Association of First-Trimester Low PAPP-A Levels (<0.2 MoM) with Maternal and Fetal Outcomes

Background and Aim: First-trimester screening is routinely performed globally to detect chromosomal abnormalities using non-invasive methods such as nuchal translucency (NT) measurements, pregnancy-associated plasma protein A (PAPP-A), and β-human chorionic gonadotropin (β-hCG). Recent studies have highlighted that low PAPP-A levels may be associated with adverse pregnancy outcomes, including pre-eclampsia, intrauterine growth restriction (IUGR), and pre-term delivery. Generally, low PAPP-A is defined as below 0.4 multiples of the median (MoM) or under the 5th percentile. However, extremely low PAPP-A, defined as levels below 0.2 MoM or under the 1st percentile, significantly increases the risk of adverse outcomes. This category has received less attention in research. Our study aims to investigate the correlation between PAPP-A levels below 0.2 MoM and adverse pregnancy outcomes. Materials and Methods: A retrospective cross-sectional study was conducted on 10,256 pregnant women who underwent first-trimester screening at Imam Khomeini Hospital in Ahvaz between January 2010 and April 2024. PAPP-A and β-hCG levels were measured, and factors such as maternal age, weight, parity, and abortion history were assessed. Data were obtained using the Fetal Medicine Foundation (FMF) software and medical records. Statistical analysis was performed using SPSS version 26. Results: Out of 10,256 pregnancies, 6,040 (6.4%) had PAPP-A levels below the 5th percentile, while 45 women had PAPP-A levels below 0.2 MoM. The average age of these women was 30.4 ± 4.812 years. Among those with PAPP-A < 0.2 MoM, 2.2% had trisomy 21, 6.7% had IUGR, 26.7% experienced gestational hypertension, and 15.6% developed pre-eclampsia. Trisomies 13 and 18 were not observed in the study population. Conclusions: Pregnant women with PAPP-A levels below 0.2 MoM showed increased incidences of trisomy 21, pre-eclampsia, gestational hypertension, and IUGR. Although low PAPP-A appears to contribute to both maternal and fetal complications, it cannot be used independently to predict adverse pregnancy outcomes. Further large-scale studies are required to better understand the implications of extremely low PAPP-A on pregnancy outcomes.