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 (

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.