Pediatric Nutrition in Practice

Early Nutrition and Long-Term Health 73

1

preventive medicine will be redefined based on
the evidence arising from the early origins of the
adult disease hypothesis. This includes the major
present causes of global death and disability [obe-
sity, diabetes, hypertension, coronary heart dis-
ease, cerebrovascular disease and several forms of
cancer (related to rates and timing of growth and
hormonal maturation as well as to obesity)].
The concept of early metabolic programming
of long-term health is supported by physiological,
epidemiological and clinical research [1–3]. Nu-
tritional and metabolic factors acting during sen-
sitive time periods of developmental plasticity
before and after childbirth have been shown to
modulate cytogenesis, organogenesis and meta-
bolic and endocrine response as well as the epi-
genetic regulation of gene expression; thereby,
they can induce metabolic programming of life-
long health and disease risk ( fig. 1 ). Specific
mechanisms by which later disease is pro-
grammed are explored and the precise nutrition-
al conditions that contribute to these processes
are being established. The current key hypothe-
ses ( fig. 2 ) on the early nutritional programming
of later adiposity, diabetes and associated non-
communicable diseases include
(1) the fuel-mediated in utero hypothesis,

(2) the accelerated postnatal growth hypothesis

and

(3) the mismatch hypothesis.

Randomized controlled trials in pregnancy

and infancy now provide strong evidence for rel-

evant programming effects of early nutrition in

humans. For example, in the LIMIT randomized

controlled trial, 2,212 pregnant overweight wom-

en (BMI ≥ 25) in South Australia were random-

ized to standard care in pregnancy or to targeted

counselling with 3 face-to-face meetings and 3

telephone contacts to consolidate the messages

[7]. The key focus was on encouraging a balanced

diet with limited intakes of refined carbohydrates

and saturated fatty acids as well as increased

physical activity. While there was no significant

effect on the primary outcome, infants born large

for gestational age (RR 0.90), there was a marked

reduction in the risk of a high birth weight >4,000

g (RR 0.81; p = 0.03; number needed to treat: 28).

This is important because the systematic review

of data from observational studies demonstrated

that a birth weight >4,000 g predicts a 2-fold in-

crease in the risk of obesity in adulthood [8].

These findings demonstrate the large preventive

potential of interventions in pregnancy and

should stimulate further research in this area.

Sensitive time

windows of

pre- and postnatal

development

Cy togenesis

Organogenesis

Metabolism

Endocrine

Gene

expression

Metabolic

modulators

Early metabolic

programming of

lifelong health

Fig. 1. Nutritional and metabolic fac-
tors during sensitive time periods of
developmental plasticity before and
after childbirth modulate cytogen-
esis, organogenesis and metabolic
and endocrine response as well as
the epigenetic regulation of gene ex-
pression; thereby, they can induce
metabolic programming of lifelong
health and disease risk. Reproduced
from Koletzko et al. [3] , with permis-
sion.

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