Brain development in fetal growth restriction: A volumetric approach using fetal MRI

Abstract

Fetal growth restriction is the failure of a fetus to achieve its full growth potential, resulting in a neonate that is small for its gestational age. The aetiology of fetal growth restriction is varied and fetal growth restriction secondary to placental insufficiency is attributed to a failure of trophoblast invasion leading to under perfusion of the uteroplacental bed. In response to the adverse conditions in-utero, fetuses tend to compensate by increasing blood flow to the essential organs such as the brain, heart, and adrenals, at the expense of other organs (cerebral redistribution). As a consequence, growth tends to be asymmetric, with maintenance of the head growth velocity while the other growth parameters tail off; an effect which is also known as the ‘brain sparing effect’. Despite this apparent brain sparing effect, children who were growth restricted in utero are at increased risk of developmental delay and behavioural problems. 30 growth restricted and 48 normally grown fetuses were recruited into this study and were imaged using both conventional ultrasound with Doppler assessment, as well as fetal MRI with ssFSE sequences through the feto-placental unit and fetal brain. A dynamic approach was taken when imaging the fetal brain to compensate for the presence of fetal motion. MR imaging of the feto-placental unit detected significant differences in placental appearance, significantly smaller volumes of intra-abdominal and intra-thoracic organs, and significantly smaller regional brain growth among growth restricted fetuses. MR studies of the placenta in fetal growth restriction demonstrated a placental phenotype in growth restricted pregnancies that is characterised by smaller placental volumes, a significant increase in the placental volume affected by apparent pathology on MRI and a thickened, globular placenta. Although placental volume increased with gestation in both groups, the placental volume remained significantly smaller in the growth restricted fetuses (p = 0.003). There was also a significant correlation between the percentage of placental volume affected by abnormal heterogeneity and the severity of fetal growth restriction (r = 0.82, p < 0.001), and an increase in the maximal placental thickness to placental volume ratio above the 95th centile for gestational age was associated with fetal and early neonatal mortality (relative risk = 7, 95%CI = 2.96 – 16.55, p < 0.001) (figure 3.6) MR studies of fetal intra-thoracic and intra-abdominal volumes showed that although the volume of the intra-thoracic and intra-abdonimal organs (heart, lungs, thymus, liver and kidney) increased as gestation increased in both groups, the volumes of all three structures remained smaller in growth restricted fetuses (p < 0.01) (Figures 4.7 - 4.9) compared with normally grown fetuses. MR studies of the fetal brain demonstrated smaller intracranial volume, total brain volume and cerebellar volume in growth restricted fetuses. In addition, growth restricted fetuses with early onset fetal growth restriction demonstrated smaller vermis height and a corresponding increase in the tegmento-vermian angle. Growth restricted fetuses also demonstrated a disproportionate decrease in extra- and intra-cerebral fluid. This thesis showed evidence of changes in regional and global organ growth in growth restricted fetuses using high resolution fetal MRI. It is hoped that future imaging studies could offer useful insights into the origins and clinical significance of these findings and its consequences for later neurodevelopment.