Placental Histopathologic Lesions Associated With Stillbirth: A Systematic Review

Stillbirth is a major contributor to perinatal mortality. Placental examination is central to stillbirth evaluation. Published evidence is heterogeneous in lesion taxonomy, sampling approaches, comparator selection, and confounder control. We conducted a systematic review following PRISMA guidelines. We searched PubMed, Embase, and Scopus and screened reference lists to identify comparative observational studies. These studies evaluated placental histopathology in stillbirth compared with live birth or other clearly defined nonstillbirth comparator groups. We included studies that estimated stillbirth associations and those providing comparative insights into lesion reporting. Data were extracted on study design, stillbirth definition, comparator characteristics, placental sampling and reporting methods, lesion definitions, and reported association measures. Risk of bias was assessed using the Newcastle-Ottawa Scale. Due to substantial clinical and methodological heterogeneity, findings were synthesized narratively with structured tabulation. Across included studies, stillbirth was consistently associated with multidomain placental pathology. This was most prominent for vascular malperfusion and obstructive or hemorrhagic injury. Recurrent signals were also observed for villous maturation and hypoxia pattern abnormalities. Inflammatory lesions frequently co-occurred with vascular findings. These results support placental vascular pathology, villous developmental abnormalities, and inflammation as recurring domains linked to stillbirth. The findings underscore the need for more standardized definitions, sampling, and reporting. Standardization is needed to improve comparability and clinical interpretability.