Midpregnancy Placental Growth Factor Screening and Early Preterm Birth.

Importance: Early preterm birth (ie, at less than 34 weeks' gestation) confers a high risk for adverse health outcomes, yet no universal screening strategy exists, preventing targeted delivery of effective interventions. Objective: To evaluate the ability of midpregnancy placental growth factor (PlGF) screening to identify pregnancies at highest risk for early preterm birth. Design, Setting, and Participants: This prospective cohort study was conducted at an urban, tertiary care center from 2020 to 2023. Participants were unselected, pregnant people with singleton pregnancies, receiving universal-access prenatal care from obstetricians, family physicians, or midwives, who underwent a PlGF test at the time of routine gestational diabetes screening, typically at 24 to 28 weeks' gestation. Data were analyzed from January to May 2024. Exposure: PlGF level less than 100 pg/mL at the time of gestational diabetes screen. Main Outcomes and Measures: The primary outcome was all early preterm birth, defined as less than 34 weeks' gestation. Secondary outcomes included iatrogenic preterm birth, spontaneous preterm birth, preeclampsia, stillbirth, and small-for-gestational-age birth weight. Results: Among 9037 unique pregnant individuals, 156 (1.7%) experienced early preterm birth (52 spontaneous births; 104 iatrogenic births). The area under the curve (AUC) for PlGF and early preterm birth was 0.80 (95% CI, 0.75-0.85). Low PlGF level was associated with early preterm birth (positive likelihood ratio [LR], 79.400 [95% CI, 53.434-115.137]; negative LR, 0.606 [95% CI, 0.494-0.742]; specificity, 99.5% [95% CI, 99.3%-99.6%]; negative predictive value, 98.9% [95% CI, 98.8%-99.1%]). Time to birth from PlGF test was significantly reduced among patients with a PlGF level less than 100 pg/mL, among whom more than 50% delivered within 50 days of testing. Individuals with a low PlGF level made up more than 30% of subsequent stillbirths (aRR, 36.78 [95% CI, 18.63-72.60]) and more than half of patients requiring iatrogenic early preterm birth (aRR, 92.11 [95% CI, 64.83-130.87]). The AUC for iatrogenic early preterm birth was 0.90 (95% CI, 0.85-0.94). Conclusions and Relevance: These findings suggest that low PlGF level (<100 pg/mL), identified at the time of routine gestational diabetes screening, may be a powerful clinical tool to identify pregnant people at risk of early preterm birth, especially in iatrogenic births. Strategic redirection of tertiary health care resources to this high-risk group could improve maternal and perinatal outcomes.