Association of maternal IL-2, IL-4, and IL-13 with intrauterine growth restriction and umbilical artery doppler: a case-control study.

Abstract

Objective: Maternal pro-inflammatory responses have been implicated in pregnancy complications. This study examined the association of maternal serum IL-2, IL-4, and IL-13 levels with intrauterine growth restriction (IUGR) and umbilical artery Doppler indices.

Methods: This case-control study was conducted at Alavi Teaching and Referral Hospital, Ardabil, Iran, from August 2024 to June 2025. Sixty singleton pregnant women (30 with IUGR and 30 with normal pregnancies) between 28-36 weeks of gestation were included. Umbilical artery resistive (RI) and pulsatility (PI) indices were assessed by a single sonographer, and serum cytokine levels were measured using ELISA. Statistical analyses (t-test, chi-square, Pearson's correlation, logistic regression) were performed with SPSS v25. The study was approved by the Ethics Committee of Ardabil University of Medical Sciences (no. 1403.049).

Results: Compared with controls, the IUGR group had higher IL-2 and lower IL-4 and IL-13 levels, as well as increased PI and RI (all P<0.05). Elevated IL-2 (OR=1.027; 95%CI: 1.011-1.044; P=0.001) and reduced IL-4 (OR=0.963; 95%CI: 0.929-0.999; P=0.042) and IL-13 (OR=0.978; 95%CI: 0.962-0.995; P=0.009) were independently associated with IUGR. IL-2 correlated positively, while IL-4 and IL-13 correlated negatively, with both Doppler indices (all P<0.05).

Conclusions: Pregnant women with IUGR exhibited a pro-inflammatory Th1-biased cytokine profile, characterized by increased IL-2 and decreased IL-4 and IL-13, which correlated with elevated umbilical vascular resistance. These findings suggest an immunologic contribution to placental dysfunction. However, given the observational design and small sample size, causal inferences cannot be made, and confirmation in larger multicenter studies is warranted.