John Langdon Down (1828-1896) described Down’s syndrome with 3 characteristics: the skin too loose for the body, flat face, and small nose.Every woman has a risk of having a baby with Down’s syndrome which depends on her age and the history of having a previous Down’s baby (background or priori risk). Diagnosis of fetal chromosomal abnormalities requires invasive testing by amniocentesis or chorionic villous sampling (CVS), both of which have a risk of miscarriage of 1%. The risk for trisomy 21 increases with maternal age and decreases with gestational age because about 30% of affected fetuses die between the 12th and 40th week of pregnancy. However the vast majority of pregnant women are young, therefore most of Down babies are in the younger age group. SCREENING in the second trimester by maternal age and various combinations of total or free b-hCG, AFP, uE3 and Inhibin A can identify 56-71% of trisomy 21 pregnancies for a false positive rate of 5% (Meta-analysis by H Cuckle, P Penn and D Wright, Semin Perinatol 2005; 29: 252-7). SCREENING in the first trimester by a combination of maternal age, fetal NT, FHR and serum free b-hCG and PAPP-A identifies about 90% of trisomy 21 pregnancies for a false positive rate of 3%. By adding other ultrasound markers: nasal bone, tricuspid regurgitation, ductus venosus Doppler and facial angle, the detection rate of 1st trimester SCREENING increases to more than 95%.