The effect of fetal gender on the prediction of Down syndrome by means of maternal serum α-fetoprotein and ultrasonographic parameters

Abstract

Our investigation was designed to use maternal serum alpha-fetoprotein and individual or combinations of ultrasonographic parameters to examine the influence of fetal gender on the prediction of Down syndrome. A cohort study of 5114 patients who underwent karyotype analysis between 13 and 22 weeks' gestation was undertaken. Maternal demographic variables, anthropometric indices, and maternal serum alpha-fetoprotein values were assessed. Fetal parameters recorded included gender, biparietal diameter, head circumference, femoral and humeral length, transverse cerebellar diameter, and nuchal fold thickness. The effect of fetal gender on maternal serum alpha-fetoprotein values and ultrasonographic parameters was assessed. Gender-specific differences between fetuses with Down syndrome and euploid fetuses were identified, and the optimal cutoff values of individual and combinations of biometric parameters were determined by receiver operating characteristic curve analysis. A total of 42 fetuses with Down syndrome were identified. Female fetuses with Down syndrome had significantly lower maternal serum alpha-fetoprotein values than their male counterparts, and maternal serum alpha-fetoprotein screening paradigms resulted in the disproportionate identification of affected female fetuses. A nuchal fold thickness > or = 5 mm was the single best ultrasonographic predictor of Down syndrome independent of fetal gender. Affected male fetuses had significantly smaller mean femoral and humeral lengths than euploid fetuses after adjustment for biparietal diameter, but only the humeral length proved a clinically useful predictor of Down syndrome. Pearson's correlation coefficient confirmed that nuchal fold thickness and humeral length were independent of each other and of maternal age and maternal serum alpha-fetoprotein levels. The optimal ultrasonographic predictor of Down syndrome was the presence of either a nuchal fold thickness > or = 6 mm or a humeral length > 3.5 to 3.7 mm below the expected value. This combination of ultrasonographic findings identified 41.7% of female and 66.7% of male fetuses with Down syndrome. Fetal gender affects the prediction of Down syndrome by both maternal serum alpha-fetoprotein and ultrasonographic parameters. Moreover, the ultrasonographic detection of Down syndrome in fetuses is greatly improved by a combination of gender-specific biometric parameters.