Biology of pregnancy‐associated plasma protein‐A in relation to prenatal diagnostics: an overview

Abstract

Pregnancy-associated plasma protein-A (PAPP-A) is highly efficient as a serum marker in first-trimester screening for chromosomal abnormalities. Furthermore, there is increasing evidence that low levels of PAPP-A in the first trimester are associated with adverse pregnancy outcomes such as preterm delivery, intrauterine growth retardation, preeclampsia, and stillbirth. PAPP-A is a glycoprotein, produced in the placenta, and it is present in the maternal circulation in increasing concentrations during pregnancy. By means of its proteolytic activity, PAPP-A functions as a regulatory protein in the insulin-like growth factor system, known to be important for placental formation and regulation of fetal growth. This overview describes aspects of biochemistry, synthesis, and biological functions of PAPP-A, with a focus on information of importance to clinicians. The clinical applications of PAPP-A are summarized, and new insights regarding the analyses of PAPP-A discussed.

Consecutive measurements show association of IGF-1 with preterm delivery in type 1 diabetic pregnancy

“…This is in line with several large cross-sectional data from non-diabetic women, who delivered preterm and had SGA neonates (3)(4)(5)(6)(7)(8). PAPP-A was attributed to play a role as early as in gestational week 10-14 in prediction of these adverse events.…”

Pregnancy-associated plasma protein A - a level in first trimester and its impact on pregnancy outcome

“…9 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. 10 IGF is thought to play an imp role in trophoblast invasion and hence the early development and vascularisation of placenta and placental bed. These early events in the formation of the placenta are critical to the pregnancy outcome and when abnormal, are associated with miscarriage, IUGR of baby, PIH, fetal death in utro, premature delivery, and even cesarean section for indications of fetal or maternal compromise.…”

Macrosomia and the IGF System: A Short Review

“…However, no difference is seen in IGFBP-3 proteolysis in sera of the fetuses themselves, even in the cases with growth restriction, which is in contrast to the maternal situation [29]. PAPP-A, a proteolytic substance of IGFBPs, is found at lower levels in diabetic women than in controls in the first trimester pregnancy and indicates less proteolysis [19,45]. The finding of an association between birth weight and IGF-1 and -2 would support this theory if reflected in data obtained early in pregnancy.…”

“…This time interval is not included in our studies. In non-diabetic women data from 1 st trimester show a correlation of PAPP-A in and fetal growth restriction [19].…”

“…Phosporylated IGFBP-1 is affected in its regulation on the bioavailability of IGF-1 as it exists in a low and high phosphorylated forms, lp-IGFBP-1 and hp-IGFBP-1. Proteolysis of IGFBPs is in part done by pregnancy-associated plasma protein A (PAPP-A), a metalloproteinase, particular in the 1 st and early 2 nd trimester [19]. This results in a predominance of IGFBPs with lowered affinities for IGFs and increased system-wide IGF bioavailability which may be detectable as excessive growth from mid-2 nd trimester.…”