The screening model in this study is based on data from SLOS pregnancies and will be tested in 1,000,000 pregnancies in which maternal serum uE3, alpha-fetoprotein, and human chorionic gonadotrophin measurements are being done as part of routine screening for Down syndrome. The screening false positive rate is projected to be 0.34%, the detection rate 62%, and the odds of being affected given a positive screening result 1:70. These rates all compare favorably with prenatal screening tests now in routine use. The study will also determine whether SLOS diagnostic studies can be carried out in maternal urine or serum, rather than amniotic fluid, thereby avoiding invasive procedures.