First-trimester pan-immune-inflammation value predicts preeclampsia in a dose-dependent linear pattern

Preeclampsia (PE), a multisystem hypertensive disorder complicating ~ 5% of pregnancies, remains a major global cause of maternal and perinatal morbidity and mortality. First-trimester screening methods are limited in accessibility and sensitivity, underscoring the need for affordable biomarkers. The pan-immune-inflammation value (PIV), derived from routine blood counts, shows potential as a predictor, but its independent predictive utility and dose-response association with PE are not yet fully defined.

In this retrospective cohort study, the association between first-trimester PIV and subsequent development of PE was evaluated. Multivariable logistic regression was used to assess PIV as an independent predictor, adjusting for confounders including maternal age, body mass index (BMI), parity, multifetal pregnancy and mode of conception (natural vs. in vitro fertilization [IVF, a method of assisted reproductive technology]). Dose-response patterns were explored using restricted cubic spline and two-piecewise linear regression models. Subgroup and interaction analyses were conducted to assess consistency across clinical strata. To improve interpretability, all PIV values in the study were divided by 100 during analysis and result presentation.

A total of 11,894 pregnant women were included (non-PE 11409, PE 485), among whom elevated first-trimester PIV/100 was significantly associated with an increased risk of PE (adjusted OR, 1.076; 95% CI, 1.041-1.112; P < 0.001). A dose-dependent increase in PE prevalence was observed across PIV quartiles, with the highest quartile associated with a 60.2% increased risk (OR, 1.602; 95% CI, 1.210-2.119; P < 0.001) compared to the lowest. Restricted cubic spline analysis suggested a nonlinear association in unadjusted models; however, an adequate linear fit was confirmed after adjustment (P for non-linearity > 0.05). Two-piecewise linear regression identified an inflection point at PIV/100 = 3.6889, but no significant threshold effect was detected (P = 0.274). The association between PIV/100 and PE remained consistent across subgroups defined by age, BMI, parity, IVF status, and plurality (all P for interaction > 0.05).

Elevated first-trimester PIV is independently and linearly associated with increased risk of PE, with no identifiable threshold effect. These findings highlight the potential utility of PIV as an accessible, inflammation-based biomarker for early PE risk stratification. Future prospective studies are warranted to validate its clinical applicability and explore integration into prenatal screening protocols.