The DV has a sphincter-like action. It appears as a narrow vessel projecting a high-velocity jet posteriorly to reach the foramen ovale. The high peak velocity in the DV, comparable with arterial velocities, probably gives the blood sufficient momentum to reach the foramen ovale without extensive mixing with the deoxygenated blood [10, 11]. Velocimetry of the DV carries new diagnostic possibilities to evaluate preload or cardiac function. The normal Doppler flow waveform of the ductus venosus indicates the continuous triphasic forward flow throughout the cardiac cycle with a peak during systole, another one during passive diastolic filling, and a smaller nadir during atrial contraction [12, 13].
Several studies investigated the diagnostic value of ductus venosus blood flow in detection of fetuses with congenital heart disease, hypoxic or congestive fetal myocardial diseases both from a clinical and a scientific point of view. There is now a well-documented association between abnormal DV flow and complicated monochrionic multiple gestation, chromosomal anomalies, and adverse fetal outcome [1,2,3, 14].
Hence came the need for sitting reference values for the ductus venosus different waves. The purpose of this study was therefore to establish longitudinal reference ranges for DV PSV, VAC, S/A ratio, RI, PI, and diameter suitable for use with serial measurements for fetal surveillance, and we have also provided the necessary terms for calculating individually conditional reference intervals suitable for individual serial measurements.
The reference ranges we have established for the DV differ slightly from those of other cross-sectional studies. In comparison, the reference ranges of DV PSV curve published by Bahlmann et al. [15] were at 14 weeks 48, at 30 weeks 65.71, and at 40 weeks 65.83, while our results were at 14 weeks 41.4, at 36 weeks 62.63, and at 40 weeks 57.11. Comparing with Axt-Fliedner et al. [16] (at 11 weeks 34.1, at 16 weeks 45.5, and at 20 weeks 57.5), our results were at 11 weeks 37.14, at 16 weeks 44.69, and at 20 weeks 51.58. Our findings were close to Bahlmann et al.’s [15] findings which had few observations for the last weeks of pregnancy, also close to Axt-Fliedner et al.’s [16] findings which had few observations in the early weeks and excluded fetuses with biometric parameters of the head and abdomen outside the 90% reference interval.
In comparison with another longitudinal study of Kessler et al. [17], the reference ranges of DV PSV were at 21 weeks 60.81, at 31 weeks 71, and remained at this level until 40 weeks) while our results were at 21 weeks 53.29, at 31 weeks 64.72, and at 40 weeks 57.11. The authors noted a linear increase in mean peak flow in the previous studies; furthermore, our reference ranges are lower than those reported in this study, as demonstrated in Fig. 8. The observed difference may most likely be due to the different statistical methods used in establishing the reference range and to the different size of the patient population.
In comparison to our reference DV A wave velocity curve with those published by Bahlmann et al. [15], Axt-Fliedner et al. [16], and Kessler et al, [17], we have demonstrated a pattern for A wave velocity with some difference in ranges. Our findings were higher than Kessler et al.’s [17] findings as shown in Fig. 9; the explanation for this difference might be that Doppler traces with mono- and biphasic flow patterns with comparably high end-diastolic velocities were included in their analysis as they were considered a normal variant, while in our study these traces were excluded. In addition, differing methods for statistical analysis may account for this difference.
In our study, DV S/A ratio nomogram had a parabolic pattern close to that found by Bahlmann et al. [15] (at 20 weeks 2.58, at 30 weeks 2.01, and at 40 weeks 1.99), that is probably attributed to the fact that the Doppler standard curves of the ductus venosus described in both studies were derived from a large patient population and show greater homogeneity of the measuring values for the individual weeks of gestation.
There was a slight difference in range compared to the work of Tongprasert et al. [18] and a wide difference when compared to Axt-Fliedner et al. [16] as shown in Fig. 10. This difference is probably depending on equipment, insonation techniques, angle correction, and racial factors. These findings suggest that each population group may probably need its own normal reference range for clinical application.
Regarding the DV PI curve, our references were close to those published by Bahlmann et al. [15] and Tongaprasert et al. [18]. We have demonstrated a pattern for PI with some difference in ranges; however, it was determined to be close to it. Per Bahlmann et al. [15], the calculated indices were associated with markedly greater reliability and less intra-individual variation than which of maximum flow velocities, and we have demonstrated that their PI pattern was like our present results at mid-gestation, but lower than our results later in pregnancy, as shown in Fig. 11. The difference may be due to that reference curves were constructed for individual measuring parameters based on growth function from a four-parameter class of monotonic continuous functions according to the smallest square principle. And the same Doppler velocimetry technique used by this study was an explanation of the similarity.
Tongaprasert et al. [18] on the other hand found that the DV indices decreased relatively rapidly at the first half of pregnancy and were relatively constant or slightly decreased during the second half of pregnancy. Therefore, the linear equation could not be used in evaluating DV velocity in the first half of pregnancy, and this may be the cause that our present results were higher than those obtained by that study. The measurement of DV indices can be achieved in most women both in early and late pregnancy, and reproducibility is well acceptable as indicated by inter- and intra-observer variations may be another explanation.
Our findings were in close relation with Axt-Fliedner et al.’s [16] findings that were characterized by a parabolic pattern; the similarity with their result was probably due to the use of the same insonation angle correction.
On the other hand, our references were higher than those obtained by Kessler et al. [17] and Pokharel et al. [19]. The difference was attributed to the fact that the former study showed a smaller sample size than our study (160 pregnancies) and the latter study did not correlate the pulsatility index with the gestational age with scattered distribution; however, their values were below 1.0 in all gestational ages.
Bahlmann et al. [15] found that the reference curve for the RI was characterized by a parabolic pattern (at 14 weeks 0.67, at 30 weeks 0.48, and at 40 weeks 0.46). Axt-Fliedner et al. [16] also showed similar results (at 11 weeks 0.77, at 14 weeks 0.69, and at 20 weeks 0.51), while our results were at 11 weeks 0.75, at 14 weeks 0.69, at 20 weeks 0.61, at 30 weeks 0.54, and at 40 weeks 0.52.
Our findings were in close relation with Bahlmann’s findings especially during 16–24 weeks, but higher than those later in pregnancy. It was demonstrated that our reference ranges were lower than those obtained by Axt-Fliedner et al. (Fig. 12); in their study, the ratios were calculated from the respective ductus venosus flow velocities; different statistical analysis and different sample size may explain the different results.
Comparing our reference ranges of DV diameter curve with those published by Pokharel et al. [19], our results were close to each other (their results were 1.08 at 17 weeks, 1.44 at 25 weeks, and 1.82 at 33 weeks) while our results are at 17 weeks 1.13, at 25 weeks 1.40, and at 33 weeks 1.71.
Our longitudinal reference ranges for the DV velocities and indices are suitable both for single observations and for serial measurements (when using the corresponding terms). Analysis of the numerical values of the parameters assessed showed similarities and disagreements compared with other studies conducted on normal pregnancies.
In general, the differences observed could have been due to the different size and age of the patient population, statistical analysis, and design of each study. And some variation in reference ranges is seen, probably depending on the equipment, sonologist experience, insonation techniques, angle correction, and positioning of the sample volume of pulsed Doppler in the DV.
The strengths of this study are (1) the adequate sample size for each gestational week; (2) large numbers of observations, each case was examined at least three times; and (3) that we also included fetuses in the late first trimester and early second trimester [11,12,13,14,15,16,17,18,19], unlike most other studies. Moreover, inter-observer variations of the measurement are acceptable.
The limitation of the present study can be multiple. The error of judgment of the radiologist during the study period cannot be excluded. The miniature size of the ductus venosus, habits of the patient while doing the procedure, and cooperativity of the patient during the study period can affect the accuracy of the results of the study.
The technical pitfalls in DV measurement should be mentioned here: this measurement is occasionally time consuming and not always simple, especially when fetuses are in an improper position.
Our longitudinal reference ranges for the DV velocities and indices are suitable both for single observations and for serial measurements (when using the corresponding terms). Analysis of the numerical values of the parameters assessed showed similarities and disagreements compared with other studies conducted on normal pregnancies.