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胎儿血红蛋白、α1-微球蛋白和血红素结合蛋白是子痫前期潜在的孕早期预测生物标志物。

Fetal hemoglobin, α1-microglobulin and hemopexin are potential predictive first trimester biomarkers for preeclampsia.

作者信息

Anderson Ulrik Dolberg, Gram Magnus, Ranstam Jonas, Thilaganathan Basky, Kerström Bo, Hansson Stefan R

机构信息

Section of Obstetrics and Gynecology, Department of Clinical Sciences Lund, Lund University, Sweden; Skåne University Hospital, Malmö/Lund, Sweden.

Department of Clinical Sciences, Lund, Infection Medicine, Lund University, Sweden.

出版信息

Pregnancy Hypertens. 2016 Apr;6(2):103-9. doi: 10.1016/j.preghy.2016.02.003. Epub 2016 Apr 13.

DOI:10.1016/j.preghy.2016.02.003
PMID:27155336
Abstract

OBJECTIVE

Overproduction of cell-free fetal hemoglobin (HbF) in the preeclamptic placenta has been recently implicated as a new etiological factor of preeclampsia. In this study, maternal serum levels of HbF and the endogenous hemoglobin/heme scavenging systems were evaluated as predictive biomarkers for preeclampsia in combination with uterine artery Doppler ultrasound.

STUDY DESIGN

Case-control study including 433 women in early pregnancy (mean 13.7weeks of gestation) of which 86 subsequently developed preeclampsia. The serum concentrations of HbF, total cell-free hemoglobin, hemopexin, haptoglobin and α1-microglobulin were measured in maternal serum. All patients were examined with uterine artery Doppler ultrasound. Logistic regression models were developed, which included the biomarkers, ultrasound indices, and maternal risk factors.

RESULTS

There were significantly higher serum concentrations of HbF and α1-microglobulin and significantly lower serum concentrations of hemopexin in patients who later developed preeclampsia. The uterine artery Doppler ultrasound results showed significantly higher pulsatility index values in the preeclampsia group. The optimal prediction model was obtained by combining HbF, α1-microglobulin and hemopexin in combination with the maternal characteristics parity, diabetes and pre-pregnancy hypertension. The optimal sensitivity for all preeclampsia was 60% at 95% specificity.

CONCLUSIONS

Overproduction of placentally derived HbF and depletion of hemoglobin/heme scavenging mechanisms are involved in the pathogenesis of preeclampsia. The combination of HbF and α1-microglobulin and/or hemopexin may serve as a prediction model for preeclampsia in combination with maternal risk factors and/or uterine artery Doppler ultrasound.

摘要

目的

近期研究表明,子痫前期胎盘无细胞胎儿血红蛋白(HbF)过量产生是子痫前期的一个新病因。本研究评估了孕妇血清中HbF水平以及内源性血红蛋白/血红素清除系统,并结合子宫动脉多普勒超声,作为子痫前期的预测生物标志物。

研究设计

病例对照研究,纳入433例孕早期(平均妊娠13.7周)妇女,其中86例随后发生子痫前期。检测孕妇血清中HbF、总无细胞血红蛋白、血红素结合蛋白、触珠蛋白和α1-微球蛋白的浓度。所有患者均接受子宫动脉多普勒超声检查。建立逻辑回归模型,纳入生物标志物、超声指标和孕妇风险因素。

结果

后来发生子痫前期的患者血清中HbF和α1-微球蛋白浓度显著升高,血红素结合蛋白浓度显著降低。子宫动脉多普勒超声结果显示,子痫前期组的搏动指数值显著更高。通过将HbF、α1-微球蛋白和血红素结合蛋白与孕妇特征产次、糖尿病和孕前高血压相结合,获得了最佳预测模型。对所有子痫前期患者,在特异性为95%时,最佳敏感性为60%。

结论

胎盘来源的HbF过量产生和血红蛋白/血红素清除机制的耗竭参与了子痫前期的发病机制。HbF与α1-微球蛋白和/或血红素结合蛋白相结合,可能与孕妇风险因素和/或子宫动脉多普勒超声一起,作为子痫前期的预测模型。

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