Editorial Commentary

Birth Weight and Hypertension

David J.P. Barker

here is substantial literature showing that birth weight

is associated with differences in blood pressure within
the reference range. These differences are found in
children and adults, but they tend to be small. A 1-kg increase
in birth weight is associated with 3 mm Hg lowering in
systolic pressure. This association is one of the associations
with low birth weight that led to the fetal origins hypothesis, which proposes that the different forms of cardiovascular disease and type 2 diabetes originate through undernutrition during fetal life and infancy.1 Undernutrition at this time
permanently changes the bodys structure and physiology.
Like other living things humans are plastic during development, and their form and function is the product of the genes
acquired at conception and of environmental influences, importantly nutrition, that regulate gene expression.
Huxley et al2 recently reviewed 103 published studies on
the association between birth weight and blood pressure.
They concluded that the association was weaker in large studies than in small ones and was, therefore, an artifact, the
product of a bias by which small studies are published only if
they show large effects. The Lancet2 published the review
under the title Unraveling the Fetal Origins Hypothesis.
This was inappropriate, for a number of reasons.
A central issue in understanding the intrauterine origins of
hypertension is reconciling the small effects of birth weight
on blood pressure within the reference range with its large
effects on the risk of hypertension requiring medication.3 One
possibility is that lesions that accompany poor fetal growth
and tend to elevate blood pressure have small effects on blood
pressure within the reference range, because counterregulating mechanisms are able to maintain normal levels. As the
lesions progress with ageing, however, these mechanisms are
no longer able to maintain homeostasis, and blood pressure
rises. There may be a cycle of rise in blood pressure resulting
in further progression of the lesions and further rise in blood
pressure. Evidence to support the development of self-perpetuating cycles comes from a study of elderly people in
Helsinki, Finland, among whom the effect of birth weight on
blood pressure was confined to these being treated for
hypertension.4 An inference is that by the time they reached
old age, most of the people with lesions acquired in utero had
developed clinical hypertension.
The opinions expressed in this editorial are not necessarily those of the
editors or of the American Heart Association.
From the Oregon Health and Science University, Heart Research
Center, Portland, Ore.
Correspondence to David J.P. Barker, Oregon Health and Science
University, Heart Research Center, 3181 SW Sam Jackson Park Rd,
L-464, Portland, OR 97201-3098. E-mail djpb@mrc.soton.ac.uk
(Hypertension. 2006;48:357-358.)
2006 American Heart Association, Inc.
Hypertension is available at http://www.hypertensionaha.org
DOI: 10.1161/01.HYP.0000236552.04251.42

There is evidence in both humans and animals that one of

the lesions acquired in utero is a reduced number of nephrons.5,6
Nephron number is calibrated to body size at the time of
nephrogenesis, which occurs at 34 weeks of gestation, and
people who had low birth weight have fewer nephrons. A
reduced nephron number leads to glomerular hyperfiltration and,
over time, to sclerosis and loss of glomerulae.
The conclusions drawn by Huxley et al2 were also unhelpful because birth weight does not have an effect on blood
pressure that is best estimated by pooling the results of all of
the published studies. Rather, the effects of the intrauterine
environment on disease are conditioned by later events. In
Helsinki, and in other studies, the effects of low birth weight
on blood pressure and hypertension are amplified by rapid
weight gain in childhood.3 This may reflect an increase in
glomerular hyperfiltration, and the consequent long-term damage, which results from the greater excretory load imposed on
the kidney by a large body. In Helsinki, birth weight also has
a greater effect on hypertension among people born into poor
families.7 This and other findings indicate that our understanding of the early origins of hypertension will require
biological insights into the long-term effects of different
paths of development, in which the effects of low birth weight
are modified by subsequent growth and by the postnatal
environment.
In the current issue of Hypertension, Davies et al8 return to
the statistical issues raised by the Lancet. In a study of 25 874
subjects they find that the association between low birth
weight and raised blood pressure is robust. They review the
literature and conclude that the weaker associations in large
studies are the result of error, generated by birth weights that
are recalled rather than recorded, and by inaccurate measurement of blood pressure in large studies carried out as part of
routine medical examinations rather than for the purposes of
research. Davies et al8 also confirm that the inverse association between low birth weight and blood pressure amplifies
with age. This is consistent with the existence of self-perpetuating cycles of rising blood pressure and renal damage.4
The fetal origins hypothesis will not be unraveled by statistical sleight of hand. Rather, we can look forward to a rapid
expansion in our knowledge of how blood pressure homeostasis is established before birth and how it may be compromised
by events in utero and during early postnatal life.

Disclosures
None.

References
1. Barker DJP. Fetal origins of coronary heart disease. Br Med J. 1995;311:
171174.
2. Huxley R, Neil A, Collins R. Unravelling the fetal origins hypothesis: is
there really an inverse association between birthweight and subsequent
blood pressure? Lancet. 2002;360:659 665.

357
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Hypertension

September 2006

3. Barker DJP, Eriksson JG, Forsen T, Osmond C. Fetal origins of adult disease:
strength of effects and biological basis. Int J Epidemiol. 2002;31:12351239.
4. Yliharsila H, Eriksson JG, Forsen T, Kajante E, Osmond C, Barker DJP.
Self perpetuating effects of birth size on blood pressure levels in elderly
people. Hypertension. 2003;41:446 450.
5. Brenner BM, Chertow GM. Congenital oligonephropathy: an inborn cause
of adult hypertension and progressive renal injury? Curr Opin Nephrol
Hypertens. 1993;2:691 695.

6. Ingelfinger JR. Is microanatomy destiny? N Engl J Med. 2003;348:

99 100.
7. Barker DJP, ForsenT, Eriksson JG, Osmond C. Growth and living conditions in childhood and hypertension in adult life: a longitudinal study.
J Hypertens. 2002;20:19511956.
8. Davies AA, Davey Smith G, May MT, Ben-Shlomo Y. Association
between birth weight and blood pressure is robust, amplifies with age, and
may be underestimated. Hypertension. 2006;48:431 436.

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Birth Weight and Hypertension

David J.P. Barker
Hypertension. 2006;48:357-358; originally published online July 31, 2006;
doi: 10.1161/01.HYP.0000236552.04251.42
Hypertension is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright 2006 American Heart Association, Inc. All rights reserved.
Print ISSN: 0194-911X. Online ISSN: 1524-4563

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