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Preterm Labor a Thing of the Past? Scientific progress on early delivery

This November, the March of Dimes gave us some mixed news about the state of preterm births in this country. On the high side, for the first time in three decades, the percentage of U.S. births that were early (before 37 weeks) had fallen for two straight years – from 12.8 percent in 2006 to 12.7 in 2007 and 12.3 in 2008.

The bad news was that the U.S. still gets a “D” grade in preterm births. The goal set by the CDC’s Healthy People initiative was 7.6 percent. And the U.S. notoriously lags behind most other developed nations (in Sweden, for example, the rate is closer to 6 percent). Preterm birth is the leading cause of newborn death – which helps explain why we also stack up poorly with other developed nations in infant mortality – and it ups the chances of NICU stays, complications like breathing difficulties, and even the chance of later intellectual disabilities.

It’s a growing consensus in the medical and public health fields: babies need as much womb-time as they can get, and every day counts. In fact, even though 37 weeks is considered full term, groups like the American College of Obstetricians and Gynecologists recommend waiting until 39 weeks to induce labor, barring medical necessity. And many doctors and hospitals are catching on and prohibiting the practice of delivering before 39 weeks – even using ultrasounds to verify a baby’s age before going forward.

The practice of elective inductions – in which a doctor schedules a delivery for a non-medical reason – is partly to blame for our high preterm birth rate. But that’s far from being the whole story. Preterm labor creeps up on women through lots of different channels – stress, personal health history, and infections are known to play a role. When it happens, bed rest or hormones can sometimes stave off contractions, but preventing preterm labor and birth is tricky, and the odds of success aren’t great.

That’s because doctors and researchers have never been able to pinpoint exactly what starts the whole process of labor and childbirth in the first place. The biological triggers that tell a mom’s body to start contractions have been a mystery.

That changed last month. A team of biochemists from the University of Texas Southwestern Medical Center in Dallas reported in the journal Nature that they had identified the exact molecular trigger that starts labor and delivery.

The researchers used the mouse uterus as a model, tracking the expression of certain genes as contractions begin (they also grew samples from the human uterus to check that the process applied to us as well). The key turned out to be that tiny micro-fragments of RNA (DNA’s single-stranded cousin) in the uterus become extra active at the end of pregnancy. As circulating progesterone levels fall, these miRNA pieces are expressed strongly.

The miRNA affect two important genes, called ZEB1 and ZEB2. These two genes keep labor at bay, because they keep levels of contraction-inducing hormones, like oxytocin, down. Rising miRNA block the two genes, letting oxytocin loose, and labor begins.

Doctors and researchers know that infections and inflammation cause women to go into labor early. So they tested this on mice, inducing labor in some with an infection and others with hormones. Sure enough, the cascade of miRNA and ZEB genes held up. Now scientists know that when a woman gets an infection, the genes and the miRNA likely kick off contractions.

With the molecular pathway to labor understood more fully, the Texas team will start looking for ways to suppress the action of the miRNA – with an eye toward therapies that could hold off pre-term labor. If it bares out in future study, the work could eventually help put the country on track toward more full-term deliveries and healthier babies. Given how poorly we’re doing when it comes to delivering healthy, full-term babies, this is a welcome advance, and one that could have big implications for future moms.

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