Predictive value of vascular endothelial growth factor and placenta growth factor for placenta accreta spectrum

Abstract

This study aimed to assess the maternal features, Vascular Endothelial Growth Factor (VEGF) and Placenta Growth Factor (PLGF) in the Placenta Accreta Spectrum (PAS); then, to determine a predictive value of VEGF and PLGF in the PAS. This prospective case-control study was conducted on 90 pregnant women including 45 PAS, and 45 Normal Placenta (NP). Maternal age, gravidity, C/S, and serum levels of VEGF and PLGF were assessed between NP and PAS, and among NP and PAS sub-groups, including Placenta Accreta (PA), Placenta Increta (PI), and Placenta Percreta (PP). The Multi-gravidity, previous C/S, maternal age, and serum level of PLGF were significantly higher in the PAS group compared to the NP group OR = 42, 8.1, 1.17, and 1.002 (p-value <.05 for all); however, there was no difference regarding serum level of VEGF (p-value >.05). The same differences were seen among NP with PA, PI, and PP sub-groups (p-value <.05 for all, but p-value >.05 for VEGF). Placenta Previa was uniformly distributed across the PAS sub-groups (p-value >.05), also the VEGF and PLGF serum levels did not differ between PAS with Previa and PAS without Previa groups (p-value >.05). A valid cut-off point for PLGF was reported at 63.55. A predictive value of PLGF for the PAS patients is presented enjoying high accuracy and generalisability for the study population.

Impact statement

• What is already known on this subject? The Placenta Accreta Spectrum (PAS), in which the placenta grows too deep in the uterine wall, is responsible for maternal-foetal morbidity and mortality worldwide; so, the antenatal diagnosis of PAS is an important key to improve maternal-foetal health. Normal placental implantation requires a fine balance among the levels of angiogenic and anti-angiogenic factors, such as the Placenta Growth Factor (PLGF), the Vascular Endothelial Growth Factor (VEGF), and soluble Fms-like tyrosine kinase-1. However, there is still controversy regarding The PLGF and VEGF level changes in PAS patients.

• What do the results of this study add? Despite traditional measuring the levels of PLGF and VEGF from the placenta at the time of delivery; in this study including 90 participants (28–34 weeks of gestation) the maternal serum levels of PLGF and VEGF were measured in advance (temporality causation), resulted in presenting a more valid cut-off point for PLGF in PAS group. In addition, the serum level of PLGF was significantly higher in the PAS and PAS sub-groups compared to the Normal Placenta group. Also, the Previa status of PAS patients did not affect the VEGF and PLGF serum levels.

• What are the implications of these findings for clinical practice and/or further research? PLGF cut-off point derived from the maternal serum level could predict PAS validly and, if used as a screening test in an earlier pregnancy, the maternal-foetal morbidity and mortality would decrease.

Keywords:

• Vascular endothelial growth factor
• placenta growth factor
• placenta accreta spectrum

Acknowledgements

The authors wish to thank Dr. Nasrin Shokrpour at Clinical Research of Nemazee Hospital of Shiraz University of Medical Sciences for his invaluable assistance in editing this manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

The study protocol was approved by Institutional Review Board (IRB) and the Medical Ethics Committee of Shiraz University of Medical Sciences (Registration code: IR.SUMS.MED.REC.1397.495 and IR.SUMS.MED.REC.1398.023).

Author contributions

Azam Farji contributed to the study design, data interpretation, and the preparation of the manuscript. She closely observed the work. Nasrin Asadi contributed to the study design, data gathering, data interpretation, and preparation of the manuscript. She closely observed the work. Mojgan Akbarzadeh Jahromi contributed to the study design, data gathering, data interpretation, and preparation of the manuscript. She closely observed the work.

Maryam Kasraeian contributed to the study design, data gathering, data interpretation, preparation of the manuscript, and revision of the manuscript. She closely observed the work.

Homeira Vafaei contributed to the study design, data gathering, data interpretation, preparation of the manuscript, and revision of the manuscript. She closely observed the work.

Marjan Zare contributed to the data collection, data analysis, and interpretation of the results. She revised the manuscript based on the reviewer’s comments and wrote the final revision. Hadi Raeisi contributed to the data analysis and interpretation of the results.

Shima Bahrami contributed to the data gathering and writing the manuscript. Sayeh Gharamani contributed to the data gathering and writing the manuscript. All of the authors read and approved the final manuscript.

Additional information

Funding

This article was extracted from the thesis written by Shima Bahrami and Sayeh Ghahramani for the degree of Obstetrics and Gynecology specialty and was financed and supported by the Research Vice-Chancellor of Shiraz University of Medical Sciences (Grant numbers: 13750 and 18119).