Objectives To investigate associations between combined first-trimester screen result, pregnancy associated plasma protein-A (PAPP-A) level and adverse fetal outcomes in women.Methods Pregnancy outcomes for 10 273 women participating in a community based first-trimester screening (FTS) programme in Western Australia were ascertained by record linkage to birth and birth defect databases. A first-trimester risk cut-olf of >= 1 in 300 defined screen positive women.Results Screen positive pregnancies were more likely to have Down syndrome and birth defects (chromosomal or nonchromosomal) than screen negative pregnancies. When birth defects were excluded, screen positive pregnancies were at increased risk of pregnancy loss, low birth weight and preterm birth. Pregnancies with low PAPP-A (<= 0.3 multiples of the median (MoM)) had higher risk of chromosomal abnormality, birth defect, preterm birth, low birth weight, or pregnancy loss, compared to those with PAPP-A >0.3 MoM. In pregnancies without birth defects, low PAPP-A was a stronger predictor of preterm birth, low birth weight or pregnancy loss than a screen positive result.Conclusions Women with positive screen or low PAPP-A were at increased risk for some adverse fetal outcomes. The sensitivity of these parameters was inSufficient to support primary screening, but increased surveillance during pregnancy may be appropriate. Copyright (c) 2008 John Wiley & Sons, Ltd.