Ultrasound Reference Ranges of the Intra-amniotic Umbilical Cord Vein: Statistical Modelling and Implications for the Detection of Intrauterine Growth Restriction

Background: The umbilical vein transports oxygen and nutrient rich blood from the placenta to the fetus. Vein parameters related to blood flow can be reduced in intrauterine growth restriction.
Aims: The principal research aims were to construct gestational age related reference ranges of the umbilical cord vein diameter, peak velocity and blood flow using a regional New South Wales population and to assess the ability of these ranges to identify intrauterine growth restriction. Secondary aims were to document simple measurement methods and investigate relationships between umbilical cord vein measurements, birthweight categories and gestational age.
Method: This was a quasi-experimental study of low risk, singleton pregnancies between 16 and 42 weeks of gestation. The umbilical cord vein diameter and peak velocity were measured using B-mode and duplex Doppler, respectively, and blood flow was calculated. Intraclass correlation coefficients assessed sonographer reliability. Linear mixed modelling analysed the relationships between the vein parameters, three birthweight categories and gestational age. Reference ranges for umbilical cord vein parameters and ratios were established using quantile regression analysis of data provided by a subgroup of “normal” pregnancies (nAGA group). A small group of moderately growth restricted fetuses (IUGR/FGR group) was used to assess the potential clinical utility of these reference ranges. Sequential plotting of data against advancing gestational age enabled investigation of longitudinal trends and slopes.
Results: Maternal characteristics and pregnancy outcomes were typical of the Australian population. Sonographer reliability showed almost perfect agreement. Birthweight category modelling demonstrated a significant difference between the categories for all three vein parameters, but overlap of the 95% confidence interval curves at some gestational ages. Reference ranges were developed and all three vein parameters increased with advancing gestational age, with diameter and blood flow exhibiting a decline in the late third trimester. In combination, the 10th percentile of the reference ranges and birthweight categories cut-offs, identified 62.2% of attendances of the IUGR/FRG group for the umbilical cord vein diameter and blood flow, whereas the peak velocity and ratios had poorer rates. The diameter was the only parameter to demonstrate a negative slope on longitudinal plotting.
Implications for clinical practice: These reference ranges provide normative data from an Australian sample. The umbilical cord vein diameter is simple to measure, had a negative slope on longitudinal plotting, and can be easily utilised in a broad range of clinical situations. The umbilical cord vein peak velocity had a poor detection rate of growth restricted data and the confidence intervals of the birthweight categories overlapped during a crucial 15 week period of fetal growth. These findings imply that peak velocity has a limited clinical application and may explain the historical neglect of this Doppler measurement. The blood flow in the umbilical cord vein identified more than half of the growth restricted data, but required two measurements and a calculation that incorporated several assumptions. No clinical benefit was identified by analysis of umbilical cord diameter and peak velocity ratios.
Conclusions: Reference ranges for the umbilical cord vein diameter, peak velocity and blood flow were developed using quantile regression from a cohort of low risk, singleton pregnancies in Central West New South Wales. The diameter reference range has the most potential to assist in the diagnosis and monitoring of fetal growth restriction in the second half of pregnancy.