Background Non-puerperal mastitis (NPM) is an umbrella term for non-specific inflammatory mastitis inflammation with unclear etiology. The objective of the current study is to characterize NPM patients and examine the determinants associated with NPM severity. Methods This study analyzed the NPM inpatients admitted to the Department of Breast Surgery, Longhua Hospital Affiliated with Shanghai University of Traditional Chinese Medicine from 2016 to 2020. We explored NPM patient characteristics through demographics, physical risks, lab tests, and medical history indicators. Multivariable logistic regression was conducted to identify the relationship between the prolactin (PRL) level and NPM severity stratified by breast structure. Findings The majority of NPM inpatients had normal breast structures and were of lower average age than those with congenital nipple deformity (p=0.002). Significant positive risk (p< 0.001) association between PRL level and NPM severity was observed among NPM inpatients with normal breast structure in both binomial (OR: 2.91; 95%CI:1.88-4.52) and ordinal regression model (OR: 3.47; 95%CI:2.39-5.08), with age as a protective factor (OR:0.94; 95%CI:0.91-0.97). For NPM patients with nipple deformity, increasing odds of NPM severity regarding higher PRL level was only observed in ordinal logistic regression, which was lower (OR: 2.21; 95%CI: 1.14-4.34; p=0.02) than their peer with normal breast structure. Interpretation The risk of NPM severe episodes is higher among patients with higher PRL levels, of which the association is stronger for NPM patients with normal breast structure, implying different pathogenesis between NPM patients with varied breast anatomy. Testification of the analysis model indicates an improvement window for the current NPM severity assessment. Funding This study was supported by the second major clinical research project of "Three-year Action Plan for Promoting Clinical Skills and Clinical Innovation in Municipal Hospitals (2020-2022)" (SHDC2020CR2051B), the National Natural Science Foundation of China (No.82104854), and Shanghai Sailing Program (20YF1449800).
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