Landmark clinical trials on preterm birth prevention that have changed clinical practice

Wanlin Li1, Maya Reddy1, Martijn A Oudijk2

  • 1Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia.

Seminars in Perinatology
|December 11, 2025
PubMed

Spontaneous preterm birth remains a leading global cause of neonatal morbidity and mortality, with lasting health socioeconomic consequences. Despite substantial research efforts over the past decades, preterm birth rates are not declining. Large cohort studies have shown that measurement of cervical length by transvaginal ultrasound is the best predictor for identifying women at risk of preterm birth, although sensitivity stays limited. While this has guided randomised clinical trials, preventive strategies remain suboptimal. Progestogens trials have long dominated the research landscape, and evidence synthesis though individual participant data indicates a potential reduction in preterm birth of approximately 30 % for women with a singleton pregnancy and a short cervix. Relative to progestogens, other potentially effective interventions, such as cervical cerclage and pessary have received limited attention, and were evaluated later or not at all. The optimal management of twin pregnancies, an important cause of preterm birth, remains uncertain. Our knowledge base on the prevention of preterm birth can be improved by research with greater uniformity in outcome measures, better prioritization, better evidence synthesis, more balanced resource allocation, and enhanced global collaboration.

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