Association of inflammatory and angiogenic biomarkers in maternal plasma with retinopathy of prematurity in preterm infants

Abstract

Objective: To investigate whether various novel inflammatory and angiogenic biomarkers in maternal plasma, alone or in combination with baseline antenatal factors, could predict retinopathy of prematurity (ROP) in preterm infants.

Methods: A retrospective cohort study was conducted on 140 premature singleton neonates born to women with preterm birth (≤32 weeks) and screened for ROP. Maternal blood obtained at the time of admission was assayed for CRP, endoglin, endostatin, IGFBP-2, IGFBP-3, IL-6, LBP, MMP-8, PlGF, S100A8/A9, TGFBI, and VEGFR-1. The primary outcome measures included severe ROP (stage 3 or higher) and type 1 ROP requiring treatment.

Results: ROP was present in 25.7% (36/140) of the study population, including 20 (14.3%) cases of severe ROP and 14 (10%) with type 1 ROP. Multiple logistic regression analyses revealed significant associations between high concentrations of maternal plasma LBP and severe ROP, and between elevated plasma IL-6 and LBP levels and type 1 ROP (all P < 0.05), while adjusting for confounders (i.e., gestational age [GA] at sampling). Prenatal prediction models for severe ROP and type 1 ROP were developed by combining plasma IL-6 or LBP levels with GA at sampling, which showed good discriminatory power (area under the curve = 0.747 and 0.854, respectively).

Conclusions: IL-6 and LBP in maternal plasma were found to be independently associated with severe ROP and type 1 ROP. Prediction models based on these biomarkers along with GA at sampling may serve as good prenatal indicators for the neonatal risk of ROP progression in women at risk of preterm birth.

Fig. 1. ROC curve analysis.

Receiver operating characteristic curve for the best combined prenatal prediction model including maternal plasma lipopolysaccharide-binding protein (LBP) or interleukin (IL)-6 for predicting (A) severe retinopathy of prematurity (ROP) or (B) vision-threatening ROP requiring treatment. (A) Area under the curve (AUC) for the plasma LBP, gestational age (GA) at sampling, and combined prenatal prediction model was 0.628, 0.704, and 0.747, respectively. (B) AUC for the plasma IL-6, GA at sampling, and combined prenatal prediction model was 0,671, 0.844, and 0.854, respectively.