Maternal Continuous Glucose Monitoring–Placenta–Fetus Axis: A Systematic Review of CGM Metrics Linked to Placental Vascular Pathology and Fetal Outcomes, with a Sentinel Discordant Case

A bstract Maternal glycemic assessment in pregnancy has advanced rapidly with continuous glucose monitoring (CGM), yet clinical interpretation has remained largely maternal-centric. Despite the widespread adoption of pregnancy-specific CGM targets, adverse placental pathology and unexpected fetal outcomes continue to occur in pregnancies labeled as “well controlled.” This disconnect prompted a systematic review of the CGM–placenta–fetus axis, with the aim of examining how CGM-derived metrics relate not only to neonatal endpoints but also to placental vascular and biological pathology. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidance, we systematically searched major bibliographic databases and trial registers, identifying 646 records. After structured screening and full-text assessment, 41 studies met inclusion criteria, encompassing randomized trials, observational cohorts, placental pathology studies, and translational investigations. Data were synthesized across CGM metrics, placental lesion patterns, and fetal outcomes, with the risk of bias assessed using established tools appropriate to study design. Rather than aggregating effect sizes, we pursued a mechanistic synthesis, integrating digital glycemic phenotypes with placental structure, transport biology, and fetal growth or programming trajectories. Across heterogeneous study designs, consistent signals emerged. Time-in-range and mean glucose, while clinically useful, frequently failed to capture glycemic instability, nocturnal dysglycemia, or postprandial exposure patterns linked to maternal vascular malperfusion, villous structural abnormalities, altered glucose transporter expression, inflammatory signaling, and epigenetic changes. Several studies documented placental–fetal discordance despite the CGM targets being met, a pattern further illustrated by a sentinel discordant case. Taken together, the evidence suggests that CGM should be understood as a biological exposure signal interpreted by the placenta, rather than solely a marker of maternal control. Reframing CGM interpretation through a placental–fetal perspective may be essential for advancing precision obstetrics and avoiding false reassurance under current guideline paradigms.