Researchers highlight possible treatment for prematurity, stillbirth

Mar 9, 2015

Cincinnati Children's Hospital researchers James Ertelt (left) and Mr. Jeremy Kinder at work in the lab.
Credit Provided / Cincinnati Children's Hospital Medical Center

One in nine babies in the United States is born premature. That's according to 2012 data from the Centers for Disease Control and Prevention

Cincinnati Children's Hospital researchers think they may have found a way to help prevent pregnancy complications like stillbirth or prematurity.

In a somewhat counter-intuitive step, doctors theorize that blocking, or refocusing, a woman's immune cells could be the answer.

Dr. Sing Sing Way is part of the team studying the role of a woman's immune system in causing pregnancy complications.
Credit Provided / Cincinnati Children's Hospital Medical Center

Dr. Sing Sing Way says microbes can cause a woman's immune system to reject a fetus as well as an infection. "What we've done is to protect the baby by preventing the maternal immune system from that rejection process," says Way.

It's a very delicate process. Way says a pregnant woman's immune system still needs to attack infections, but the idea is to protect the baby from an over-reactive immune response.

Researchers tested their theory on mice. Way says the next step is test the therapy on non-human primates. He says it's still years away from being tested in humans.

The results were published in the March 9 issue of the Journal of Clinical Investigation.

About the research
 

Cincinnati Children's Hospital explains how the theory was tested using mice:

When researchers infected pregnant mice with Listeria, they found specialized subsets of first-responder immune cells (neutrophils and macrophages) that rapidly infiltrate the placenta. These inflammatory cells produce high levels of a chemoattractant protein, CXCL9. This paves the way for harmful T cells that specifically recognize and attack the fetus.

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After infection in pregnant mice, it leads to fetal resorption and stillbirth.

The researchers then discovered that selectively neutralizing CXCL9 activity by blocking its receptor on T cells, CXCR3, kept harmful immune cells from infiltrating the placenta. This prevented stillbirth.

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Researchers also conducted tests to see if blocking CXCR3 would apply to pregnancy complications not caused by prenatal infection. The team used an approach where fetal injury was instead caused by depleting a protective immune-suppressive subset of maternal T cells called regulatory T cells. These cells naturally expand in women during healthy pregnancies, but not in pregnancies complicated by preeclampsia or spontaneous abortion. They found that CXCR3 blockade prevented fetal loss after the depletion of regulatory T cells.