First-Trimester Maternal CALLY Index Is Associated With Fetal Growth Restriction.

Abstract

Background: Fetal growth restriction (FGR) is a major cause of perinatal morbidity and is frequently associated with placental malperfusion related to inflammatory and immune dysregulation. This study evaluated whether the first-trimester maternal C-reactive protein-albumin-lymphocyte (CALLY) index, a composite marker reflecting systemic inflammation, nutritional status, and immune competence, is associated with subsequent FGR.

Methods: This retrospective case-control study included 105 singleton pregnancies (69 FGR cases and 36 controls) at a tertiary center. FGR was diagnosed according to Delphi consensus criteria. The first-trimester CALLY index was calculated as (albumin × lymphocyte count) / CRP. Placental histopathology was evaluated according to the Amsterdam Placental Workshop Group criteria. Group comparisons were performed using the Mann-Whitney U test and chi-square or Fisher's exact test, and diagnostic performance was assessed using receiver operating characteristic (ROC) analysis.

Results: The CALLY index was significantly lower in the FGR group compared with controls (0.065 vs 0.170, p < 0.001). FGR cases also had lower birthweight (1910 vs 3120 g, p < 0.001) and placental weight (344.5 vs 585 g, p < 0.001). Maternal vascular malperfusion (MVM) was more frequent in the FGR group (39.1% vs 13.9%, p = 0.015), while fetal vascular malperfusion (FVM) showed borderline significance (63.8% vs 41.7%, p = 0.050). ROC analysis demonstrated modest discriminatory ability for identifying FGR (AUC = 0.739, 95% CI: 0.652-0.826). A CALLY threshold ≤0.1265 yielded 75.4% sensitivity and 66.7% specificity. After adjustment for maternal age, low CALLY remained significantly associated with FGR (adjusted OR: 6.118, 95% CI: 2.529-14.799, p < 0.001). Early-onset FGR cases (≤34 weeks) showed the lowest CALLY values (0.051). Additional ROC analyses for placental malperfusion endpoints showed limited discriminatory ability (AUCs: 0.592-0.636), indicating that CALLY is not a reliable standalone predictor of placental pathology.

Conclusions: A low first-trimester maternal CALLY index is associated with subsequent FGR. Its modest discriminatory ability for FGR (AUC = 0.739) suggests it may serve as a complementary tool in multi-parameter risk assessment, particularly when integrated with clinical and sonographic findings. However, the limited performance for placental malperfusion endpoints indicates that CALLY should not be used as a standalone test for predicting placental pathology. Further prospective studies are needed to define its clinical role.