DOI:10.1111/j.1549-8719.2011.00089.
Intrauterine Growth Restriction and Developmental
Programming of the Metabolic Syndrome: A Critical
Appraisal
UTA NEITZKE, THOMAS HARDER, AND ANDREAS PLAGEMANN
Clinic of Obstetrics, Division of Experimental Obstetrics, Charité-University Medicine Berlin, Berlin, Germany
Address for correspondence: Professor Andreas Plagemann, MD, Clinic of Obstetrics, Division of Experimental Obstetrics, Charité-University
Medicine Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail: andreas.plagemann@charite.de
Received14 September 2010; accepted 18 January 2011.
ABSTRACT
According to the ‘‘small baby syndrome hypothesis,’’ low
birthweight and intrauterine growth restriction (IUGR) occurring
in westernized countries mainly through altered placental flow,
have been linked to increased metabolic syndrome risk in later
life. Independency and causal mechanisms of this
phenomenological association are a matter of controversy. By
means of epidemiological as well as experimental methods, using
meta-analyses and different rodent models of pre- and ⁄ or
neonatal malnutrition and altered placental flow (uterine artery
ligation; Lig), we systematically addressed the phenomenon. Our
data and systematic literature analysis revealed that neither
epidemiological nor experimental evidence seems to exist linking
prenatal underfeeding, low birthweight, IUGR, or decreased
placental flow in rats (Lig-model) as independent risk factors
to increased metabolic syndrome risk in later life. Rather, pre-
and ⁄ or neonatal overfeeding, elevated birthweight, rapid
neonatal weight gain, and especially increased adiposity during
Please cite this paper as: Neitzke, Harder, and Plagemann (2011). Intrauterine Growth Restriction and Developmental Programming of the Metabolic
Syndrome: A Critical Appraisal. Microcirculation 18(4), 304–311.
INTRODUCTION
For about 20 years, an association between low birthweight
and higher risk of developing cardiovascular diseases and
symptoms of the metabolic syndrome at adult age has been
frequently discussed and has gained widespread attention
as the so-called fetal origins hypothesis on a ‘‘small baby
syndrome’’ [3,16–18]. In a cohort of men and women born
between 1920 and 1943 in Hertfordshire and Preston, UK,
the groups of C.N. Hales and D.J.P. Barker observed an
increasing risk of coronary heart disease, hypertension, and
metabolic syndrome with falling birthweight [2–4,18]. This
phenomenological association was confirmed in a consider-
able number of epidemiological studies. In newborns with
304
Invited Review
critical periods of perinatal life may increase long-term risks.
Perinatally acquired microstructural and epigenomic alterations
in regulatory systems of metabolism and body weight seem to
be critical, leading to a cardiometabolic risk disposition
throughout life. While experimental data in Lig-offspring seem
to be considerably biased, prenatal stress and postnatal
overfeeding ⁄ rapid neonatal weight gain might be causally linked
to a long-term deleterious outcome in growth restricted
newborns. From a clinical point of view, prevention of causes of
IUGR, as well as avoidance of perinatal overnourishment, might
be prophylactic approaches to avoid perinatal programming of
cardiometabolic risks.
Key words: low birthweight, bilateral uterine artery ligation,
animal models, meta-analysis, small baby syndrome
Abbreviations used : AGA, appropriate for gestational age; CI,
confidence interval; IUGR, intrauterine growth restriction; LP, low
protein; NL, normal litters; OR, odds ratio; SGA, small for
gestational age; SL, small litters.
a low birthweight, a higher risk of impaired glucose toler-
ance and diabetes [11,13,28,30,45], and cardiovascular
diseases including hypertension and stroke at adult age, has
been demonstrated [8,27,33,46,49,51].
Despite the overwhelming number of studies and epide-
miological data on the ‘‘small baby syndrome,’’ mecha-
nisms which underly these associations are still unclear. As
the prevalence of both IUGR and the metabolic syndrome
are still increasing, research on mechanisms is urgently
needed to allow the development and implementation of
prevention strategies.
During recent years, our group has used two major
approaches to explore the relationships between IUGR, low
birthweight, and later risk of diseases: first, we performed a
ª 2011 John Wiley & Sons Ltd, Microcirculation, 18, 304–311
 Intrauterine Growth Restriction and Developmental Programming
series of systematic reviews and meta-analyses on the pub-
lished evidence on these topics. Second, we used animal
experiments to verify potential causal mechanisms and rele-
vant exposures.
SYSTEMATIC REVIEWS AND META-
ANALYSES
As already mentioned, low birthweight has been widely
suggested to lead to an increased risk of developing the
metabolic syndrome at adult age. However, it has been
long known that overweight and obesity play a key role in
the pathogenesis of the metabolic syndrome and its main
components, such as hyperinsulinemia, insulin resistance,
and hyperglycemia. Consequently, one would expect that
low birthweight is also associated with an increased risk of
overweight during later life. However, this is not the case.
In a systematic review of the published literature analyzing
a total of 35 studies from 16 countries which included data
from 980,450 participants, we found that 89% of the pub-
lished studies showed a linear positive relationship between
birthweight and later risk of overweight, that is, the higher
the birthweight was, the higher was the risk of overweight
[24]. In only 8% of the studies was a U-shaped relationship
observed, with both high and low birthweight being associ-
ated with increased overweight risk. Notably, in none of the
so-far published studies was a linear inverse relationship
found, as it has often been claimed to exist in the context
of the ‘‘small baby syndrome’’ (Figure 1).
A U-shaped relationship has also been observed in our
meta-analysis on the association between birthweight and
risk of type 2 diabetes. Compared with normal birthweight
(2,500–3,999 g), low birthweight (<2,500 g; OR: 1.47, 95%
CI: 1.26–1.72) as well as high birthweight (>4,000 g; OR:
1.36, 95% CI: 1.07–1.73) were related to an increased risk
of developing type 2 diabetes later in life. Both meta-
regression analysis and categorical analysis confirmed the
Figure 1. A systematic review of the published literature reveals that in
the majority of studies, birthweight is positively related to risk of
overweight in later life, whereas no study has so far shown a linear
inverse relationship [24].
ª 2011 John Wiley & Sons Ltd, Microcirculation, 18, 304–311
existence of a U-shaped relationship between birthweight
and risk of type 2 diabetes. In detailed examinations of the
data set, no indication for publication bias or other forms
of bias were found [22,41].
In the context of the ‘‘small baby syndrome hypothesis,’’
it has also been suggested that low birthweight and ⁄ or
IUGR might be related to an increased risk of type 1 diabe-
tes during childhood. In a recent meta-analysis, we
explored the current evidence on this issue and found that
low birthweight was rather followed by a nonsignificantly
decreased risk of type 1 diabetes in later life (OR: 0.82,
95% CI: 0.54–1.23). In contrast, high birthweight was asso-
ciated with a small, but significant increase in risk (OR:
1.17, 95% CI: 1.09–1.26) [23].
While much of the attention has focused during recent
years on metabolic diseases, it might be of equal impor-
tance to know whether low birthweight and ⁄ or IUGR are
linked to other groups of chronic, life-threatening diseases,
like certain types of cancer. We therefore performed two
further meta-analyses, which aimed to investigate the rela-
tionship between birthweight and tumors of the central
and peripheral nervous system. For astrocytoma, the most
common solid tumor in childhood, we observed that low
birthweight was associated with a nonsignificantly
decreased risk (OR: 0.85, 95% CI: 0.58–1.25), whereas high
birthweight was associated with an increased tumor risk
(OR: 1.38, 95% CI: 1.07–1.79). Similarly, for medulloblas-
toma, low birthweight was a nonsignificant risk factor (OR:
1.64, 95% CI: 0.42–6.48), whereas high birthweight was
significantly associated with increased risk (OR: 1.27, 95%
CI: 1.02–1.60) [20]. A U-shaped relationship was observed
in our meta-analysis on birthweight and risk of neuroblas-
toma. For this most common solid tumor in the first year
of life, we found that both low birthweight (OR: 1.24, 95%
CI: 1.0–1.55), as well as high birthweight (OR: 1.19, 95%
CI: 1.04–1.36), was associated with an increased neuroblas-
toma risk [21].
Taken together, the epidemiological data published so
far suggest that low birthweight is not a risk factor for
overweight ⁄ obesity in later life, which would be a logical
precondition to allow a causal relationship between low
birthweight and later development of the metabolic
syndrome and its cardiovascular components. Furthermore,
data also show that the relationship between birthweight
and later risk of type 2 diabetes is not linearly inverse as it
has been claimed by many researchers, but U-shaped: both
low and high birthweight are related to later type 2 diabetes
to a similar degree. Such a U-shaped relationship can also
be found for some types of cancer of the nervous system.
However, epidemiological studies alone are insufficient
to prove causality behind such observed associations, and
cannot elucidate pathophysiological mechanisms. Therefore,
it is necessary to develop and use animal models, which
305
 U. Neitzke et al.
can provide insights into causal relationships as well as
etiopathological mechanisms.
ROLE OF LOW BIRTHWEIGHT PER SE:
ANIMAL MODELS
A number of animal models have been developed during
recent years to reduce birthweight and investigate mecha-
nisms of fetal and perinatal programming according to the
‘‘small baby syndrome hypothesis.’’ Rodent models of mater-
nal malnutrition during pregnancy are among the most often
used models. In these studies, malnutrition is mainly
induced either by feeding an LP diet or by semistarvation
[8,15,26,36]. In both models, offspring show a reduced mean
birthweight as compared with control offspring. However,
despite showing this phenomenological similarity to human
newborns being SGA or having IUGR, in particular, off-
spring of rat dams fed LP diet during pregnancy did not
show the spectrum of metabolic and cardiovascular altera-
tions observed in the epidemiological and clinical studies dis-
cussed above [39]. In particular, these offspring showed a
permanently reduced instead of increased body weight
throughout juvenile and adult age [26,36,39], reduced
instead of increased food intake [38,39], and normal or even
improved, but not impaired glucose tolerance in adulthood
[15,38]. No hyperinsulinemia indicating insulin resistance
but rather a reduced insulin secretion was found [31,38].
Development of metabolic disturbances at juvenile and adult
age could be shown only after dietetic provocation [53], but
even under these circumstances, LP offspring remained
underweight [38]. In studies from our group, LP offspring
also did not develop increased blood pressure [39]. Finally,
B bilateral uterine artery ligation (Lig; black
306
offspring of LP-malnourished dams even had a higher life
expectancy than controls [35].
Moreover, it should be considered that maternal malnutri-
tion during pregnancy is an important problem in develop-
ing countries, whereas IUGR in western industrialized
countries mostly results from decreased placental blood flow,
for example, due to maternal hypertension [14]. Bilateral
uterine artery ligation probably has been the most important
rodent model for many decades to investigate IUGR caused
by placental insufficiency [10]. Initially, Wigglesworth devel-
oped this model with unilateral ligation of the uterine artery
in the last trimester of pregnancy to achieve growth restric-
tion in the offspring [52]. As it has been claimed that uterine
artery ligation will decrease placental flow, this model was
widely used and cited in the literature and has been modified
by many investigators to a bilateral uterine artery ligation to
investigate the consequences of IUGR and causal factors of
the ‘‘small baby syndrome’’ [47].
Our group performed a large-scale experimental investi-
gation of this model with bilateral uterine artery ligation
during the last trimester of pregnancy in rats (Lig). Off-
spring were followed up from birth until weaning on day
21 of life and were compared with offspring of mother rats
with sham ligation during pregnancy [32]. In these experi-
ments, bilateral uterine artery ligation did not lead to
reduced mean birthweight after spontaneous delivery in
rats (Figure 2A). Neither increased prevalence of IUGR nor
neonatal catch-up growth occurred in the offspring.
Instead, Lig caused a reduction in primary litter size and
possibly resulted in survival of the stronger and heavier
fetuses. During follow-up, no differences in body weight
occurred and no data indicating the development of
Figure 2. (A) Neither birthweight (left) nor
body weight at weaning (day 21 of life; right)
differs between offspring of rat dams with
bars) and those of sham-operated rat dams
(ShL; white bars). Data are means ± SD (n).
(B) Evidence of publication bias in studies on
bilateral uterine artery ligation during the
third trimester of rats. The funnel plot (left)
shows an inverse relationship between study
size and effect size (own study: circled), as
compared with a fictitious funnel plot of an
ideal meta-analysis without publication bias
(right) [32].
ª 2011 John Wiley & Sons Ltd, Microcirculation, 18, 304–311
 Intrauterine Growth Restriction and Developmental Programming
increased diabetogenic and ⁄ or adipogenic risk were
apparent in Lig weanlings [32].
To clarify the sources for the discrepancies between our
observations and those reported in the literature by other
groups, we performed a systematic review and meta-analy-
sis of the literature on the model of bilateral uterine artery
ligation in rats [32]. These analyses gave an indication for
severe problems regarding the quality of reporting in the
published studies as well as for the presence of bias.
Remarkably, in none of the 13 studies included in the sys-
tematic review has an increased percentage of growth-
restricted pups been described. Five of the 13 studies
reported an active selection of low-birthweight pups from
primary litters for further investigation. Furthermore, we
found indication for publication bias in the literature on
the model. This means that the birthweight difference
between offspring of rat dams with uterine artery ligation
and sham ligation appeared to be mainly caused by a selec-
tive publication of smaller studies, which used for their
analysis only a few selected pups from the primary litter
with a low birthweight of unknown reason. The funnel
plot, which is an meta-analytic tool for the analysis of pub-
lication bias, appeared strongly asymmetric with a gap at
the bottom right indicating a missing (nonpublication) of
smaller studies with smaller or even positive mean differ-
ences in birthweight between Lig offspring and control
pups (Figure 2B). Our meta-analysis thereby gave a clear
indication that the Lig model does not reproducibly lead to
reduced mean birthweight. The larger the study was, the
smaller was the difference between the investigated groups,
tending toward zero in the largest studies. This tendency
was supported by the results from our own experiments
with a large amount of offspring and a tendency toward
even higher birthweight in surviving Lig pups.
Further problems and sources of bias appeared when
those studies, which conducted investigations on long-term
outcome in Lig offspring, were analyzed. Only five of the
studies used definitely growth-restricted rats for further
investigation. In none of these studies did either rapid neo-
natal weight gain or catch-up growth occur in offspring of
Lig dams [32]. Remarkably, in a recent study, disturbances
in lipid metabolism were found not only in offspring of
rats with uterine artery ligation during pregnancy but also
in those of dams with sham ligation, as compared with off-
spring of untreated control dams [34].
Taken together, bilateral uterine artery ligation during
the last trimester in rats does not reproducibly lead to
IUGR in the spontaneously born offspring. Keeping in
mind the inconclusive results obtained in nutrition-based
models of low birthweight discussed above, one has to con-
sider that there is a general paucity of animal ⁄ rodent models
which convincingly investigate an independent impact of a
low birthweight on subsequent health risks like diabetes,
ª 2011 John Wiley & Sons Ltd, Microcirculation, 18, 304–311
hypertension and symptoms of the metabolic syndrome rel-
evant to humans in the western world.
ROLE OF NEONATAL NUTRITION AND
BODY WEIGHT GAIN IN LOW-
BIRTHWEIGHT BABIES: A ‘‘GENUINE’’
ANIMAL MODEL
For many years, however, our group has suggested that a
causal mechanism underlying an increased risk of meta-
bolic and cardiovascular alterations after low birthweight
might be neonatal overnutrition [9]. In rats, this exposure
can be elegantly mimicked by a slight manipulation during
the early postnatal period. In the so-called ‘‘small litter
(SL)’’ model, reduction in the number of pups in the pri-
mary litter from about 12 to only three pups per nest
results in a surplus of milk for each offspring [1,12]. Addi-
tionally, the composition of the milk is changed toward an
increased fat content [11]. Raising rats in SL results in the
development of a metabolic-syndrome-like phenotype at
juvenile and adult age. These pups show an increased food
intake, permanent overweight with increased fat deposition,
hyperinsulinemia, impaired glucose tolerance, hypertrigly-
ceridemia and an increased systolic blood pressure [42–44].
Using this well-established overnutrition regimen, we
developed a new, genuine rat model of low birthweight
with consecutive neonatal overfeeding. Spontaneously
delivered pups from normal, untreated rat dams were
defined as being SGA if their birthweight was below the
lower limit of the 95% confidence interval of the mean
birthweight of all pups of the same litter and sex. These
SGA pups were randomly distributed among two groups:
one group was overnourished neonatally by raising them in
SL (three pups per nest), whereas the other group was
raised in normal litters of 12 pups per nest. Pups, which
had a birthweight AGA, that is, within the limits of the
95% confidence interval for litter and sex, served as con-
trols [19].
Neonatal overnutrition of SGA pups in SL resulted in an
increased neonatal weight gain. From day 7 of life onwards,
they did not further show a difference in body weight, as
compared with the control AGA pups raised in normal
litters. In contrast, SGA pups raised in ‘‘normal litters’’
caught up in body weight not until day 60 of life. After
day 60 of life, no further differences in body weight were
observed among the three groups. During glucose tolerance
tests at adult age, neonatally overnourished SGA rats
showed significantly increased blood glucose levels at
90 minutes, hyperinsulinemia and a significantly increased
insulin ⁄ glucose-ratio, indicating the development of insulin
resistance. In contrast, no differences in metabolic profile
were found in SGA pups raised in normal litters, as
compared with controls (Figure 3) [19].
307
 U. Neitzke et al.
Figure 3. Rats born small for gestational age (SGA) develop
hyperinsulinemia and insulin resistance only if they were overnourished
neonatally by raising them in small litters (SL). Body weight and
metabolic parameters (blood glucose, plasma insulin, insulin ⁄ blood
glucose ratio (IRI ⁄ BG), leptin) at day 360 day of life in rats with normal
birthweight raised in normal litters (normal nutrition; AGA-in-NL; white
bars; n = 70), as compared with SGA rats raised in NL (normal
nutrition; SGA-in-NL; gray bars; n = 14) or SGA rats overnourished in SL
(SGA-in-SL; black bars; n = 14). Data are means ± SD, shown as
percentage of AGA-in-NL levels. *p < 0.05 (post hoc t-test) [19].
The hypothesis of the ‘‘small baby syndrome’’ implies
that having a low birthweight per se increases the risk of
developing symptoms of the metabolic syndrome. This
relationship could not be confirmed in our experiments at
all. Rather, newborn rats with low birthweight (SGA pups)
showed an increased risk of developing diabetogenic distur-
bances only if they were exposed to neonatal overnutrition,
in tendency even if only ‘‘relative’’ neonatal overfeeding
was provided (SGA-in-NL; Figure 3).
DISCUSSION
It is crucial for the entire discussion on the possible causes
and consequences of low birthweight, SGA and ⁄ or IUGR
that birthweight is understood to be only a crude or proxy
indicator of exposures and conditions during prenatal life.
In that sense, to consider low birthweight per se as a risk
factor for later cardiometabolic diseases appears to be ques-
tionable, at least. Rather, it is likely that particular expo-
sures in utero which cause or go along with low
birthweight might offer a causal link here. In particular,
prenatal stress, smoking during pregnancy, infections, alco-
hol as well as cardiovascular diseases during pregnancy, on
the one hand, may reduce birthweight and, on the other
hand, might lead to rather specific functional disorders,
which in turn are accompanied by an increased cardiomet-
abolic risk. In this context, it is also important to consider
that, in the meanwhile, the results from a number of stud-
ies suggest that maternal undernutrition during pregnancy
is a highly unlikely cause here, at least with respect to west-
ernized countries. This view is also supported by epidemio-
308
logical studies. It is worth noting that, in both of the large
historical geographical association studies on the conse-
quences of maternal undernutrition during pregnancy for
later risk of overweight, metabolic and cardiovascular dis-
eases, the Dutch Famine Study [50] and the Leningrad Siege
Study [48], no impact of gestational undernutrition on
birthweight was observed.
As discussed above in detail, the results from the animal
models appear to be inconclusive because either (a) birth-
weight is not reproducibly reduced, as in the Lig model, or
(b) adipogenic, metabolic and ⁄ or cardiovascular risk is not
reproducibly increased, as in the low-protein model. Fur-
thermore, the most frequently used nonrodent model to
investigate the ‘‘small baby syndrome,’’ the sheep, [6] has an
epitheliochorial placenta, which substantially differs from the
hemochorial placenta in humans and rodents in important
features of nutrient transport such as, for example, an almost
absent transport of fatty acids, etc. [37].
In the context of our data obtained in the ‘‘genuine’’
rodent model described above, one has to consider that
also in some of the animal studies from other authors, neo-
natal overnutrition might have ‘‘biased’’ the results. In the
LP or semistarvation model, cessation of undernutrition
after birth without cross-fostering the offspring onto con-
trol rats, as it has been performed regularly by many inves-
tigators in the field, results in exposing the offspring to a
rat dam which develops reactive hyperphagia during the
suckling period, probably resulting in overnutrition of the
offspring during neonatal life.
In the meanwhile, a number of epidemiological and clin-
ical studies speak in favor of such a critical role of the neo-
natal period, of neonatal overnutrition and of neonatal
rearing conditions for the long-term outcome of ‘‘small
babies.’’ For example, Hofman et al. [25] showed that chil-
dren born with low birthweight, no matter if they were
term ‘‘small for gestational age’’—newborns or if they were
preterm ‘‘appropriate-for-gestational-age’’—newborns, had
a reduced insulin sensitivity indicating an increased risk of
developing type 2 diabetes. The finding that the risk among
AGA children who were born prematurely is similar to the
risk among SGA children which were born at term argues
strongly against diminished prenatal food supply as a cau-
sal factor for later outcome [40]. Rather, in particular, in
underweight newborns, increased weight gain in early
infancy as a proxy for neonatal overnutrition might lead to
an increased risk of developing metabolic and cardiovascular
disturbances [7,11].
CONCLUSION
Finally, it should be stressed that there is no doubt that
IUGR per se is an established risk factor for a number
of short-term as well as long-term complications and
ª 2011 John Wiley & Sons Ltd, Microcirculation, 18, 304–311
 Intrauterine Growth Restriction and Developmental Programming

diseases, such as impaired renal function and cardiovascu-
lar diseases [5,29]. However, a critical estimation of cur-
rent epidemiological, clinical and experimental data
indicates that low birthweight per se is not an independent
risk factor for the development of overweight and subse-
quent metabolic syndrome. One of the most often used
animal models in this context, bilateral uterine artery liga-
tion during the third trimester of pregnant rats, does not
reproducibly lead to growth restriction in spontaneously
born offspring and is therefore hardly a suitable model to
examine pathophysiological causes of the ‘‘small baby syn-
drome.’’ Rather, pre- and ⁄ or neonatal overfeeding, rapid
neonatal weight gain, and especially increased adiposity
with its hormonal and metabolic sequelae during critical
periods of perinatal life may increase long-term cardiomet-
abolic risks. One major challenge for future research in
this field therefore is to establish new animal models
allowing the identification of really causal risk factors
across the spectrum of birthweight, to enable the develop-
ment of prevention strategies.
ACKNOWLEDGMENTS
This work was supported by the German Research Founda-
tion (DFG; PL 241 ⁄ 3, 241 ⁄ 4, 241 ⁄ 5).

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Fink H, Rohde W, Dörner G. Perinatal eleva- AUTHOR BIOGRAPHIES
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formation of hypothalamic galaninergic
neurons, and syndrome X-like alterations
in adulthood of neonatally overfed rats.
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Uta Neitzke, MD, is a pediatrician at
44. Plagemann A, Heidrich I, Götz F, Rohde Ernst von Bergmann Hospital in Pots-
W, Dörner G. Obesity and enhanced dia- dam, Germany. She graduated in 2010
betes and cardiovascular risk in adult rats ‘‘with highest honor’’ with her thesis
due to early postnatal overfeeding. Exp
on experimental aspects of perinatal
Clin Endocrinol 99: 154–158, 1992.
45. Rich-Edwards JW, Colditz GA, Stampfer
programming in animal models for
MJ, Willett WC, Gillman MW, Hennekens the ‘‘small-baby-syndrome’’ at the
CH, Speizer FE, Manson JE. Birthweight Division of Experimental Obstetrics
and the risk for type 2 diabetes mellitus in at the Clinic of Obstetrics, Charité
adult women. Ann Intern Med 130: 278–
Berlin, Germany.
284, 1999.
46. Rich-Edwards JW, Stampfer MJ, Manson
JE, Rosner B, Hankinson SE, Colditz GA,
Willett WC, Hennekens CH. Birth weight
and risk of cardiovascular disease in a
cohort of women followed up since 1976.
BMJ 315:396–400, 1997.
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Intrauterine growth retardation leads to
the development of type 2 diabetes in the
rat. Diabetes 50: 2279–2286, 2001.
48. Stanner SA, Bulmer K, Andrès C, Lantseva Thomas Harder, MD, MSc, is Deputy
OE, Borodina V, Poteen VV, Yudkin JS. Head of the Division of Experimental
Does malnutrition in utero determine dia-
Obstetrics at Charité. His research is
betes and coronary heart disease in adult-
hood? Results from the Leningrad siege focussed on epidemiological and
study, a cross sectional study. BMJ 315: experimental studies on perinatal
1342–1349, 1997. programming. He has published more
49. Stein CE, Fall CHD, Kumaran K, Osmond C, than 160 abstracts, book chapters and
Cox V, Barker DJ. Fetal growth and coro-
journal articles.
nary heart disease in South India. Lancet
348: 1269–1273, 1996.
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LH. Intrauterine famine exposure and body
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Grobbee DE, Uiterwaal CS. Birth size and
coronary heart disease risk score in young
ª 2011 John Wiley & Sons Ltd, Microcirculation, 18, 304–311
 Intrauterine Growth Restriction and Developmental Programming

Andreas Plagemann, MD, is ordinary
Professor and Head of the Division of
Experimental Obstetrics at Charité. His
research deals with epidemiological,
clinical as well as experimental studies
on the long-term epigenetic and inter-
generative consequences of altered con-
centrations of hormones and nutrients
during critical periods of fetal and neo-
natal life. Dr. Plagemann has published
some 100 original papers, 40 reviews
and book chapters as well as about 120
abstracts in peer-reviewed journals. He
was awarded with national and interna-
tional research prizes in the fields of
diabetes and obesity and has been per-
manently funded since 20 years by the
German Research Foundation (DFG),
the Federal Ministries of Research in
Germany (BMFT, BMBF), and other
non-profit organizations.

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