Predictive Role of Maternal Mid-Gestational Inflammatory Biomarkers in Preterm Birth: A Prospective Cohort Study

Abstract

Spontaneous Preterm birth is a leading cause of neonatal complications, primarily driven by inflammatory processes. This is the 1st study involving pregnant women in Pakistan to examines the relationship between elevated mid-gestational levels of serum inflammatory markers and the risk of preterm delivery, to advance early prediction and prevention strategies. A prospective cohort of 500 pregnant women was recruited initially and followed until delivery. Biomarker analysis included 186 women with spontaneous preterm birth and 140 randomly selected term controls. Maternal baseline data and blood samples were collected and followed up until delivery to measure inflammatory markers by ELISA. Biomarker concentrations were compared using Welch’s ANOVA with Games–Howell post-hoc testing. Multinomial logistic regression was performed to examine associations with mPTB and vPTB, with adjustment for maternal age, BMI, and parity. Serum levels of Hs-CRP, C3, and IL-6 were significantly higher in both moderate preterm (mPTB) and very preterm (vPTB) groups compared controls across the trimesters. Hs-CRP and IL-6 levels were particularly elevated, with P < 0.001 in both trimesters. After adjustment for maternal age, BMI, and parity, second-trimester hs-CRP was associated with mPTB (aOR 1.265, 95% CI 1.024–1.563; P = 0.029) and vPTB (aOR 2.134, 95% CI 1.622–2.806; P < 0.001), while IL-6 was also associated with both outcomes. In the third trimester, IL-6 remained associated with mPTB, whereas hs-CRP, C3, and IL-6 were significantly associated with vPTB; hs-CRP showed the largest association (aOR 2.702, 95% CI 1.644–4.441; P < 0.001). ROC analysis showed stronger discrimination for vPTB than mPTB, with hs-CRP demonstrating the highest AUCs for vPTB in the second (0.914) and third trimesters (0.947). These findings suggest that elevated hs-CRP and IL-6 levels are associated with an increased risk of spontaneous preterm birth, particularly vPTB. hs-CRP and IL-6 showed the most consistent associations and stronger discriminatory performance for vPTB, although external validation is required before clinical application.