#4-32E. Predicting the Unthinkable: Angiogenic Markers and Stillbirth Risk (JAMANetwOpen, 2026)

Can early identification of angiogenic imbalance prevent unexplained stillbirths? Stillbirth remains a devastating global health challenge, often linked to underlying placental dysfunction. This nested case-control study conducted in Bangladesh investigated the association between the maternal circulating soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio and stillbirth risk. The core finding demonstrates that an elevated sFlt-1:PlGF ratio, specifically utilizing clinically relevant cutoffs such as greater than 38, is significantly associated with an estimated 13-fold increased odds of fetal death. When critically appraising this evidence, clinicians must consider limitations such as the relatively small sample size of stillbirth cases and the reliance on a single-time-point biomarker measurement, which restricts a comprehensive understanding of temporal changes preceding fetal demise. Despite these constraints, the study holds immense clinical relevance for physicians; it emphasizes the potential of incorporating angiogenic biomarker screening into routine antenatal care to effectively identify high-risk pregnancies. Applying these markers could eventually guide targeted monitoring and early interventions, proving especially valuable for reducing the persistent burden of adverse pregnancy outcomes.

Citation: Lee MSS, Christiani DC. Maternal Circulating sFlt-1:PlGF Ratio and Stillbirth. JAMA Network Open. 2026. DOI: 10.1001/jamanetworkopen.2026.7652

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