Low pregnancy-associated plasma protein A level in the first trimester

Objective

To review the recent evidence behind the association of low levels (ie, below the fifth percentile) of pregnancy-associated plasma protein A (PAPP-A) with adverse perinatal outcomes and to integrate new findings with the recommendations made by the Society of Obstetricians and Gynaecologists of Canada in 2008.

Quality of evidence

A review of recently published articles revealed that current evidence is sparse and mixed for the association of low PAPP-A level with small size for gestational age, preterm delivery, hypertensive disorders of pregnancy, and stillbirth. There is limited evidence that suggests an association between low PAPP-A levels and spontaneous pregnancy loss. Recent studies suggest that low PAPP-A levels are associated with abnormal placentation, which might be the root cause of the adverse perinatal outcomes of interest.

Main message

The evidence behind the association of low PAPP-A levels with adverse perinatal outcomes is both lacking and mixed. However, recent data do suggest an association between low PAPP-A levels and abnormal placentation. This emerging topic currently lacks strong evidence-based guidelines, yet has potential important implications for perinatal outcomes. Collaboration with obstetric specialists regarding pregnant women who have low PAPP-A levels in the context of normal first-trimester aneuploidy screening results might aid clinical decision making about pregnancy and placental surveillance.

Conclusion

While the clinical meaning of a low PAPP-A level detected in the context of normal fetal aneuploidy screening remains under debate, pregnant patients with such results should be counseled that at present no strong evidence exists to justify an ongoing ultrasound surveillance program.