Premature birth, meaning a baby arrives three or more weeks before the due date, affects about 10% of pregnancies worldwide, according to Stanford Medicine professor Brice Gaudilliere.
The triggers of human labor are still incompletely understood, the researchers say, making it hard to keep it from starting too early.
So Gaudilliere and his colleagues tried a workaround. They built computer versions of pregnant women’s immune systems, called digital twins, and tested drugs on those virtual patients before any pregnant patient had to take them. The idea was to weed out weak candidates early, so only the most promising ones ever reach a person.
One pairing came out ahead: aspirin and the acid reflux medicine lansoprazole. The team has since taken it into animal testing and toward a human trial, but no results from people have been announced, and the combination remains experimental.
The study was published Oct. 21 in Science Advances.
A Quarter Of A Billion Cells Trained The Model
These twins copy only the immune system, with no fetus and no full pregnancy in the simulation.
In the Science Advances study, the team collected blood from pregnant women and exposed immune cells from those samples to different drugs. Gaudilliere says they measured responses from a quarter of a billion cells to train the algorithm.
A second dataset followed: measurements gathered over time from 63 pregnancies, linked to clinical outcomes. That helped the model connect immune patterns to real outcomes and account for differences between patients.
The finished system is called SIMCO, short for Simulated Immune Modeling of Clinical Outcomes. From a small blood sample, it predicts how a patient’s immune cells will react to a drug and what that could mean for her clinically.
“You’re making the prediction for one individual based on knowledge of millions of single cells from dozens of patients,” said co-lead author Jakob Einhaus.
Researchers checked its predictions of time to labor against what actually happened and described the forecasts as accurate.
Labor May Run On An Immune Clock
The approach rests on a timetable the immune system appears to follow during pregnancy.
Early on, the immune system adjusts so the body tolerates a fetus that’s immunologically different from the mother. Later, immune changes, including a shift toward pro-inflammatory signals, help prepare the body for labor. If those signals activate too early, they can contribute to early labor.
The team builds on about two decades of Stanford research into these shifts. Prematurity is the leading cause of death among children younger than 5 worldwide, according to Stanford, and Gaudilliere says it has been decades since doctors got a new drug-based way to prevent preterm birth.
Related: 7 Ways to Strengthen Your Immune System Naturally
Nine Drug Regimens Took Turns On The Twins
Nine candidates went in, and one pairing of existing medicines pulled ahead.
The researchers ran nine possible regimens through the system to see whether each would speed up or slow a patient’s modeled immune progression toward labor, comparing treated and untreated versions across multiple copies of every person’s twin.
The candidates came from a drug-repurposing pipeline built by a group led by Marina Sirota at the University of California, San Francisco, all chosen because they were already known to be safe in pregnancy.
The standout was aspirin paired with lansoprazole, which is sometimes prescribed during pregnancy for acid reflux.
Earlier research found that low-dose aspirin alone modestly reduces the risk of premature birth. Gaudilliere says the pairing was predicted to strengthen immune processes that support continuing a pregnancy while inhibiting those that trigger labor. His team interprets that as the two drugs working together.
Folic Acid Had A Surprise Of Its Own
The screen flagged a second candidate that’s already part of pregnancy advice.
Folic acid also slowed the modeled march toward labor. It’s already recommended during pregnancy to reduce the risk of spinal cord defects in the fetus.
“We’re giving folic acid for spina bifida prevention, but maybe, unknowingly, we’re also helping the maternal immune system adapt to pregnancy,” Einhaus said.
Nothing so far shows that folic acid prevents early labor in people.
Now Comes The Test In People
Stanford reports the team has FDA permission to try the pairing in a human clinical trial.
That permission is for testing, and the combination isn’t approved for preventing premature birth. The trial is described as starting, but whether anyone has enrolled, how many people it will include, and which doses it will use remain open questions. No dose-specific safety data for the pairing has been described, so nothing here can guide someone pregnant.
Gaudilliere says the team is on the brink of making a real impact on preterm birth, and that it has moved from discovery work to patient testing in a short time.
The twins might end up doing more than ranking drugs. The researchers suggest they could eventually help identify likely responders and nonresponders, which could make trials more targeted, though that hasn’t been shown yet.
Would you trust a computer simulation to help pick a pregnancy treatment, or would you want human trial results first?
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