Fetal Lateral Ventricular Width: What Should Be Its Upper Limit?

Article Fetal Lateral Ventricular Width: What Should Be Its Upper Limit? A Prospective Cohort Study and Reanalysis of the Current and Previous Data Benny Almog, MD, Ronni Gamzu, MD, PhD, Reuven Achiron, MD, Ofer Fainaru, MD, Yaron Zalel, MD Objective. The upper limit of the fetal atrial width in normal fetuses is debated. This was a prospective cohort evaluation of the lateral ventricular width with special regard to the upper limit of its size. Methods. Measurements of fetal atrial ventricular size were obtained by abdominal ultrasonography in 427 male and female fetuses between 20 and 40 weeks gestation of normal singleton pregnancies. In addition, reanalysis of previous data (8 studies) and the current data was performed to produce a pooled mean and SD. Results. The mean ventricular width ± SD was 6.2 ± 1.2 mm. The ventricular width did not show significant modification throughout gestation. Reanalysis of the current and previous studies (8216 cases) yielded a pooled mean of 6.4 ± 1.2. Conclusions. According to the current and previous studies, the upper cutoff of fetal ventricular atrium width should be 10 mm. This cutoff represents a range of approximately 3 SDs above the pooled mean, corresponding to a 99.74% confidence interval. Key words: fetal cerebral lateral ventricle; mild ventriculomegaly; prenatal diagnosis; ultrasonography. Abbreviations CI, confidence interval Received May 7, 2002, from the Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel (B.A., R.G., O.F.); and Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center, Tel- Hashomer, Israel; affiliated with Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel (R.A., Y.Z.). Revision requested June 28, 2002. Revised manuscript accepted for publication July 23, 2002. Address correspondence and reprint requests to Benny Almog, MD, Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel-Aviv Sourasky Medical Center, 6 Weizman St, Tel-Aviv 64239, Israel. Ventriculomegaly is one of the most common sonographically detected fetal abnormalities. It has a substantial adverse effect on fetal outcome 1,2 and may be associated with additional abnormalities. Because of its serious implications, it has become an important part of routine prenatal ultrasonographic evaluation. Various components of the ventricular system can be measured and used to define ventriculomegaly. Currently, transverse measurement of the atrium is commonly suggested as the point of reference. 3 A measurement of greater than 10 mm, which represents 2.5 to 4 SDs above the mean, has been considered abnormal in most series. 3 10 Nonetheless, many fetuses with isolated mild ventriculomegaly, i.e., atrial enlargement of greater than 10 mm, turned out to have no abnormalities on neonatal assessment. This finding raises the question of whether the statistically computed cutoff value of 10 mm is appropriate. 11 Differences in fetal measurements in different population groups and differences between sexes 2003 by the American Institute of Ultrasound in Medicine J Ultrasound Med 22:39 43, 2003 0278-4297/03/$3.50

Lateral Ventricular Size should make this decision even more complicated. 8,12 15 Accordingly, we conducted a prospective cohort study in 427 normal pregnancies and reanalysis of additional 7789 cases to evaluate the atrial size of the lateral ventricle throughout gestation with special regard to its upper limit. Materials and Methods A prospective cohort study was conducted to establish the range of the atria of the cerebral lateral ventricle in normal gestation. The study group consisted of pregnant women who fulfilled the following criteria: (1) history of regular menses and a known date of the beginning of the last menstrual period; (2) gestational age based on sonographic measurement of the crownrump length in early pregnancy (in cases in which the last menstrual period crown-rump length difference was >10 days, the pregnancy was dated by the crown-rump length measurements); (3) a fetus whose estimated fetal weight was between the 10th and 90th percentiles; (4) absence of maternal disease; and (5) absence of fetal malformations. Ventricular size was obtained during routine ultrasonographic examination performed to rule out malformations and during routine third-trimester ultrasonographic follow-up. Each patient was examined only once during the study by 1 examiner (Y.Z.). Ultrasonography was performed with an abdominal 3.5- to 5-MHz curvilinear transducer (Synergy; Diasonics, Tirat Carmel, Israel; or Ultramark HDI 3000; Philips Medical Systems, Bothell, WA). Freeze-frame ultrasonographic capabilities and electronic on-screen calipers were used for the measurements. Ventricular width at the atria was measured slightly above the level of the thalami. The electronic calipers were positioned perpendicular to the falx along the inner aspect of the echogenic line corresponding to the ventricular wall (Fig. 1). Each measurement was repeated 3 times in each fetus, and the mean size was determined. The coefficient of variation was calculated to show intraobserver variability. Linear regression of atrial width on gestational age was calculated. Means and 5% and 95% confidence intervals (CIs) of the ventricular width for consecutive gestational ages were calculated. SDs reported by the different series were combined by the following equation Figure 1. Ventricular width at the atria measured slightly above the level of the thalami. The electronic calipers are positioned perpendicular to the falx along the inner aspect of the echogenic line corresponding to the ventricular wall. for pooled SDs: {[(n 1 1) SD 12 + (n 2 1) SD 22 +... + (n k 1) SD k2 ]/n 1 + n 2 +... n k K} 0.5, where n was the number of the series. All data processing was performed by SPSS for Windows 9.0 (SPSS Inc, Chicago, IL), and P.05 was considered statistically significant. Results Measurements of ventricular width were obtained in 427 fetuses between 20 and 40 weeks gestation. The intraobserver variability, as determined by the coefficient of variation, was 2.2%. The mean ventricular width ± SD was 6.2 ± 1.2 mm. The ventricular width did not show significant modification throughout gestation. Table 1 presents the means, SDs, 5% and 95% CIs, and 4 SDs above the means of ventricular width for consecutive gestational ages between 20 and 40 weeks. Ventricular width as a function of gestational age was expressed by the following regression equation: atrial width (millimeters) = 3.87 + 0.09 gestational age (weeks). The correlation coefficient, r = 0.38, was found to be highly statistically significant (P <.0001). However the positive statistical correlation was not clinically significant. Figure 2 presents a scatterplot of ventricular width (millimeters) in relation to gestational age (weeks), showing a regression line with the 98% CI. 40 J Ultrasound Med 22:39 43, 2003

Almog et al Table 1. Ventricular Width According to Gestational Age Ventricular Width, mm Gestational Percentile Age, wk No. of Cases Mean SD 5th 95th 4 SD > Mean 20 21 38 5.89 1.12 4.79 8.50 10.37 22 23 106 5.66 0.72 4.50 7.06 8.54 24 25 77 6.04 0.97 4.60 7.77 9.92 26 27 35 6.01 1.21 3.90 9.00 10.85 28 29 52 6.38 1.26 4.35 9.11 11.42 30 31 30 6.57 1.02 4.28 7.80 10.65 32 33 26 6.77 1.46 4.20 8.90 12.6 34 35 31 7.22 1.12 5.46 9.28 11.71 36 40 32 6.92 1.50 4.00 9.80 12.92 Table 2 presents mean ventricular widths and SDs of this study and 8 previous studies. The pooled mean (6.4 mm) ± 3 SDs correspond to 10 mm as an upper limit. Discussion We conducted this study to obtain data on the normal upper limit of fetal ventricular atrial width in fetuses without abnormalities and, thus, to reanalyze the upper limit of these measurements in the literature. The mean ventricular width ± SD was 6.2 ± 1.2 mm. The ventricular width did not show significant modification throughout gestation, as was previously stated. 11 This stability gives the atrial size great potential utility for sonologists in prenatal diagnosis. McGahan and Phillips 16 were the first to turn attention to the ventricular atrium in 1983. Siedler and Filly 17 retrospectively reviewed 90 examinations and showed a range of atrial measurement between 4 and 8 mm. Cardoza et al 4 retrospectively evaluated 100 healthy fetuses and found a mean atrial size ± SD of 7.6 ± 0.6 mm. These authors were the first to suggest 10 mm as the upper cutoff, being computed as 4 SDs above the mean. Other studies presented lower averages, however, usually with a higher SD (Table 2), as in this and our past series. 7 Several studies supported the use of 10 mm as the upper limit of the ventricular atrial width by the use of either 2 or 4 SDs above the mean. 4,7,8,9,18 Conversely, Pretorius et al 19 and Hilpert et al 3 suggested higher upper normal limits such as 11 and 12 mm, respectively. The pooled average of all these studies (8216 cases) ± SD is 6.4 ± 1.2 mm. The 10-mm cutoff represents a range of approximately 3 SDs above the mean, corresponding to a 99.74% CI. This upper limit, however, should also be validated by the clinical outcomes of borderline dilatation (10 12 mm). The clinical significance of isolated mild ventriculomegaly, i.e., an atrial diameter of 10 to 15 mm, was recently evaluated in 2 reviews. 11,20 It was concluded that even in its mildest form (10 12 mm of dilatation), a 3.7% rate of abnormal karyotypes and a 7.7% rate of developmental delay were encountered. Thus, it should be suggested that atrial size of 10 to 12 mm should be defined as a borderline pathologic condition, which requires further follow-up and consideration of additional Figure 2. Scatterplot of ventricular width (millimeters) in relation to gestational age (weeks) showing the regression line with the 98% CI. J Ultrasound Med 22:39 43, 2003 41

Lateral Ventricular Size Table 2. Measurement of the Lateral Ventricular Atrium in Populations Without Abnormalities According to Different Series Ventricular Width, mm Authors No. of Cases Mean SD 3 SD > Mean 4 SD > Mean Hilpert et al 3 608 6.5 1.5 11 12.5 Cardoza et al 4 100 7.6 0.6 9.4 10 Pilu et al 5 171 6.9 1.3 10.8 12.1 Heiserman et al 6 52 6.5 1.3 10.4 11.7 Achiron et al 7 5400 6.6 1.2 10.2 11.4 Patel et al 8 219 6.1 1.3 10 11.3 Farrell et al 9 739 5.4 1.2 9 10.2 Alagappan et al 10 500 6.6 1.4 10.8 12.2 This study 427 6.2 1.2 9.8 11 Calculated average 8216 6.4 1.2 10 11.2 evaluations (i.e., karyotype). Accordingly, ventriculomegaly represents a range of pathologic conditions from isolated mild ventriculomegaly to the dismal situation of hydrocephalus with associated defects. This study further highlights the upper limit of ventricular size, which is highly significant with regard to fetal abnormalities in the presence of ventriculomegaly. References 1. Cochrane DD, Miles ST, Nimrod C, Still DK, Sugerman RG, Wittman BK. Intrauterine hydrocephalus and ventriculomegaly: associated abnormalities and fetal outcome. Can J Neurol Sci 1985; 12:51 59. 2. Chervenak FA, Duncan C, Ment LR, et al. Outcome of fetal ventriculomegaly. Lancet 1984; 2:179 181. 3. Hilpert PL, Hall BE, Kurtz AB. The atria of the fetal lateral ventricles: a sonographic study of normal atrial size and choroid plexus volume. AJR Am J Roentgenol 1995; 164:731 734. 4. Cardoza JD, Goldstein RB, Filly RA. Exclusion of fetal ventriculomegaly with a single measurement: the width of the lateral ventricular atrium. Radiology 1988; 169:711 714. 5. Pilu G, Reece A, Goldstein I, Hobbins JC, Bovicelli L. Sonographic evaluation of the normal developmental anatomy of the fetal cerebral ventricles, II: the atria. Obstet Gynecol 1989; 73:250 256. 6. Heiserman J, Filly RA, Goldstein RB. The effect of measurement errors on the sonographic evaluation of ventriculomegaly. J Ultrasound Med 1991; 10: 121 124. 7. Achiron R, Achimmel M, Achiron A, et al. Fetal mild idiopathic lateral ventriculomegaly: is there a correlation with fetal trisomy? Ultrasound Obstet Gynecol 1993; 3:89 92. 8. Patel MD, Goldstein RB, Tung S, Filly RA. Fetal cerebral ventricular atrium: difference in size according to sex. Radiology 1995; 194:713 715. 9. Farrell TA, Hertzberg BS, Kliewer MA, Harris L, Paine SS. Lateral ventricles: reassessment of normal values for atrial diameter at US. Radiology 1994; 193:409 411. 10. Alagappan R. Browning PD, Laorr A, McGahan JP. Distal lateral ventricular atrium reevaluation of normal range. Radiology 1994; 193:405 408. 11. Bronsteen RA, Comstock CH. Central nervous system anomalies. Clin Perinatol 2000; 27:791 812. 12. Hertzberg BS, Kliewer MA, Bowie JD. Fetal ventriculomegaly: misidentification of the true medial boundary of the ventricle at US. Radiology 1997; 205:813 816. 13. Lei H, Wen SW. Ultrasonographic examination of intrauterine growth for multiple fetal dimensions in a Chinese population. Am J Obstet Gynecol 1998; 178:916 921. 14. Thilaganathan B, Khare M, Williams B, Wathen NC. Influence of ethnic origin on nuchal translucency screening for Down s syndrome. Ultrasound Obstet Gynecol 1998; 12:112 114. 42 J Ultrasound Med 22:39 43, 2003

Almog et al 15. Westerway SC, Davidson A, Cowell S. Ultrasonic fetal measurement: new Australian standards for the new millennium. Aust N Z J Obstet Gynaecol 2000; 40:297 302. 16. McGahan JP, Phillips HE. Ultrasonic evaluation of the size of the trigone of the fetal ventricle. J Ultrasound Med 1983; 2:315 319. 17. Siedler DE, Filly RA. Relative growth of higher fetal brain structures. J Ultrasound Med 1987; 6:573 576. 18. Filly RA, Goldstein RB. The fetal ventricular atrium: fourth down and 10 mm to go. Radiology 1994; 193:315 317. 19. Pretorius DH, Drose JA, Manco-Johnson ML. Fetal lateral ventricular ratio determination during the second trimester. J Ultrasound Med 1986; 5:121 124. 20. Pilu G, Falco P, Gabrielli S, Perolo A, Sandri F, Bovicelli L. The clinical significance of fetal isolated cerebral borderline ventriculomegaly: report of 31 cases and review of the literature. Ultrasound Obstet Gynecol 1999; 14:320 326. J Ultrasound Med 22:39 43, 2003 43