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已发表论文
妊娠早期母体血清SHH水平作为预测子痫前期潜在生物标志物的评估
Authors Deng C, Zhang S, Li C, Yang Z, Guo Q, Cheng Y
Received 10 September 2025
Accepted for publication 15 January 2026
Published 29 January 2026 Volume 2026:18 566603
DOI https://doi.org/10.2147/IJWH.S566603
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Vinay Kumar
Caifeng Deng,1,* Si Zhang,2,* Chanyu Li,1 Zhiling Yang,1 Qin Guo,3 Yanmian Cheng4
1Department of Gynecology and Obstetrics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 2Department of Emergency Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 3Department of Orthopedics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 4Department of Infectious Diseases, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yanmian Cheng, Department of Infectious Diseases, The First Affiliated Hospital of Chengdu Medical College, No. 278, The Middle Section of Baoguang Avenue, Xindu District, Chengdu, Sichuan, 610500, People’s Republic of China, Email 18215577119@163.com Qin Guo, Department of Orthopedics, The First Affiliated Hospital of Chengdu Medical College, No. 278, The Middle Section of Baoguang Avenue, Xindu District, Chengdu, Sichuan, 610500, People’s Republic of China, Email 513497978@qq.com
Objective: To determine whether first-trimester maternal serum Sonic Hedgehog (SHH) predicts subsequent preeclampsia and to compare its predictive performance with soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF).
Materials and Methods: In a prospective cohort study, women with singleton pregnancies were enrolled at 8– 13 weeks’ gestation, clinical data were recorded, and fasting serum was collected. SHH, sFlt-1, and PlGF were quantified by ELISA in triplicate with coefficients of variation < 10%. Associations between SHH and subsequent preeclampsia were tested using multivariable logistic regression with adjusted confounders; discriminative ability was evaluated by ROC analysis and stratified for early-onset (≤ 34 weeks) and late-onset (> 34 weeks) preeclampsia.
Results: Among 2532 enrolled pregnancies, 271 developed preeclampsia and 2261 remained normotensive. First-trimester SHH concentrations were significantly lower in pregnancies that later developed preeclampsia, with the greatest decrement in early-onset disease. Compared to the highest SHH tertile, adjusted odds of preeclampsia were higher in the middle (OR 2.64; 95% CI 1.334– 5.38) and lowest tertiles (OR 5.21; 95% CI 3.15– 8.42). SHH achieved an AUC of 0.86 (95% CI 0.62– 0.91), with 81.46% sensitivity and 76.58% specificity at 58.26 ng/mL; sFlt-1 and PlGF yielded AUCs of 0.71 and 0.62, respectively. Performance was strongest for early-onset preeclampsia with an AUC of 0.93 (95% CI 0.67– 0.97); sensitivity 87.73%; specificity 82.43% at 62.37 ng/mL, and modest for late-onset preeclampsia with an AUC of 0.75 (95% CI 0.54– 0.86); sensitivity 73.42%; specificity 68.24% at 55.78 ng/mL.
Conclusion: Lower maternal serum SHH level in the first trimester is independently associated with later development of preeclampsia and provides clinically significant early prediction, particularly for early-onset disease. Incorporating SHH into first-trimester multiparametric screening alongside maternal factors and angiogenic markers may improve risk stratification and enable earlier prophylaxis and individualized antenatal surveillance.
Keywords: Sonic Hedgehog protein, first-trimester, biomarker, preeclampsia, extravillous trophoblast
1Department of Gynecology and Obstetrics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 2Department of Emergency Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 3Department of Orthopedics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 4Department of Infectious Diseases, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yanmian Cheng, Department of Infectious Diseases, The First Affiliated Hospital of Chengdu Medical College, No. 278, The Middle Section of Baoguang Avenue, Xindu District, Chengdu, Sichuan, 610500, People’s Republic of China, Email 18215577119@163.com Qin Guo, Department of Orthopedics, The First Affiliated Hospital of Chengdu Medical College, No. 278, The Middle Section of Baoguang Avenue, Xindu District, Chengdu, Sichuan, 610500, People’s Republic of China, Email 513497978@qq.com
Objective: To determine whether first-trimester maternal serum Sonic Hedgehog (SHH) predicts subsequent preeclampsia and to compare its predictive performance with soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF).
Materials and Methods: In a prospective cohort study, women with singleton pregnancies were enrolled at 8– 13 weeks’ gestation, clinical data were recorded, and fasting serum was collected. SHH, sFlt-1, and PlGF were quantified by ELISA in triplicate with coefficients of variation < 10%. Associations between SHH and subsequent preeclampsia were tested using multivariable logistic regression with adjusted confounders; discriminative ability was evaluated by ROC analysis and stratified for early-onset (≤ 34 weeks) and late-onset (> 34 weeks) preeclampsia.
Results: Among 2532 enrolled pregnancies, 271 developed preeclampsia and 2261 remained normotensive. First-trimester SHH concentrations were significantly lower in pregnancies that later developed preeclampsia, with the greatest decrement in early-onset disease. Compared to the highest SHH tertile, adjusted odds of preeclampsia were higher in the middle (OR 2.64; 95% CI 1.334– 5.38) and lowest tertiles (OR 5.21; 95% CI 3.15– 8.42). SHH achieved an AUC of 0.86 (95% CI 0.62– 0.91), with 81.46% sensitivity and 76.58% specificity at 58.26 ng/mL; sFlt-1 and PlGF yielded AUCs of 0.71 and 0.62, respectively. Performance was strongest for early-onset preeclampsia with an AUC of 0.93 (95% CI 0.67– 0.97); sensitivity 87.73%; specificity 82.43% at 62.37 ng/mL, and modest for late-onset preeclampsia with an AUC of 0.75 (95% CI 0.54– 0.86); sensitivity 73.42%; specificity 68.24% at 55.78 ng/mL.
Conclusion: Lower maternal serum SHH level in the first trimester is independently associated with later development of preeclampsia and provides clinically significant early prediction, particularly for early-onset disease. Incorporating SHH into first-trimester multiparametric screening alongside maternal factors and angiogenic markers may improve risk stratification and enable earlier prophylaxis and individualized antenatal surveillance.
Keywords: Sonic Hedgehog protein, first-trimester, biomarker, preeclampsia, extravillous trophoblast