Our objective of this study was to investigate whether first trimester serum pregnancy-associated plasma protein-A (PAPP-A) differed amongst pregnancies with placenta previa-accreta and non-adherent placenta previa and healthy pregnancies by a retrospective cohort analysis.
A total of 177 pregnant females were included in the study, as follows: 35 cases of placenta previa-accreta, 30 cases of non-adherent placenta previa, and 112 cases of BMI and age matched, healthy pregnant controls. PAPP-A multiples of the median (MoM) were acquired from laboratory data files in 1 January 2017–30 September 2019. The probable maternal serum biochemical predictor of placenta accreta was analyzed by using multiple logistic regression analysis.
PAPP-A MoM of placenta previa-accreta group was significantly higher than those of the non-adherent placenta previa group and control group (p = 0.009 < 0.05, p < 0.001). Serum PAPP-A was found to be significantly positively associated with placenta accreta after adjusted gestational week at time of blood sampling, BMI, age, smoking, and previous cesarean section history (OR: 3.51; 95% CI: 1.77–6.94; p = 0.0003 < 0.05). In addition, smoking (OR: 9.17; 95% CI: 1.69–49.62; p = 0.010 < 0.05) and previous cesarean section history (OR: 2.75; 95% CI: 1.23–6.17; p = 0.014 < 0.05) were also significantly associated with placenta accreta.
Increased first trimester serum PAPP-A was significantly positively associated with placenta accreta, suggesting that the potential role of PAPP-A in identifying pregnancies at high risk for placenta accreta. Smoking and previous cesarean section history may be the risk factors for accreta in placenta previa patients.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Pregnancy-associated plasma protein-A
Body mass index
Multiples of the median
Su HW, Yi YC, Tseng JJ, Chen WC, Chen YF, Kung HF, Chou MM (2017) Maternal outcome after conservative management of abnormally invasive placenta. Taiwan J Obstetr Gynecol 56(3):353–357. https://doi.org/10.1016/j.tjog.2017.04.016
Higgins MF, Monteith C, Foley M, O’Herlihy C (2013) Real increasing incidence of hysterectomy for placenta accreta following previous caesarean section. Eur J Obstet Gynecol Reprod Biol 171(1):54–56. https://doi.org/10.1016/j.ejogrb.2013.08.030
Silver RM (2015) Abnormal placentation: placenta previa, vasa previa, and placenta accreta. Obstet Gynecol 126(3):654–668. https://doi.org/10.1097/AOG.0000000000001005
Tikkanen M, Paavonen J, Loukovaara M, Stefanovic V (2011) Antenatal diagnosis of placenta accreta leads to reduced blood loss. Acta Obstet Gynecol Scand 90(10):1140–1146. https://doi.org/10.1111/j.1600-0412.2011.01147.x
Comstock CH, Love JJ Jr, Bronsteen RA, Lee W, Vettraino IM, Huang RR, Lorenz RP (2004) Sonographic detection of placenta accreta in the second and third trimesters of pregnancy. Am J Obstet Gynecol 190(4):1135–1140. https://doi.org/10.1016/j.ajog.2003.11.024
Brown BP, Meyers ML (2020) Placental magnetic resonance imaging Part II: placenta accreta spectrum. Pediatr Radiol 50(2):275–284. https://doi.org/10.1007/s00247-019-04521-2
SfM-FM PC, Belfort MA (2010) Placenta accreta. Am J Obstet Gynecol 203(5):430–439. https://doi.org/10.1016/j.ajog.2010.09.013
Yu N, Cui H, Chen X, Chang Y (2017) First trimester maternal serum analytes and second trimester uterine artery Doppler in the prediction of preeclampsia and fetal growth restriction. Taiwan J Obstetr Gynecol 56(3):358–361. https://doi.org/10.1016/j.tjog.2017.01.009
Buke B, Akkaya H, Demir S, Sagol S, Simsek D, Basol G, Barutcuoglu B (2018) Relationship between first trimester aneuploidy screening test serum analytes and placenta accreta. J Maternal-fetal Neonatal Med 31(1):59–62. https://doi.org/10.1080/14767058.2016.1275546
Thompson O, Otigbah C, Nnochiri A, Sumithran E, Spencer K (2015) First trimester maternal serum biochemical markers of aneuploidy in pregnancies with abnormally invasive placentation. BJOG Int J Obstetr Gynaecol 122(10):1370–1376. https://doi.org/10.1111/1471-0528.13298
Pilalis A, Souka AP, Antsaklis P, Daskalakis G, Papantoniou N, Mesogitis S, Antsaklis A (2007) Screening for pre-eclampsia and fetal growth restriction by uterine artery Doppler and PAPP-A at 11–14 weeks’ gestation. Ultrasound Obstetr Gynecol 29(2):135–140. https://doi.org/10.1002/uog.3881
Pijnenborg R, Dixon G, Robertson WB, Brosens I (1980) Trophoblastic invasion of human decidua from 8 to 18 weeks of pregnancy. Placenta 1(1):3–19. https://doi.org/10.1016/s0143-4004(80)80012-9
Krantz D, Goetzl L, Simpson JL, Thom E, Zachary J, Hallahan TW, Silver R, Pergament E, Platt LD, Filkins K, Johnson A, Mahoney M, Hogge WA, Wilson RD, Mohide P, Hershey D, Wapner R, First Trimester Maternal Serum B, Fetal Nuchal Translucency Screening Study G (2004) Association of extreme first-trimester free human chorionic gonadotropin-beta, pregnancy-associated plasma protein A, and nuchal translucency with intrauterine growth restriction and other adverse pregnancy outcomes. AmJ Obstetr Gynecol 191(4):1452–1458. https://doi.org/10.1016/j.ajog.2004.05.068
Yaron Y, Cherry M, Kramer RL, O’Brien JE, Hallak M, Johnson MP, Evans MI (1999) Second-trimester maternal serum marker screening: maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, estriol, and their various combinations as predictors of pregnancy outcome. Am J Obstet Gynecol 181(4):968–974. https://doi.org/10.1016/s0002-9378(99)70334-0
Khong TY (2008) The pathology of placenta accreta, a worldwide epidemic. J Clin Pathol 61(12):1243–1246. https://doi.org/10.1136/jcp.2008.055202
Livrinova V, Petrov I, Samardziski I, Jovanovska V, Boshku AA, Todorovska I, Dabeski D, Shabani A (2019) Clinical importance of low level of PAPP-A in first trimester of pregnancy—an obstetrical dilemma in chromosomally normal fetus. Open Access Macedonian J Med Sci 7(9):1475–1479. https://doi.org/10.3889/oamjms.2019.384
Dugoff L, Hobbins JC, Malone FD, Porter TF, Luthy D, Comstock CH, Hankins G, Berkowitz RL, Merkatz I, Craigo SD, Timor-Tritsch IE, Carr SR, Wolfe HM, Vidaver J, D’Alton ME (2004) First-trimester maternal serum PAPP-A and free-beta subunit human chorionic gonadotropin concentrations and nuchal translucency are associated with obstetric complications: a population-based screening study (the FASTER Trial). Am J Obstet Gynecol 191(4):1446–1451. https://doi.org/10.1016/j.ajog.2004.06.052
Di Mascio D, Cali G, D’Antonio F (2019) Updates on the management of placenta accreta spectrum. Minerva Ginecol 71(2):113–120. https://doi.org/10.23736/S0026-4784.18.04333-2
Jauniaux E, Jurkovic D (2012) Placenta accreta: pathogenesis of a 20th century iatrogenic uterine disease. Placenta 33(4):244–251. https://doi.org/10.1016/j.placenta.2011.11.010
Fitzpatrick KE, Sellers S, Spark P, Kurinczuk JJ, Brocklehurst P, Knight M (2012) Incidence and risk factors for placenta accreta/increta/percreta in the UK: a national case-control study. PLoS ONE 7(12):e52893. https://doi.org/10.1371/journal.pone.0052893
Walter AJ, McCullough AE, Patel MD, Cornella JL (1999) Placenta increta presenting as delayed postabortal hemorrhage. Obstet Gynecol 93(5 Pt 2):846. https://doi.org/10.1016/s0029-7844(98)00571-7
Silver RM, Barbour KD (2015) Placenta accreta spectrum: accreta, increta, and percreta. Obstet Gynecol Clin North Am 42(2):381–402. https://doi.org/10.1016/j.ogc.2015.01.014
Dombrowski MP, Bottoms SF, Saleh AA, Hurd WW, Romero R (1995) Third stage of labor: analysis of duration and clinical practice. Am J Obstet Gynecol 172(4 Pt 1):1279–1284. https://doi.org/10.1016/0002-9378(95)91493-5
Leijnse JEW, de Heus R, de Jager W, Rodenburg W, Peeters LLH, Franx A, Eijkelkamp N (2018) First trimester placental vascularization and angiogenetic factors are associated with adverse pregnancy outcome. Pregnancy Hypertens 13:87–94. https://doi.org/10.1016/j.preghy.2018.04.008
Zelop C, Nadel A, Frigoletto FD Jr, Pauker S, MacMillan M, Benacerraf BR (1992) Placenta accreta/percreta/increta: a cause of elevated maternal serum alpha-fetoprotein. Obstet Gynecol 80(4):693–694
Hung TH, Shau WY, Hsieh CC, Chiu TH, Hsu JJ, Hsieh TT (1999) Risk factors for placenta accreta. Obstet Gynecol 93(4):545–550. https://doi.org/10.1016/s0029-7844(98)00460-8
Dreux S, Salomon LJ, Muller F, Goffinet F, Oury JF, Sentilhes L (2012) Second-trimester maternal serum markers and placenta accreta. Prenatal Diagn 32(10):1010–1012. https://doi.org/10.1002/pd.3932
Garrido-Gomez T, Ona K, Kapidzic M, Gormley M, Simon C, Genbacev O, Fisher SJ (2017) Severe pre-eclampsia is associated with alterations in cytotrophoblasts of the smooth chorion. Development 144(5):767–777. https://doi.org/10.1242/dev.146100
Christians JK, Beristain AG (2016) ADAM12 and PAPP-A: Candidate regulators of trophoblast invasion and first trimester markers of healthy trophoblasts. Cell Adhes Migr 10(1–2):147–153. https://doi.org/10.1080/19336918.2015.1083668
Di Lorenzo G, Ceccarello M, Cecotti V, Ronfani L, Monasta L, Vecchi Brumatti L, Montico M, D’Ottavio G (2012) First trimester maternal serum PIGF, free beta-hCG, PAPP-A, PP-13, uterine artery Doppler and maternal history for the prediction of preeclampsia. Placenta 33(6):495–501. https://doi.org/10.1016/j.placenta.2012.03.003
Kupferminc MJ, Tamura RK, Wigton TR, Glassenberg R, Socol ML (1993) Placenta accreta is associated with elevated maternal serum alpha-fetoprotein. Obstet Gynecol 82(2):266–269
Vyshka G, Capari N, Shaqiri E (2010) Placenta increta causing hemoperitoneum in the 26th week of pregnancy: a case report. J Med Case Rep 4:412. https://doi.org/10.1186/1752-1947-4-412
Shellhaas CS, Gilbert S, Landon MB, Varner MW, Leveno KJ, Hauth JC, Spong CY, Caritis SN, Wapner RJ, Sorokin Y, Miodovnik M, O’Sullivan MJ, Sibai BM, Langer O, Gabbe SG, Eunice Kennedy Shriver National Institutes of H, Human Development Maternal-Fetal Medicine Units N (2009) The frequency and complication rates of hysterectomy accompanying cesarean delivery. Obstet Gynecol 114(2 Pt 1):224–229. https://doi.org/10.1097/AOG.0b013e3181ad9442
Silver RM, Landon MB, Rouse DJ, Leveno KJ, Spong CY, Thom EA, Moawad AH, Caritis SN, Harper M, Wapner RJ, Sorokin Y, Miodovnik M, Carpenter M, Peaceman AM, O’Sullivan MJ, Sibai B, Langer O, Thorp JM, Ramin SM, Mercer BM, National Institute of Child H, Human Development Maternal-Fetal Medicine Units N (2006) Maternal morbidity associated with multiple repeat cesarean deliveries. Obstet Gynecol 107(6):1226–1232. https://doi.org/10.1097/01.AOG.0000219750.79480.84
Kingdom JC, Hobson SR, Murji A, Allen L, Windrim RC, Lockhart E, Collins SL, Soleymani Majd H, Alazzam M, Naaisa F, Shamshirsaz AA, Belfort MA, Fox KA (2020) Minimizing surgical blood loss at cesarean hysterectomy for placenta previa with evidence of placenta increta or placenta percreta: the state of play in 2020. Am J Obstet Gynecol. https://doi.org/10.1016/j.ajog.2020.01.044
Ruiz-Perez R, Delgado Lopez-Cozar E, Jimenez-Contreras E (2010) Principles and criteria used by the National Evaluation Committee of Research Activity (CNEAI-Spain) for the assessment of scientific publications: 1989–2009. Psicothema 22(4):898–908
Luo L, Sun Q, Ying D, Wu X, Yan P, Yang Y, Chen Z (2019) Scoring system for the prediction of the severity of placenta accrete spectrum in women with placenta previa: a prospective observational study. Arch Gynecol Obstet 300(3):783–791. https://doi.org/10.1007/s00404-019-05217-6
Genbacev O, Zhou Y, Ludlow JW, Fisher SJ (1997) Regulation of human placental development by oxygen tension. Science 277(5332):1669–1672. https://doi.org/10.1126/science.277.5332.1669
Tantbirojn P, Crum CP, Parast MM (2008) Pathophysiology of placenta creta: the role of decidua and extravillous trophoblast. Placenta 29(7):639–645. https://doi.org/10.1016/j.placenta.2008.04.008
Usta IM, Hobeika EM, Musa AA, Gabriel GE, Nassar AH (2005) Placenta previa-accreta: risk factors and complications. Am J Obstet Gynecol 193(3 Pt 2):1045–1049. https://doi.org/10.1016/j.ajog.2005.06.037
This study was supported by the Research Fund for Academician Lin He New Medicine, China (No. JYHL2018FMS15).
Conflict of interest
The authors declare that they have no competing interests.
Ethics approval and consent to participate
The study was approved by the Human Ethics Committee of the Affiliated Hospital of Jining Medical University (Shandong, China) (2019-zr-016).
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Wang, F., Chen, S., Wang, J. et al. First trimester serum PAPP-A is associated with placenta accreta: a retrospective study. Arch Gynecol Obstet (2021). https://doi.org/10.1007/s00404-020-05960-1
- First trimester serum
- Placenta accreta