Underhill Lori A, Avalos Nora, Tucker Richard, Zhang Zheng, Messerlian Geralyn, Lechner Beatrice
1 Warren Alpert Medical School at Brown University, Providence, RI ,USA.
2 Department of Pediatrics, Women and Infants Hospital, Providence, RI, USA.
Reprod Sci. 2019 Mar 21:1933719119831790. doi: 10.1177/1933719119831790.
Preterm birth is a leading cause of neonatal mortality in the US and globally, with preterm premature rupture of fetal membranes (PPROM) accounting for one third of preterm births. Currently no predictive diagnostics are available to precisely assess risk and potentially reduce the incidence of PPROM. Bigycan and decorin, the main proteoglycans present in human fetal membranes, are involved in the physiological maturation of fetal membranes as well as in the pathophysiology of preterm birth. The serum protein sex hormone-binding globulin (SHBG) has recently been identified as a predictor of spontaneous preterm birth. We hypothesize that the balance between serum decorin and biglycan on one hand and SHBG on the other hand may provide insight into the status of the fetal membranes in early pregnancy, thereby predicting PPROM prior to symptoms. Using chart review, 18 patients with confirmed cases of PPROM were identified from 2013-2016. Second trimester residual serum was retreived from freezer storage for these cases along with 5 matched controls for each case. The biomarkers biglycan, decorin and SHBG were analyzed first separately, then in combination to determine their ability to predict PPROM. The predictive score for the combined model displays an AUC = 0.774. The ROC curve of the predicted score has an optimal threshold of 0.238 and a sensitivity and specificity of 0.72 and 0.84 respectively. This prenatal serum panel is a promising serum screening-based biochemical model to predict PPROM in asymptomatic women.
早产是美国乃至全球新生儿死亡的主要原因,胎膜早破(PPROM)占早产的三分之一。目前尚无预测性诊断方法可精确评估风险并潜在降低PPROM的发生率。双糖链蛋白聚糖和核心蛋白聚糖是人类胎膜中的主要蛋白聚糖,它们参与胎膜的生理成熟以及早产的病理生理过程。血清蛋白性激素结合球蛋白(SHBG)最近被确定为自发性早产的预测指标。我们假设,一方面血清核心蛋白聚糖和双糖链蛋白聚糖之间的平衡,另一方面与SHBG之间的平衡,可能有助于了解早孕期胎膜的状态,从而在出现症状之前预测PPROM。通过病历回顾,从2013年至2016年确定了18例确诊为PPROM的患者。从冷冻库中提取这些病例的孕中期残留血清,并为每个病例匹配5名对照。首先分别分析生物标志物双糖链蛋白聚糖、核心蛋白聚糖和SHBG,然后联合分析以确定它们预测PPROM的能力。联合模型的预测评分显示曲线下面积(AUC)=0.774。预测评分的ROC曲线最佳阈值为0.238,敏感性和特异性分别为0.72和0.84。这种产前血清检测方法是一种很有前景的基于血清筛查的生化模型,可用于预测无症状女性的PPROM。