NEW YORK (Reuters Health) - Thanks to assisted reproductive technology, thousands of infertile couples bring home a bundle of joy each year. Despite the benefits of giving the stork a helping hand, however, the technology may increase the risk of low birth weight and birth defects, new research suggests.

Though higher than in naturally conceived children, the odds that a child conceived through assisted reproductive technology will have a birth defect or be underweight are still low, the findings indicate.

But potential parents should take this extra risk into account when deciding whether to use assisted reproductive technology (ART), experts say.

"The decision about whether to undergo an assisted reproductive technology procedure is very personal," according to Dr. Laura A. Schieve, of the Centers for Disease Control and Prevention in Atlanta, Georgia. For patients considering ART, the research "may help inform their decisions," Schieve told Reuters Health.

ART includes in vitro fertilization (IVF), in which a woman's eggs are harvested and then fertilized with a man's sperm in the laboratory. The resulting embryos are then transferred into the uterus. In some cases, the man's sperm is injected directly into eggs in a procedure called intracytoplasmic sperm injection (ICSI).

ART is well known to increase a woman's odds of having twins, triplets or even more babies since several embryos are usually transferred to the uterus to increase the chance that a pregnancy will result. In cases of multiple births, it is not unusual for babies to weigh less than normal.

Some studies have found that ART also increases the risk that so-called singleton babies--those born alone--will weigh less than normal. But due to problems with how these studies were conducted, this link is not definitive.

Now, in the March 7th issue of The New England Journal of Medicine , Schieve and her colleagues report the results of a study that confirms the increased risk of low birth weight among babies conceived via ART.

The researchers compared the 1997-1998 rate of low birth weight among more than 42,000 ART-conceived children with the rate in nearly 3.4 million naturally conceived US children.

"Over 3% of low birth weight and over 4% of very low birth weight infants born in 1997 were conceived with assisted reproductive technology, six times the number expected based on the frequency of these procedures," Schieve told Reuters Health. Much of the increase was due to the high frequency of multiple births linked to ART, she said. The rate of low birth weight babies was similar in multiple births that occurred naturally and in those that resulted from ART.

"However, we also found that singleton infants conceived using ART had twice the low birth weight risk as the general US population of singleton births," Schieve said. This increased risk was present even after the researchers accounted for the mother's age and prior pregnancies and whether a baby was born prematurely.

"Infants who have a low or very low birth weight are at increased risk for a host of medical complications and death during the first year of life," Schieve said. She added that these infants also have a higher-than-average risk for long-term problems such as developmental disorders.

In another study reported in the same issue, researchers found that birth defects were much more common in children conceived via ART. Dr. Jennifer J. Kurinczuk, then a researcher at the Institute for Child Health Research at the University of Western Australia in Perth, and colleagues compared the incidence of birth defects in 301 infants conceived via ICSI, 837 conceived via IVF and 4,000 conceived naturally.

By age 1 year, 8.6% of children in the ICSI group and 9% in the IVF group had been diagnosed with at least one major birth defect. In contrast, only 4.2% of naturally conceived children had birth defects. After the investigators accounted for several factors that could have influenced the risk of birth defects, such as the mother's age and the sex of the baby, ICSI and IVF children were twice as likely to have a birth defect.

Even when Kurinczuk and her colleagues considered only singleton infants, children conceived through ART were still more likely to have birth defects. Kids conceived through ART were also more likely to have multiple birth defects.

The results of the study are sure to be controversial, Kurinczuk, who is now at the University of Leicester in the UK, told Reuters Health. The increased risk of birth defects "should not necessarily deter people from having the procedures," according to Kurinczuk, "but they need to take them into consideration when making a fully informed choice." The results of the study should be taken into account along with the other known risks of ART, such as higher odds of having multiple births, she said.

There are several possible explanations for the increased risk of birth defects, Kurinczuk and her colleagues note. Infertile couples tend to be older, which can make pregnancy riskier. It is also possible that the underlying cause of infertility could affect the risk. Drugs taken to encourage ovulation or to maintain a pregnancy in the early months could also be involved, and some aspect of the ART technique itself may be harmful.

Even though the risk of birth defects and low birth weight is higher in ART-conceived infants, most such children are healthy, according to Dr. Allen A. Mitchell of Boston University School of Public Health in Massachusetts.

"The likelihood of having a term singleton infant of normal birth weight is about 94%, and the likelihood of having an infant who is free of major defects is about 91%," Mitchell states in a related editorial.

Still, uncovering the causes of the increased risk of birth defects and low birth weight is critical, the editorialist adds. He points out that the number of IVF procedures skyrocketed during the late 1990s. As more and more couples undergo ART, it is possible that some of these couples may not be truly infertile, meaning that they would have conceived on their own if they had tried for a few more months, Mitchell states.

If infertility itself is to blame for birth defects and low birth weight, then having couples who are not truly infertile undergo ART will not increase the risk of these problems, he notes. But if the drugs used in ART or the procedure itself raises the risk of defects or low birth weight, "then the use of ART for couples who are not infertile would result in unfortunate and avoidable excess risks," according to Mitchell.

SOURCE: The New England Journal of Medicine 2002;346:725-737, 769-770.