Hormonal clock predicts premature births.

About 6 months into a pregnancy, some anxious parents-to-be stash a suitcase at the front door and nervously wait day and night for that moment when the mother's labor starts and the mad rush to the hospital begins.

Future parents may know better when that dash will begin, if a report in the May Nature Medicine proves accurate. More important, the new work may help physicians understand and prevent premature delivery, which often places the life of the still-developing fetus at great risk.

A team of English and Australian researchers, led by Roger Smith of the John Hunter Hospital in Newcastle, Australia, found that the amount of a particular hormone in the mother's blood can predict, at a remarkably early point in gestation, whether birth will occur prematurely, on time, or late.

The researchers followed the pregnancies of 485 women. At 16 to 20 weeks into the normal 40-week gestation period, they measured the maternal blood concentrations of corticotropin-releasing hormone (CRH), a chemical that the placenta begins to secrete early in the second trimester.

Smith's group compared those early measurements to times of birth. The 24 women who delivered prematurely (defined as less than 37 weeks of gestation) had shown an average of 3.64 times more CRH in their blood than women who gave birth on time (37 to 42 weeks). Those who delivered late had had slightly less CRH than the on-time women, although this case was not as statistically sound.

The authors and John R.G. Challis of the University of Western Ontario in London, in an accompanying editorial, interpret the new data as a ticking "placental clock'' that determines the length of a pregnancy. They express surprise, moreover, that this clock establishes the length at such an early stage.

Past research on CRH had shown that its concentration in the mother's bloodstream rises dramatically as a baby's delivery date approaches. For most of a pregnancy, another protein binds to CRH and blocks its hormonal actions. Smith's team suggests that when CRH concentrations rise high enough to overwhelm the obstructing protein, the delivery process begins.

Puzzling out CRH's role in human pregnancy has proved difficult, notes Hans H. Zingg of the Royal Victoria Hospital at McGill University in Montreal, because the hormone apparently plays no important role during pregnancy in other animals, such as mice.

Zingg also argues that it remains unknown whether CRH or the placenta even starts the clock going. "I think they're looking at the hands of the clock and not the clock itself," says Zingg. He adds that unexpected events, such as infections, may break the rhythm of a pregnancy clock.

Despite those and other outstanding questions, researchers suspect that clinical experiments in which physicians try to lower CRH concentrations to prevent premature labor are not far off. "It's certainly a strategy that merits investigation,'' says reproductive physiologist Peter W. Nathanielsz of Cornell University.