PAPP-A and free β-hCG measured prior to 10 weeks is associated with preterm delivery and small-for-gestational-age infants

Objective: To evaluate whether measuring pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotrophin (β-hCG) before 10 weeks of gestation affect the association between these biomarkers and adverse pregnancy outcomes.

Methods: Singleton pregnant women (9450) who attended the prenatal screening program, Aarhus University Hospital, Denmark, were included. Maternal serum levels of PAPP-A and free β-hCG were measured between week 8 and 13 weeks and 6 days. The risk of preterm delivery (<37 weeks) and small for gestational age (SGA) (<the fifth centile) was evaluated in relation to PAPP-A and free β-hCG < 0.4 multiples of the median, stratified according to early (<10 weeks) or late (≥ 10 weeks) biochemical testing.

Results: A stronger association between low PAPP-A and SGA was found with early serum sampling compared to late, but the difference was not statistically significant [odds ratio (OR) 3.2 vs 1.8; P value = 0.11]. This difference did not apply to PAPP-A and preterm delivery. For free β-hCG, a stronger association with preterm delivery was found with early testing (OR 1.9 vs 1.1; P value = 0.31), whereas this difference was not found regarding SGA.

Conclusion: Biochemical testing before 10 weeks does not affect the association between low PAPP-A and free β-hCG and adverse pregnancy outcomes. Whether the association is actually stronger with early testing, requires further study.