Suitability of rapid aneuploidy detection for prenatal diagnosis

To determine the suitability of replacing full karyotype analysis with molecular genetic rapid aneuploidy detection (RAD) methods, in particular quantitative fluorescence polymerase chain reaction (QF-PCR), for prenatal diagnosis in amniotic fluid samples obtained by amniocentesis.

We reviewed all fetal karyotypes done at our centre between August 29, 2000, and February 28, 2006. Outcome measures included (1) the proportion of prenatal samples with abnormal karyotypes that would not have been detected by RAD, as a whole and for each indication, and (2) pregnancy outcome for each chromosome abnormality that was predicted to be clinically significant or of uncertain significance and would not have been detected by RAD.

Of the 6411 karyotypes reported in the study period, 70 (1.09%) were abnormal karyotypes which would not have been detected by RAD alone. These included 32 cases (0.50%) predicted to confer no increased risk to the fetus, 17 (0.27%) predicted to have a low risk of fetal abnormality, and 21 (0.33%) with an uncertain or high risk of fetal abnormality. If full karyotype was added for nuchal translucency greater than 3.5 mm, structural fetal abnormality on ultrasound, or parental balanced chromosome rearrangement, only five uncertain or high risk cases (0.08%) would not have been detected by RAD alone.

These results suggest that if the policy of offering full karyotype analysis to all women were to be changed to a policy of offering RAD alone to women without other risk factors such as fetal abnormalities on ultrasound, increased nuchal translucency, or history of chromosome abnormality, this would mean that a chromosome abnormality with a substantial risk of clinically significant fetal abnormality would be missed in fewer than 1/1000 amniocenteses. Our results are similar to others previously reported.