Comment
Early nutrition and adult outcomes: pieces of the puzzle
The association between nutrition in early life and
long-term health has been of interest for decades.
Since the articulation of the fetal origins hypothesis by
David Barker and colleagues,1 there has been debate
about the implications of fetal undernutrition and
early childhood growth on outcomes of importance
in adult health and risks of chronic diseases. Both
epidemiological and animal studies have shown that
the risk of metabolic syndrome is signicantly increased
after exposure to suboptimum nutrition during crucial
periods of development.1 The importance of these
ndings greatly increased after reports about the global
burden of non-communicable diseases and risk factors
were published in December, 2012.2
Evidence for the importance of early nutrition for
adult outcomes was derived initially from obser-
vational cohort studies3 and was rearmed by analysis
of outcome data from several cohort studies in 2008.4
This analysis4 was focused on a meta-analysis of
coecients from dierent sites: birthweight, weight
and length Z scores, and stunting at age 2 years.
In The Lancet, Linda Adair and colleagues5 report
ndings from a study in which they pooled data
from ve birth cohorts and investigated how linear
growth and relative weight gain in several age ranges
aected adult outcomes. They report that higher
birthweight was associated with an adult body-mass
index of greater than 25 kg/m (odds ratio 128,
95% CI 121135) and a reduced likelihood of short
stature (049, 044054) and of not completing
secondary school (082, 078087). Faster linear
growth was also strongly associated with reduced
likelihood of short adult stature (age 2 years: 023,
020052; mid-childhood 039, 036043) and of
not completing secondary school (age 2 years: 074,
067078; mid-childhood 087, 083092). Faster
relative weight gain was associated with an increased
risk of adult overweight (age 2 years: 151, 143160;
mid-childhood 176, 169191) and elevated blood
pressure (age 2 years: 107, 101113; mid-childhood:
122, 115130).
Notwithstanding the key ndings, several limitations
of this pooled analysis should be recognised. The
authors had to make do with disparate information
about socioeconomic status and income, and impute
www.thelancet.com Published online March 28, 2013 http://dx.doi.org/10.1016/S0140-6736(13)60716-3
some information that was missing. Although they Published Online
March 28, 2013
adjusted for maternal education and socioeconomic http://dx.doi.org/10.1016/
status (largely assets rather than income), other S0140-6736(13)60716-3
potential confounding factors (eg, household and See Online/Articles
http://dx.doi.org/10.1016/
learning environment) could not be assessed in relation S0140-6736(13)60103-8
to attained schooling. Several additional limitations
preclude rm conclusions. Little or no information was
available about maternal nutrition and micronutrient
status. Additionally, Adair and colleagues do not
report any outcomes related to intrauterine growth
retardation or gestational age at birth, and merely
report association with birthweight, which might
be oversimplied. Being small for gestational age at
term, and especially preterm, has now been recognised
as a major risk factor for excess newborn and infant
mortality6 and accounts for a substantial proportion of
child stunting (unpublished). Prematurity is associated
with increased risks of metabolic syndromes in later life.7
Potential variations in body composition of newborn
babies might not be captured by mere measurement of
birthweight or size. So-called thin-fat infantsie, small
newborn babies that have elevated body fat content
have been described8 and could be associated with
increased risks of insulin resistance in childhood.9
These limitations aside, Adair and colleagues nd-
ings5 are some of the most important from existing
cohorts linking early childhood nutritionespecially
birthweight and improved patterns of linear growth
with long-term outcomes. They have clear implications
Andrew Aitchison/In Pictures/Corbis
1
 Comment
for public health policy and nutrition interventions. As
shown by an analysis of evidence-based interventions,10
a focus on improvements in nutrition in pregnancy
and linear growth in the rst 2 years of life could lead
to substantial reductions in stunting and improved
survival. These improvements form the basis for the
emphasis on the rst 1000 days of life, which has
been used eectively to scale up nutrition activities.11
However, this tenet could be too simplistic, because
it focuses on care during pregnancy and ignores the
vital contribution of maternal health and nutrition
in the periods before and just after conception to
intrauterine and postnatal growth. Evidence supports
an association between micronutrient supplemen-
tation around the time of conception and DNA
methylation12 and increased methylation of the IGF2
genes in childhood,13 indicating that these factors
could aect linear growth postnatally. Although
Adair and colleagues analysis of birth outcomes in
the international cohorts does not shed light on the
importance of maternal health and nutrition before
conception, these factors might be just as important as
postnatal factors and should be investigated.
What is the way forward? Although the evidence
emerging from observational studies such as Adair
and colleagues is important for policy, well designed
prospective studies with appropriate interventions
and follow-up are clearly needed. The outcomes should
include elements of child development, education,
employment, and earnings, which would allow improved
estimation of eect on human capital. Although
expensive and dicult to organise and implement, such
cohort studies are a crucial investment for the future
and, in view of the interest in human development in the
post-2015 era, should be prioritised for funding.
2 www.thelancet.com Published online March 28, 2013 http://dx.doi.org/10.1016/S0140-6736(13)60716-3
Zulqar A Bhutta
Division of Women and Child Health, Aga Khan University,
Karachi 74800, Pakistan
zulqar.bhutta@aku.edu
I declare that I have no conicts of interest.
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2 Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden
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in 21 regions, 19902010: a systematic analysis for the Global Burden of
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4 Victora CG, Adair L, Fall C, et al, for the Maternal and Child Undernutrition
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5 Adair LS, Fall CHD, Osmond C, et al, for the COHORTS group. Associations
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ve birth cohort studies. Lancet 2013; published online March 28. http://
dx.doi.org/10.1016/S0140-6736(13)60103-8.
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9 Lakshmi S, Metcalf B, Joglekar C, Yajnik CS, Fall CH, Wilkin TJ. Dierences in
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10 Bhutta ZA, Ahmed T, Black RE, et al, for the Maternal and Child
Undernutrition Study Group. What works? Interventions for maternal and
child undernutrition and survival. Lancet 2008; 371: 41740.
11 Save The Children. Nutrition in the rst 1000 days: state of the worlds
mothers 2012. May, 2012. http://www.savethechildren.ca/document.
doc?id=195 (accessed March 21, 2013).
12 Cooper WN, Khulan B, Owens S, et al. DNA methylation proling at
imprinted loci after periconceptional micronutrient supplementation in
humans: results of a pilot randomized controlled trial. FASEB J 2012;
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13 Steegers-Theunissen RP, Obermann-Borst SA, Kremer D, et al.
Periconceptional maternal folic acid use of 400 microg per day is related to
increased methylation of the IGF2 gene in the very young child. PLoS One
2009; 4: e7845.