PAPPA and Down syndrome: The increased levels of extracellular C19MC microRNAs during the first trimester of gestation may be related to down-regulation of some proteins and hormones that have been studied as potential early markers for gestational hypertension, preeclampsia, SGA, preterm delivery, miscarriages, stillbirth or Dowńs syndrome (e.g. pregnancy-specific glycoproteins (SP1), PAPP-A, LHCGR (Table 4, S1, S2 Tables).