More Than Genes I: When Environment Programs the Fetus

11/27/2009 08:47 am ET | Updated Nov 17, 2011

On the morning of September 11, 2001, some 3000 people died in front of our eyes in a crazy scene of airliners crashing into skyscrapers and of those skyscrapers crumbling within minutes. Anyone downtown in Manhattan that day, or anyone anywhere in front of a television screen who watched the collapse of the twin towers of the World Trade Center, has the memory of it seared into their psyche. The entire appalling event -- from Manhattan to the Pentagon to a small field in Shanksville, Pennsylvania -- sent political shockwaves across America and around the world that have not yet subsided. We now call that day "9/11" as a signature shorthand for the catastrophe, a logo for an event whose details quickly occupied the mind of nearly everyone on the planet.

But like many catastrophic events, there was more to 9/11 than most people realize.

Not long afterward, a few miles north of "Ground Zero" -- the empty ground where the World Trade Center once stood -- a pediatrics group at the Mt. Sinai School of Medicine, together with others there and at the Bronx Veterans Affairs Medical Center, began to ask a simple question: Was it possible the shock of the 9/11 catastrophe had caused effects in the fetuses of pregnant women who lived close to the disaster?

The Mt. Sinai research team went on a hunt for pregnant women who had been in the vicinity of the World Trade Center at 9 a.m. on the 11th of September 2001. They published advertisements in local newspapers. They distributed flyers in lower Manhattan. They sent letters to 3000 obstetricians in the greater New York City area. They found 187 women who had been pregnant and present in any one of five exposure zones around Ground Zero, including 12 women who were in the towers at the time of the attack. As a comparison group, they used 174 pregnant women who had been nowhere near the World Trade Center on the morning of the catastrophe.

The researchers analyzed every piece of relevant information available about the pregnant women in both groups and about the infants born to them in subsequent weeks or months. On August 6, 2003, they published a short letter in a medical journal. The concluding paragraph of the letter had no ambiguities:

"We found an apparent association between maternal exposure to the World Trade Center disaster and intra-uterine growth retardation, suggestion that this event had a detrimental impact on exposed pregnancies ... Possible long-term effects on infant development are unclear and will require continuing follow-up."

Two years later, the Mt. Sinai research group published three papers on their findings in three different medical journals. To sum up their conclusions: The cause of intrauterine growth retardation in the infants was apparently not dust and smoke inhaled by the pregnant mothers, but maternal psychological stress and cortisol secretion effects, as indicated by measures of below-normal cortisol levels in their infants.

The findings of the Mt. Sinai research group are not isolated. Since the late 1990s, fetal effects have been found from earthquakes, ice storms, and floods, with varying later outcomes for the children: childhood verbal deficits, depression, schizophrenia, and so on.

Do we know the mechanism for these effects? There's more than one possibility, but consider the following: On 9/11, when a pregnant woman was close enough to experience the traumatic World Trade Center event, her adrenal glands secreted the powerful stress hormone cortisol. Her cortisol entered the placenta. Not all of her cortisol was broken down by the placenta, and some of it got through to the fetus and increased the fetal blood cortisol level. Recent studies in fact show a positive correlation between maternal and amniotic fluid cortisol levels. On 9/11, to compensate for increased local cortisol, the fetal adrenals reduced their own cortisol secretion to keep the total level down. But since that happened while the fetus itself was developing, the result was fetal production of cortisol that might not have been just transiently reduced, but permanently reduced. One effect could be retarded intrauterine growth as a consequence of an altered homeostatic balance. Another effect would be low cortisol levels in infancy (as found by the Mt. Sinai group) and later consequences difficult to assess. In other words, during development the fetus adapted to a new environmental condition as if that condition would be permanent.

In modern pediatrics and developmental neuropsychology, this adaptation is called "fetal programming" or "prenatal programming." It's a new concept. The general idea is that during development important physiological parameters can be reset by environmental events -- and the resetting can endure into adulthood and even affect the following generation -- in this case, producing a transgenerational nongenetic stress disorder.

When new ideas arise in the sciences, it often takes time for the ideas to meander into public awareness. Such is the case with the idea of fetal programming -- an idea that first became prominent in clinical medicine in the 1980s. At the moment it's one of the buzzing terms in some areas of psychology and pediatrics.

In my next account in this series, we'll 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 More Than Genes: What Science Can Tell Us About Toxic Chemicals, Development, and the Risk to Our Children. Author: Dan Agin. Oxford University Press, 2009.]