OBJECTIVE This study aimed to determine whether pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (β-hCG), a disintegrin and metalloprotease 12 (ADAM12), and placenta protein 13 (PP13) in the first trimester, and uterine artery Doppler (UAD) in the second trimester, predict preeclampsia and fetal growth restriction (FGR). MATERIALS AND METHODS Maternal serum levels of PAPP-A, free β-hCG, ADAM12, and PP13 at 11-13+6 weeks of gestation and bilateral uterine artery pulsatility index (PI) at 22-24 weeks of gestation were measured in a nested case-control study within a prospective cohort. The serum analytes and Doppler measurements were compared for uncomplicated pregnancies and pregnancies complicated by preeclampsia and FGR. The efficacy of biochemical and Doppler measurements for the prediction of preelampsia and FGR was investigated. RESULTS Compared with gestational age-matched controls (n = 200), the mean PAPP-A and ADAM12 were lower (P < 0.001, P < 0.05) in pregnancies complicated by preeclampsia (n = 462) and FGR (n = 350). The median uterine artery mean PI was higher (P < 0.001) in preeclampsia and FGR groups. However, the median free β-hCG and PP13 were not significantly different from normal (P > 0.05). In screening for preeclampsia and FGR, assuming a fixed false positive rate (FPR) of 10%, the detection rates were 72% and 68% for a combination of PAPP-A, ADAM12, and UAD, respectively. CONCLUSION First trimester PAPP-A and ADAM12 levels and second trimester uterine artery PI are associated with adverse pregnancy outcomes. The combination of biochemical markers and UAD improves the screening efficiency for the prediction of preeclampsia and FGR.