Predicting fetal growth early in pregnancy with non-invasive MRI: Validation in a preclinical model

Project Summary Nearly 50% of all pregnancies complicated by fetal growth restriction (FGR) go undetected until after birth, despite improvements in obstetric imaging and management. To avoid stillbirth, if FGR is detected, many babies are delivered preterm and may face poor outcomes associated with immature organs. Early diagnosis

of FGR and the ability to predict abnormal fetal oxygenation later in gestation would improve outcomes for these babies not only during pregnancy and the neonatal period but also throughout life. Currently there are no methods for early second trimester diagnosis of placental dysfunction leading to poor fetal growth early in

the second trimester. Developing safe diagnostic tests of placental and fetal function is therefore critical to improving population health. This project will use Magnetic Resonance Imaging (MRI) of the placenta and fetus to comprehensively model and measure markers of placental maturation, growth and

function in FGR. Importantly, Magnetic Resonance Imaging (MRI) is safe and can image the whole fetus and placenta throughout pregnancy, providing rich complementary information to existing ultrasound imaging data. We hypothesise that MRI in early gestation used to measure placental function and oxygenation will

1) predict fetal growth several weeks later and 2) correlate with gene and protein expression of molecular markers of the regulation of placental growth, transport and function in late gestation. In SA1, we will perform predictive MRI scans at 80 and 105d gestation in sheep (term, 150d), which is equivalent in body weight and brain maturation to a human fetus at ∼20 and 28 weeks gestation, and again

at 130d gestation (equivalent to a term human fetus). These predictive MRI scans will measure placental diffusion, oxygen saturation in the fetal blood in the placenta, placental oxygen consumption and oxygen delivery to the uterus and the fetus. A late gestation scan will be a validation MRI to show placental and fetal

function and growth and thus the predictive capacity of the earlier scans. We will address SA2 by measuring the functional response of the placenta to an increase in maternal oxygenation during each MRI session. This will allow us to determine if pregnancies complicated by FGR have a different response in placental

function from normal pregnancies. This is important as it may act as a diagnostic test in addition to normal placental function as determined by MRI. SA3 will be addressed by collecting samples of the placenta to measure gene and protein markers that are known to regulate growth and to be markers of maturation and/or

dysfunction on the day after the last MRI. These studies will determine if MRI can be used to measure placental function early in the second trimester to diagnose FGR and to predict fetal growth and outcome in the third trimester. This will allow us to determine if there is a relationship between the noninvasive MRI data

and molecular regulation of placental growth and thus identification of potential targets for intervention to improve placental and fetal growth in the future.