Poster Presentation & Flash Talk 46th Annual Meeting of the Fetal and Neonatal Physiological Society 2019

Introduction: Fetal Growth Restriction (FGR) is a common complication of pregnancy. FGR is associated with learning and behavioural deficits later in life and motor dysfunction including cerebral palsy. Pre-clinical data and human MRI studies show FGR disrupts neuronal connectivity in the developing brain. We hypothesize that subtle, but key changes in neuronal microstructure contribute to neurological deficits observed in children that were born growth restricted. In this study we are assessing the neuro-developmental impact of early onset FGR by looking at gross and microstructural development of neuronal cell populations in the third trimester of fetal sheep.

Methods: FGR is induced via single umbilical artery ligation (SUAL) in twin ovine pregnancies at 88 days gestation. Ewes and fetuses underwent post-mortem at 110d (n=14), 127d (n=12) and 138d (n=12) gestation (term is 150 days).

Brains were collected for analysis of key components of neuronal cell morphology and cellular connectivity including dendritic spine architecture via golgi analysis and neuronal maturation via immunohistochemistry.

Results: This is an ongoing study; to date all animal have been completed and brains collected, and neuronal analysis is being completed. Unsurprisingly, the degree of growth restriction worsened with increasing gestational age. At 127 and 138dGA FGR fetal sheep were lighter and at 138d GA fetuses also had larger brain weights, compared to AG counterparts (table 1.).

Conclusion: Our data confirms the clinical applicability of SUAL to induce FGR. We are now well placed to characterise disruption to neuronal morphology and brain connectivity, which will inform the pathological changes underpinning long term learning and behavioural deficits in growth restricted infants. Our findings will provide the basis for studying antenatal treatments to improve brain development.