VELOCITY : evaluating fetal growth in pregnancies complicated by pre-existing diabetes

Pre-existing diabetes complicates over 4,000 pregnancies each year in the UK. Adverse outcomes in these pregnancies remain unacceptably high, with perinatal mortality five times higher than that of the general population. Current modalities of monitoring fetal growth fall short in accurately detecting pathological deviations in fetal growth. My PhD set out to explore pregnancies complicated by pre-existing diabetes through interrogation of longitudinal measures of fetal growth (using fractional thigh volume, TVol), placental function (using placental growth factor, PlGF) and glycaemic profiles (using continuous glucose monitoring, CGM). It was hypothesised that pathological deviations of fetal growth in pregnancies complicated by pre-existing diabetes can be detected earlier and more accurately by combining advanced longitudinal fetal biometry measurements, continuous glucose monitoring and placental biomarkers. Over a 5-year period, 253 participants were recruited across two tertiary-level units. TVol has been shown to be highly reproducible within a clinical setting of image acquisition and was comparable in reproducibility to the current clinical gold-standard of determining fetal growth, abdominal circumference. Fetal growth in diabetes was accelerative from the 2nd trimester onwards and TVol was the most sensitive marker of fetal growth. Furthermore, with the application of delta TVol Z score, a subset of pregnancies within the LGA group demonstrated an obvious accelerative growth trajectory and an adverse neonatal outcome: the Macrosomic group. Within the Macrosomic group, abnormal levels of PlGF were identified suggesting a pathological process of placental dysfunction occurring in combination with accelerative growth. The CGM data further highlighted significantly higher glucose levels, for longer period of times and across all trimesters, in the Macrosomic group in comparison to the LGA group. The combination of these novel assessments of pregnancy wellbeing in the context of diabetes has allowed a more in-depth appreciation of the complex relationship between glycaemia, fetal growth and placental function observed in pregnancies complicated by pre-existing diabetes and may allow a progressive step forward in improving the outcomes for both mother and baby.