The Crystallized Clues of the Placenta: A Systematic Review of CalcificationPatterns and Their Prognostic Value in Obstetric Risk Management

<p> Introduction: Placental calcification, traditionally considered a benign feature of placental aging, may indicate pathology when it appears early or progresses excessively. This review examines its prognostic value, the limitations of the Grannum grading system, and the role of advanced ultrasound-based assessments. </p><p> Methods: Following PRISMA 2020 guidelines, we systematically searched PubMed, Scopus, Web of Science, and Embase, with additional manual reference checks (January 1990–March 2025). Eligible studies evaluated placental calcification by ultrasound and reported outcomes including fetal growth restriction (FGR), preeclampsia, preterm birth, stillbirth, or related neonatal complications. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Newcastle–Ottawa Scale or AMSTAR-2. </p><p> Results: From 2,181 records, 48 studies were included. Early or excessive calcification, particularly before 34 weeks, was consistently associated with increased risks of FGR, hypertensive disorders, preterm birth, and stillbirth. The Grannum grading system showed limited sensitivity and prognostic utility. Advanced imaging modalities, including 3D/4D ultrasound, Doppler vascular indices, and shear-wave elastography, improved diagnostic granularity. Combining morphological, hemodynamic, and biomarker data (e.g., placental growth factor, sFlt-1) further enhanced predictive performance. Certainty of evidence was generally low to moderate due to methodological heterogeneity. </p><p> Discussion: Findings suggest that placental calcification is not invariably physiologic but may reflect active pathological processes. Multimodal ultrasound and biomarker integration hold promise, though standardization and validation are needed. </p><p> Conclusion: Placental calcification, when assessed with modern multiparametric imaging, can serve as a clinically actionable marker of placental insufficiency. Multicenter prospective studies are essential to refine definitions, harmonize protocols, and validate predictive models for precision obstetrics.