Fetal cerebral blood flow redistribution: an analysis of Doppler reference charts and the association of different thresholds with adverse perinatal outcome

Objectives: The objectives of the study were: 1) to compare published Doppler reference charts of the ratios of the middle cerebral and umbilical arteries, the cerebro-placental or the umbilical- cerebral ratio; and 2) to assess the association of thresholds of these charts with short-term composite adverse neonatal outcome in a cohort of women considered at risk of late preterm fetal growth restriction. Methods: 1) Reference charts for the cerebro-placental or umbilical-cerebral ratio were searched in PubMed. Algorithms for plotting the median and the 10th or the 90th percentile against gestational age were extracted from the publication or calculated from published tables. 2) Data from a prospective European multicenter observational cohort study of singleton pregnancies at risk of fetal growth restriction at 32+0 to 36+6 weeks of gestation (n=856) were used to compare the charts for their association with composite adverse outcome. Composite adverse outcome comprised both abnormal condition at birth and major neonatal morbidity. Fetal arterial Doppler measurements were collected longitudinally during this study. Results: 1) Ten studies with reference charts for the cerebro-placental or the umbilical-cerebral ratio were retrieved. The 10th or the 90th percentiles showed large differences, while median values were more similar. In the range of 28 - 36 weeks there was no relation between UCR - CPR and gestational age. 2) Comparison of percentile thresholds, multiple of the median (MoM) values as calculated from these charts, or absolute values, showed a similar association with the composite adverse study outcome, both after univariable analysis and after adjustment for gestational age, estimated fetal weight and preeclampsia. The adjusted odds ratio for the composite adverse outcome of an absolute umbilical-cerebral ratio ≥0.9 (≥1.75 MoM) or an absolute cerebro-placental ratio <1.1 was 3.3 (95% CI 1.7 - 6.4), and of an absolute umbilical-cerebral ratio ≥0.7 - <0.9 (≥1.25 - <1.75 MoM) or of an absolute cerebro-placental ratio ≥1.11 - <1.43 this was 1.6 (95% CI 0.9 - 2.9). Conclusions: In the gestational age range 32 to 36 weeks adjustment of the cerebro-placental or the umbilical-cerebral ratio for gestational age is not necessary. The adoption of absolute cerebro-placental or umbilical-cerebral ratio thresholds, independent of reference charts, is feasible and is easier for clinical use than referring to percentiles or other gestational age normalized units. The high variability in percentile thresholds among the commonly used reference charts impedes reliable diagnosis and clinical management of late preterm fetal growth restriction. This article is protected by copyright. All rights reserved.