Non-influence of fetal gender on ductus venosus Doppler flow in the first trimester

Authors


Abstract

Objectives

Recent findings have suggested that ductus venosus blood flow may be influenced by fetal gender. The aim of this study was to investigate further the influence of fetal gender on ductus venosus Doppler flow in the first trimester.

Methods

This was a cross-sectional and retrospective study performed between January 1998 and January 2003. A total of 932 fetuses at between 10 and 14 weeks' gestation were included. The following inclusion criteria were used: singleton gestation; crown–rump length between 39 and 84 mm; and absence of fetal anomalies. The following variables of the ductus venosus were evaluated: peak velocity during ventricular systole (S-wave) and diastole (D-wave); nadir during atrial contraction in late diastole (A-wave); pulsatility index for veins (PIV); peak velocity index for veins (PVIV); and time-averaged maximum velocity (TAMXV).

Results

Four hundred and forty-eight (48.1%) female and 484 (51.9%) male fetuses were included in the study. Comparing males and females at between 10 and 14 weeks' gestation, there was no statistically significant difference in S-wave, D-wave, A-wave, PIV, PVIV or TAMXV.

Conclusions

Our study suggests that fetal gender does not influence ductus venosus blood flow in the first trimester. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.

Introduction

In recent years the fetal venous system, particularly the ductus venosus, has been the focus of much research1–4. The normal pattern of the ductus venosus waveform is characterized by high-velocity flow during ventricular systole (S-wave) and diastole (D-wave) and forward flow during atrial contraction (A-wave). This pattern may be altered in first-trimester fetuses with certain structural or genetic defects5–8, and Doppler studies of the fetal circulation have demonstrated the importance of the ductus venosus in first-trimester screening for fetal chromosomal abnormalities9, 10. An abnormal ductus venosus blood-flow velocity waveform is also associated with a high probability of underlying major cardiac defects11, and the association between the ductus venosus and cardiac function is well known12.

Indirect evidence that early fetal cardiovascular development may be independent of gender was provided by McKenna et al., who reported no significant difference between male and female fetal heart rate during the first trimester13. In 2003, Prefumo et al. suggested that ductus venosus blood flow may be influenced by fetal gender14, but this observation has not so far been confirmed by other studies. It is important to evaluate ductus venosus blood flow parameters using correct nomograms, because abnormal values may be associated with cardiac anomalies or chromosomal abnormalities. If gender-related differences exist, then correction of risk should be performed according to gender. The aim of this study was to investigate the influence of fetal gender on ductus venosus flow, as measured by Doppler sonography, in the first trimester.

Methods

This was a cross-sectional retrospective study performed between January 1998 and January 2003. A total of 932 fetuses at between 10 and 14 weeks' gestation were evaluated at Gennus, Belo Horizonte, Brazil. Gestational age was calculated from the date of the last menstrual period and confirmed by crown–rump length (CRL) measurement. The following inclusion criteria were used: singleton gestation; CRL between 39 and 84 mm; and absence of fetal anomalies.

After delivery all the patients were given a follow-up questionnaire, in which they were asked to confirm the fetal gender and also to inform us about any subsequently diagnosed health disorders of the baby. Hospital records were reviewed to determine delivery outcomes. All fetuses with negative A-wave, abnormal karyotypes or structural anomalies were excluded.

Ultrasound examinations were performed by two physicians certified by The Fetal Medicine Foundation (fmf@fetalmedicine.com). All examinations were performed using an Aspen (Acuson, Mountain View, CA, USA) ultrasound system with the high-pass filter set at 50 Hz. The ductus venosus was identified using color Doppler in a right ventral mid-sagittal plane. The pulsed Doppler gate was placed in the distal portion of the umbilical sinus. Special care was taken to avoid contamination from the intrahepatic portion of the umbilical vein, left hepatic vein or inferior vena cava. The insonation angle was kept below 30°. After the typical sonogram of the ductus venosus had been obtained, at least five consecutive waveforms were recorded9, 11, 15.

The following variables were evaluated: peak velocity during ventricular systole (S-wave) and diastole (D wave), nadir during atrial contraction in late diastole (A-wave), pulsatility index for veins (PIV), peak velocity index for veins (PVIV) and time-averaged maximum velocity (TAMXV). For inter-group comparison, Student's t-test or Mann–Whitney U-test was used, depending on whether there was a Gaussian distribution of the variables. Measurements were transformed to the corresponding Z-scores ((measurement − mean)/standard deviation), with the mean and standard deviation previously adjusted for CRL16. Statistical analysis was performed using SPSS 14.0 and Windows Microsoft Excel, and values of P < 0.05 were considered statistically significant. This study was approved by the local ethical committee (Origem clinic).

Results

A total of 932 singleton gestations between 10 and 14 weeks were consecutively enrolled into this study, including 448 (48.1%) female and 484 (51.9%) male fetuses. This sample size would enable the detection of a 0.2 SD difference with a power of at least 84.8%. PIV and PVIV Z-scores differed significantly from the normal distribution and the Mann–Whitney U-test was used to assess differences in these variables between male and female fetuses. All other variables were normally distributed and Student's t-test was used for inter-group comparison. Comparing the male and female fetuses at between 10 and 14 weeks, and adjusting for CRL, there was no statistically significant difference in S-wave, D-wave, A-wave, PIV, PVIV or TAMXV (Table 1).

Table 1. Ductus venosus Doppler parameters for the S-wave velocity, D-wave velocity, time-averaged maximum velocity (TAMXV), A-wave velocity, peak velocity index for veins (PVIV) and pulsatility index for veins (PIV) converted into Z-scores ((measurement − mean)/SD) adjusted for crown–rump length (expressed as mean ± SD)
ParameterAll (n = 932)Female (n = 448)Male (n = 484)P
  • *

    Student's t-test.

  • Mann–Whitney U-test.

S-wave Z-score− 0.0105 ± 1.00080.0261 ± 1.0195− 0.0444 ± 0.98300.283*
TAMXV Z-score0.0271 ± 0.99400.0706 ± 1.0198− 0.0131 ± 0.96890.199*
A-wave Z-score0.0342 ± 1.05340.0359 ± 1.05670.0327 ± 1.05130.965*
PIV Z-score− 0.7035 ± 1.0820− 0.6974 ± 1.0701− 0.7091 ± 1.09400.907
D-wave Z-score0.0398 ± 0.98870.0899 ± 0.9976− 0.0066 ± 0.97920.137*
PVIV Z-score− 0.0459 ± 1.0818− 0.0679 ± 1.0856− 0.0256 ± 1.07900.787

Discussion

The development of the heart begins during the third week of gestation, initially producing fast and irregular contractions capable of pumping blood through the vessels. However, only at the end of the fourth week may the cardiac beats be identified on ultrasound examination17. The ductus venosus appears during the sixth week, from the confluence of the hepatic sinusoids, owing to the alterations of the blood pressure and vascular morphology, developing as an isolated canal from the hepatic circulation. The ductus venosus is completely formed by 8 weeks. By 10 weeks, the Doppler pattern across the atrioventricular valves can reveal the existence of the biphasic (A and E) waves17–19.

In 2003 Prefumo et al.14 reported a study including 153 fetuses at between 10 and 14 weeks' gestation that suggested that ductus venosus Doppler indices in the first trimester may be influenced by fetal gender. The authors reported that the mean Z-score values of PIV, S-wave and TAMXV were significantly lower in male than in female fetuses. A-wave velocities, however, did not differ. In contrast, our study revealed no statistically significant difference in ductus venosus blood flow between male and female fetuses at between 10 and 14 weeks' gestation. These findings were confirmed when we also tested for differences in the values after adjustment for CRL. Therefore we conclude that the same nomogram for ductus venosus Doppler parameters should be used for fetuses of both genders. If there is a difference in ductus venosus development between male and female fetuses, it may be very small, or impossible to measure using Doppler ultrasound in early gestation.

One important limitation of our study is that measurements were performed by two different operators, unlike the study by Prefumo et al., in which measurements were performed by a single operator14. We did not test the interobserver variability so we cannot be sure if there was any systematic difference between the two operators, thus it is possible that interobserver variability may have masked real differences between male and female fetuses. However, our study suggests that fetal gender does not influence first-trimester ductus venosus blood flow.

Ancillary