The purpose of this study was to determine the association between first trimester trisomy 21 screening markers (free human chorionic gonadotropin- β ., pregnancy associated plasma protein A , and nuchal translucency) and adverse pregnancy outcome. This was a cohort study of 8012 patients enrolled in a National Institute of Child Health and Human Development sponsored study of first trimester trisomy 21 and 18 screening. Trisomy 21 and 18 risk results and individual marker levels in unaffected pregnancies and pregnancies with adverse outcomes were evaluated. PAPP- A <1st percentile (OR 5.4, 95% CI 2.8- 10.3) and PAPP- A <5th percentile (OR 2.7, 95% CI 1.9- 3.9) and free β - hCG <1st percentile (OR 2.7, 95% CI 1.3- 5.9) were associated with increased risk of intrauterine growth restriction (IUGR) with positive predictive values of 24.1% , 14.1% , and 14.3% , respectively. PAPP- A <5th percentile (OR 2.3 95% CI 1.1- 4.7) and nuchal translucency >99th percentile (OR 3.5, 95% CI 1.1- 11.3) were associated with increased risk of preterm delivery before 34 weeks. Increased risk at screening for trisomy 21 and 18 identified 16 of the 29 other chromosomal abnormalities (55% ). Low free β - hCG, low PAPP- A, and increased nuchal translucency were all associated with an increased rate of fetal abnormality. Extreme values of first trimester free β - hCG, PAPP- A, and nuchal translucency are all associated with adverse outcomes. The especially high predictive value for IUGR of PAPP- A levels below the 1st percentile suggests that patients within this group may benefit from increased surveillance for this condition. The purpose of this study was to determine the association between first trimester trisomy 21 screening markers (free human chorionic gonadotropin- β., Pregnancy associated plasma protein A, and nuchal translucency) and adverse pregnancy outcome. This was a cohort study of 8012 patients enrolled in a National Institute of Child Health and Human Development sponsored study of first trimester trisomy 21 and 18 screening. Trisomy 21 and 18 risk results and individual marker levels in unaffected pregnancies and pregnancies with adverse outcomes were. PAPP- A <1st percentile (OR 5.4, ​​95% CI 2.8- 10.3) and PAPP-A <5th percentile (OR 2.7, 95% CI 1.9- 3.9) and free β -hCG <1st percentile (OR 2.7, 95% CI 1.3- 5.9) were associated with increased PAPI-A <5th percentile (OR 2.3 95% CI 1.1-4.7) and nuchal translucency> 99th percentile (OR 3.5 95% CI 1.1-4.7) and positive predictive value of 24.1%, 14.1%, and 14.3% , 95% CI 1.1-11.3) were associated with increased risk of preterm delivery before 34 weeks. Increased risk at screening for trisomy 21 and 18 identified 16 of the other chromosomal abnormalities (55%). Low free β - hCG, low PAPP- A, and increased nuchal translucency were all associated with an increased rate of fetal abnormality. Extreme values ​​of first trimester free beta-hCG, PAPP-A, and nuchal translucency are all associated with adverse outcomes. The especially high predictive value for IUGR of PAPP-A levels below the 1st percentile suggests that the patients within this group may benefit from increased surveillance for this condition.