Utility of minor ultrasonographic markers in the prediction of abnormal fetal karyotype at a prenatal diagnostic center

OBJECTIVE: This study was undertaken to assess the value of minor ultrasono graphic markers in predicting significant karyotypic abnormalities. STUDY DESIGN: A total of 2743 fetuses (14-24 weeks' gestation) prospectivel y underwent a detailed ultrasonographic survey before genetic amniocentesis . Criteria for 8 minor ultrasonographic markers were established. Odds rati os for significant karyotypic abnormalities in the presence of minor ultras onographic markers were calculated with the chi 2 and Fisher exact tests. RESULTS: Of the fetuses, 14.6% had a single minor ultrasonographic marker, 2.1% had greater than or equal to 2 minor ultrasonographic markers, and 2.7 % had greater than or equal to 1 major ultrasonographic abnormality One hun dred four fetuses (3.8%) had an abnormal karyotype. Compared with a normal ultrasonographic examination result a single minor ultrasonographic marker increased the risk of karyotypic abnormality 5.7-fold (95% confidence inter val, 3.5-9.3), whereas multiple minor markers increased the risk of an abno rmal karyotype 12-fold (95% confidence interval, 5.5-26.5). When they were identified ultrasonographically in isolation, echogenic bowel, 2-vessel umb ilical cord. echogenic intracardiac foci, choroidal separation, and choroid plexus cysts were statistically associated with an abnormal karyotype. Whe n minor markers were identified in clusters of greater than or equal to 2, echogenic bowel, short femur, 2-vessel umbilical cord, echogenic intracardi ac foci, and mild ventriculomegaly were significantly predictive of karyoty pic abnormality. With respect to the a priori aneuploidy risk of 1:26 and t he a priori Down syndrome risk of 1:50, a normal ultrasonographic examinati on result reduced the risks to 1:67 and 1:120, respectively. The use of min or ultrasonographic markers in addition to major ultrasonographic abnormali ties increased the detection of karyotypic abnormality from 27.9% to 68.3%. For trisomy 21 the sensitivity rose from 16.4% to 67.3%. CONCLUSIONS: Significant karyotypic abnormality risk assessment by ultrason ography was greatly enhanced by the addition of minor ultrasonographic mark ers. Further, clusters of minor ultrasonographic markers greatly increased the likelihood of karyotypic abnormality compared with a single minor marke r. A completely normal ultrasonographic examination result reduced the risk of an abnormal karyotype by 62%. inclusion of minor ultrasonographic marke rs in the genetic sonogram in a high-risk population will allow the detecti on of 68% of fetuses with karyotypic abnormalities with a false-positive ra te of 17%.