Association of low levels of first trimester Pregnancy Associated Plasma Protein (PAPP-A) with adverse pregnancy outcomes: An observational study

Abstract

Objectives: To explore the effects of low levels of first trimester Pregnancy Associated Plasma Protein-A (PAPP-A) on adverse pregnancy outcomes. Design: Single centre retrospective observational study. Setting: District general hospital. Population: Women with singleton pregnancies with low PAPP-A, attending Heatherwood and Wexham Park Hospital for first trimester combined screening for Down syndrome. Methods: Data was collected from Astraia Database and CMiS maternity system. Multiple linear regression models for birth weight and gestational age at delivery were developed after adjusting for confounding variables. Logistic regressions were dichotomised for preterm delivery into <34 weeks and ≥ 34 weeks, birth weight centiles, into <10 th centile and ≥10 th centile, and pre-eclampsia versus no pre-eclampsia. Main outcome measures: Preterm birth, small for gestational age (SGA) and pre-eclampsia. Results: PAPP-A levels of ≤0.4MoM is associated with SGA <10 th centile at p=0.04 with a positive predictive value (PPV) of 83.3% and negative predictive value (NPV) of 79.3%. Similarly, association with preterm birth <34 weeks is also significant at p=0.05 with PPV of 66% and NPV of 87.4%. A significant association with pre-eclampsia (p=0.6) could not be identified. In our study data of PAPP-A ≤0.4 MoM, for every 0.1MoM fall in PAPP-A, there was a reduction in birth weight by 78gm and an earlier birth by 5.3 days. Conclusion: There is an increased likelihood of preterm delivery and SGA with progressive reduction of PAPP-A levels below ≤0.4 MoM.