Neutrophil and Neutrophil-to-Lymphocyte Ratio as Clinically Predictive Risk Markers for Recurrent Pregnancy Loss

We aimed at exploring the value of neutrophil and neutrophil-to-lymphocyte ratio (NLR) as predictive risk markers for recurrent pregnancy loss (RPL) by conducting a retrospective case-control study and a systematic review and meta-analysis. This retrospective case-control study was conducted in an academic hospital from January 2012 to June 2018 and 133 cases of women with RPL and 140 control women. In parallel, we conducted a systematic review and meta-analysis on the value of NLR and neutrophil in RPL risk assessment. Neutrophil and NLR were higher in the women with RPL than those in the controls (median [interquartile range]: 4.32 [3.31-6.18] vs. 3.76 [2.78-4.81], p = 0.001; 2.17 [1.47-3.16] vs. 1.74 [1.40-2.34], p = 0.001). After the cut-off value of the neutrophil and NLR was determined to be 6.3 x 10(9)/L and 3.16, the prevalence of RPL became significantly increased in the high-neutrophil and the high-NLR group compared to the low-neutrophil and the low-NLR group (76.3% vs. 44.2%, p < 0.001; 66.6% vs. 44.5%, p < 0.001). Univariate logistic regression analysis indicated that high-neutrophil and high-NLR were risk factors for RPL, with ORs of 4.06 (95% CI: 1.84-8.95) and 2.49 (95% CI: 1.31-4.71), respectively. Multivariate logistic regression analysis indicated that high-neutrophil was a risk factor for RPL, with OR of 4.91 (95% CI: 1.66-14.50). Meta-analysis of 5 case-control studies (including the present study) indicated that increased neutrophil and NLR may be risk factors for RPL, with SMDs of 0.63 (95% CI: 0.45-0.80) and 0.61 (95% CI: 0.39-0.83). Based on current findings and the meta-analysis, this study indicated that neutrophil and NLR might be valuable for predicting RPL; more studies with large sample are needed to verify this conclusion. The mechanism of the association between neutrophil and RPL needs to be explored in further studies.