Combating premature births

A tiny baby's dark eyes and nose peak out from the blanket she's swaddled in, her little fingers grip the edge.

Combating premature births

Births before 37 weeks are linked to early intrauterine inflammation. Researchers have developed a molecule that inhibits this.
December 21, 2016

In the birthing unit at CHU Sainte-Justine in Montréal, receptionists are used to welcoming terribly stressed-out mothers-to-be. Their pregnancy is far from over, yet symptoms are already present: contractions, cramping, heavy bleeding, pelvic pressure, back pain, and so on.

Between 5 and 15 percent of all babies are born premature, and prematurity is the world’s leading cause of death among newborns. Fortunately, this state of affairs may soon be ancient history thanks to a new molecule, known as “101.10,” which keeps babies from arriving too soon.

Developed by a team led by neonatologist Sylvain Chemtob, a CHU Sainte-Justine researcher and the lead author of the study, 101.10 has already produced very conclusive results in mice. “Our molecule is highly effective at low concentrations,” enthuses research associate Christiane Quiniou.

“Premature births are a widespread public health problem, and their rate is not going down,” deplores Mathieu Nadeau-Vallée, a pharmacology doctoral student at the Université de Montréal who is supervised by Chemtob. Amazing medical advances in the last few years improved the chances of survival of babies born between 22 and 37 weeks (out of 40), but they haven’t managed to delay births predicted to be premature. “Current drugs are able to reduce uterine contractions, but they can extend gestation by only a few days at most and often cause undesirable side effects,” the student adds. The psychological consequences on the family and the risk of long-term health problems for the child are still a problem.

To better understand the mechanism behind the new molecule that was developed at CHU Sainte-Justine and whose discovery was published in The Journal of Immunology in August 2015, you need to know how premature birth works. “We know that, with a full-term delivery, normal inflammation in uterine tissue is generally what triggers contractions,” explains Nadeau-Vallée. “We’ve observed that infections can trigger the inflammatory process too early and cause premature delivery.”

On that subject, interleukin-1 (IL-1) has been interesting to researchers for 25 years. It’s a very important protein that is involved in all inflammatory processes. It is present in abnormally high amounts in women giving birth prematurely.

In addition, when it is administered in high doses to mice and monkeys, it triggers delivery. But at the same time, it acts as a bodyguard for developing fetuses, protecting them from infections, among other things.

The ideal scenario would therefore be one where inflammation is prevented and the protective effect is preserved. “And as it happens,” says Quiniou, “the defining feature of our new molecule is that it blocks part of IL-1’s biological effect” — basically keeping only the best part.

Perfecting 101.10 took ten years of research. First, Quiniou modified and optimized it. She then tested it in vitro and checked its effectiveness on inflammatory diseases such as arthritis. “The results were encouraging,” she says, “so we moved on to the next step: prove that our little molecule is effective at preventing premature birth.”

That was when Nadeau-Vallée entered the scene. He used pregnant mice. “Throughout the summer of 2014, I monitored them at the pet store,” he recalls. “When I saw that only the females we had treated with 101.10 were not giving birth prematurely, I knew we had succeeded!”

But the doctoral student didn’t stop at that first success. He repeated the experiment, this time simulating an infection in the mice. Again, those who received the new therapeutic treatment were the only ones to carry to term. An unprecedented advance!

Is this tiny peptide made of just seven amino acids a miracle molecule? Time will tell. Chemtob’s team is now collaborating with leading prematurity researchers from universities in Alberta and Adelaide, Australia.

This article was translated from its original, which appeared in French in the January/February 2016 issue of Quebec Science magazine.