7 July 2003
Says Disease Tendencies Begin in Womb
the end of World War II, Germany blockaded food to the largest cities
in the Netherlands. Nearly two decades later, when boys born to
women who were pregnant during the ensuing famine underwent military
physicals, doctors noticed something puzzling: The young men were
unusually prone to obesity.
oddity would become one of the cornerstones of a theory of disease
that has been gaining acceptance in recent years. A growing body
of evidence suggests that poor nutrition, stress and other factors
can affect a woman's developing fetus in subtle but fundamental
ways, predisposing offspring to health problems as adults. These
include heart disease, diabetes, stroke, cancer and even possibly
psychiatric conditions such as schizophrenia, bipolar disorder and
living things develop, and human beings are no exception, they are
very sensitive to the environment. And that includes the environment
inside the womb," said David Barker of the University of Southampton
in England, a leading proponent of the "fetal origins of adult
disease" hypothesis. "Structures and systems of the body
are different according to the conditions during development."
provocative theory goes far beyond the well-known health problems
that underdeveloped premature babies suffer, the genetic diseases
or frailties children can inherit and the physical and developmental
disabilities infants can be born with when pregnant women drink,
smoke, use drugs or take medicine dangerous to the fetus. According
to the theory, babies born a normal size with no genetic defects
or family history of disease and in otherwise good health can nevertheless
be fated to future problems because of subtle changes triggered
in the womb.
the fetus is at specific, critical points in development, different
organs in the body -- the pancreas, the brain -- are more vulnerable
than others to a stressful situation," said Kent Thornburg
of the Oregon Health Sciences University. "If they get too
much of the stress hormone cortisol, or are malnourished, these
organs will then undergo what we call programming. They will try
to adjust in a way that will give them a survival advantage. But
that modifies their gene expression for life in ways that may not
in fact be advantageous."
theory still has many skeptics, but it could help explain some of
the most important public health problems, such as the epidemics
of obesity in the United States and other parts of the world. It
could also shed light on some of the most puzzling health mysteries,
such as why immigrants and their descendants are more prone to heart
disease, obesity, diabetes -- and perhaps even some forms of mental
illness -- when they move from poor to rich nations.
always knew that nutrition was important for mothers. But it never
dawned on us the magnitude of the importance," Thornburg said
. "It means fetal development is really responsible for the
health of our population. Population health has always been discussed
in terms of what adults do as adults. Now we realize that what may
be more important is what happens to you before you're born."
evidence has come from studies around the world, ranging from following
large numbers of people over long periods to link adult health with
exposures in the womb, to detailed lab work demonstrating that the
offspring of animals can be affected by feeding their mothers certain
diets or exposing them to stressful conditions.
on these and other findings, some researchers suspect excess stress
hormones and other nuances in female body chemistry may have an
impact in the earliest stages of development, perhaps before a fertilized
egg implants in the womb, or even when the eggs are still maturing.
actually have to worry about pre-pregnant women. If the hypothesis
is true, then we need to be worrying about making sure adolescent
girls are adequately nourished so they reach their genetic growth
potential and are giving the right signals to their kids" when
they become pregnant, said Aryeh D. Stein of Emory University.
some cases, it appears the changes can become a legacy that is passed
on for generations. In the July issue of the American Heart Association's
journal Stroke, Barker is publishing a study that suggests high
rates of stroke that have plagued parts of England and the United
States for decades may be the result of poverty in those regions
confirmed, the fetal origins idea could have profound implications,
opening up broad new avenues of research and public health measures,
such as wider use of nutritional supplements before and during pregnancy
to reduce the toll from some of the most common chronic diseases.
reason people are excited is because these prenatal conditions may
be preventable," said Stephen Buka of the Harvard School of
Public Health. "And by reducing them we may reduce the frequency
of these devastating conditions."
researchers are keenly aware that the theory could make women even
more anxious about their future children's well-being, or prompt
recriminations against women for endangering the health of their
progeny. But proponents say the responsibility goes far beyond the
behavior of individual women. Instead, it lies with prevailing conditions
in society and environmental factors that are largely beyond women's
we're talking about the fetal origins of adult disease, there's
a danger that we get into a blame game with women," said Matthew
Gillman of Harvard Medical School. "We have to watch out for
some cases, the effects could be the result of a malfunction in
the placenta, the tissue that provides sustenance to the fetus,
that has nothing to do with what a woman does.
however, do question the theory on scientific grounds, saying there
could be many other explanations for the associations that researchers
have attributed to fetal programming.
not sure the associations are causal, and I'm not sure that even
if they are they're important from a public health point of view,"
said Michael Kramer of McGill University in Canada. "It's a
lot easier and sexier to study that than why kids are spending too
much time in front of the television. But that's a lot more important."
argue that the evidence for the theory is strong and getting stronger,
buttressed by rapidly accumulating animal research, large observational
studies of people, the latest insights into subtle variations in
how the same genes behave in different individuals and a deepening
understanding of human development. More than 700 scientists from
43 countries gathered outside London in June for the second international
meeting devoted to the theory.
were able to answer the critics, of which there have been not a
few," Barker said.
strongest evidence is for heart disease. Barker's initial finding
that people who are born small -- around six or seven pounds --
were much more likely to develop heart disease as adults has been
confirmed by a number of later studies. The exact mechanism remains
unclear, but animal and human studies suggest that smaller babies
experienced inadequate nutrition in the womb. As a result, their
bodies developed in ways that would help them survive in a world
where food is scarce.
mom early on signals to the fetus what the environment is really
like. 'You're going to grow up in a poor environment, so you'd better
slow down your growth trajectory,' " Stein said. "If the
fetus is then born into a poor environment, then the kid is well
adapted. But if the fetus ends up being born into a different environment,
where food is abundant and work is sedentary, then this fetus will
be maladapted and deposit fat too easily."
mechanisms could increase the risk for obesity and high blood pressure.
It could also explain why rates of obesity and heart disease tend
to skyrocket when people move from poor countries to rich ones.
bodies are programmed to be very efficient with energy. They don't
seem to have the capacity to handle high-energy diets without storing
a lot of fat," Thornburg said. "The data is so overwhelming
that there's no doubt in my mind that this phenomenon is real and
cancer, researchers suspect that exposure to unusually high or low
levels of hormones or growth factors in the womb may affect the
resulting child's subsequent risk for certain malignancies.
Michels of Harvard Medical School found that women who were heavy
at birth appear to have twice the usual risk of breast cancer as
adults. "It's the opposite of the cardiovascular risk,"
evidence has been mounting for some psychiatric conditions.
think it's quite plausible that events during pregnancy, along with
genes, influence the development of the nervous system and the development
of what later on will be mental illness," Buka said.
born after difficult pregnancies and deliveries appear to be at
greatest risk. Some evidence suggests the mother's immune system,
or exposure to infections, could affect the developing fetus's brain,
consensus in the field is that it's not a specific infection itself
but the mom's immune system fighting off the infection that has
adverse impacts on the child's developing neurological system,"
immune system could also play a role in the increased risk of schizophrenia
among some groups after they move to more industrialized societies.
you come from the Caribbean, where it's warm, to cold raw England.
Your body isn't prepared to fight off all the new infections you're
suddenly exposed to. If you live in crowded, sneezy London, your
contact with infections increases," Buka said.
assortment of research is underway or in the planning stages to
validate the theory and tease out the causes and mechanisms.
National Institutes of Health is planning the National Children's
Study, which would follow 100,000 children from the womb onward
to determine which social, physical, environmental and other factors
influence their health.
another study already underway, known as Project Viva, Gillman and
colleagues at Harvard are following more than 2,100 women who gave
birth since 1999. Researchers collected a wide range of data about
the women before their babies were born, including their diets,
exercise and whether they were exposed to violence or other stressful
Stein and his colleagues at Emory and Columbia University are starting
a follow-up study to further examine the offspring of the "Dutch
Hunger Winter" to try to determine exactly what aspects of
the diet may be responsible.
is cutting-edge research," Michels said. "And it's really