In recent years, some studies have found that congenital heart disease and intrauterine growth retardation can induce aberrant arterial elasticity after birth and that this alteration have already existed during the fetal period (1–4). Abnormalities in arterial elastic function will have a profound impact on the development of the cardiovascular system over the course of an individual’s life. Therefore, prenatal assessment of arterial elastic function is essential for the monitoring of potentially impaired vascular function throughout pregnancy as well as early intervention and prevention after birth (5). Ultrasound has become the most effective means of prenatal examination due to its advantages of being non-invasive, economical and convenient. Studies attempted to objectively evaluate the elastic properties of fetal arteries through various methods and discovered that aortic elastic properties varied dynamically with increasing gestational age (GA) (6–8). There are many indices for evaluating the elastic properties of arteries via ultrasound, among which compliance, distensibility, the stiffness index, Peterson’s elastic modulus, and pulse wave velocity are commonly used (9, 10). Although the values of these indices are associated with blood pressure, there is no parameter regarding blood pressure in human fetuses due to the inaccessibility of fetal vessels, except when an invasive approach is adopted (11). In previous research on fetal arterial elastic properties, some scholars have explored differences in aortic inner diameter alterations to indirectly evaluate arterial elasticity (12, 13). However, there are only a few studies on this aspect at present, and these studies are limited by the sample size and different GAs of fetuses. As a result, we set out to evaluate the development trend of fetal arterial elastic characteristics by measuring the maximum systolic diameter (Dmax), the minimum diastolic diameter (Dmin) and the diameter distensibility of the aortic sinotubular junction, as well as to establish reference ranges for Dmax, Dmin and diameter distensibility in the hope that these could serve as simple tools for analyzing vessel function.

Images of 504 fetuses were successfully acquired with satisfactory quality and were available for offline analysis. However, 14 data sets were later excluded since the aortic valve was not visible. Therefore, the remaining 490 data sets with successful measurements were used for statistical analysis. The majority of the participants (270 [55.10%]) were nulliparous. The mean maternal age ± SD was 26.38 ± 6.77 years (range, 18–43 years). All were healthy Chinese women residing in Hunan, China. Intraobserver variability and interobserver variability in the observation index measurements were both found to have good agreements, as shown in Table 1. The Dmax and the Dmin increased significantly as GA increased, while diameter distensibility decreased (P < 0.001). The best-fitting equations for predicted values and SDs based on independent variables (GA, BPD, and FL) are shown in Tables 2, 3. These equations were validated by constructing a Z-score for each variable. The normality of the residuals and Z-scores were demonstrated in a P-P plot (see Figures 2, 3). In addition, the Z-scores were equally distributed above and below 0 across the entire range of GAs, as well as following a standard normal distribution. The number of Z-scores distributed outside the range of ± 2 SD was as expected: approximately 10% of the values, as seen in Figures 4, 5.

Z-scores for each measured value for Dmax, Dmin, and diameter distensibility could readily be calculated as follows: Taking GA and diameter distensibility as examples, Z-score = (observed diameter distensibility– predicted value)/predicted SD (the predicted diameter distensibility and SD are available from the equations in Tables 2, 3). An example of a Z-score calculation for a given measurement is as follows: actual measured diameter distensibility = 10.5% at 24 weeks gestation. With the equations in Tables 2, 3, the predicted diameter distensibility at 24 weeks’ GA = −0.98–0.03*GA + 4.48*GA^3*10^–6 = 0.344; predicted SD of diameter distensibility at 24 weeks’ = 0.14–0.255*GA*10^–3 = 0.816; and the Z-score = (0.105–0.344)/0.816 = −2.93. Therefore, this fetus had a low diameter distensibility, at 2.93 SD below the predicted mean excursion for a fetus at 24 weeks’ GA, which was out of the normal range.

The elastic properties of the ascending aorta are important components of the arterial system’s elastic nature. These elastic properties play an important role in maintaining normal cardiovascular physiology due to the pulsatile blood flow generated during systole (17, 18). Damage to the elasticity of the ascending aorta will result in a widening of pulse pressure, an increase in mean arterial pressure, and a decrease in coronary blood perfusion (19). Early identification of fetuses with abnormalities in elastic properties is becoming increasingly important.

To the best of our knowledge, this study firstly demonstrated decreased ascending aortic diameter distensibility along with increasing GA in normal fetuses and established the Z-scores models of fetal ascending aortic diameter distensibility.

The present data reveal that aortic diameter distensibility decreases with increasing GA in the normal fetus, indicating decreases in aortic elastic properties with structural maturation during the fetal period. According to zoological research, when fetal blood pressure rises during pregnancy, so does the expression of elastin, and as the elastic fibers gradually transform from a microfibrillar scaffold in early pregnancy to an elastin-microfibril composite, they have increased intrinsic mechanical properties (expressible in material properties such as moduli). To adapt to the strong mechanical load after birth, the aortic wall undergoes mature changes (20).

This result is consistent with previous findings in infants (6) and fetuses (7). Akira and Yoshiyuki (6) analyzed aortic stiffness in both preterm and term infants with appropriate GA and demonstrated that the stiffness index was considerably increased with increasing GA. Taketazu et al. (7) examined phasic variations in ascending aortic diameter along with Doppler flow in normal fetuses with GA between 18 and 38 weeks and found that aortic compliance was dramatically reduced with increasing GA. However, our findings contradicted the report of Miyashita et al. (12). They analyzed abdominal aortic diameter distensibility in 100 normal fetuses and discovered that there was no significant change in aortic diameter distensibility with GA. We speculated the disparity between our study and Miyashita et al.’s report may be related to the discrepancy in the aortic segment and the sample size.

This study employed the Z-score model to reflect the diameter distensibility of the fetal ascending aorta as a multiple of SD, and gave the typical 90% range of Z-score, that is, when Z-score is within the ± 1.65 range, the greater the absolute value of Z-score, the greater the deviation from the mean, although it remains within the normal range. If the absolute value of the Z-score is greater than 1.65, the elastic properties of the ascending aorta are thought to be abnormal. In addition to GA, this study incorporated BPD and FL as independent variables to establish the Z-score model of diameter distensibility. It was found that increasing the independent variables more accurately and dynamically reflected the variation in the distensibility index of the ascending aorta with the biological parameters of the fetus itself. For skeletal dysplasia, Z-scores based on GA are the preferred reference due to unreliable measurements of bone structures. For renal malformation or oligohydramnios, Z-scores based on FL are appropriate because they are easy to obtain and relate mostly to fetal size.

Diameter distensibility may possibly be a promising sonographic marker for vascular function in the fetal period since the measurement is straightforward and reproducible. Only a few research have previously established the normal reference value range for the elastic properties of the normal fetal aorta. Moreover, these studies are based on small sample sizes, complex measurement methods, and poor repeatability. Although the potential clinical usefulness of diameter distensibility needs to be further explored, the results presented in this study may serve as a baseline reference for evaluating impaired vascular elastic properties in high-risk pregnancies.

There were several limitations in this study. Firstly, although ECG monitoring in the fetal period cannot define the end-systole and end-diastole timepoints, we confirmed the timepoints as the frame before the aortic valve closes and the frame before the aortic valve opens separately. The high frame frequency (range 180–230 fps) is able to guarantee the accuracy of timepoints. Secondly, despite the fact that the total sample size was sufficient, there were discrepancies among the various GA groups, particularly with fewer cases (<20 cases) collected in less than 20 weeks and larger than 38 weeks.

In summary, this study revealed that normal fetuses have decreased ascending aortic diameter distensibility with increasing GA and established the Z-scores models of fetal ascending aortic diameter distensibility vs. GA, BPD, and FL. These models have the potential to be beneficial for evaluating aortic elastic properties in the fetal period.

The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by the Institutional Review Board for Ethics of the Central hospital of Yueyang. The Institutional Review Board for Ethics of the Second Xiangya Hospital of Central South University. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.

SZ contributed to conception, design of the study, and wrote the first draft of the manuscript. FC, AY, LC, YL, DZ, and SZ organized the database. FC and LY performed the statistical analysis. FC wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.