Isolated fetal choroid plexus cysts: role of ultrasonography in establishment of the risk of trisomy 18.

OBJECTIVE: The significance of isolated choroid plexus cysts found by ultrasonographic scan during the second trimester as a marker for trisomy 18 is still debated. We analyzed our data and reviewed the series published in the English-language literature to calculate the likelihood ratio of trisomy 18 in the presence of isolated choroid plexus cysts; that is, the factor by which the individual risk of trisomy 18 is increased in the presence of isolated choroid plexus cysts. STUDY DESIGN: Likelihood ratios were calculated as ratio of the sensitivity to the false-positive rate. Sensitivity was defined as the rate of isolated choroid plexus cysts detected at midgestation among fetuses with trisomy 18. False-positive rate was defined as the rate of choroid plexus cysts detected at midgestation in the population without trisomy 18. The sensitivities of all published series reporting rates of choroid plexus cysts at the time of the first ultrasonographic examination between 14 and 24 weeks' gestation in populations with trisomy 18 and in low-risk populations were included in the analysis. To these we added all cases of trisomy 18 diagnosed at our institution during the period January 1, 1988, through June 30, 1998, in which prenatal ultrasonographic examination was performed between 14 and 24 weeks' gestation. RESULTS: The prevalence of second-trimester ultrasonographic detection of isolated choroid plexus cysts among fetuses with trisomy 18 was 6.7% (13/194), whereas that in the population without trisomy 18 was 0.9% (752/79,583). The likelihood ratio associated with isolated choroid plexus cysts was therefore 7.09 (95% confidence interval, 3.97-12.18). CONCLUSION: The presence of isolated second-trimester choroid plexus cysts increases the base risk of trisomy 18 by a factor of 7.09. This likelihood ratio can be multiplied by the risk calculated according to maternal age to obtain the individual risk of trisomy 18 and thus permit more accurate counseling of the patient.

Critical reappraisal of the utility of sonographic fetal femur length in the prediction of trisomy 21.

Measurement of femur length (FL) has been advocated as part of a genetic sonogram for the prediction of Down syndrome (DS). However its predictive ability has been inconsistent. We have studied the diagnostic value of this sonographic parameter in a prospective cohort of women with singleton gestations undergoing genetic sonogram between 14 and 22 weeks because of advanced maternal age or family history of aneuploidies. Genetic sonograms were performed at a mean gestational age of 17.0 weeks (range 14-22). DS was diagnosed in 30 fetuses, while 888 were euploid. Mean+/-SD observed/expected (O/E) values of FL (1.00+/-0.10 versus 0.97+/-0.01, p=0.07) were not significantly different between euploid and DS fetuses. Comparison of the regression equations of FL versus biparietal diameter revealed that while the intercepts were not significantly different between euploid and DS fetuses, the difference in slopes reached significance (p=0.04) suggesting that the predictive ability of FL may increase with advancing gestational age. In addition, a MEDLINE search (National Library of Medicine) was conducted for articles published between 1985 and 1998 on fetal femur length in the prediction of trisomy 21. Review of the published literature on the subject suggests that FL is not a consistent or reliable sonographic predictor of DS. Published thresholds of FL should not be used outside of the Institution from which they originated, and each Institution should establish whether this parameter has predictive ability in its own population.

Critical appraisal of the use of nuchal fold thickness measurements for the prediction of Down syndrome.

OBJECTIVE: Nuchal fold thickness is the best ultrasonographic predictor of fetal trisomy 21. However, the risk assigned on the basis of the commonly used threshold of nuchal fold thickness >/=6 mm does not take into consideration the significant associations between nuchal fold thickness and gestational age and between maternal age and Down syndrome. We propose a new method of calculating Down syndrome probability that takes into account both gestational age at examination and previously assessed probability of Down syndrome. STUDY DESIGN: Nuchal fold thickness was measured at ultrasonographic examination at 14 to 22 weeks' gestation without previous knowledge of the fetal karyotype. Nuchal cystic hygromas were excluded from analysis. Statistical analyses included correlation, logistic regression to control for other ultrasonographic predictors of trisomy 21 and for maternal age, receiver operating characteristic curve, and likelihood ratios (defined as the ratio of the sensitivity to the false-positive rate). P <.05 was considered significant. RESULTS: Mean gestational age at ultrasonography was 16.9 weeks' gestation (range, 14-22 weeks' gestation). Mean (+/-SD) nuchal fold thickness in fetuses with trisomy 21 (4.7 +/- 1.6 mm; n = 29) was greater than in euploid fetuses (3.2 +/- 0.9; n = 780; P <.001). Logistic regression analysis established that nuchal fold thickness was a significant predictor of trisomy 21 independent both of the other ultrasonographic markers and of maternal age (P <.001). Regression analysis showed that nuchal fold thickness was significantly correlated with gestational age among both fetuses with trisomy 21 and euploid fetuses and that the regression line of fetuses with trisomy 21 had a slope similar to that of euploid fetuses. The difference between observed and expected nuchal fold thicknesses on the basis of the biparietal diameter (as a function of gestational age) was used to obviate the confounding effect of gestational age. Differences between observed and expected nuchal fold thicknesses were then used to calculate likelihood ratios. These likelihood ratios could then be multiplied by the individual prior probability to obtain a patient-specific Down syndrome probability. CONCLUSION: Nuchal fold thickness is correlated with gestational age in both euploid fetuses and fetuses with Down syndrome. Use of the difference between observed and expected nuchal fold thicknesses to determine likelihood ratios allows the calculation of individual posterior probabilities of Down syndrome that take into consideration both gestational age and maternal age.

Best second trimester sonographic markers for the detection of trisomy 21.

We analyzed all genetic sonograms obtained during a 6 year period to establish the independent ability of the following sonographic markers of aneuploidy in the diagnosis of trisomy 21: structural anomalies, cardiac abnormalities, nuchal fold thickness of 6 mm or greater, bowel echogenicity, choroid plexus cysts, and renal pyelectasis. With the exception of bowel echogenicity and choroid plexus cysts, the sonographic markers were more common in trisomy 21 than euploid fetuses (all P < 0.001). Logistic regression analysis demonstrated that cardiac anomalies (odds ratio = 255; 95% confidence interval, 25, 2592), other structural anomalies (odds ratio = 25; 95% confidence interval, 6, 97), and nuchal fold thickness of 6 mm or greater (odds ratio = 13; 95% confidence interval, 3, 50) were the only independent predictors of trisomy 21. The false-positive rate and sensitivity were 5.3% (48 of 898) and 59.2% (13 of 22), respectively, when any of the sonographic markers significant at univariate analysis was considered, and 3.1% (28 of 898) and 54.5% (12 of 22), respectively, when any of the predictors at multivariate analysis was present. Because a considerable overlap of sonographic markers exists among trisomy 21 fetuses, use of those that are not independent predictors leads to an increase in false-positive rate without a gain in sensitivity.

Ultrasonographic differential diagnosis of fetal intracranial interhemispheric cysts.

OBJECTIVE: Ultrasonographic differentiation between intracranial supratentorial interhemispheric pathologic cystlike lesions and those related to physiologic median structures is essential because the latter have no clinical relevance, whereas the former may carry a poor prognosis. We reviewed our experience with 19 consecutive cases of interhemispheric hypoechoic lesions without parenchymal involvement diagnosed between January 1990 and June 1997 to establish their clinical significance and provide prenatal ultrasonographic criteria to distinguish between pathologic cystlike lesions and those related to physiologic midline structures. STUDY DESIGN: All patients underwent targeted prenatal scans of intracranial anatomy to establish the relationship between the fluid collections and the surrounding parenchymal and ventricular structures. In addition, a detailed anatomic survey was performed to rule out associated malformations. Follow-up, including neurologic examination, imaging, autopsy evaluation, or a combination was performed in all cases. Statistical analysis used the Wilcoxon rank sum test, the Fisher exact test, and the chi2 test for trend. P <.05 was considered significant. RESULTS: Cystlike lesions related to physiologic median structures (n = 12) included enlargement of the cavum septi pellucidi (n = 3), enlargement of the cavum vergae (n = 2), and cysts of the velum interpositum (n = 7). These lesions were unilocular and had a median size of 10 mm (range 10-30 mm); they resolved in 5 cases and remained stable in the remainder. They were not associated with overt abnormalities, other than borderline ventriculomegaly in 2 cases. Pediatric follow-up (median 26 months, range 3-84 months) showed normal neurodevelopment in all cases. Pathologic cystlike lesions (n = 7) were significantly larger (median 40 mm, range 10-80 mm, P =.004) and had a significantly worsening trend, growing more at serial prenatal ultrasonographic examinations (P =.039) than fluid collections related to physiologic median structures. Moreover, prenatal ultrasonographic evidence of associated intracranial abnormalities, in the form of partial or total agenesis of the corpus callosum and overt hydrocephalus, was present in 5 of 7 cases of pathologic cystlike lesions and in none of the 12 related to physiologic structures (P =.002). Median gestational age at diagnosis was not different between those with cystlike lesions related to physiologic median structures and those with pathologic lesions (30 and 31 weeks, respectively). Among the latter group, 1 pregnancy was voluntarily terminated, 1 infant died at 4 months of age, 2 infants had neurodevelopmental delay, and 3 infants were neurologically healthy at a mean follow-up of 43 months. Cyst shunting was necessary in 5 of 6 cases. CONCLUSIONS: Interhemispheric cystlike lesions related to physiologic structures can be prenatally distinguished from pathologic fluid collections on the basis of location, cyst size, change in size with time, and absence of associated anomalies.