Beryl R. Benacerraf

The Genetic Sonogram A Method of Risk Assessment for Down Syndrome in the Second Trimester

Objective. To determine the risk of Down syndrome in fetuses with sonographic markers using the Bayes theorem and likelihood ratios. Methods. We prospectively evaluated the midtrimester sonographic features of fetuses with Down syndrome and compared them with euploid fetuses. Patients were referred for an increased risk of aneuploidy and evaluated for the presence of structural defects, a nuchal fold, short long bones, pyelectasis, an echogenic intracardiac focus, and hyperechoic bowel. All fetuses underwent amniocentesis at the time of sonographic assessment. The sensitivity, specificity, and likelihood ratios for markers were calculated both as nonisolated and isolated findings. Results. There were 164 fetuses with Down syndrome and 656 euploid fetuses. The presence of any marker resulted in sensitivity for the detection of Down syndrome of 80.5% with a false‐positive rate of 12.4%. The absence of any markers conferred a likelihood ratio of 0.2, decreasing the risk of Down syndrome by 80%. As an isolated marker, the nuchal fold had an “infinite” likelihood ratio for Down syndrome; a short humerus had a likelihood ratio of 5.8, whereas structural anomalies had a likelihood ratio of 3.3. Other isolated markers had low likelihood ratios because of the higher prevalence in the unaffected population. The likelihood ratios for the presence of 1, 2, and 3 of any of the markers were 1.9, 6.2, and 80, respectively. Conclusions. Although an isolated marker with a low likelihood ratio may not increase a patients risk of Down syndrome, the presence of such a marker precludes reducing the risk of aneuploidy. Clusters of markers appear to confer a higher risk.

Management of asymptomatic ovarian and other adnexal cysts imaged at US: Society of Radiologists in Ultrasound Consensus Conference Statement.

The Society of Radiologists in Ultrasound convened a panel of specialists from gynecology, radiology, and pathology to arrive at a consensus regarding the management of ovarian and other adnexal cysts imaged sonographically in asymptomatic women. The panel met in Chicago, Ill, on October 27-28, 2009, and drafted this consensus statement. The recommendations in this statement are based on analysis of current literature and common practice strategies, and are thought to represent a reasonable approach to asymptomatic ovarian and other adnexal cysts imaged at ultrasonography.

A sonographic sign for the detection in the second trimester of the fetus with Down's syndrome

Sonographic structural surveys were made at the time that 904 amniocenteses were performed for genetic evaluation in the second trimester. A sonographic sign was identified which places the fetus at high risk for having Downs syndrome.

Sonographic scoring index for prenatal detection of chromosomal abnormalities.

Current indications for cytogenetic evaluation leave the majority of Down syndrome fetuses undetected. Using advanced maternal age and low maternal serum alpha‐fetoprotein (AFP) levels as criteria, only 40% of fetuses with Down syndrome (trisomy 21) are identified (positive predictive value, 0.4% to 1%). We evaluate the sonographically detectable physical features of second trimester fetuses to determine whether these features are more sensitive and specific than maternal age for detecting fetuses with abnormal karyotypes. From March 1, 1990, to September 1, 1991, more than 5,000 fetuses between 14 and 20 weeks of development were referred for genetic amniocentesis because of advanced maternal age or abnormal AFP levels. Forty‐three of these 5,000 fetuses were later found to have autosomal trisomies by karyotype (32 with trisomy 21, nine with trisomy 18, and two with trisomy 13). A sample of 588 consecutive normal fetuses from the total of more than 5,000 amniocenteses performed during this period of time was used as our control group for statistical analysis. The sonographic features of these 588 normal second trimester fetuses and the 43 trisomic fetuses recorded prospectively prior to knowledge of the karyotype were evaluated statistically. The femur and humerus lengths, nuchal fold, renal pelvic dimension, and major structural defects were compared in the normal and trisomic fetuses. On the basis of our results, a weighted sonographic score was developed to optimize the detection of fetuses at risk for aneuploidy. Using our previously published formulas and criteria for a short femur and humerus, 17/32 (53%) fetuses with Down syndrome and 23/588 (3.9%) of the normal fetuses were identified. Twenty two of 32 Down syndrome fetuses (69%) and 2/588 (0.34%) of normals had a nuchal fold > or = 6 mm, and 11 of 32 Down syndrome fetuses and all those with trisomies 18 and 13 had a major anomaly detected sonographically. The following scoring system was developed for the detection of aneuploidy: nuchal fold = 2, major structural defect = 2, and short femur, short humerus, and pyelectasis = 1 each. Selecting fetuses with a score of > or = 2 would identify 26/32 (81%) Down syndrome fetuses, and 9/9 (100%) and 2/2 (100%) fetuses with trisomies 18 and 13 respectively, but only 26/588 (4.4%) of the normal fetuses. Using the sonographic score of 2 results in a positive predictive value for a 1/250 risk group of 6.87% for identifying Down syndrome fetuses and 7.25% for all three trisomies.(ABSTRACT TRUNCATED AT 400 WORDS)

A randomized, placebo-controlled, double-blind study evaluating the efficacy of leuprolide acetate depot in the treatment of uterine leiomyomata

Thirty-eight premenopausal women with uterine leiomyomata were enrolled in a randomized, double-blind, placebo-controlled study evaluating the efficacy of depot leuprolide acetate (LA), a gonadotropin-releasing hormone agonist, in decreasing uterine volume. Eighteen women received intramuscular (IM) depot LA 3.75 mg every 4 weeks for 24 weeks (group A); 20 women received IM placebo with the same injection schedule (group B). Group A patients had a mean reduction in pretreatment uterine volume from 505 +/- 93 cu cm (mean +/- standard error of the mean) to 305 +/- 57 cu cm after 12 weeks (P less than 0.05 versus pretreatment) and 307 +/- 57 cu cm after 24 weeks of therapy (P less than 0.05 versus therapy (P less than 0.05 versus pretreatment). At 3 months after cessation of therapy, the mean uterine volume in group A had increased to 446 +/- 92 cu cm (P less than 0.05 versus week 24). Group B patients had no significant change in uterine volume over the 24-week treatment period. These results suggest that depot LA therapy may significantly decrease uterine volume in patients with leiomyomata, but that regrowth of uterine size occurs shortly after cessation of therapy.

Mild fetal lateral cerebral ventriculomegaly: Clinical course and outcome

The neonatal, pathologic outcome and karyotypic abnormalities are reported for 44 fetuses with mild ventriculomegaly diagnosed antenatally. Seventeen of these 44 fetuses (39%) had other ultrasonographic defects, and five (12%) had abnormal karyotypes. Five pregnancies were electively aborted and three other fetuses died in the neonatal period. Twenty-six (72%) of the remaining 36 live-born neonates are developmentally and clinically normal at 3 to 18 months of age. Twenty-one of these 26 had isolated mild ventriculomegaly as the only ultrasonographic finding. The other 10 live-born infants are developmentally impaired, and five of these 10 had mild ventriculomegaly as the only prenatal ultrasonographic abnormality. In conclusion, these data show that fetuses with mild ventriculomegaly have a lower incidence of associated anomalies and a better outcome than fetuses with more severe ventricular dilatation, as reported in the literature. The majority of fetuses with mild ventriculomegaly as an isolated finding and a normal karyotype are developing normally.

Echogenic intracardiac focus: A sonographic sign for fetal down syndrome

Objective To determine whether an echogenic intracardiac focus identified in the second-trimester fetus is related to an increased risk of Down syndrome. Methods During a 10-month period, all women with singleton gestations who underwent second-trimester genetic amniocentesis for non-imaging indications were evaluated prospectively by prenatal sonography. The presence or absence of an echogenic intracardiac focus was noted. Karyotypic information was obtained on each fetus. Results Among the 1334 patients in the study group, 66 fetuses (4.9%) had an echogenic intracardiac focus. Four of 22 fetuses (18%) with trisomy 21 had an echogenic intracardiac focus, compared with 62 (4.7%) of 1312 fetuses without Down syndrome who also had an echogenic intracardiac focus (P = .004). Sonographic identification of an echogenic intracardiac focus was associated with a fourfold increased risk of Down syndrome (risk ratio 4.3, 95% confidence interval 1.5–12.3). The overall prevalence of Down syndrome in our study population was 1.6%. The sensitivity, specificity, and positive predictive value for using the presence of an echogenic intracardiac focus to identify a fetus with Down syndrome was 18.2, 95.3, and 6.1%, respectively. Extrapolating to a lower risk population, the positive predictive value of an echogenic intracardiac focus for detecting Down syndrome in patients at an age-based risk of one in 250, one in 500, and one in 1000 was calculated to be 1.53, 0.77, and 0.39% respectively. Conclusions Fetuses with an echogenic intracardiac focus have a significantly increased risk of Down syndrome. Although most fetuses with this finding are normal, patients carrying fetuses with an echogenic intracardiac focus should be counseled about the increased risk of trisomy 21.

Sonographically estimated fetal weights: Accuracy and limitation

To determine the accuracy of our ultrasonographically predicted birth weights we studied 1301 women delivered of infants within a week of an obstetric ultrasonogram to compare the ultrasonographically predicted birth weights with the actual birth weights. The fetuses varied from 700 to 5800 gm and were consecutive singleton fetuses in vertex presentations delivered at a single institution. Overall 74% of the infants had birth weights within 10% of the ultrasonographic estimates and 42% had birth weights within 5% of the ultrasonographic estimates. The presence of oligohydramnios or polyhydramnios made no difference in the percent errors. The sensitivity for identifying a fetus with macrosomia (birth weight greater than 4000 gm) with an estimated weight of greater than or equal to 4000 gm was 65%. The specificity or percent of fetuses correctly identified ultrasonographically as not macrosomic was 90%. If fetuses predicted by ultrasonography to be greater than 3800 gm were included, the sensitivity for the prediction of macrosomia rises to 82% but the specificity would be 79%. There appears to be a fixed limitation to obtaining estimated fetal weights by ultrasonography, even in large series, because these data reaffirm the success and limitations of other methods used to estimate fetal weight previously reported in the literature.

The sonographic diagnosis of Dandy-Walker and Dandy-Walker variant: associated findings and outcomes.

Outcomes of pregnancies with sonographically diagnosed Dandy–Walker (DW) or Dandy–Walker variant (DWV) syndromes vary widely. We examined our own experience with these diagnoses in an effort to identify those sonographic features that best predicted neonatal outcome. We identified 50 fetuses with DW and 49 with DWV diagnosed sonographically. Eighty‐six per cent of fetuses with DW and 85% of fetuses with DWV had other sonographically identifiable anomalies, the most common being ventriculomegaly (DW: 32%; DWV: 27%) and cardiac defects (DW:38%; DWV: 41%). Forty‐six per cent and 36% of available karyotypes in cases of DW and DWV, respectively, were abnormal. 50 out of 99 women in our series elected pregnancy termination. Only three pregnancies with DW resulted in a living infant, and only one of these had a normal paediatric examination at six‐week follow‐up. Thirteen out of 49 infants with DWV survived the neonatal period and 7 of 13 were reported initially as normal infants, including six with an isolated finding of DWV. We conclude that overall, the prognosis for these posterior fossa defects is grim but not uniformly fatal. The presence of other anomalies is associated with the worst prognosis. Isolated Dandy–Walker variant has the highest chance of leading to a normal neonate. Copyright

In utero pulmonary artery and aortic growth and potential for progression of pulmonary outflow tract obstruction in tetralogy of fallot

OBJECTIVES This study was designed to define patterns of pulmonary artery and aortic growth in fetuses with tetralogy of Fallot and to determine the potential for in utero progression of right ventricular outflow tract obstruction. BACKGROUND Despite an abundance of reports documenting the prenatal diagnosis of tetralogy of Fallot, there is little information about its course in utero. METHODS Pulmonary artery and ascending aortic diameters were measured from prenatal and postnatal echocardiograms of 16 fetuses with tetralogy of Fallot, initially studied at 23.6 +/- 6.0 (mean +/- SD) weeks of gestation. Fetuses were classified retrospectively as having mild and severe tetralogy of Fallot according to whether the pulmonary artery circulation was (severe, n = 5) or was not (mild, n = 11) ductus arteriosus dependent at birth. RESULTS Initial main pulmonary artery diameter was small for gestational age in 9 fetuses, large in 2 and normal in 5 compared with data from 57 gestational age-adjusted normal fetal studies; it was significantly smaller in the group with severe tetralogy of Fallot (p = 0.05). The initial main pulmonary artery/aortic diameter ratio was also smaller for the group with severe tetralogy of Fallot (0.50 +/- 0.15 vs. 0.73 +/- 0.14 in the group with mild tetralogy of Fallot, p = 0.01). Initial aortic and branch pulmonary artery diameters tended to be normal or near normal for age. In eight fetuses serially studied, main and branch pulmonary artery growth was normal or reduced during prenatal follow-up. Pulmonary artery growth was most reduced in two fetuses in the group with severe tetralogy of Fallot, resulting in pulmonary artery hypoplasia at birth. Two fetuses with valvular pulmonary atresia at birth had previously shown anterograde pulmonary outflow in midgestation, suggesting progression of pulmonary outflow obstruction. CONCLUSIONS The postnatal spectrum of pulmonary artery size in tetralogy of Fallot can be attributed to variable patterns of growth in utero. Main pulmonary artery size, main pulmonary artery/aortic diameter ratio and pattern of pulmonary artery growth may be predictive of the severity of postnatal pulmonary outflow obstruction. Pulmonary atresia can develop in utero in some fetuses with tetralogy of Fallot.