Association Between First-Trimester Maternal Serum Pregnancy-Associated Plasma Protein-A and Adverse Pregnancy Outcome

Abstract

Pregnancy-associated plasma protein-A (PAPP-A) is a glycoprotein derived from trophoblasts that cleaves insulin-like growth factor-binding proteins and augments the action of insulin growth factor. Maternal levels of PAPP-A are higher in primigravid and multiple pregnancies, and correlate positively with placental weight. Apart from being a marker of aneuploidy, low PAPP-A levels could be evidence of impaired placental formation and implantation. This retrospective review attempted to determine whether first-trimester PAPP-A levels are associated with intrauterine growth restriction, preterm delivery, or stillbirth. Pregnancy outcomes were sought in a medical records review and by postal questionnaire. All 827 women having serum PAPP-A estimates had a normal karyotype. Along with 2 neonatal deaths and 6 intrauterine deaths, 13 newborn infants had a birth weight below the third percentile and 55 weighed below the 10th percentile. Ninety-six women delivered prematurely. Four of the 6 intrauterine deaths were associated with a low maternal serum PAPP-A level less than 0.5 multiples of the median (MOM). Infant mortality was 3.8% in pregnancies with a PAPP-A level less than 0.5 MOM and 0.27% in those with higher levels for a relative risk of 13.75. Low levels of PAPP-A were associated with birth weight below the 10th percentile, but not with weight below the third percentile. Low maternal PAPP-A levels did not correlate with preterm delivery. This study indicates that low first-trimester levels of PAPP-A in maternal serum are associated with adverse fetal outcomes, including fetal death in utero and intrauterine growth retardation. An estimate of PAPP-A, by itself or combined with antenatal ultrasonography, might help assess the risk of such outcomes in high-risk pregnancies.