Preterm birth (PTB), defined as delivery between 20 0/7 weeks and 36 6/7 weeks of gestation, remains a major public health challenge both nationally and globally.1,2 In the United States (U.S.), the Centers for Disease Control and Prevention report that 65 percent of infant deaths occur among infants born preterm.3 Infants born at earlier gestational ages experience the greatest morbidity and mortality, with those delivered before 28 weeks facing a risk of death nearly 170 times higher than term infants.4 Worldwide, PTB is the leading cause of death in children under five years of age.5

Beyond the immediate risk of infant death, prematurity carries long-term consequences for survivors, including chronic health problems and intellectual disabilities.6,7 Despite advances in research and the development of interventions, PTB rates have not substantially improved. Global PTB rates have remained largely stable between 2010 and 2020, while in the U.S. the rate increased steadily from 2014 through 2019, showed a slight decline in 2020, and then rose again in 2021.8, 9, 10, 11 Most recently, the U.S preterm birth rate was 10.4 % in 2024, unchanged from 2023 (Fig. 1) .12 The economic burden is also significant adding approximately $26.2 billion annually to U.S. health expenditures.13

The etiology of PTB is complex and multifactorial, with maternal, fetal, and placental contributors. Proposed mechanisms include inflammation, uterine overdistention, cervical insufficiency, and genetic predisposition.14,15 Medically indicated preterm births contribute to neonatal morbidity but are beyond the scope of this review. We focus on spontaneous PTB, summarizing current approaches to prediction with an emphasis on early identification to inform preventative and therapeutic strategies.