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First-Trimester Hemoglobin-to-RDW Ratio in Pregnancies Subsequently Complicated by Preeclampsia: Association, Discrimination, and Clinical Interpretability in a Retrospective Cohort
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DOI：10.3390/jcm15166234.png)
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Abstract
En 中文
Background/Objectives: Preeclampsia is a heterogeneous hypertensive disorder of pregnancy, and accessible hematologic indices may reflect maternal physiologic differences before the clinical syndrome becomes evident. This study evaluated whether the first-trimester hemoglobin-to-red cell distribution width (Hb/RDW) ratio was associated with later documented preeclampsia and assessed its discrimination, relation to disease severity, and association with maternal–neonatal outcomes in a tertiary-care cohort. Methods: This retrospective cohort study included 224 singleton pregnancies managed at a tertiary referral center between January 2024 and December 2025. Data extraction, anonymization, and analysis were performed after ethics approval (Approval No. 72; 2 March 2026). Participants were categorized as preeclampsia-negative (n = 131) or preeclampsia-positive (n = 93). Preeclampsia and severe features were defined according to American College of Obstetricians and Gynecologists criteria. The Hb/RDW ratio was calculated from routine first-trimester complete blood count parameters obtained before clinical diagnosis or final outcome classification. ROC analysis, multivariable logistic regression, multicollinearity assessment, events-per-variable evaluation, calibration testing, and exploratory incremental discrimination analyses were performed. Results: The first-trimester Hb/RDW ratio was higher in pregnancies later complicated by preeclampsia. Single-marker ROC analysis showed moderate discrimination (AUC = 0.687; bootstrap 95% CI: 0.618–0.755). At the 0.63 cut-off, sensitivity was 89.2%, specificity 47.3%, positive predictive value 54.6%, and negative predictive value 86.1%. In the primary multivariable model, Hb/RDW remained associated with later preeclampsia (adjusted OR per 0.1-unit increase = 1.45; 95% CI: 1.22–1.72; p < 0.001). However, Hb/RDW was not independently associated with severe preeclampsia among affected patients, fetal growth restriction, or composite maternal morbidity. VIF values ranged from 1.00 to 1.07. Secondary models for fetal growth restriction and composite maternal morbidity had borderline events-per-variable values and were interpreted as exploratory. Conclusions: First-trimester Hb/RDW was associated with later documented preeclampsia in this retrospective tertiary-care cohort, but its single-marker performance was modest and specificity was limited. The ratio should be interpreted as an inexpensive research marker of hematologic phenotype rather than a stand-alone screening, diagnostic, or management tool. Prospective multicenter validation with standardized first-trimester sampling and adjustment for hematinic and nutritional variables is required before clinical implementation.
Keywords:
first trimester
preeclampsia
hemoglobin-to-RDW ratio
red cell distribution width
hematologic biomarkers
retrospective cohort
discrimination
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