Precision medicine prevents early births

Around 10% of babies are born before their due date, with premature birth being a significant cause of death for children under five worldwide. While advanced medical care in the U.S. helps premature babies survive, many face long-term health issues. Researchers at Stanford Medicine’s March of Dimes Prematurity Research Center are studying unexplained premature births to find ways to prevent them.

David Stevenson, MD, the Harold K. Faber Professor in Pediatrics and senior associate dean of maternal and child health, said, “One of our purposes is to discover ways to decrease the recurrence of preterm birth since women who have had one premature baby are at higher risk for having another.” 

Stevenson, colleague Gary Shaw, and collaborators conducted a study on hormone injections to prevent prematurity. They found genetic differences between women who benefited from the injections and those who did not. Their research demonstrates how precision medicine can tackle challenging medical issues. Stevenson and Shaw discuss their efforts to understand and combat premature birth.

Premature birth is a big concern, especially in the U.S., where one in 10 babies are born too soon. For African Americans, it’s one in five. It’s a leading cause of child mortality globally. Families face challenges beyond the NICU, needing support for years. Prematurity costs society about $30 billion yearly. Precision medicine is applied to understand different causes of premature birth, allowing targeted interventions for each case.

This study revisited the efficacy of progesterone injections in preventing premature birth. Progesterone regulates uterine activity, reducing contractions and inflammation, a common trigger for early labor. Despite promising initial findings, subsequent trials yielded inconsistent results, prompting FDA withdrawal of approval. 

Prior studies may have lacked precision in selecting candidates for progesterone treatment. By analyzing biological samples from a cohort of women in Alabama, we identified genetic markers that may predict response to progesterone injections. This research signals the potential for more targeted progesterone therapy, offering hope for improved outcomes among women at risk of premature birth.

Researchers wondered if there were differences between the people who responded to treatment and those who didn’t, even though the treatment didn’t work. They decided to look at samples collected from pregnant women after they had already been treated to see if there were any clues in their genes. 

They used whole-genome sequencing to search for genetic differences related to premature birth and checked for mutations that might affect how women responded to progesterone injections. Interestingly, They found essential clues in parts of the genome that scientists don’t fully understand yet, showing the potential of this approach for discovering new insights.

Researchers compared their approach to traditional genome screening: it’s like identifying people by their specific address rather than just their ZIP code. Using a complex algorithm, They identified over 1,000 genetic variants across 300 genes, indicating why some patients don’t respond to progesterone. Interestingly, mutations in genes related to uterine contractions, not inflammation, were the issue. 

These women couldn’t benefit from progesterone as it couldn’t control their contractions during pregnancy, making them more vulnerable to premature labor triggers. Their findings pave the way for personalized treatment, where patients can be screened early for these mutations and avoid unnecessary progesterone injections. Additionally, their results suggest potential drugs that could help these individuals, which will be further tested in lab and animal studies.

Precision medicine offers promising avenues for preventing dangerously early births by targeting individual genetic factors and physiological mechanisms associated with premature labor. Tailored interventions based on genetic analysis and physiological insights could significantly improve outcomes for both mothers and babies at risk of premature birth. Further research and clinical trials are warranted to validate these findings and translate them into practical interventions for clinical use.

Journal reference:

CHENG WANG, YUEJUN JESSIE WANG, et al., Integrative analysis of noncoding mutations identifies the druggable genome in preterm birth. Science Advances. DOI: 10.1126/sciadv.adk1057.

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