Meta-analysis for the relationship between circulating pregnancy-associated plasma protein A and placenta accreta spectrum

Background: Changes in circulating pregnancy-associated plasma protein A (PAPP-A) have been observed in women with a placenta accreta spectrum (PAS). However, no consensus has been reached according to the previous studies. Our study investigated the relationship between circulating PAPP-A and PAS risk through a systematic review and meta-analysis.Methods: Studies comparing the circulating level of PAPP-A between pregnant women with and without PAS were obtained by searching the Medline, Cochrane Library, Embase, CNKI, and Wanfang databases from the inception of the databases until February 12, 2023. Heterogeneity was considered in the pooling of results via a random-effects model.Results: Eight observational studies were obtained for the meta-analysis, which included 243 pregnant women with PAS and 1599 pregnant women without PAS. For all these women, the first-trimester circulating level of PAPP-A was measured by immunoassay and reported as multiples of the median (MoM) values. The pooled results showed that compared to those who did not develop PAS, women with PAS had significantly higher first-trimester serum level PAPP-A (mean difference: 0.43 MoM, 95% confidence interval [CI]: 0.30 to 0.56, P < .001; I2 = 32%). Furthermore, a high first-trimester serum PAPP-A level was related to a high PAS risk (odds ratio: 2.89, 95% CI: 2.13 to 3.92, P < .001; I2 = 0%). Sensitivity analysis which excluded one study at a time, also obtained similar results (p all < 0.05).Conclusion: Pregnant women with a high serum PAPP-A level in the first trimester may be at an increased risk for PAS.