Association of serum PAPP-A levels in first trimester with small-for-gestational-age and adverse pregnancy outcomes: systematic review and meta-analysis

OBJECTIVES: To determine association, and predictive ability, of first trimester maternal serum pregnancy associated plasma protein A (PAPP-A) with adverse pregnancy outcomes.

METHOD: Searches of Medline, Embase and CINAHL (inception-September 2015) for studies including pregnant women with first trimester PAPP-A and assessment of pregnancy outcomes.Study characteristics, quality and results extracted. Meta-analysis of odds ratios (OR), and likelihood ratios (LR) and 95% confidence intervals (CI).

RESULTS: Thirty-two studies including 175,240 pregnancies. PAPP-A <5(th) centile had a moderate association with: Birthweight <10(th) centile OR 2.08 (95% CI 1.89 - 2.29), <5(th) centile OR 2.83 (95% CI 2.52 - 3.18); pre-eclampsia OR 1.94 (95% CI 1.63 - 2.30), preterm birth <37 weeks OR 2.09 (95% CI 1.87 - 2.33), and composite adverse outcome OR 3.31 (95% CI 1.80 - 5.11). The predictive ability was poor: Birthweight <10th centile LR + ve 1.96 (95% CI 1.58 -2.43), LR-ve 0.93 (95% CI 0.89 - 0.98); Birthweight <5th centile LR + ve 2.65 (95% CI 2.35 -2.99), LR-ve 0.85 (95% CI 0.74 - 0.98); PTB <37 weeks LR + ve 1.84 (95% CI 1.41 - 2.39), LR-ve 0.92 (95% CI 0.87 - 0.98).

CONCLUSIONS: First trimester low maternal serum PAPP-A is associated with adverse pregnancy outcome but predictive values are poor. Further work should address PAPP-A as a continuous variable in combination with other prognostic markers as a prediction model. This article is protected by copyright. All rights reserved.