Breastfeeding and risk of child obesity: Breastfeeding and risk of child obesity Kathryn G. Dewey, PhD Program in International and Community Nutrition University of California, Davis


Study selection criteria: Study selection criteria N andgt; 100 per feeding group Age at follow-up andgt; 3 y Outcome = % overweight or obese


Studies in preschool children: Studies in preschool children 1Only among white children whose mothers did not smoke


Studies in school-aged children: Studies in school-aged children


Studies in older adolescents: Studies in older adolescents


Slide6: Additive interactions of maternal prepregnancy BMI and breastfeeding on childhood overweight. Li et al. Obesity Res 2005;13:362-371 (2-14 years of age) andlt; 25 25-29 andgt; 30 Maternal BMI 31.5 6.0


Breastfeeding and childhood obesity – a systematic review. Arenz et al. Intl J Obes, 2004; 28:1247-56.: Breastfeeding and childhood obesity – a systematic review. Arenz et al. Intl J Obes, 2004; 28:1247-56. Source: Arenz et al. Intl J Obes, 2004 AOR 0.78 (0.71, 0.85)


Effect of infant feeding on the risk of obesity across the life course: a quantitative review of published evidence. Owen et al. Pediatrics 2005;115:1367-77.: Effect of infant feeding on the risk of obesity across the life course: a quantitative review of published evidence. Owen et al. Pediatrics 2005;115:1367-77. Reviewed 61 studies; 28 with odds ratio estimates OR for any BF, all studies: 0.87 (0.85-0.89) For infants: OR = 0.50 (0.26-0.94) For young children: OR = 0.90 (0.87-0.92) For older children: OR = 0.66 (0.60-0.72) For adults: OR = 0.80 (0.71-0.91) Adjusted for SES, parental BMI andamp; maternal smoking) for any BF, all studies: AOR = 0.93 (0.88-0.99) Protective effect of BF stronger in 4 studies in which initial feeding groups were exclusive: OR = 0.76 (0.70-0.83) Stronger relationship with longer duration of BF: OR = 0.81 (0.77-0.84) for BF andgt; 2 mo OR = 0.89 (0.86-0.91) for any BF duration


Bergmann et al. (Germany)N=480; BMI at 0-6 y: Bergmann et al. (Germany) N=480; BMI at 0-6 y Percentage of children andgt; 90th percentile


Poulton & Williams (New Zealand)N=1,037, born 1972-73BMI at 3, 5, 7, 9, 11, 13, 15, 18, 21, 26 y: Poulton andamp; Williams (New Zealand) N=1,037, born 1972-73 BMI at 3, 5, 7, 9, 11, 13, 15, 18, 21, 26 y In those BF andgt; 6 mo, a lower risk of obesity was observed at 9-18 years of age, but not at younger ages (3-8 years) or in adulthood (andgt; 18 years) Is puberty / adolescence a critical period, when the influence of infant feeding mode is most clearly expressed?


Is there a dose-response relationship between BF duration and lower risk of child obesity?: Yes No Bogen Hediger Grummer-Strawn O-Callaghan Von Kries Wadsworth Toschke Li Liese Victora Gillman Burke Poulton (trend) Nelson (in girls) Is there a dose-response relationship between BF duration and lower risk of child obesity?


Is there a dose-response relationship between BF duration and lower risk of child obesity?: Harder et al. Duration of breastfeeding and risk of overweight: a meta-analysis. Am J Epidemiol 2005;162:1-7. Included 17 studies: Duration BF OR andlt; 1 mo 1.00 1-3 mo 0.81* 4-6 mo 0.76* 7-9 mo 0.67* andgt; 9 mo 0.68* * Significantly different from reference group. [No control for potential confounders.] Is there a dose-response relationship between BF duration and lower risk of child obesity?


Slide13: Does exclusivity of breastfeeding matter? Bogen et al. Obesity Research 2004;12:1527-1535 Relationship between obesity at age 4 y and duration of breastfeeding and concurrent formula use for whites (solid line) and blacks (dashed line)


Breastfeeding duration and obesity at 4 y among white children whose mothers did not smoke during pregnancy [Bogen et al., 2004]: Breastfeeding duration and obesity at 4 y among white children whose mothers did not smoke during pregnancy [Bogen et al., 2004] BF duration AOR Never 1.00 andlt; 8 wk 0.97 8-15 wk w/ FF 0.84 8-15 wk w/o FF 0.80 16-26 wk w/ FF 0.86 16-26 wk w/o FF 0.71* andgt; 26 wk w/ FF 0.70* andgt; 26 wk w/o FF 0.55* * p andlt; 0.05, adjusted for maternal age, education, parity, marital status, pregnancy conditions, delivery method, child sex, birth weight, birth order, birth year. Inclusion of maternal BMI did not alter the results.


Breastfeeding and subsequent obesity: potential explanations: Breastfeeding and subsequent obesity: potential explanations Learned self-regulation of energy intake Metabolic programming Insulin Leptin Consequences of high protein intake in early life Residual confounding by attributes of mothers and/or family environment


Learned self-regulation of energy intake: Learned self-regulation of energy intake Breastfeeding allows infant to control intake based on internal satiety cues Bottle-fed infants may be encouraged to finish bottle even if they are full This may lead to later differences in ability to self-regulate energy intake


Infant self-regulation of breast milk intake K.G. Dewey & B. Lonnerdal Acta Paediatr Scand 1986; 75: 893-8: Infant self-regulation of breast milk intake K.G. Dewey andamp; B. Lonnerdal Acta Paediatr Scand 1986; 75: 893-8 18 exclusively breastfeeding mothers stimulated milk supply by daily expression of extra milk for 2 wk. All but 4 increased milk volume by andgt; 73 g/d. Among the 14 infants with access to increased milk volume, most increased intake in the first 2 d, but returned to near baseline levels of intake after 1-2 wk Intake increased more in fatter than leaner infants Breastfed infants self-regulate milk intake


Differences in milk intake between BF and FF infants increase between 1 and 5 mo: Differences in milk intake between BF and FF infants increase between 1 and 5 mo b b b a a a b b b,c c a Dewey et al., EB 2004


Response to introduction of solid foods differs between breastfed and formula-fed infants: Response to introduction of solid foods differs between breastfed and formula-fed infants In BF infants, breast milk intake declines when solid foods are introduced In FF infants, formula intake does not decline when solid foods are introduced Heinig et al., Acta Paediatr 1993;82:999-1006


Effects of over-feeding in early life?: Effects of over-feeding in early life? Animal studies In baboons, overfeeding in infancy   fat depot mass during puberty, especially in females (Lewis et al., 1986) Human studies Rapid weight gain during infancy is correlated with childhood obesity (Ong et al., 2000; Stettler et al., 2002; Cameron et al., 2003; Ekelund et al., 2006)


Stettler et al. (U.S.)Pediatrics 2002;109:194-199: Stettler et al. (U.S.) Pediatrics 2002;109:194-199 N=19,397 children born 1959-65 Outcome: BMI andgt; 95th percentile at age 7 y Rate of weight gain during the first 4 mo was associated with risk of child obesity, even after adjustment for weight at 1 year Almost 20% of obesity attributable to having a high rate of weight gain 0-4 mo


Weight gain in the first week of life and overweight in adulthood. Stettler et al. Circulation 2005;111:1897-1903.: Weight gain in the first week of life and overweight in adulthood. Stettler et al. Circulation 2005;111:1897-1903. N= 653 formula-fed infants, measured frequently during infancy andamp; again at 20-32 y of age 32% were overweight as adults Weight gain during the first week of life was identified as the most sensitive period regarding the association with adult overweight: AOR for each 100-g increase was 1.28 (1.08-1.52) [adjusted for sex, birth weight, type of formula, age at follow-up, maternal andamp; paternal weight status, income] Weight gain during the first week of life ranged from 0 to 400 g


Infant feeding, plasma insulin & weight gain: Infant feeding, plasma insulin andamp; weight gain Formula-fed infants have higher plasma insulin levels and prolonged insulin response at 6 d of age (Lucas et al., 1981) Higher insulin levels stimulate greater fat deposition, and have been associated with subsequent  weight gain andamp; obesity in Pima Indian children 5-9 y of age (Odeleye et al., 1997)


Infant feeding and plasma leptin: Infant feeding and plasma leptin Plasma leptin is a key regulator of appetite and body fatness Breastfeeding may affect leptin levels during infancy and later in life Early diet of preterm infants is associated with leptin concentration at 13-16 y of age (Singhal et al., 2002)


Ratio of leptin concentration to fat mass at 13-16 y of age, by tertile of human milk intake by preterm infants in early life (median + 95% CI, n=191, p = 0.006; Singhal et al., 2002): Ratio of leptin concentration to fat mass at 13-16 y of age, by tertile of human milk intake by preterm infants in early life (median + 95% CI, n=191, p = 0.006; Singhal et al., 2002)


Infant feeding and plasma leptin:postulated mechanism (Singhal et al., 2002): Infant feeding and plasma leptin: postulated mechanism (Singhal et al., 2002) Greater body fatness during infancy 'programs' the leptin-dependent feedback loop to be less sensitive to leptin later in life (i.e. greater leptin resistance) Greater leptin resistance contributes to overeating and obesity In rats, overfeeding before weaning leads to overweight and leptin resistance in later life (Plagemann et al., 1999)


Early protein intake and subsequent body fatness: Early protein intake and subsequent body fatness Formula-fed infants consume 66-70% more protein than breastfed infants at 3-6 mo; by 12 mo, intakes may be 5-6 times the requirement High protein intake stimulates higher insulin secretion  adipose tissue deposition Association between high protein intake in early life and overweight in childhood reported by Rolland-Cachera et al. (1995) and Scaglioni et al. (2000), but not by Dorosty et al. (2000)


Residual confounding?: Residual confounding? Child feeding practices andamp; parental control over feeding Mothers who breastfed for andgt; 12 mo reported lower levels of control over feeding at 18 mo (Fisher et al., 2000) Duration of BF associated with less restrictive behavior regarding child feeding at 1 year. Compared to FF mothers, restrictive behavior much less likely among mothers who EBF for 6 mo [OR 0.27] (Taveras et al., 2004) Highly controlling feeding practices may interfere with child’s ability to self-regulate energy intake (Birch et al., 2003)


Residual confounding? (cont): Residual confounding? (cont) Physical activity Breastfeeding associated with healthier lifestyle, greater physical activity? Some studies controlled for physical activity and results were still significant


Residual confounding? Analysis of sibling pairs: Residual confounding? Analysis of sibling pairs Nelson et al. Epidemiology 2005;16:247-53. In full cohort, odds of being overweight decreased as BF duration increased, at least among girls In sibling pairs, no evidence of BF effect Adjusted for age, sex, birth order and LBW status Did not have data on exclusivity of BF Gillman et al. Epidemiology 2006;17:112-114. N=5614 siblings 9-14 y. Compared overweight in sibs BF longer than mean for sibship with sibs BF shorter than mean Sibs who were BF longer (mean diff 3.7 mo) had lower OR for overweight: 0.94 for each 3.7 mo increase in BF duration OR for within-family analysis close to overall estimate, suggesting little residual confounding


Summary of BF & obesity studies: Summary of BF andamp; obesity studies 17 of the 21 studies showed an association between breastfeeding and a lower risk of obesity All of the studies that took into account the exclusivity of BF showed a significant association 13 of the 16 studies that controlled for maternal BMI showed a significant association In meta-analysis, duration of BF showed a dose-response relationship with risk of child obesity. Lowest risk was for andgt; 6 mo of BF


Explanations?: Explanations? Not solely due to lower fatness during first 2 y Potential mechanisms include: Learned self-regulation of energy intake Metabolic programming due to differences in milk composition, protein intake, fatness and/or rate of weight gain in early life Residual confounding, e.g. by child feeding practices, physical activity


Clinical & public health implications: Clinical andamp; public health implications Provides further evidence to promote breastfeeding However, role of breastfeeding is probably small compared to other factors such as parental overweight, dietary practices and physical activity Relationship less evident in African-Americans and Hispanics – not clear why