INTRODUCTION Ectopic pregnancy (EP) is a potentially life-threatening condition and early diagnosis still remains a challenge, causing a delay in management leading to tubal rupture. OBJECTIVES To identify putative plasma biomarkers for the detection of tubal EP and elucidate altered biochemical pathways in EP compared to intrauterine pregnancies. METHODS This case-control study included prospective recruitment of 39 tubal EP cases and 89 early intrauterine pregnancy controls. Plasma samples were biochemically profiled using proton nuclear magnetic resonance spectroscopy (1H NMR). To avoid over-fitting, datasets were randomly divided into a discovery group (26 cases vs 60 controls) and a test group (13 cases and 29 controls). Logistic regression models were developed in the discovery group and validated in the independent test group. Area under the receiver operating characteristics curve (AUC), 95% confidence interval (CI), sensitivity, and specificity values were calculated. RESULTS In total 13 of 43 (30.3%) metabolite concentrations were significantly altered in EP plasma (p < 0.05). Metabolomic profiling yielded significant separation between EP and controls (p < 0.05). Independent validation of a two-metabolite model consisting of lactate and acetate, achieved an AUC (95% CI) = 0.935 (0.843-1.000) with a sensitivity of 92.3% and specificity of 96.6%. The second metabolite model (D-glucose, pyruvate, acetoacetate) performed well with an AUC (95% CI) = 0.822 (0.657-0.988) and a sensitivity of 84.6% and specificity of 86.2%. CONCLUSION We report novel metabolomic biomarkers with a high accuracy for the detection of EP. Accurate biomarkers could potentially result in improved early diagnosis of tubal EP cases.

中文翻译：

---

异位妊娠中新型诊断生物标志物的代谢组学鉴定。

引言异位妊娠（EP）是一种潜在的威胁生命的疾病，早期诊断仍然是一个挑战，导致治疗延迟，导致输卵管破裂。目的确定用于血浆输卵管EP检测的假定血浆生物标志物，并阐明与宫内妊娠相比EP中改变的生化途径。方法这项病例对照研究包括前瞻性募集39例输卵管EP病例和89例宫内早期妊娠对照。使用质子核磁共振波谱（1H NMR）对血浆样品进行生化分析。为了避免过度拟合，将数据集随机分为发现组（26例vs 60例对照）和测试组（13例和29例对照）。在发现组中开发了逻辑回归模型，并在独立测试组中对其进行了验证。计算接收器工作特性曲线（AUC）下的面积，95％置信区间（CI），灵敏度和特异性值。结果在EP血浆中，共有43种代谢产物中的13种（30.3％）浓度发生了明显变化（p <0.05）。代谢组学分析在EP和对照之间产生了显着分离（p <0.05）。由乳酸和乙酸组成的两个代谢物模型的独立验证获得了AUC（95％CI）= 0.935（0.843-1.000），灵敏度为92.3％，特异性为96.6％。第二种代谢物模型（D-葡萄糖，丙酮酸，乙酰乙酸酯）表现良好，AUC（95％CI）= 0.822（0.657-0.988），灵敏度为84.6％，特异性为86.2％。结论我们报告了一种新型的代谢组学生物标志物，可用于检测EP。