03/18/2010 05:12 am ET | Updated Nov 17, 2011

More Than Genes III: Pregnancy, Toxic Environments, and Fetal Vulnerability

When it comes to babies, it's easy to frighten people. It's natural for pregnant women to feel besieged by the idea of environmental toxic impacts on the developing fetus. The reality is that we're all besieged by this idea. But is it better to be ignorant of the dangers?

Here's a young woman named Kate at a party with her husband on the Upper West Side in Manhattan. She's twenty-five years old, a teacher happily married to an attorney, and she wants children. It's someone's birthday party, a happy occasion, and Kate has been sipping vodka tonics one after the other and enjoying herself.

Although she doesn't know it yet, Kate is pregnant. The embryo is just beginning the second week of gestation. In 35 or 36 weeks she'll have a baby boy, and soon after birth the baby will have physical problems, mental problems, and an unpredictable future.

Some women can do heavy drinking during early pregnancy and nothing much happens to the child they carry. Kate isn't one of those women. The embryo in her uterus is vulnerable to a sudden increase in blood alcohol. Or maybe Kate's body detoxifies alcohol too slowly. We don't know the mechanisms for individual vulnerabilities. Kate's child, the child she yearns to have, will be diagnosed with fetal alcohol syndrome, including a related cardiac defect and mental deficits.

Kate is an educated responsible woman. If she knew she was pregnant, she would certainly not drink alcohol. The problem is that she doesn't know that she's pregnant yet, a common situation among women in the early days after conception.

The placenta is the organ that acts as the interface between the mother and the developing embryo or fetus. Although the placenta acts as a filter and detoxifying system, its efficiency differs from one woman to the next and we don't yet understand the details of the differences.

For the developing embryo, ethyl alcohol (ethanol, the alcohol we drink), usually passes through the placenta intact. Ethanol is an environmental toxic chemical -- with embryo damage caused not by air pollution, water pollution, or food pollution, but by a woman aware or not yet aware that she's pregnant, for example, a woman drinking too much at an innocent birthday party.

Yes, it's insidious, and it's unfortunate that we started being serious about this problem only a few decades ago.

Let's consider wine. I like wine, especially Italian wine, maybe because I once lived in Italy. Wine is important in Italy, and the custom in rural towns and villages is to drink moderate amounts of wine with meals every day. Binge drinking is rare, except among the young and in cities. But binge drinking is not the only way alcohol can be dangerous for an embryo or fetus.

One of the oldest parts of Italy is Rome and the area around Rome, the region called Lazio. In the region of Lazio 62 percent of women drink alcohol prior to pregnancy and 53 percent during pregnancy. Twelve percent of pregnant women in Lazio drink 7 or more drinks a week. Some Italian women who ordinarily don't drink regularly start drinking during pregnancy because of a popular belief in Italy that moderate alcohol has benevolent effects during pregnancy.

So is it harmful to the fetus? Yes, it's harmful to the fetus. Currently, 3.5 percent of the children in Lazio have the markers of fetal alcohol spectrum disorder (FASD). That's the highest prevalence of FASD in the Western world and more than 3 times the prevalence in the United States.

Prenatal developmental damage by alcohol is an example of the high vulnerability of the embryo and fetus to chemical impacts. Consumption of alcohol is dangerous for the fetus, but just as dangerous are synthetic chemicals produced by industrial pollution, environmental contaminants in our air, water, and food. More than 80,000 new synthetic chemicals have been introduced into our environment in the past 50 or 60 years, and only a few hundred of these have been studied for toxic impacts on development. Toxicologists estimate that during the nine months of gestation, the developing fetus is about 100 times more vulnerable to environmental impacts than children or adults. There are good biological reasons for this vulnerability, and a look at the reasons helps us understand some important features of development and the dangers of toxic exposure.

The human egg cell (ovum) is the largest cell in the body, on average 145 microns in diameter (average human hair width is 100 microns, or 0.1 millimeters), which means the egg cell is visible to the naked eye. The ovum is about 15 times larger than ordinary cells such as skin cells and liver cells, but it's still no larger than a dot, smaller than the period at the end of this sentence. The profound glory of human reproduction, the wonder of wonders, is that under the right circumstances and during about 277 days, this biological dot is capable of turning itself into a 7-pound infant ready to scream at you to look smart and give it some food and attention.

Fetal development is a consequence of cascades of biochemical reactions, cascades of gene expression, cellular movements, tissue formation, and organ construction. A cascade is a succession of sequentially interdependent events, each event both triggered by the event preceding it and itself acting as a trigger for the next event. Human development from conception to birth involves many thousands of cascades, sequences of events with specific vulnerabilities at specific times -- and the possibility for several vulnerabilities at any single time.

The whole developmental mix of cascades moves forward by both internal triggers and triggering by interactions with the local cellular environment. So the first important cause of prenatal vulnerability is complexity: the sheer complexity at many levels of prenatal development means that an enormous number of different and important process points are available for disruptive impacts.

Another important cause of prenatal vulnerability is pace, the high rate of cellular proliferation necessary to transform a single microscopic cell (the fertilized ovum) into a six- or seven-pound newborn infant that consists of trillions of cells specialized and arranged to constitute the human body externally and internally -- albeit in the small of the infant. It's estimated that in the human developing prenatal brain and nervous system about 250,000 new neurons are generated each minute at the peak of cell proliferation during gestation. The high rate of cell proliferation means a high rate of metabolism, a high rate of chemical synthesis, a high rate of cellular rearrangements and migrations, a high rate of conversion of maternal nutrients into fetal cells and tissues, and so on. In prenatal development, everything is happening rapidly, and the consequence is that if any specific process has its rate changed up or down by an unscheduled impact with the local environment, the result may be anything from a subtle bending of development in one direction or another to a lethal corruption that kills the embryo or fetus.

The third major cause of the vulnerability of prenatal development involves size and simple physics. If a small permeable mass -- for example, a cluster of cells -- is exposed to a chemical that easily penetrates cells, that chemical can reach all parts of the mass quickly by simple random diffusion. With larger masses, the diffusion time to reach all parts increases dramatically. But as late as the 6th week of gestation, the human embryo is still only a quarter of an inch in length, has no developed circulatory system, and any freely permeating chemical that gets into the embryo by any route will quickly diffuse throughout the embryo to impact every embryonic cell.

Throughout the embryonic period, until the 10th week of gestation, the situation is not much better. At the 10th week, when we begin to call the developing embryo a "fetus," we're dealing with an embryo/fetus about two inches in length, indeed recognizable as a vaguely human form, but still small enough for simple diffusion to quickly distribute any permeating chemical entity throughout its body.

Small size facilitating distribution by simple diffusion is one of the reasons the early weeks of prenatal development are so vulnerable to certain chemical impacts. The other important reason is that the effects of impacts on the early part of development can be multiplied as the cascades of development proceed.

For example, there's mounting evidence that a critical window of vulnerability for fetal alcohol spectrum disorder occurs very early -- during and shortly after the blastocyst stage--and that the impact of alcohol is on early gene expression in the developing embryo. Given this evidence, the most reasonable assumption is that concentrations of alcohol (or other toxic chemicals) too low to produce gross morphological disruptions may cause subtle and yet unknown changes in the connections between nerve cells in the developing brain. There is certainly evidence of troubles in cognitive performance of children whose mothers drank only moderate amounts of alcohol during pregnancy -- and there's evidence of later cognitive effects after fetal exposure to many industrial pollutants.

In my next blog, we'll consider various fetal impacts and mental illness in children and adults. Previous articles in the series are available from my Huffington Post page at

[Parts of the above text are adapted from the new book 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.]

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