Small Beginnings, Big Impacts: Brain Development in Early-Onset Fetal Growth Restriction

Abstract

Fetal growth restriction (FGR) is a common pregnancy complication associated with impaired placental function and an increased risk of adverse neurodevelopmental outcomes. However, the mechanisms underlying altered brain development in FGR remain poorly understood. This thesis aimed to investigate fetal brain development and maturation in early-onset FGR using advanced neuroimaging techniques, including magnetic resonance imaging (MRI) and three-dimensional (3D) ultrasound, complemented by deep-learning analyses. First, we demonstrated that fetuses with early-onset FGR have significantly smaller total brain volumes compared to healthy controls, particularly affecting the cerebellum. These differences were partly explained by overall reduced head size, but region-specific vulnerabilities suggest selective brain vulnerability. Second, we showed that automated volumetric assessment using 3D ultrasound is feasible and provides results comparable to MRI, enabling are more cost-effective objective evaluation of fetal brain development. In addition to volumetric differences, we assessed brain maturation using both visual and deep-learning approaches. FGR fetuses exhibited delayed cortical maturation, independent of brain size, supporting the concept of altered neurodevelopment beyond growth restriction alone. However, this maturation delay was not independently predictive of short-term neonatal outcomes. Finally, we explored the relationship between placental dysfunction and brain development, highlighting the importance of the placenta–brain axis in shaping fetal neurodevelopment. Together, these findings demonstrate that early-onset FGR is associated with both reduced brain growth and delayed maturation. The integration of advanced imaging and automated analysis offers new opportunities for objective, antenatal assessment of fetal brain development and may contribute to improved risk stratification and clinical care.