PAPP-A is produced by the placental trophoblasts. It is a ‘protease’ for insulin-like growth factor (IGF) binding proteins 4 and 5. This means it has the ability to help release IGF from these binding proteins so that it is free to interact with its cell receptor. IGF is thought to play an important role in trophoblast invasion and hence the early development and vascularization of the placenta and the placental bed. These early events in formation of the placenta are critical to pregnancy outcome and, when abnormal, are associated with miscarriage, intrauterine growth restriction (IUGR) of the baby, pregnancy-induced hypertensive disorders, fetal death in utero, premature delivery, and even cesarean section for indications of fetal or maternal compromise. It has been postulated that LOW levels of PAPP-A, resulting in less release of IGF, could be a pathway by which placentation abnormalities occur that culminate in these poor pregnancy outcomes. PAPPA is also present in unstable atherosclerotic plaques, and circulating levels are elevated in acute coronary syndromes which may reflect the instability of the plaques. PAPPA may be a marker of unstable angina and acute myocardial infarction. This test is usually performed as a screening tool for Down’s syndrome. It can also be used in combination with free hCG and the ultrasound Nuchal Translucency test to enhance the detection rate of Down’s syndrome and other fetal abnormalities. See also Prenatal First Trimester Screen.