Pediatric Nutrition in Practice

Early Nutrition and Long-Term Health 75

1

A protective effect of breastfeeding was also
found in a number of studies in other popula-
tions, whereas others found no benefit. System-
atic reviews and meta-analyses of cohort, case-
control or cross-sectional studies concluded that
breastfeeding provides a modest but consistent
protective effect [10]. However, these conclusions
are only based on observational data, because
healthy infants cannot be assigned to breastfeed-
ing on a randomized basis, and, hence, residual
confounding cannot be excluded with certainty.
The only published cluster randomized trial on
breastfeeding promotion found no effects on lat-
er obesity, but basically all infants participating
in this trial in Belarus had been breastfed, and the
intervention only inf luenced the duration of
breastfeeding [11]. Thus, this study does not pro-
vide sufficient statistical power to allow conclu-
sions on the effects of early breastfeeding versus
formula feeding on later obesity [1 2].
Various hypotheses have been raised on po-
tential causes for a protective effect of breastfeed-
ing. The establishment of a biological plausibility
and the elucidation of mechanisms which medi-
ate the protective effect of breastfeeding would
lend support to a causal effect of breastfeeding.
We proposed t hat its protective ef fect is at least in
part due to lower growth rates in the first year as
compared to formula-fed infants and is mediated
by a lower protein content of human milk relative
to formula.
Populations of breastfed infants show higher
weight and length gains during the first year of

life than formula-fed infants, and more rapid

weight gain in infancy and the second year of life

predisposes to childhood overweight and obesity

[10]. These growth differences between breastfed

and formula-fed populations are most likely due

to differences in metabolizable substrate intakes.

Infants at ages of 3–12 months have a 10–18%

higher energ y intake per kilogram body weight if

fed formula as compared to breastfed infants.

Even larger is the difference in protein intake per

k i log r a m b o dy we i g ht , w h ic h i s 55 – 8 0 % h i g he r i n

formula-fed than in breastfed infants. In epide-

miological studies, high protein intakes in early

childhood, but not the intakes of energy, fat or

carbohydrate, were significantly related to an

early adiposity rebound and to a high childhood

BMI, corrected for parental BMI. Thus, a high

protein intake with infant formula in excess of

metabolic requirements might predispose to an

increased obesity risk in later life, a concept re-

ferred to as the ‘early protein hy pothesis’. This is-

sue has been studied in a large randomized clini-

cal trial with allocation of healthy term infants to

formulae with higher and lower protein contents

(the European Childhood Obesity Project). The

study showed that a lowering of the protein sup-

ply from infant and follow-on formulae closer

to levels provided with breast milk normalizes

growth up to the age of 2 years relative to the

growth of breastfed populations [13]. Further fol-

low-up of the participating children at the age of

6 years demonstrated a very marked, lasting ef-

fect of reducing the protein content of infant and

Ta b l e 1. Obesity prevalence and RR at 6 years of age in children randomized to receive formula with lower or higher
protein content in infancy as well as the prevalence in a non-randomized reference group of children breastfed in
infancy

Low protein
content

High protein

content

Unadjusted RR,

OR (95% CI)

p Adjusted RR,

OR (95% CI)

p Breastfed

group

4.4% 10% 2.43 (1.12 – 5.27) 0.064 2.87 (1.22 – 6.75) 0.016 2.9%

From Weber et al. [14].

Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 72–77
DOI: 10.1159/000369235