Shyu Ing-Luen, Tsai Yung-Chieh, Kuo Tian-Ni, Shiue Yow-Ling
Department of Obstetrics and Gynecology, Chi Mei Medical Center, Tainan, Taiwan.
Institute of Biomedical Sciences, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan.
Am J Reprod Immunol. 2025 Jun;93(6):e70087. doi: 10.1111/aji.70087.
Gestational diabetes mellitus (GDM) constitutes a significant health concern during pregnancy, warranting a thorough investigation into potential prognostic markers. Pregnancy-associated plasma protein-A (PAPP-A), which is present at high levels during pregnancy, exhibits altered concentrations even before the clinical diagnosis of GDM, highlighting its potential as an early biomarker for this condition. This systematic review and meta-analysis aimed to review and synthesize the latest evidence comprehensively to explore the correlation between maternal PAPP-A levels and the development of GDM, drawing from the most recent publications available.
PubMed, EMBASE, and Cochrane CENTRAL were searched systematically up to June 2, 2024. Cohort and case-control studies reporting PAPP-A levels in GDM and non-GDM women with singleton pregnancy were eligible for inclusion. The quality of studies was measured using the Newcastle-Ottawa scale (NOS). Standardized mean differences (SMDs) of PAPP-A levels between GDM and non-GDM, and odds ratios (ORs) of the association between PAPP-A and GDM were pooled, with heterogeneity assessed using the Cochran Q test and I statistic. Sensitivity analysis was employed (PROSPERO ID: CRD42024580169).
Nineteen studies involving 92 200 pregnant women were included in the systematic review and meta-analysis. The gestational age at sampling varied from 10 to 14 weeks. Meta-analysis revealed a significantly lower PAPP-A level among women with GDM compared with those without (pooled SMD = -0.31, 95% CI: -0.56 to -0.06). Furthermore, meta-analysis revealed that women with a low PAPP-A level had a significantly higher risk of developing GDM (pooled OR = 1.75, 95% CI: 1.45-2.11). Despite observed publication bias, sensitivity analysis affirmed the robustness of the results.
This updated systematic review and meta-analysis underscored the prognostic significance of maternal PAPP-A levels with respect to the development of GDM. Low PAPP-A level is associated with an increased risk of GDM. These findings advocate for the inclusion of PAPP-A assessment in the clinical evaluation of GDM risk.
妊娠期糖尿病（GDM）是孕期一个重大的健康问题，需要对潜在的预后标志物进行深入研究。妊娠相关血浆蛋白A（PAPP-A）在孕期含量较高，甚至在GDM临床诊断之前其浓度就已发生变化，这凸显了它作为该疾病早期生物标志物的潜力。本系统评价和荟萃分析旨在全面回顾和综合最新证据，以探讨孕妇PAPP-A水平与GDM发生之间的相关性，参考的是最新可得的出版物。
截至2024年6月2日，系统检索了PubMed、EMBASE和Cochrane CENTRAL。纳入报告单胎妊娠GDM和非GDM女性PAPP-A水平的队列研究和病例对照研究。使用纽卡斯尔-渥太华量表（NOS）评估研究质量。汇总GDM和非GDM之间PAPP-A水平的标准化均数差（SMD）以及PAPP-A与GDM关联的比值比（OR），使用Cochran Q检验和I统计量评估异质性。采用敏感性分析（PROSPERO编号：CRD42024580169）。
系统评价和荟萃分析纳入了19项涉及92200名孕妇的研究。采样时的孕周从10周到14周不等。荟萃分析显示，与未患GDM的女性相比，患GDM的女性PAPP-A水平显著更低（汇总SMD = -0.31，95%CI：-0.56至-0.06）。此外，荟萃分析显示，PAPP-A水平低的女性患GDM的风险显著更高（汇总OR = 1.75，95%CI：1.45 - 2.11）。尽管观察到发表偏倚，但敏感性分析证实了结果的稳健性。
这项更新的系统评价和荟萃分析强调了孕妇PAPP-A水平对GDM发生的预后意义。PAPP-A水平低与GDM风险增加相关。这些发现主张在GDM风险的临床评估中纳入PAPP-A评估。
