Evaluation of Posterior Fossa Biometric Measurements on Fetal MRI in the Evaluation of Dandy-Walker Continuum.

BACKGROUND AND PURPOSE: Dandy-Walker malformation, vermian hypoplasia, and Blake pouch remnant represent a continuum of anomalies and are common reasons for referral for fetal MR imaging. This study aimed to determine biometric measurements that quantitatively delineate these 3 posterior fossa phenotypes. MATERIALS AND METHODS: Our single-center institutional review board approved a retrospective analysis of all fetal MRIs for posterior fossa malformations, including Dandy-Walker malformation, vermian hypoplasia, and Blake pouch remnant. Measurements included the anterior-to-posterior pons, craniocaudal and anterior-to-posterior vermis, lateral ventricle size, and tegmentovermian and posterior fossa angles. Measurements were compared with normal biometry and also between each subgroup. RESULTS: Thirty-three fetuses met the criteria and were included in the study. Seven were designated as having Dandy-Walker malformation; 16, vermian hypoplasia; and 10, Blake pouch remnant. No significant group interactions with adjusted mean gestational age for tegmentovermian and posterior fossa angles were observed. The tegmentovermian angle was significantly higher in Dandy-Walker malformation (109.5° [SD, 20.2°]) compared with vermian hypoplasia (52.13° [SD, 18.8°]) and Blake pouch remnant (32.1° [SD, 17.9°]), regardless of gestational age. Lateral ventricle sizes were significantly higher in Dandy-Walker malformation at a mean of ≥23.1 weeks' gestational age compared with vermian hypoplasia and Blake pouch remnant. The anterior-to-posterior and craniocaudal vermes were significantly smaller in Dandy-Walker malformation compared with vermian hypoplasia and Blake pouch remnant at mean of ≥23.1 weeks' gestational age. CONCLUSIONS: Dandy-Walker malformation can be described in relation to vermian hypoplasia and Blake pouch remnant by an increased tegmentovermian angle; however, other potential qualifying biometric measurements are more helpful at ≥23.1 weeks' gestational age. Because they fall along the same spectrum of abnormalities, the difficulty in distinguishing these entities from one another makes precise morphologic and biometric descriptions important.

Effect of outliers and nonhealthy individuals on reference interval estimation.

BACKGROUND: Improvement in reference interval estimation using a new outlier detection technique, even with a physician-determined healthy sample, is examined. The effect of including physician-determined nonhealthy individuals in the sample is evaluated. METHODS: Traditional data transformation coupled with robust and exploratory outlier detection methodology were used in conjunction with various reference interval determination techniques. A simulation study was used to examine the effects of outliers on known reference intervals. Physician-defined healthy groups with and without nonhealthy individuals were compared on real data. RESULTS: With 5% outliers in simulated samples, the described outlier detection techniques had narrower reference intervals. Application of the technique to real data provided reference intervals that were, on average, 10% narrower than those obtained when outlier detection was not used. Only 1.6% of the samples were identified as outliers and removed from reference interval determination in both the healthy and combined samples. CONCLUSIONS: Even in healthy samples, outliers may exist. Combining traditional and robust statistical techniques provide a good method of identifying outliers in a reference interval setting. Laboratories in general do not have a well-defined healthy group from which to compute reference intervals. The effect of nonhealthy individuals in the computation increases reference interval width by approximately 10%. However, there is a large deviation among analytes.

Effect of maternal hypercholesterolemia on fetal sterol metabolism in the Golden Syrian hamster.

The fetus obtains a significant amount of cholesterol from de novo synthesis. Studies have suggested that maternal cholesterol may also contribute to the cholesterol accrued in the fetus. Thus, the present studies were completed to determine whether diet-induced maternal hypercholesterolemia would affect fetal sterol metabolism. To accomplish this, maternal plasma cholesterol concentrations were increased sequentially by feeding hamsters 0.0%, 0.12%, 0.5%, and 2.0% cholesterol. At 11 days into a gestational period of 15.5 days, cholesterol concentrations and sterol synthesis rates were measured in the three fetal tissues: the placenta, yolk sac, and fetus. In the placenta and yolk sac, the cholesterol concentration increased significantly when dams were fed as little as 0.12% cholesterol (P < 0.0167), and sterol synthesis rates decreased in dams fed at least 0.5% or 2% cholesterol, respectively (P < 0.0167). In the fetus, changes in fetal cholesterol concentration and sterol synthesis rates occurred only when dams were fed at least 0.5% cholesterol, which corresponded to a greater than 2-fold increase in maternal plasma cholesterol concentrations. When the cholesterol concentration in the fetal tissues in each animal was plotted as a function of maternal plasma cholesterol concentration, a linear relationship was found (P < 0.001). These studies demonstrate that sterol homeostasis in fetal tissues, including the fetus, is affected by maternal plasma cholesterol concentration in a gradient fashion and that sterol metabolism in the fetus is dependent on sterol homeostasis in the yolk sac and/or placenta.

A robust approach to reference interval estimation and evaluation.

We propose a new methodology for the estimation of reference intervals for data sets with small numbers of observations or for those with substantial numbers of outliers. We propose a prediction interval that uses robust estimates of location and scale. The SAS software can be readily modified to do these calculations. We compared four reference interval procedures (nonparametric, transformed, robust with a nonparametric lower limit, and transformed robust) for sample sizes of 20, 40, 60, 80, 100, and 120 from chi 2 distributions of 1, 4, 7, and 10 df. chi 2 distributions were chosen because they simulate the skewness of distributions often found in clinical chemistry populations. We used the root mean square error as the measure of performance and used computer simulation to calculate this measure. The robust estimator showed the best performance for small sample sizes. As the sample size increased, the performance values converged. The robust method for calculating upper reference interval values yields reasonable results. In two examples using real data for haptoglobin and glucose, the robust estimator provides slightly smaller upper reference limits than the other procedures. Lastly, the robust estimator was compared with the other procedures in a population where 5% of the values were multiplied by a factor of 5. The reference intervals were calculated with and without outlier detection. In this case, the robust approach consistently yielded upper reference interval values that were closer to those of the true underlying distributions. We propose that robust statistical analysis can be of great use for determinations of reference intervals from limited or possibly unreliable data.