Pregnancy-associated plasma protein A is a protein produced by the placental trophoblasts and is one of the markers used in prenatal genetic testing. Low levels of this protein are a possible biochemical marker for fetuses with chromosomal anomalies.

Integrated prenatal screening (IPS) combines measurements from a nuchal translucency ultrasound and two blood tests to estimate the chances of Down’s Syndrome, Trisomy 18, and neural tube defect. IPS measures first trimester maternal serum levels of PAPP-A, first trimester fetal nuchal translucency, second trimester maternal serum levels of beta-HCG, estriol, inhibin-A, and alpha-fetaprotein (AFP). The first set of blood work and ultrasound are done between 11 and 13+6 weeks gestational age; the second set of blood work is done between 15 and 20+6 weeks gestational age (preferably between 15 and 17 weeks). IPS testing will pick up 85-95% of cases of Down’s syndrome (depending on maternal age) and has a false positive rate of 2-6%. The false positive rate is higher in women over age 40 (11%). If access to nuchal translucency ultrasound is not available, a Serum Integrated Prenatal Screen (SIPS) may be used instead. The detection rate for Down’s may be slightly lower with SIPS compared to IPS.

Several studies have found that low levels of first trimester PAPP-A are associated with an increased risk of adverse obstetrical outcomes. In the FASTER Trial (First and Second Trimester Evaluation of Risk), low levels of first trimester PAPP-A (< 5th percentile) were associated with an increased risk of low birthweight, preterm birth, stillbirth, gestational hypertension, fetal loss lesser than/= 24 weeks, placental abruption, and preterm premature rupture of the membranes (PPROM). However, the positive predictive value (PPV) of PAPP-A levels was too low to make it a worthwhile clinical tool.

In summary low PAPP-A levels are associated with certain fetal chromosomal anomalies and may be a marker for an increased risk of other adverse obstetrical outcomes but given the low PPV of a low PAPP-A there’s no value in doing PAPP-A levels unless it’s part of integrated prenatal screening.

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