Barker pioneered the idea that the epidemic of coronary heart disease in Western countries
in the 20th century, which paradoxically coincided with improved standards of living
and nutrition, has its origin in fetal life. Indeed, there is substantial evidence
associating low birthweight because of fetal growth restriction with an increased
risk of vascular disease in later adult life. These conclusions led to the second
part of the Barker hypothesis, the thrifty phenotype, in which adaptation to undernutrition
in fetal life leads to permanent metabolic and endocrine changes. Such changes are
beneficial if the undernutrition persists after birth but may predispose the individual
to obesity and impaired glucose tolerance if conditions improve. The hypothesis assumes
that a poor nutrient supply during a critical period of in utero life may “program”
a permanent structural or functional change in the fetus, thereby altering the distribution
of cell types, gene expression, or both. The fetus, in response to placental undernutrition
and to maintain sufficient vascular supply to the brain, decreases resistance to blood
flow in the middle cerebral artery. Simultaneously, because of the limited blood supply
to the fetus, the arterial redistribution process is accompanied by increased resistance
to flow to other fetal vital organs, such as the heart, kidneys, liver, and pancreas.
It may explain why individuals exposed to ischemic changes in utero develop dyslipidemia,
lower nephron number, and impaired glucose tolerance, all factors contributing to
metabolic syndrome later in life. Nevertheless, support for the hypotheses comes mainly
from studies in rodents and retrospective epidemiologic studies. This review focused
on ultrasound and Doppler studies of human fetal growth restriction in several fetal
organs: the placenta, fetal circulation, brain, heart, kidneys, adrenal glands, liver,
and pancreas. Support for the hypothesis was provided by animal studies involving
conditions that create fetuses with growth restriction with effects on various fetal
organs and by human studies that correlate impaired fetal circulation with the in
utero development and function of fetal organs.
Key words
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Article info
Publication history
Published online: September 01, 2021
Accepted:
August 19,
2021
Received in revised form:
August 19,
2021
Received:
June 24,
2021
Footnotes
The authors report no conflict of interest.
Identification
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