Unveiling the role of pregnancy associated plasma protein-A in idiopathic preterm labour: a review

Asmita Kaundal

doi:10.18203/2320-1770.ijrcog20253127

Authors

Asmita Kaundal Department of Obstetrics and Gynecology, AIIMS, Bilaspur, Himachal Pradesh, India

DOI:

https://doi.org/10.18203/2320-1770.ijrcog20253127

Keywords:

Pregnancy associated plasma protein-A, Pregnancy outcome, Preterm birth, Adverse pregnancy outcome

Abstract

Idiopathic preterm birth (IPTB) is birth before 37 weeks in the absence of any identifiable cause for preterm labour. Prediction and prevention of preterm birth can significantly reduce the burden of morbidity and mortality associated with under-five mortality across the world. Pregnancy-associated plasma protein-A (PAPP-A), a glycoprotein secreted by the placenta and playing an important role in early placenta development through regulation of the IGF system, has emerged as an excellent biomarker for the prediction of preterm birth. This narrative review aims to understand the possible mechanism by which it is linked to preterm birth and its potential as a predictive biomarker for idiopathic preterm birth.

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References

American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins Obstetrics. Practice Bulletin No. 171: Management of Preterm Labor. Obstet Gynecol. 2016;128(4):e155-64. DOI: https://doi.org/10.1097/AOG.0000000000001711

Ohuma EO, Moller AB, Bradley E, Chakwera S, Hussain-Alkhateeb L, Lewin A, et al. National, regional, and global estimates of preterm birth in 2020, with trends from 2010: a systematic analysis. Lancet. 2023;402(10409):1261-71. DOI: https://doi.org/10.1016/S0140-6736(23)00878-4

Perin J, Mulick A, Yeung D, Villavicencio F, Lopez G, Strong KL, et al. Global, regional, and national causes of under-5 mortality in 2000-19: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet Child Adolesc Health. 2022;6(2):106-15. DOI: https://doi.org/10.1016/S2352-4642(21)00311-4

Kjeldsen CMN, Oxvig C. The Proteinase PAPP-A has Deep Evolutionary Roots Outside of the IGF System. Genome Biol Evol. 2025;17(3):evaf042. DOI: https://doi.org/10.1093/gbe/evaf042

Ceballos Medina A, Gómez-Acebo I, Gallego de Largy CC, Alonso-Molero J, Vilares Calvo S, Odriozola Feu JM, et al. Study of first-trimester serum levels of β-hCG and PAPP-A as a screening test for fetal development of intrauterine growth restriction. BMC Pregnancy and Childbirth. 2025;25(1):1-9. DOI: https://doi.org/10.1186/s12884-025-07787-7

Tzanaki I, Makrigiannakis A, Lymperopoulou C, Al-Jazrawi Z, Agouridis AP. Pregnancy-associated plasma protein A (PAPP-A) as a first trimester serum biomarker for preeclampsia screening: a systematic review and meta-analysis. J Maternal-Fetal Neonat Med. 2025;38(1):2448502. DOI: https://doi.org/10.1080/14767058.2024.2448502

Kaundal A, Gupta U, Bhattcharjee J. Role of pregnancy associated plasma protein-A and doppler velocimetry in the assessment of fetomaternal outcome in high risk pregnancy. Int J Reprod Contracept Obstet Gynecol. 2019;8(5):1981-9. DOI: https://doi.org/10.18203/2320-1770.ijrcog20191955

Bowman CJ, Streck RD, Chapin RE. Maternal-placental insulin-like growth factor (IGF) signaling and its importance to normal embryo-fetal development. Birth Defects Res B. 2010;17:10-8. DOI: https://doi.org/10.1002/bdrb.20249

Goetzinger KR, Cahill AG, Macones GA, Odibo AO. Association of first-trimester low PAPP-A levels with preterm birth. Prenat Diagn. 2010;30(4):309-13. DOI: https://doi.org/10.1002/pd.2452

Kirkegaard I, Uldbjerg N, Petersen OB, Tørring N, Henriksen TB. PAPP-A, free β-hCG, and early fetal growth identify two pathways leading to preterm delivery. Prenat Diagn. 2010;30(10):956-63. DOI: https://doi.org/10.1002/pd.2593

Dane B, Dane C, Batmaz G, Ates S, Dansuk R. First trimester maternal serum pregnancy-associated plasma protein-A is a predictive factor for early preterm delivery in normotensive pregnancies. Gynecol Endocrinol. 2013;29(6):592-5. DOI: https://doi.org/10.3109/09513590.2013.788626

Pummara P, Tongsong T, Wanapirak C, Sirichotiyakul S, Luewan S. Association of first-trimester pregnancy-associated plasma protein A levels and idiopathic preterm delivery: A population-based screening study. Taiwan J Obstet Gynecol. 2016;55(1):72-5. DOI: https://doi.org/10.1016/j.tjog.2015.12.007

Pakniat H, Elmizadeh K, Senobare N. Relationship between low PAPP-A levels and preterm delivery. J Mazandaran Univ Med Sci. 2019;29(175):57-64.

Swiercz G, Zmelonek-Znamirowska A, Szwabowicz K, Armanska J, Detka K, Mlodawska M, et al. Evaluating the predictive efficacy of first trimester biochemical markers (PAPP-A, fβ-hCG) in forecasting preterm delivery incidences. Sci Rep. 2024;14(1):16206. DOI: https://doi.org/10.1038/s41598-024-67300-6

World Health Organization. Born too soon: decade of action on preterm birth. Available at: https://creativecommons.org/licenses/by-nc-sa/3. 0/ig o/). Accessed on 05 July 2025.