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Immunopathol Persa. Inpress.
doi: 10.34172/ipp.44060
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First‑trimester maternal serum aneuploidy markers as predictors of placenta accreta spectrum and placenta previa; a retrospective case–control study

Soudabeh Kazemi Aski 1 ORCID logo, Samaneh Kheirab 1 ORCID logo, Misa Naghdipour 1 ORCID logo, Zahra Hamidi Madani 1* ORCID logo, Habib Eslami-Kenarsari 2 ORCID logo

1 Department of Obstetrics and Gynecology, Reproductive Health Research Center, Al-Zahra Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
2 Department of Epidemiology and Biostatistics, Vice-Chancellorship of Research and Technology, Guilan University of Medical Science, Rasht, Iran
*Corresponding Author: Zahra Hamidi Madani, Email: Tannaz.hamidi1369@gmail.com

Abstract

Introduction: Placenta previa and placenta accreta spectrum (PAS) are major causes of obstetric hemorrhage and peripartum hysterectomy, yet reliable tools for early risk stratification remain limited. First‑trimester serum aneuploidy screening, including measurement of pregnancy‑associated plasma protein‑A (PAPP‑A) and free beta-human chorionic gonadotropin (β‑hCG), is routinely performed in many settings and may reflect underlying placental dysfunction.

Objectives: This study aimed to evaluate whether these widely available first‑trimester markers are associated with subsequent placenta previa and PAS and to assess their potential diagnostic performance for early identification of women at increased risk.

Patients and Methods: This retrospective case–control study included singleton pregnancies undergoing routine first‑trimester aneuploidy screening at Alzahra Hospital, Rasht (2021–2022), comparing women with placenta previa or PAS to uncomplicated controls. Demographic characteristics, obstetric data, and first‑trimester serum PAPP‑A and free β‑hCG values were extracted from medical and laboratory records and compared between three groups.

Results: Our results indicate that increased first‑trimester PAPP‑A levels were independently associated with both placenta previa and PAS, with adjusted odds ratios (ORs) of 7.46 and 6.26, respectively. At a cut‑off of 1.41 multiples of the median (MoM), PAPP‑A achieved area under the curves (AUCs) of 0.768 and 0.785, with sensitivities of 80 and 75 and specificities of 65 and 65 for placenta previa and PAS, respectively. Free β‑hCG was likewise independently associated with placenta previa and PAS (OR 3.52 and 4.31, respectively) and, at a cut‑off of 1.45 MoM, yielded AUCs of 0.696 and 0.770, with sensitivities of 70 and 80 and specificities of 70 and 70 for placenta previa and PAS, respectively.

Conclusion: First‑trimester maternal serum aneuploidy markers such as PAPP‑A and free β‑hCG levels are independently associated with both placenta previa and PAS and show acceptable diagnostic performance, supporting their potential use in early risk stratification for these placental disorders.


Citation: Kazemi Aski S, Kheirab S, Naghdipour M, Hamidi Madani Z, Eslami-Kenarsari H. First‑trimester maternal serum aneuploidy markers as predictors of placenta accreta spectrum and placenta previa; a retrospective case–control study. Immunopathol Persa. 2026;x(x):e44060. DOI:10.34172/ipp.44060.
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