BY CHARLES CLAWSON

A new study shows that a panel of tests developed by Stanford medical researchers can better gauge a pregnant woman's risk of transmitting a damaging infection known as toxoplasmosis to her fetus. Researchers say this could dramatically reduce abortions among women concerned about the infection's effect on their unborn children.

According to a study conducted by the researchers, 60 percent of the pregnant women who underwent standard tests for toxoplasmosis either registered a false-positive or had their test results misinterpreted. When informed that the additional tests indicated they had little chance of passing the infection on to their fetuses, only 0.4 percent of these women chose to abort their pregnancies. In comparison, 17.2 percent of the women whose positive result was confirmed by the additional tests terminated their pregnancies.

"This is a wake-up call for this country to recognize the importance of appropriate serologic testing for pregnant women," said Jack Remington, MD, professor of medicine (infectious diseases and geographic medicine) and leader of the study team. "We're facing a problem with incorrect interpretations of tests, and tests on the market that are inadequate. My hope is that reference laboratories can be set up throughout the United States to perform testing that is far more accurate and would help prevent unwarranted abortions."

The study's findings are published in January's issue of the American Journal of Obstetrics and Gynecology.

The toxoplasmosis infection results from ingesting the common microscopic parasite Toxoplasma gondii, or toxoplasma, through the consumption of undercooked or raw meat. It can also result from contact with infected cat feces. Nearly a third of adults in the United States and Europe have been infected by the microbe, which they carry for life as cysts in their organs. The acute infection is mild and often without symptoms in those with healthy immune systems.

As with German measles, a woman infected prior to her pregnancy has essentially no chance of giving birth to an infected child. "But if the woman first becomes infected during pregnancy, her fetus is at severe risk of becoming infected," Remington said. "And that infection can cause disastrous results in the newborn -- blindness, epilepsy, psychomotor retardation or mental retardation."

Between 1,000 and 4,000 infants born in the United States each year have congenital toxoplasma infections. Infected newborns often appear healthy at birth, but if the infection is unrecognized and thus untreated, 90 percent later suffer disabilities such as mental retardation, blindness or epilepsy.

A woman infected during the first trimester of pregnancy has a 15 percent chance of passing the parasite to her fetus. When the infection occurs later in pregnancy, the risk increases. Women infected during their third trimester have a 60 percent chance of transmitting the parasite to their unborn children

"If you don't screen the mother for the appearance of antibodies, she won't know because the infection is almost always asymptomatic," Remington said. "That is the tragedy."

A pioneer of toxoplasma research, Remington in the early 1970s developed the IgM test, which is the standard test for toxoplasmosis. IgM is the first antibody created when the body is infected or immunized. Initially researchers believed a positive test for IgM meant a recently acquired infection. However, the IgM antibody for toxoplasmosis is uncharacteristic in that it may persist for a year or more -- far beyond the point at which an infected mother
could transmit the microbe to her fetus. Remington said some physicians continue to misinterpret the IgM test results, leading to many unwarranted abortions.

"The IgM test is still one of the very best tests we have to make us suspicious that the patient may have been infected recently," Remington said. "It does not mean she was but suggests the possibility. What we have attempted through the years is to develop a panel of tests to help clarify whether the patient has indeed been recently infected. We've now developed such a panel."

The tests have been used with a high degree of success at the Palo Alto Medical Foundation, where Remington holds a research appointment in addition to his faculty appointment at Stanford. Because faulty tests and incorrect interpretations persist throughout the country, the U.S. Food and Drug Administration has suggested that other laboratories send serum from IgM-positive tests to the foundation's lab for more accurate testing. The foundation is the only site in the country to offer the battery of new tests. "The majority of the tests were developed in our laboratories and just aren't available elsewhere in the U.S.," Remington said.

The newest test is the avidity test, which measures how strongly IgM antibodies bind to the toxoplasma antigens. A strong bond indicates the infection is not recent. "This applies to women tested within the first three to four months of pregnancy who have a positive IgM test," Remington said. "We can for the first time -- with a very high degree of accuracy -- tell a woman that if she has a high avidity test, there is no risk to her fetus."

Currently, the only certain method of measuring the risk of congenital toxoplasmosis involves screening women for antibodies at the beginning of, and during, pregnancy. Such screenings are a routine part of prenatal care in France but not in the United States where officials are concerned about the cost of widespread screening.

"If I could tell pregnant women just one thing," Remington said, "it would be: Eat all your meat well cooked."

Remington's Stanford colleagues in the study include: Oliver Liesenfeld, MD, postdoctoral fellow; Byron Brown, Jr., PhD, professor of health research and policy; Kristin Cobb, MS; Julie Parsonnet, MD, associate professor of infectious diseases and geographic medicine; and Jose Montoya, MD, assistant professor of infectious diseases and geographic medicine.