11/29/2009 03:30 pm ET | Updated Nov 17, 2011

More Than Genes II: Fetal Programming, The Hunger Winter, And Behavior

The essence of the fetal programming idea is that impacts on local fetal cellular environments can change gene expression during the developmental construction of tissues and organs, and these changes can result in long-range consequences for the function of those tissues and organs during childhood and adulthood.

What about behavior? Let's use the term "fetus" in a generic sense to cover all of development from conception to birth. In humans that's nine months of gestation, a nine-month developmental period during which environmental impacts can apparently affect not only later physical health but also later mental health. The developing brain, after all, like any other part of the fetus, is a possible target for environmental impacts, and it's a safe assumption that whatever affects the developing brain has the potential to shape childhood behavior after birth -- and also the potential to shape adult behavior.

The evidence for fetal programming is clear. Researchers have already correlated heart disease and diabetes with fetal growth, measurements of head circumference and body length at birth. We can see those effects, but more subtle effects on various physiological systems, in particular on the developing nervous system, are difficult to detect, and measurements of later behavior are often even more difficult. Despite the research problems in defining relations between environmental impacts on the developing fetus and later behavior and intelligence, there's a general consensus among neuropsychologists, neurotoxicologists, and pediatricians that such impacts and consequence may be of tremendous importance. Certainly, there's already enough evidence in the research literature to support this idea.

The concept of fetal programming, of the developmental origins of health and disease, came out of the Dutch "Hunger Winter" -- a startling episode in science and history.

During the Second World War, the Netherlands was occupied by Germany, and in the fall of 1944, in retaliation for a railroad strike to aid the Allies, the Nazis began a brutal nine-month repression that cut off food supplies to the population of the western part of the Netherlands. Eighteen thousand Dutch people slowly starved to death. Comparing populations, this would be the equivalent of more than 600,000 people dying of starvation in America.

From September, 1944 to May, 1945, a major fraction of the Dutch population lived on less than 1000 calories a day. People suffered from chronic hunger and the diseases produced by malnutrition. The starving population ate anything at hand in order to survive, including tulip bulbs.

Later, for several reasons, this tragedy came to have a unique significance for science: 1) the famine was sharply circumscribed in time and place; 2) the affected population had major problems obtaining food elsewhere, so for those affected, the famine conditions were relatively constant; 3) the population was ethnically homogeneous and without marked prior differences in dietary patterns; 4) the official food rations were known for weekly periods, so that the number of calories available could be estimated by place and time of birth; 5) the evidence was that the availability of food was largely unaffected by social class; 6) long-term follow-up was possible, since individuals in Holland could be traced through national population registers.

The Dutch Hunger Winter provided science and clinical medicine with a population of pregnant mothers and fetuses experiencing malnutrition in first, second, or third trimesters, plus the childhood and adult medical histories of the fetuses that survived, and similar histories of the children of those fetuses.

No famine has ever had its transgenerational consequences so carefully tabulated and examined. The fetal programming idea that derived from it resulted in a cascade of research -- a cascade that's now reshaping pediatrics and developmental psychobiology.

In my next blog, we will begin to look at what we know about the relation between fetal programming, fetal impacts, postnatal behavior, and mental illness.

[Parts of the above text are adapted from Dan Agin's book More Than Genes: What Science Can Tell Us About Toxic Chemicals, Development, and the Risk to Our Children. Oxford University Press, 2009.]