IVD Technology Magazine | IVDT Article Index

Originally published January, 1997

IVD Technology News

Advances for treatment of preterm labor feed demand for new diagnostics

Studies on new treatment approaches for preterm labor are paving the way for use of diagnostic tests that predict prematurity.

That's bright news for two Northern California biomedical companies: Sunnyvale-based Adeza Biomedical Corp. and Dublin-based Biex, Inc. Thanks to therapeutic advances, Adeza's upcoming point-of-care kit--based on its fetal fibronectin enzyme assay--is generating considerable buzz in the obstetric community, as is Biex's estriol assay.

Predicting preterm labor has been a medical challenge throughout the ages. Causes are multifactorial and, despite intense research, they remain somewhat mysterious. Both IVD tests demonstrate better sensitivity and specificity in prediction than does reliance on a risk factor, although physical signs--contractions, cervical dilatation, vaginal bleeding--have until now been the gold standard.

By measuring saliva estriol levels, the Biex Salest test promises improved prediction for preterm labor.

The only FDA-approved treatment, ritodrine, often proves intolerable to patients. Racing heartbeats in both mother and baby are a common side effect of the drug. These side effects frequently lead to maternal noncompliance, says T. Murphy Goodwin, MD, an obstetrician at the University of Southern California School of Medicine. He and his colleagues demonstrated that an experimental therapy--an antagonist to oxytocin known as antocin--could slow uterine contractions with the same effectiveness as ritodrine, but without producing the high degree of side effects (Obstet Gynecol, September, 88:33­ 36, 1996). Magnesium sulfate is also coming into more use, according to the medical literature.

But it isn't just new approaches that have Goodwin and his coauthors feeling upbeat. In his quest for a better way to halt preterm labor's progress, Goodwin has also found that the two new diagnostic tests shed some light on cause and effect.

For instance, a positive result from the Adeza assay seems to be associated with subclinical infection, he says. Biex's product, on the other hand, seems to identify what Goodwin calls the fallout from "a precocious fetus"--a cascade of events that seem to start with early biochemical changes originating with the developing baby.

"One of the past problems is that preterm labor was treated as if it was just one thing," he says. Ritodrine, which slows smooth-muscle contractions, doesn't target the cause but treats the result, a contracting uterus.

But the two new diagnostics, while both aimed at detecting early labor onset, seem to point to separate causes, at least to some extent, Goodwin observes. Biex's test, which measures estriol levels in saliva, seems linked to changes of fetal origin, which cause elevation of levels of this weak estrogen. The Adeza test, on the other hand, may be positive more often in cases of microbial infection, Goodwin says.

There are big advantages to having such information. Antocin seems to work most beneficially for preterm labor associated with biochemical alterations; antibiotics are the appropriate treatment for infection-related uterine activity. The two tests may soon be used together to get more clinically useful information.

Adeza currently has a 10-minute, one-step, point-of-care product in a premarket approval (PMA) clinical trial. Meanwhile, PMA-related clinical trials are under way for Biex's estriol-collection test, which simply requires women to "drool into a tube," explains Fred Voss, PhD, Biex's vice president for R&D. The saliva sample is sent to a lab for analysis, usually with an 18- to 24-hour turnaround. The company expects to make its PMA application early this year. Voss says the Biex assay will give physicians a way of detecting the changes directly linked to "the uterus's preparation for contraction and labor." Still unanswered, he acknowledges, is why early-onset labor can't be fully explained by fetal changes or microbial invasion. "For all of our understanding of some of the causes, we still don't know the full story," Voss concedes. "In some women, stress seems to play a role," he says, adding that this is another piece of the puzzle and "something harder to pin down."--A.S.