analyses of birth weight mapped to a region on chromosome 10q22, providing further evidence of shared genetic influences on birth weight, childhood body weight, hip circumference, and FM in Hispanic children. Infant feeding practices. With respect to infant feeding practices, the predominant milk source was human milk only in 34% of cases for a median duration of mo (27). Mixed feeding of human milk and formula was reported in 24% of cases. Formula only was used in 42% of cases for a median duration of mo. Solid foods were introduced at a mean of mo for all cases. Neither exclusive nor partial breast-feeding was associated with the risk of childhood obesity. Nor was the age of introduction to solid foods related to the risk of obesity. Childhood diet intake. Adjusted for FFM and FM, total energy intake assessed by 2 24-h diet recalls (29) was positively associated with the risk of childhood obesity (P ¼ 0.003). Carbohydrate, as a percentage of energy intake, was inversely related to the risk (P ¼ 0.03). In a laboratory-based test of eating behavior (30), ad libitum energy intake at dinner and amount of energy consumed in the absence of hunger were associated with increased obesity risk (P ¼ 0.001). Childhood physical activity. Physical activity, as reflected by total accelerometry counts (31), was protective against obesity risk. Television viewing (h/wk) was related to increased risk of obesity. OR for obesity increased with the percentage of awake time spent in sedentary activity and decreased with the time spent in light activity. Multiple logistic regression identified independent risk factors for childhood obesity in this cohort of Hispanic children (Table 1). AOR were significant for age, birth weight, maternal obesity, paternal obesity, number of children in the family, and the percentage of awake time spent in sedentary activity. SUMMARY Epidemiological studies have identified several risk factors for childhood obesity, including infant-feeding practices. Breastfeeding appears to have a small but consistent protective effect against childhood obesity. Residual confounding may exist, but then again, human milk is exquisitely suited for optimal infant growth and development and uniquely may modulate neuroendocrine and immunologic pathways involved in the regulation of body weight. Nevertheless, other genetic and environmental determinants such as SES, parental obesity, parental smoking, birth weight, and rapid infancy weight gain far supersede infantfeeding practices as risk factors for childhood obesity. QUESTION AND ANSWER SESSION [Q1]: If part of the relationship of maternal obesity to child obesity is mediated by less breast-feeding, then you are overcontrolling by putting maternal obesity in the model. I think that all investigation in this field needs to carefully consider the possible mechanisms and adjust or construct their models accordingly. If part of the reason for higher rate of overweight in non-breast-fed children has to do with gaining more energy by bottle, just because it is easier and there is less opportunity for selfregulation by the baby, then the only category where that would be ruled out would be exclusive breast-feeding. [Dr. Butte]: If there is a mechanism for the protective effect of breast-feeding, it is unlikely that it will be discovered through epidemiological or observational studies because of confounding. For instance, if breast-feeding is having an effect on later rates of weight gain, you need to carefully assess complementary feeding and what was happening during and beyond that period. Our study provided a cross-sectional view of what was going on during childhood, but I certainly do not know what was going on in the interim. I leave open the possibility that human milk may have a unique programming effect on neuroendocrine or immunological pathways during intrauterine development and during that first year of life, when the brain is developing, but I do not think we are going to get those answers from the epidemiological studies. [Q2]: I was wondering if you had stratified your results by sex and saw differences between males and females, especially because males and females metabolize LDL and triglycerides differently. [Dr. Butte]: No, we did not stratify for sex, but we always control for sex in our models. [Q3]: The issue of noise is a matter of noise to signal; every measurement has some noise in it; and if the signal is large enough you pick the signal up despite the noise. So, for instance, a 91% signal, which is what we saw for yes-or-no recall of breastfeeding, is an enormously good signal; you need very little to pick that up. The critical factor is the sample size; the bigger the sample size, the less the noise plays a role, and with an infinite sample size, noise plays no role whatsoever. In studies that are negative, it is very important to look at that noise-to-signal ratio because you will conclude that something is not there when in fact it is just noise. [Dr. Butte]: The quality of the epidemiological studies in this area has improved greatly, both in sample size and in the assessment of confounding factors. There seems to be a small Risk factors for childhood obesity 415S

5 consistent protective effect of breast-feeding on later obesity, even though we cannot rule out the possibility of confounding. What I was trying to get across is that there are other, stronger predictors of childhood obesity that should be considered in evaluating the potential effect of the early infant feeding factors on later childhood obesity in research studies and public policy. Other articles in this symposium include references (32 34). Literature Cited 1. Owen CG, Martin RM, Whincup PH, Davey Smith G, Cook DG. Effect of infant feeding on the risk of obesity across the life course: a quantitative review of published evidence. Pediatrics. 2005;115: Owen CG, Martin RM, Whincup PH, Davey Smith G, Gillman MW, Cook DG. The effect of breastfeeding on mean body mass index throughout life: a quantitative review of published and unpublished observational evidence. Am J Clin Nutr. 2005;82: Harder T, Bergmann R, Kallischnigg G, Plagemann A. 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