SAN DIEGO – Since the birth of the first "test tube baby" in 1978, more than 3 million children have been born through assisted reproductive technology. Since none of them are older than 31, scientists are just beginning to understand the long-term differences between people conceived this way and conventionally.

"It's fair to say that overall these children do well," Andre Van Steirteghem, a professor emeritus at the Brussels University Centre for Reproductive Medicine in Belgium, said Sunday here at the annual meeting of the American Association for the Advancement of Science. "But there are a few more problems with these children."

Van Steirteghem compared the health of 300 children born through assisted reproductive technologies (ART), such as in-vitro fertilization, to 266 who were conceived naturally. He found that generally these kids are just as healthy, but the ART babies do have a small elevated risk for some issues such as low birth weight and birth defects.

"Overall, it is a reassuring message, but we have to continue to follow up and look at the long-term effects," he said.

Other recent studies have found that children born through ART have about a 3.5 times greater chance of developing respiratory disease, and are roughly three times more likely of being born with defects of the brain and spinal cord, such as spina bifida and anencephaly.

Carmen Sapienza, a professor of pathology at Temple University Medical School in Philadelphia, Penn., recently studied how some chromosomes can be altered in children born through in-vitro fertilization and other ART processes, compared to children conceived in the traditional way. He found that five to 10 percent of certain chromosome modifications, called DNA methylation, were different between the two groups of kids, and that these differences caused changes in whether certain genes would be expressed.

"My interest is in epigenetics – how does the environment interact with your genome?" he said. "Those kids spent their first three days in a Petri dish, versus the other kids who spent their first three days in mom."

Sapienza said differences between the culture media used in the Petri dish compared to the chemicals in the mother's womb, and the different amounts of oxygen in the two environments, could affect the genes.

However, in this study and other comparisons of test tube babies to conventionally conceived kids, researchers can't be sure whether the differences measured are due to the technologies themselves, or stem from the fact that the parents are infertile, which may mean they are passing down genes associated with other health problems as well.

"We're bypassing nature's barriers to fertilization by defective gametes," said Dolores Lamb, a professor of urology at the Baylor College of Medicine in Houston. She explained that sometimes infertility is nature's way of preventing disorders from being passed down.

"The good news is the couples get to experience parenthood, but what we don't know is whether these children will be infertile as their parents were," Lamb said.

Research indicates both the parents' infertility and assisted reproductive technologies are playing a role in the results with ART children.

Adding to the issues is the fact that parents who use fertility treatments and in-vitro fertilization are much more likely to have twins, triplets and other multiples. While most of these children are also just fine, multiples have higher rates of low birth weight and other disorders too. But the scientists stressed that even after controlling for multiple births, children born through ART are at greater risk for a variety of issues.

Ultimately, time and more research will help explain the consequences of this new era in reproduction, the scientists said.