The purpose of this study was to determine whether maternal serum levels of pregnancy associated plasma protein A, free beta subunit human chorionic gonadotropin, or nuchal translucency size are associated with obstetric complications. Data were obtained from the First and Second Trimester Evaluation of Risk trial. Pregnancy associated plasma protein A and free beta subunit human chorionic gonadotropin levels were analyzed, and nuchal translucency was measured between 10 weeks 3 days and 13 weeks 6 days of gestation in 34,271 pregnancies. Women with pregnancy associated plasma protein A of ≤ 5th percentile were significantly more likely to experience spontaneous fetal loss at ≤ 24 weeks of gestation, low birth weight, preeclampsia, gestational hypertension, preterm birth (P <. 001) and stillbirth, preterm premature rupture of membranes, and placental abruption (P <. 02). Nuchal translucency at ≥ 99th percentile and free beta subunit human chorionic gonadotropin at ≤ 1st percentile were associated with an increased risk of spontaneous loss at ≤ 24 weeks of gestation (adjusted odds ratios, 3.90, 3.62, respectively; P <. 001). Low preg nancy associated plasma protein A levels in the first trimester were associated strongly with a number of adverse pregnancy outcomes. Low free beta subunit human chorionic gonadotropin levels and large nuchal translucency were both associated with early fetal loss. The purpose of this study was to determine whether maternal serum levels of pregnancy associated plasma protein A, free beta subunit human chorionic gonadotropin, or nuchal translucency size are associated with obstetric complications. Pregnancy associated plasma protein A and free beta subunit human chorionic gonadotropin levels were analyzed, and nuchal translucency was measured between 10 weeks 3 days and 13 weeks 6 days of gestation in 34,271 pregnancies. Women with pregnancy associated plasma protein A of ≤ 5th percentile were significantly More likely to experience spontaneous fetal loss at <24 weeks of gestation, low birth weight, preeclampsia, gestational hypertension, preterm birth (P <.001) and stillbirth, preterm premature rupture of membranes, and placental abruption (P <.02). Nuchal translucency at ≥ 99th percentile and free beta subunit human chorionic gonadotropin at ≤ 1st percentile were associated with an increased risk of spontaneous loss at ≤ 24 weeks of gestation (adjusted odds ratios, 3.90, 3.62, respectively; P <001). Low preg nancy associated plasma protein A levels in the first trimester were associated strongly with a number of adverse pregnancy outcomes. Low free beta subunit human chorionic gonadotropin levels and large nuchal translucency were both associated with early fetal loss.