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Aly Hartman avoided sodas, crowds and gas fumes and switched to organic fruits during pregnancy.
(Christina House, For The Times)
Mounting evidence suggests that fetuses are surprisingly susceptible to outside influences such as food, environmental pollutants, even stress.
If Aly Hartman could have placed herself in a protective bubble for the duration of her recent pregnancy, she would have done so.
The Marina del Rey woman, 28, cut out alcohol, sodas and caffeine. She replaced her sugary breakfast cereal with crackling oat bran, quit eating Taco Bell MexiMelts and began stocking up on organic fruits and vegetables. She ducked back into her car while pumping gas and, when driving, sped around vehicles emitting thick fumes. She avoided crowds and handshakes, bought all-natural cleaning products and stopped wearing perfumes and lotions.
The child-talent agent admits her safety measures may seem a bit extreme, but she may actually be a model for all pregnant women.
What women eat, touch and breathe during pregnancy now appears to be more important to their babies' health than anyone ever imagined. Mounting scientific evidence suggests that fetuses are surprisingly susceptible to outside influences, such as food, environmental chemicals and pollutants, infections, even stress. Under this theory -- called fetal programming -- babies are born not just with traits dictated by their parents' genes, such as brown eyes and olive skin. They may be born with a tendency to develop asthma, diabetes or other illnesses based on what their mothers ate and were exposed to during pregnancy.
Already known were the obvious, and serious, risks posed by smoking, drinking and drug use. Now researchers are homing in on subtler changes in the fetal environment that can influence a child's health even into adulthood. In one of the most widely relevant examples, given the nation's growing waist size, research has shown that pregnant women with diets high in fat and sugar give birth to children who are more likely to become obese, perhaps because their fat cells are "programmed" in utero for later obesity.
In short, the daily experiences of a pregnant woman may be far from benign.
"Fetal life and early infancy are now recognized as periods of remarkable susceptibility to environmental hazards," says Dr. David Barker, a British researcher who is widely credited with recognizing the link between low birth weight and later cardiovascular disease. "The diets of mothers have massive long-term effects on their babies."
Once confined to experts in fetal health, fetal programming is now attracting scientists who study adult conditions, such as diabetes, heart disease, cancer, asthma, schizophrenia and infertility. By understanding the origins of susceptibility, they hope to understand how such diseases might be prevented, says Jerry Heindel, a biochemist and scientific program administrator at the National Institute of Environmental Health Sciences.
"People are realizing that maybe they've been looking at the wrong time frame for the role of environment and disease," says Heindel, who developed a program at the institute to study the fetal basis for disease.That's not to say that Heindel and other fetal-programming experts are suggesting pregnant women take every possible precaution for fear of dooming their children. Such research is in its infancy, and many questions and controversies remain, Heindel says. And he adds: Diseases are caused by a combination of genes and environment or by many factors that collude.
Still, many fetal-programming experts say reproductive-age men and women need to know that they probably have more control over their children's future health than they realize.
"You can't help but be a little bit scared of everything that could go wrong," says Hartman. "There are a lot of things outside of your control. But I was surprised to learn how much is in my control."
Evidence of susceptibility
History has delivered several sobering reminders that the human fetus is vulnerable to outside influences. Birth defects caused by medications such as thalidomide in the late 1950s and more recently the acne drug Accutane demonstrate that doses that have little effect on an adult can cause devastating changes in a fetus.
"The early teaching was that the placenta offered incredible protection against the fetus," says Dr. Philip Landrigan, chairman of the department of Community and Preventive Medicine at Mount Sinai School of Medicine in New York City. "Thalidomide was the first episode that made the medical profession and public realize that the placenta is not some sort of impervious barrier."
But the most jarring part of the fetal-programming hypothesis -- and the hardest to prove -- is that even seemingly harmless doses of ubiquitous substances at the wrong stage of development can produce deleterious effects.
Pollutants such as exhaust may cross the placenta and affect a fetus. Studies link pollution to low birth weight.
(Stephen Osman, Los Angeles Times)
"More recently we've recognized that you can still have these effects in the absence of disastrous damage," Landrigan says. "We've come to realize that if a pregnant woman eats a half-a-dozen cans of tuna fish at the wrong time of pregnancy, that might be harmful."
Contamination of fish with very high concentrations of methylmercury from industrial sources has caused clusters of severe birth defects in several places around the world. But more recent research, including three large epidemiological studies, suggests that even methylmercury concentrations commonly found in the United States can cause subtle changes in the fetus, such as lower IQ and decreased cognitive performance in childhood, Landrigan says.
Other studies have linked low levels of the vitamin folate and increased levels of the amino acid homocysteine with an increased risk of schizophrenia. In a study published in January in the Archives of General Psychiatry, researchers found that high homocysteine levels in the third trimester doubled schizophrenia risk in the offspring, perhaps by altering brain structure or function or through subtle damage to the placenta to reduce oxygen delivery to the fetus. And increasingly, scientists fear that fetuses and young children may be harmed by pesticides and pollutants that, at the same level, cause no measurable harm in adults. For example, some common pesticides are thought to be so-called endocrine disrupters, chemicals that change hormone function in utero and can affect reproductive organ development and function later in life. A study in the March issue of Human Reproduction found that women who ate more than seven servings a week of beef during pregnancy had sons who were more likely to have poor sperm quality as adults -- possibly due to the hormones fed to cattle.
Likewise, levels of air pollutants commonly found in many urban areas may cross the placenta of a pregnant woman and affect her fetus. More than a dozen studies worldwide have linked air pollution to low birth weight, stillbirth and intrauterine growth retardation. According to the World Health Organization, air pollution can impair lung function in the womb.
The implications of fetal programming are profound, Heindel says. Some preliminary research suggests that an environmental influence in pregnancy may not only affect the fetus but also future generations as well.
For example, pregnant women who took the medication diethylstilbestrol -- used from 1938 to 1971 to prevent miscarriage and other problems in pregnancy -- gave birth to daughters with higher risks of infertility, menstrual irregularities and a rare genital-tract cancer after puberty. Now the children of the so-called DES daughters are reaching adult age, and studies suggest that the defect may persist into a third generation.
Sons of the DES daughters have a higher risk of hypospadias, a misplaced opening of the penis. Daughters of the DES daughters may have altered reproductive tract function, according to a study published last year.
Scientists refer to such changes as epigenetics. During critical time periods of human development, the body alters gene expression (even though the DNA sequence itself is unchanged), which may lead to a predisposition to disease in the offspring.
"That means what your grandmother was exposed to could affect your health today," says Heindel. "That is what makes this so scary. The data is so scanty at this time that we don't know how strong that is. If it turns out to be true, it could be very important."
Mixed benefits
Not all exposures are bad. Research published last year in the Archives of Disease in Childhood, showed that pregnant women consuming supplements of omega-3 fatty acids were more likely to have babies with good hand-eye coordination and language comprehension.
But that finding highlights the dilemma pregnant women often face: Trying to eat healthy can sometimes increase the likelihood of toxic chemical exposures.
To use the fish research, some types of fish contain not just omega-3 fatty acids but high levels of mercury and other toxic chemicals. As a result, pregnant women are advised to eat no more than 12 ounces of seafood a week. And a study published online in April in the journal Thorax found that the children of women who ate lots of apples during pregnancy had less asthma later in life than did the children of women who ate few apples. Sounds good. But apples can also contain high levels of pesticides which, research shows, might be harmful to a developing fetus, acting as endocrine disrupters or causing neurological damage.
The advice is dizzying and can seem to change yearly. Even the current recommendation to abstain completely from alcohol isn't as ironclad as many women think. In England, the Department of Health and British Medical Assn. recently changed their recommendations on alcohol use in pregnancy, advising women to avoid it completely. The previous recommendation was to limit alcohol to not more than one or two drinks once or twice a week. The revised recommendation was not based on any new scientific evidence, however, and could frighten women, according to one doctor writing in the British Medical Journal.
Some aspects of fetal programming seem almost beyond anyone's control. Infections from particular viruses, bacteria or parasites are known to cause birth defects. But studies even suggest that getting the flu while pregnant might be harmful (it's linked in several studies to a higher risk of schizophrenia in offspring). And a pregnant woman's emotional trauma from such events as job loss, divorce or the death of a loved one has been shown in several studies to increase the risk of birth defects and autism.
"Stress is probably really important. Infections during pregnancy may be important," Heindel says. "Any kind of environmental influence could perturb programming."
Advice isn't clear-cut
But advising pregnant women is difficult.
"Physicians always have to walk a delicate line between frightening people to death and, on the other hand, providing them with bland and meaningless reassurances," Landrigan says. "But we in the profession need to do a better job of getting this information out to the public. I think this [fetal-programming] message is not as widely appreciated as it should be."
He advises people to think about which chemicals to use and store in their homes and whether to buy organic foods and nontoxic products.
"This is all about empowering people with information," he says.
Good information isn't always easy to find, however. Lawmakers should make more of an effort to define which substances may harm a fetus, at what amounts and when, says Brenda Eskenazi, an epidemiologist at UC Berkeley and director of the Children's Center for Environmental Health. Most laws on toxic exposures are based on levels that could affect an adult -- not a child or developing fetus, who are thought to be even more vulnerable. To that end, a state law passed last year established a biomonitoring program that will assess the presence and concentration of designated chemicals in Californians by testing blood, urine and breast milk samples.
Scientists also need to find better ways to measure toxic exposures. In a notable study published last month in the journal Genome Biology, researchers found they could identify individual toxins at work in zebrafish embryos by reading the specific gene expression. The research offers a potential method of identifying the effects of toxins on developing vertebrate embryos to see if they are harmful and, if so, at which times in fetal development.
"A lot of our problem in this whole field is the ability to measure exposure," Eskenazi says. "Some laboratories are developing new and great ways of measuring chemical exposures. Many of these exposures are short-lived, and we may not be picking them up. But they can have long-term consequences."
Although many questions about fetal programming remain, enough is now known to alert consumers, says Eskenazi.
Hartman, who had a healthy baby girl late last month, agrees.
"Knowledge is power," she says. "The more you can know about having healthy babies, the better."
Studies show that a mother's diet can cause changes in the fetal brain that may affect a person's appetite control.
(Carlos Osorio, Associated Press)
Fourteen percent of U.S. preschoolers are overweight. This fact alone points to perhaps the strongest evidence for the effects of fetal programming.
Multiple studies have shown that either underfeeding or overfeeding the fetus during pregnancy can affect how a child's body will respond to food over a lifetime, increasing the risk for diabetes, heart disease and hypertension.
Pioneering research in the late 1980s by British physician David Barker showed that babies weighing 6 pounds or less are more likely to have an increased risk for heart disease, Type 2 diabetes and hypertension. It is the disparity between the prenatal environment and the nutritional environment after birth that appears to cause abnormalities in energy metabolism, endocrine functions and organ development.
Given the modern environment of preschoolers in Western countries -- marked by a lack of exercise, and diets high in calories, fat and sugar -- this disparity creates a problem, Barker and other researchers say.
"The fetus is reading the environment during development and is using that to predict what the environment will be once it's born," says Jerry Heindel, a fetal-programming expert at the National Institute of Environmental Health Sciences. "If the fetus gets poor nutrition, it will set itself up to be able to adjust to that. If it has poor nutrition during life, it will do quite well. But later in life, if nutrition changes and becomes like the food we're eating today, that is a mismatch, and that will increase the susceptibility to disease."
At a recent nutrition conference in Boston sponsored by Tufts University's Friedman School of Nutrition Science and Policy, the audience of nutritionists and nutrition researchers is rapt as Barker elaborates on this provocative message: Attempts to prevent such common chronic diseases as heart disease, stroke, high blood pressure and diabetes have largely failed because the origins of such diseases most likely begin in the womb.
"We were hoping and praying that we could fix chronic illness by fixing the diets of middle-age people," says Barker, an epidemiologist at the University of Southampton, United Kingdom, and Oregon Health & Science University. "But if we want to arrest the epidemic of chronic disease, we need to start early in life."
The idea has been slow to catch on.
"In other fields where people study butterflies, turtles and frogs, they have known for a long time that fetal development is very plastic and that any type of stress in the environment can cause a different phenotype in the animal," Heindel says. "In humans, people thought it was just genetics. But humans are just like these other animals." Today, U.S. doctors are primarily concerned about excessive weight gain during pregnancy. That too appears to program a fetus for metabolic problems later in life.
Exposure to a high level of blood sugar or fat before birth can change the development of fat cells and the pathways in the brain that regulate appetite, says Beverly Muhlhausler, a researcher at the University of South Australia's Early Origins of Adult Health Laboratory and an authority on fetal diet and adult disease.
"What research is now showing is that consuming an excessive amount of high-fat, high-sugar foods during pregnancy can alter the development of the baby in such a way that predisposes that individual to becoming obese later in life," she says.
Scientists from Kaiser Permanente's Center for Health Research recently found that children of pregnant women untreated for high levels of blood sugar were 89% more likely to be overweight and 82% more likely to be obese by the time they were ages 5 to 7 compared with children born to women who had normal blood sugar levels during pregnancy. The study was published last month in Diabetes Care.
One of Muhlhausler's studies in sheep found that fat cells in fetal sheep whose mothers had been fed a high number of calories during late pregnancy produced natural substances that promoted fat storage.
Further, a mother's diet may also cause changes in the fetal brain that later influence appetite and food preference.
"These individuals are less able to switch off their appetite and stop eating even when they've consumed enough calories. And this also makes them more prone to weight gain," she says.
A similar study in August in the British Journal of Nutrition found that pregnant rats fed a diet of processed junk food subsequently gave birth to baby rats that also preferred junk food.
"There is so much emphasis put on a child's eating habits at school, but research is telling us more and more that the pathway to obesity can start long before the child gets to school age," Muhlhausler says.
"One of my dreams as a researcher is to be able to get the message out that what you eat during pregnancy has a huge impact on your child's development and long-term health prospects."
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