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

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.

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.

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.

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.