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.
University of Sydney, Department of Obstetrics and Gynaecology, Perinatal Research Group, North Shore Obstetric and Gynaecological Ultrasound, Kolling Institute and Pacific Laboratory Medicine Sevices, Royal North Shore Hospital, Sydney, Australia