The purpose of this study is to compare the levels of maternal serum pregnancy–associated plasma protein-A at the first trimester in pregnancies complicated by impaired placental diseases, such as preeclampsia (PE), intrauterine fetal growth restriction (IUGR), and gestational hypertension (GH), with those in pregnancies without the development of any of these outcomes to expand the knowledge of how this protein behaves in the different impaired placental diseases. This current work is an observational study based on a prospective cohort. Pregnancy-associated plasma protein-A was measured in 422 patients who had completed maternal-perinatal outcomes. Comparisons of pregnancy characteristics and the biomarker between outcome groups (PE, IUGR, gestational hypertension, and not impaired placental outcomes) were analyzed. PAPP-A MoM in the IUGR (0.8 IQR: 0.6–0.9) and GH groups (0.5 IQR: 0.3–1.4) compared to the PE group (1.06 IQR: 0.66–1.52) was significantly lower (p < 0.005). Pregnant women who developed early-onset PE (1.11 IQR 1.08–1.18) presented significant differences with the IUGR group (0.83 IQR: 0.59–0.98; p = 0.002) and those who developed preterm-PE (1.19 IQR: 0.66–1.58; p = 0.045). The results demonstrate that the levels of PAPP-A at first trimester in the sample of women who developed PE, and specially term-PE, were higher than those in women who developed GH or IUGR. The GH group had the lowest PAPP-A values in this sample of pregnant women. Research in a population with a high prevalence of preeclampsia is still lacking and deserves more extended studies to define if these patients could have different rates of PAPP-A.