Association between first‐trimester placental growth factor and preterm birth: A prospective cohort study

BACKGROUND: Preterm birth (PTB) is a leading cause of global neonatal mortality and long-term complications. Placental growth factor (PlGF) is a key regulator of placental vascular development; however, prospective evidence regarding the association between its first-trimester levels and the risk of PTB remains insufficient. This study aimed to investigate the association between first-trimester PlGF levels and PTB, including its subtypes. METHODS: This was a single-center prospective cohort study. From August 2023 to October 2025, a total of 1448 women with singleton pregnancies at 11-13 + 6 weeks of gestation were enrolled at Peking University International Hospital. Peripheral blood was collected during the first trimester for the measurement of PlGF concentration. Raw PlGF concentrations (pg/mL) were converted to multiples of the median (MoM) using the Fetal Medicine Foundation online calculator. The primary outcome was PTB, defined as delivery between 28 and < 37 weeks of gestation. The association between PlGF and PTB was assessed using multivariable log-binomial regression, restricted cubic splines, and Cox proportional hazards models. RESULTS: Among the 1448 participants, 80 (5.5%) experienced PTB. Lower first-trimester PlGF-MoM was associated with an increased risk of PTB after adjustment for maternal characteristics (adjusted risk ratio = 0.303, 95% confidence interval: 0.14-0.61). Restricted cubic spline analysis demonstrated a significant nonlinear association (p for nonlinearity <0.001), with higher PTB risk observed primarily among women with lower PlGF-MoM levels. Time-to-event analysis further showed that higher PlGF-MoM was associated with a lower cumulative incidence of PTB (adjusted hazard ratio = 0.56, 95% CI: 0.35-0.88). Incorporating PlGF-MoM into a clinical prediction model modestly improved discrimination (area under the curve from 0.590 to 0.684, P = 0.01), although predictive performance remained limited. CONCLUSION: Lower first-trimester PlGF-MoM was associated with an increased risk of PTB in this prospective cohort, showing a nonlinear exposure-response pattern. First-trimester PlGF might provide additional information for early identification of women at higher risk of PTB; however, its clinical utility requires validation in larger and diverse populations.