Transcript Does Breastfeeding Protect Against Childhood Obesity?

Breastfeeding and risk of child
obesity
Kathryn G. Dewey, PhD
Program in International and Community Nutrition
University of California, Davis
Study selection criteria
N > 100 per feeding group
 Age at follow-up > 3 y
 Outcome = % overweight or obese

Studies in preschool children
Author, year,
site
N, age
Feeding groups
Outcomes
Results
[*p < 0.05]
Armstrong,
32,200
2002, Scotland 3-4 y
EBF vs. EFF at 6-8
wk
BMI > 95th
BMI > 98th
AOR 0.72*
AOR 0.70*
Bogen, 2004,
USA1
73,458
4y
BF < 8 wk, 8-15 wk,
16-26 wk, > 26 wk
(+/- concurrent FF)
BMI > 95th
AOR 0.71 for
16-26 wk w/o
FF*
Hediger, 2001,
USA
2,685
3-5 y
Ever BF vs. EFF
(+ dur. full BF)
BMI 85-94th
BMI > 95th
AOR 0.63*
AOR 0.84
GrummerStrawn, 2004,
USA
177,304 BF < 1, 1-3, 3-6, 6-12, BMI > 95th
(12,587) or > 12 mo, vs. EFF
4y
AOR for White,
non-Hisp
0.70* (6-12 mo)
0.49* (> 12 mo)
O’Callaghan,
3,909
1997, Australia 5 y
BF duration
BMI 85-94th
BMI > 95th
NS
Burke, 2005,
Australia
EFF vs. BF < 4 mo, 58, 9-12, > 12 mo
BMI > 95th
Highest risk in
BF < 4 mo*
2,087
1-8 y
1Only among white children whose mothers did not smoke
Studies in school-aged children
Author, year, site
N, age Feeding groups Outcomes
Results
Von Kries, 1999,
Germany
9,357
5-6 y
Ever BF vs. EFF
(+ dur. EBF)
BMI > 90th
BMI > 97th
AOR 0.79*
AOR 0.75*
Wadsworth, 1999,
UK
3,731
6y
Ever BF vs. EFF
(+ dur. BF)
BMI > 90th
BMI > 97th
RR 0.95
RR 0.88
Bergmann, 2003,
Germany
480
6y
BF > or < 3 mo
BMI > 90th
BMI > 97th
AOR 0.53*
AOR 0.46*
Reilly, 2005,
UK
8,234
7y
EBF > 2 mo or <
2 mo, vs. EFF
BMI > 95th
Lower risk if
EBF*, if nonsmoking mother
Toschke, 2002,
Czech Republic
33,768
6-14 y
Ever BF vs. EFF,
(+ duration BF)
BMI > 90th
BMI > 97th
AOR 0.80*
AOR 0.80*
Liese, 2001,
Germany
2,108
9-10 y
Ever BF vs. EFF
(+dur. BF, EBF)
BMI > 90th
AOR 0.66*
Gillman, 2001,
USA
15,341
9-14 y
Pred BF vs. Pred
FF 0-6 mo
BMI > 95th
AOR 0.78*
Studies in older adolescents
Author, year, site N, age
Feeding groups Outcomes
Kvaavik, 2005,
Norway
635
13 y
BF > 3 mo vs.
EFF
BMI > 95th
AOR 0.15*
Kramer, 1981,
Canada
427
12-18y
Ever BF vs. EFF
(+dur. full BF)
> 120% median
weight for ht
RR 0.31*
Tulldahl, 1999,
Sweden
781
17-18y
EBF > vs. < 2 mo
BMI > 85th
RR 0.70*
Poulton, 2001,
New Zealand
1,037
3-26 y
BF > 6 mo vs.
EFF
BMI > 25 kg/m2 AOR 0.25-1.01
Li, 2003,
UK
2,631
4-18 y
Duration BF vs.
BF < 1 wk
BMI > 95th
AOR 0.68-2.02
Victora, 2003,
Brazil
2,250
Duration Pred BF
18 y (♂)
BMI > 85th
skinfolds > 90th
Significant
linear trend
Nelson, 2005,
USA
11,998
850 sib
pairs
12-21 y
BMI > 85th
AOR 0.78* (F)
AOR 0.83 (M)
NS for sib pairs
BF > 9 mo vs.
EFF
Results
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)
31.5
35
30
25
20
% Overweight
15
10
5
0
6.0
never
<4 mo
>4 mo
Breast-feeding (months)
> 30
25-29
Maternal
< 25
BMI
Breastfeeding and childhood obesity – a
systematic review. Arenz et al. Intl J Obes, 2004;
28:1247-56.
O'Callaghan 1997
Bergmann 2003
Hediger 2001
Li 2003
Poulton 2001
von Kries 1999
Liese 2001
Toschke 2001
Gillman 2001
Meta-analysis
0
AOR 0.78 (0.71, 0.85)
Source: Arenz et al. Intl J Obes, 2004
1
Adjusted odds-ratio
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.
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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 & 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 > 2 mo
 OR = 0.89 (0.86-0.91) for any BF duration
Bergmann et al. (Germany)
N=480; BMI at 0-6 y
Percentage of children > 90th percentile
Poulton & 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 > 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
(> 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
Bogen
Grummer-Strawn
Von Kries
Toschke
Liese
Gillman
Poulton (trend)
Nelson (in girls)
No
Hediger
O-Callaghan
Wadsworth
Li
Victora
Burke
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
< 1 mo
1.00
1-3 mo
0.81*
4-6 mo
0.76*
7-9 mo
0.67*
> 9 mo
0.68*
* Significantly different from reference group. [No control for
potential confounders.]
Does exclusivity of
breastfeeding matter?
Bogen et al. Obesity
Research 2004;12:15271535
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]
BF duration
Never
< 8 wk
8-15 wk w/ FF
8-15 wk w/o FF
16-26 wk w/ FF
16-26 wk w/o FF
> 26 wk w/ FF
> 26 wk w/o FF
AOR
1.00
0.97
0.84
0.80
0.86
0.71*
0.70*
0.55*
* p < 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
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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

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
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This may lead to later differences in ability to selfregulate energy intake
Infant self-regulation of breast milk intake
K.G. Dewey & B. Lonnerdal
Acta Paediatr Scand 1986; 75: 893-8
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18 exclusively breastfeeding mothers stimulated
milk supply by daily expression of extra milk for 2
wk. All but 4 increased milk volume by > 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
Milk Intake (ml/d)
Differences in milk intake between BF and
FF infants increase between 1 and 5 mo
1200
1100
1000
900
800
700
600
b
b
b
a
a
1 mo
b
c
b
a
a
3 mo
Age (mo)
Dewey et al., EB 2004
b,c
5 mo
BF
FF-C
FF-MP
FF-LP
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?

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

N=19,397 children born 1959-65

Outcome: BMI > 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
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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.
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N= 653 formula-fed infants, measured frequently
during infancy & 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 & paternal weight
status, income]
Weight gain during the first week of life ranged
from 0 to 400 g
Infant feeding, plasma insulin & 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 & obesity in Pima
Indian children 5-9 y of age (Odeleye et al., 1997)
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
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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 1316 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)
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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

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?

Child feeding practices & parental control over
feeding
 Mothers who breastfed for > 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)

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
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
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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 doseresponse relationship with risk of child obesity.
Lowest risk was for > 6 mo of BF
Explanations?
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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
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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