Placental pathology in low birth weight live births: A systematic review of histopathological patterns, mechanistic insights, and clinical implications

Background: Low birth weight (LBW) (<2,500 g) is a major public health problem around the world, and it is a significant cause of neonatal morbidity and mortality. The increasing evidence suggests that the placenta is a major player in the pathophysiology of LBW in a broad range of structural and functional disorders that affect fetal growth..
Objective: To conduct a systematic review of the current literature to identify and summarize the existing knowledge of placental histopathological changes related to LBW live births and to pinpoint the underlying mechanisms and their clinical significance.
Methods: For studies that were published from January 2000 to December 2025, a comprehensive systematic literature search was done on PubMed, Scopus, Web of Science, and Embase. Original studies of placental histopathological findings in LBW live births were included and excluded.Original articles that studied placental histopathological findings in LBW live births were included and excluded. The selection of the studies, extraction of data, and methodological quality assessment were done following the PRISMA guidelines.
Results: Forty-four studies were eligible for inclusion in the synthesis. Maternal vascular malperfusions (MVM), fetal vascular malperfusions (FVM), villous infarction, increased (syncytial) knot formation, distal villous hypoplasia and chronic inflammatory lesions (villitis of unknown etiology [VUE]) were the most common placentopathies associated with LBW. Taken together, these histopathological patterns equate to chronic uteroplacental insufficiency, which includes an impaired perfusion, chronic hypoxia, and inflammatory activation. Mechanistically, endothelial dysfunction, oxidative stress, angiogenic, and immune dysregulation were identified as major pathways interacting with each other to cause placental injury and fetal growth restriction.
Conclusion: Placental histopathology is important both for mechanistic and diagnostic understanding of the causes of LBW. Combination of placental morphological assessment with clinical and perinatal parameters may aid risk stratification, early detection of high risk pregnancies and targeted prevention and therapeutic interventions.