Beyond “Well-Controlled” Diabetes in Pregnancy: A Systematic Review of Fetal Functional Changes Suggestive of Occult Fetopathy

ABSTRACT Pregnancy is often classified as “well controlled” when maternal glycemic indices fall within recommended targets and fetal growth remains within expected limits. However, emerging evidence suggests that these criteria may not fully reflect fetal biological status. This systematic review aimed to synthesize current evidence on functional and molecular fetal alterations associated with diabetic pregnancy despite apparently adequate metabolic control , with particular attention to patterns suggestive of occult fetopathy. A comprehensive search of MEDLINE, Embase, and Scopus was conducted without date or language restriction, and study selection followed PRISMA 2020 guidance. Observational studies, imaging-based investigations, biomarker analyses, and selected mechanistic studies reporting fetal, neonatal, or long-term offspring outcomes were included. Forty-two studies met the inclusion criteria and were analyzed using a narrative synthesis due to methodological heterogeneity. Across studies, functional differences in cardiac deformation, atrial dynamics, ventricular synchrony, renal perfusion, and neurodevelopmental imaging parameters were reported , even in the presence of normal fetal growth and conventional Doppler findings. These observations were described across diverse populations and study designs, and in some cohorts were associated with later cardio-renal or neurodevelopmental outcomes , although causal inference remains limited. Placental and metabolic biomarker findings further indicate that average glycemic measures may not capture temporal variability or adaptive placental responses relevant to fetal physiology. Taken together, these findings highlight a recurring discrepancy between conventional markers of glycemic control and reported fetal functional parameters. This synthesis is presented as a hypothesis-generating framework , emphasizing that current evidence reflects associations rather than established mechanisms. While not intended to redefine clinical practice, the findings suggest that reliance on growth-based and averaged metabolic indicators alone may overlook aspects of fetal adaptation in diabetic pregnancy.