Integrated 1

The Integrated 1 test (pregnancy-associated plasma protein A, PAPP-A; also known as pappalysin 1) is employed in first‑trimester integrated prenatal screening to estimate the likelihood of Down syndrome, trisomy 18, and open neural tube defects. The maternal serum measurement is interpreted alongside nuchal translucency and other clinical inputs, with final risk calculation reported after the second‑trimester specimen is tested; this is a screening tool and is not diagnostic. Maternal serum PAPP‑A may also contextualize risk for adverse pregnancy outcomes when considered with nuchal translucency and clinical parameters, but it is not intended for stand‑alone diagnosis.

Pregnancy‑associated plasma protein A (PAPP‑A) is a zinc‑binding metalloproteinase synthesized by placental trophoblast and decidua and released into maternal blood as a high–molecular‑weight complex. PAPP‑A cleaves insulin‑like growth factor–binding proteins, thereby increasing IGF bioavailability to support placental growth; it can also inactivate certain circulating proteases and modulate maternal immune responses. Maternal serum concentrations rise with advancing gestation and correlate with estradiol during placentation (weeks 7–14). Between 8 and 14 weeks, reduced PAPP‑A is observed in fetuses with chromosomal aneuploidies, most prominently trisomies 21, 18, and 13, and levels may be markedly low in syndromes featuring multiple malformations such as Cornelia de Lange syndrome. PAPP‑A is interpreted with nuchal translucency in the first trimester and, in an integrated protocol, typically combined with second‑trimester markers; as a single marker it is most informative at 8–9 weeks, and its value for aneuploidy risk assessment decreases after 14 weeks. Low first‑trimester PAPP‑A is associated with increased risk for pregnancy complications. Integrated screening involves two specimens (first and second trimester), and risk estimates are issued when both are completed. This approach is for screening; positive results prompt diagnostic confirmation, such as chorionic villus sampling or amniocentesis with genetic analysis. Trace PAPP‑A is present in nonpregnant individuals, and elevations can occur after atheromatous plaque disruption in acute coronary syndromes, though it is not widely applied in routine cardiology testing.