The association between first trimester AFP to PAPP-A ratio and placentally-related adverse pregnancy outcome.
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Hughes, A. E., Sovio, U., Gaccioli, F., Cook, E., Charnock-Jones, S., & Smith, G. (2019). The association between first trimester AFP to PAPP-A ratio and placentally-related adverse pregnancy outcome.. Placenta, 81 25-31. https://doi.org/10.1016/j.placenta.2019.04.005
Introduction Low maternal serum levels of pregnancy-associated plasma protein A (PAPP-A) measured in the first trimester and high levels of alpha fetoprotein (AFP) measured in the second trimester have been associated with adverse pregnancy outcomes reflective of placental insufficiency, and there is a synergistic relationship between the two. We investigated the utility as a screening test of a simple ratio of maternal serum AFP to PAPP-A (AFP:PAPP-A) measured in the first trimester. Methods We studied 4057 nulliparous women with a singleton pregnancy from the Pregnancy Outcome Prediction (POP) study. We studied the predictive ability for adverse outcome of the AFP:PAPP-A ratio measured in the first trimester with and without correction for maternal weight and gestational age at measurement. We compared the AFP:PAPP-A ratio with corrected AFP and PAPP-A on their own and in combination. Results An AFP:PAPP-A ratio >10 was associated with placentally-related adverse outcomes, including fetal growth restriction (risk ratio (RR) 3.74, 95% confidence interval (CI) 2.30-6.09), severe preeclampsia (RR 2.12, 95% CI 1.39-3.25) and stillbirth (RR 5.05, 95% CI 1.48-17.18). The ratio performed favorably in predicting adverse pregnancy outcomes when compared with corrected measurements of either AFP or PAPP-A, and was equivalent to a model combining the two. Its predictive ability was not affected by correction for maternal weight or gestational age at measurement. Discussion An elevated maternal AFP:PAPP-A ratio in the first trimester is associated with placentally-related adverse outcomes in a cohort of unselected nulliparous women.
Humans, Placenta Diseases, Fetal Weight, Pregnancy-Associated Plasma Protein-A, alpha-Fetoproteins, Pregnancy Outcome, Predictive Value of Tests, Parity, Pregnancy, Pregnancy Trimester, First, Adult, Female, Biomarkers
The POP study was supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (Women’s Health theme), and project grants from the Medical Research Council (United Kingdom; G1100221) and the Stillbirth and neonatal death society (Sands). The study was also supported by Roche Diagnostics (provision of equipment and reagents for analysis of AFP and PAPP-A), by GE Healthcare (donation of two Voluson i ultrasound systems for the POP study), and by the NIHR Cambridge Clinical Research Facility, where all research visits took place. AEH was an Academic Clinical Fellow funded by NIHR. Funders played no role in the decision to submit this manuscript for publication.
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
External DOI: https://doi.org/10.1016/j.placenta.2019.04.005
This record's URL: https://www.repository.cam.ac.uk/handle/1810/292386
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Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/