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Surprising Study Finds Possible Culprit in Preterm Births

By R&D Editors | November 10, 2016

Researchers have uncovered a surprising possible trigger for some preterm births: calcium buildup in the womb, similar to the kind that stiffens older people’s arteries or causes kidney stones.

Ohio researchers studying more than 100 pregnant women found that when a mom-to-be’s water breaks too early, the culprit seems to be abnormal calcium deposits that make the normally elastic amniotic sac prone to rupture.

It’s a small study and more research is needed to prove if calcification really is behind this baffling kind of prematurity and if so, what to do about it. But the research, reported Wednesday in Science Translational Medicine, raises the possibility of investigating interventions.

“To have a new potential mechanism for one significant form of preterm birth is quite exciting,” said Dr. Edward McCabe, chief medical officer of the March of Dimes, who wasn’t involved in the study.

Premature birth — being born before 37 weeks of pregnancy — can cause lifelong health problems, and babies who are very premature can die. Sometimes there’s an obvious cause for prematurity, such as an infection. Yet most of the time, doctors can’t explain what triggers preterm birth in an otherwise healthy pregnant woman.

Dr. Irina Buhimschi of Nationwide Children’s Hospital took a closer look at a curiosity: Calcified plaques have often been spotted in placentas after birth — both preterm and full term — and no one knows why.

But abnormal calcification is well-known to play a role in a number of disorders. Clusters of minerals, known as calciprotein particles, that float in the blood may be deposited in soft tissue instead of the skeleton, leading to such problems as artery-stiffening atherosclerosis or kidney stones.

Could that process go awry in preterm birth, too? Buhimschi’s team found higher concentrations of the calcium-containing deposits in the amniotic sac when a mom’s water broke prematurely than with full-term births or other types of preterm births.

Amniotic fluid can produce calciprotein particles, the team found — and with preemies, that fluid also contains lower levels of a protein named fetuin-A that’s supposed to keep those deposits from being dumped in the wrong place, like the amniotic sac. Lab experiments found those deposits led to less flexible fetal membranes.

“We’ve shown that formation of these particles in amniotic fluid is unhealthy, and we need to keep it in check,” Buhimschi said.

Importantly, testing mom’s blood didn’t uncover any signal that a problem was brewing. Buhimschi said the problem may be restricted just to the amniotic fluid — if the fetus’ own organs simply don’t produce enough fetuin-A to protect itself. But that would pose a barrier to uncovering at-risk pregnancies, because testing amniotic fluid is risky.

It’s a plausible theory, said Dr. Catherine Spong, a maternal-fetal specialist at the National Institute of Child Health and Human Development.

But “the clinical relevance of this finding remains to be explored,” Spong cautioned. “Preferably noninvasive methods for detection might allow for the development of interventions or the opportunity for prevention.”

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