Peasley, Rachel Laura; (2025) Novel phenotype definition and management of Fetal Growth Restriction occurring late in pregnancy. Doctoral thesis (MD (Res)), UCL (University College London).

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Abstract

Aims and Objectives: Define a new late fetal growth restriction (FGR) neonatal phenotype based on antenatal ultrasound (USS) parameters associated with placental insufficiency and adverse NNO. (Aim 1-Chapter 4) Assess the impact of antenatal USS parameters to risk stratify late FGR to allow a “low-risk” group expectant management to 41 weeks. (Aim 2-Chapter 5) Evaluate a new FGR risk stratification and management protocol versus a pre-clinic implementation cohort. (Aim 3-Chapter 6) Develop an outcome model of prediction. Methods: Women were reviewed in the UCLH late FGR clinic and evaluated prospectively (February 2018 – September 2019). Late FGR USS diagnostic criteria included ≥32 weeks and EFW <10th centile, or EFW >10th centile with abdominal circumference (AC) drop ≥50 centiles, cerebroplacental ratio (CPR)<5th centile or umbilical artery pulsatility index (UmbA PI) >95th centile. Late FGR pregnancies were risk-stratified by USS (UtA Doppler, EFW centile, AC drop, CPR, UmbA Doppler), maternal biochemistry and comorbidities. Low-risk FGR were conservatively managed to 41 weeks and high-risk FGR pregnancies advised delivery at 37-38 weeks. Individual elements of adverse NNO were identified from literature review, core outcomes and a local expert Neonatologist. Association between antenatal USS parameters and adverse NNO was explored (Aim 1). Late FGR pregnancies managed before the “late fetal FGR clinic management protocol” were evaluated as a comparison group (Aim 2). A multiple parameter model for outcome prediction was developed using a time series analysis (Aim 3). Results: There were 321 pregnancies in the late FGR clinic included in the study; 165 “high-risk” and 156 “low-risk” and 323 pregnancies in the pre-clinic cohort. Compared to the high-risk late FGR clinic and the “low-risk” pre-clinic cohorts; the “low-risk” late FGR clinic had significantly less overall adverse NNO 44.9 vs 57.6% OR 0.6 (0.4-0.9) p=0.04. No difference was found in severe adverse NNO or maternal outcome. In a time series analysis including fetuses managed according to clinician’s expertise and local guideline prior to the implementation of the new protocol, adverse NNO was lower in the “new” versus the “old” group (56.5 vs 63% OR 0.8 (0.5-1.3) p=0.319. The predictive model showed that the lowest risk of adverse NNO in low-risk pregnancies was with delivery at 39-40 weeks with increased risk after 41 weeks. Conclusions: I defined a new neonatal phenotype of the baby affected by late FGR in both SGA and AGA fetuses and successfully implemented the UCLH late FGR clinic. I antenatally defined and showed high- and low-risk FGR pregnancies were associated with a higher and lower risk of adverse NNO. I showed that low-risk late FGR expectantly managed to full term had improvement in NNO with no increase in neonatal mortality or adverse maternal outcome. The impact of my protocol was confirmed in a time series analysis and I developed a model for prediction of outcome which showed that the lowest risk of adverse NNO was with delivery at 39-40 with increased risk after 41 weeks where risk of prematurity is low and the risk of pregnancy associated complications start to increase.

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