Alpha-1 antitrypsin emerges as a potential target for preventing spontaneous preterm birth: Study

Researchers at the University of Oulu have identified alpha-1 antitrypsin as a potential target for preventing spontaneous preterm birth. In a large genetic study of more than 200,000 mothers, a variant in the SERPINA1 gene, which encodes alpha-1 antitrypsin, was associated with shorter pregnancies. In experiments in mice, treatment with human alpha-1 antitrypsin prevented inflammation-induced preterm birth.

Globally, preterm birth continues to be one of the most significant challenges in maternal and child health. In Finland, 5–6 per cent of babies – around 2,500 each year – are born preterm, and the overall rate of preterm birth has not declined. Despite decades of research, effective treatments to prevent preterm birth remain limited.

Genetic factors are known to influence the length of pregnancy, and researchers have identified around 30 genes that contribute to it. A research group studying pregnancy and childbirth at the University of Oulu and Oulu University Hospital has investigated the role of several of these genes to better understand the mechanisms underlying preterm birth. Their work has drawn on resources including placentas donated after delivery, the FinnGen Research Project, and experimental models of preterm birth.

In a recently published study, the researchers found an association between the Pi*Z variant of the SERPINA1 gene, which encodes alpha-1 antitrypsin, and a shorter gestational duration. The finding builds on the team’s earlier work, in which it was shown that alpha-1 antitrypsin levels are lower in the placentas of mothers who delivered preterm compared to those who gave birth term. Furthermore, rare SERPINA1 variants were observed in families with recurrent preterm births.

In the current study, mothers carrying two copies of the SERPINA1 Pi*Z variant had pregnancies that were, on average, nine days shorter than those of mothers carrying other forms of the SERPINA1 gene. In addition, a high body mass index appeared to further increase the risk of preterm birth in this group.

The SERPINA1 Pi*Z variant is known to reduce the production of alpha-1 antitrypsin and can lead to alpha-1 antitrypsin deficiency. According to the researchers, the findings support the idea that alpha-1 antitrypsin is involved in the biological mechanisms underlying preterm birth. With this perspective, the researchers investigated the potential protective effect of alpha-1 antitrypsin in an experimental model. In these experiments, administration of human alpha-1 antitrypsin prevented inflammation-induced preterm birth in mice. The effect was particularly promising in mice with alpha-1 antitrypsin deficiency. Further studies are under way to investigate its efficacy and safety in greater detail.

“Our results suggest that alpha-1 antitrypsin is involved in the mechanisms underlying preterm birth and that it could potentially be used to help prevent preterm birth in the future,” says Anu Pasanen, Postdoctoral Researcher at the University of Oulu and one of the co-authors of the study.

Reference:

Koivulehto, E., Pasanen, A., Haapalainen, A.M. et al. AAT/SERPINA1 Pi*Z variant linked to gestational length and preterm birth prevention via AAT in mice. Nat Commun (2026). https://doi.org/10.1038/s41467-026-76643-9