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利用一组血清蛋白生物标志物为早期孕妇开发自发性早产预测模型:一项巢式病例对照研究。

Development of a spontaneous preterm birth predictive model using a panel of serum protein biomarkers for early pregnant women: A nested case-control study.

作者信息

Liang Shuang, Chen Yuling, Jia Tingting, Chang Ying, Li Wen, Piao Yongjun, Chen Xu

机构信息

Tianjin Central Hospital of Gynecology Obstetrics/Nankai University Affiliated Maternity Hospital, Tianjin, China.

Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin, China.

出版信息

Int J Gynaecol Obstet. 2025 Feb;168(2):701-708. doi: 10.1002/ijgo.15876. Epub 2024 Aug 27.

DOI:10.1002/ijgo.15876
PMID:39189090
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11726131/
Abstract

OBJECTIVE

To develop a model based on maternal serum liquid chromatography tandem mass spectrometry (LC-MS/MS) proteins to predict spontaneous preterm birth (sPTB).

METHODS

This nested case-control study used the data from a cohort of 2053 women in China from July 1, 2018, to January 31, 2019. In total, 110 singleton pregnancies at 11-13 weeks of pregnancy were used for model development and internal validation. A total of 72 pregnancies at 20-32 weeks from an additional cohort of 2167 women were used to evaluate the scalability of the model. Maternal serum samples were analyzed by LC-MS/MS, and a predictive model was developed using machine learning algorithms.

RESULTS

A novel predictive panel with four proteins, including soluble fms-like tyrosine kinase-1, matrix metalloproteinase 8, ceruloplasmin, and sex-hormone-binding globulin, was developed. The optimal model of logistic regression had an AUC of 0.934, with additional prediction of sPTB in second and third trimester (AUC = 0.868).

CONCLUSION

First-trimester modeling based on maternal serum LC-MS/MS identifies pregnant women at risk of sPTB, which may provide utility in identifying women at risk at an early stage of pregnancy before clinical presentation to allow for earlier intervention.

摘要

目的

建立基于母血清液相色谱串联质谱(LC-MS/MS)蛋白质的模型,以预测自发性早产(sPTB)。

方法

这项巢式病例对照研究使用了2018年7月1日至2019年1月31日期间中国2053名女性队列的数据。总共110例妊娠11 - 13周的单胎妊娠用于模型开发和内部验证。另外从2167名女性队列中选取72例妊娠20 - 32周的妊娠用于评估模型的可扩展性。母血清样本通过LC-MS/MS进行分析,并使用机器学习算法建立预测模型。

结果

开发了一种包含四种蛋白质的新型预测组合,包括可溶性fms样酪氨酸激酶-1、基质金属蛋白酶8、铜蓝蛋白和性激素结合球蛋白。逻辑回归的最优模型AUC为0.934,对孕中期和孕晚期的sPTB有额外预测能力(AUC = 0.868)。

结论

基于母血清LC-MS/MS的孕早期建模可识别有sPTB风险的孕妇,这可能有助于在临床表现出现之前的妊娠早期识别有风险的女性,以便进行早期干预。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d304/11726131/732670949449/IJGO-168-701-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d304/11726131/f3a73b433a8f/IJGO-168-701-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d304/11726131/82e92547f300/IJGO-168-701-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d304/11726131/732670949449/IJGO-168-701-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d304/11726131/f3a73b433a8f/IJGO-168-701-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d304/11726131/82e92547f300/IJGO-168-701-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d304/11726131/732670949449/IJGO-168-701-g002.jpg

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本文引用的文献

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Am J Obstet Gynecol MFM. 2020 May;2(2):100084. doi: 10.1016/j.ajogmf.2019.100084. Epub 2020 Jan 9.
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Incidence and trend of preterm birth in China, 1990-2016: a systematic review and meta-analysis.中国 1990-2016 年早产发生率及趋势的系统评价和荟萃分析。
BMJ Open. 2020 Dec 12;10(12):e039303. doi: 10.1136/bmjopen-2020-039303.
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Metabolomic biomarkers in midtrimester maternal plasma can accurately predict the development of preeclampsia.
孕中期母体血浆代谢组学标志物可准确预测子痫前期的发生。
Sci Rep. 2020 Sep 30;10(1):16142. doi: 10.1038/s41598-020-72852-4.
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Serum Decorin, Biglycan, and Extracellular Matrix Component Expression in Preterm Birth.血清核心蛋白聚糖、大软骨素蛋白聚糖和细胞外基质成分在早产中的表达。
Reprod Sci. 2021 Jan;28(1):228-236. doi: 10.1007/s43032-020-00251-1. Epub 2020 Aug 17.
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MicroRNAs isolated from peripheral blood in the first trimester predict spontaneous preterm birth.孕早期从外周血中分离出的微小RNA可预测自发性早产。
PLoS One. 2020 Aug 13;15(8):e0236805. doi: 10.1371/journal.pone.0236805. eCollection 2020.
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Affinity-Enhanced Multimeric VEGF (Vascular Endothelial Growth Factor) and PlGF (Placental Growth Factor) Variants for Specific Adsorption of sFlt-1 to Restore Angiogenic Balance in Preeclampsia.增强亲和力的多聚体 VEGF(血管内皮生长因子)和 PlGF(胎盘生长因子)变体,用于特异性吸附 sFlt-1,以恢复子痫前期的血管生成平衡。
Hypertension. 2020 Oct;76(4):1176-1184. doi: 10.1161/HYPERTENSIONAHA.120.14974. Epub 2020 Jul 6.
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Short- and Long-Term Outcomes of Extremely Preterm Infants in Japan According to Outborn/Inborn Birth Status.日本极早产儿根据出生地点(院外/院内)的短期和长期结局。
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