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

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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.

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Fig. 1: ROC curve analysis.

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Data availability

The dataset for this study is available from the corresponding author upon reasonable request.

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Funding

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (No. 2020R1F1A1048362). The funders had no role in the design of this study, data collection, data analyses, data interpretation, or in the writing of this manuscript.

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Author notes

  1. These authors contributed equally: Jae Shin Song, Se Joon Woo.

Authors and Affiliations

  1. Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

    Jae Shin Song & Se Joon Woo

  2. Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

    Kyo Hoon Park, Kyong-No Lee & Yu Mi Kim

  3. Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

    Hunmin Kim

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  1. Jae Shin Song
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Contributions

JSS: protocol/project development, data analysis, manuscript writing/editing. SJW: protocol/project development, data analysis, manuscript writing/editing. KHP: conceptualization, protocol/project development, supervision, funding acquisition, data analysis, manuscript writing/editing. HK: data collection or management, data analysis, manuscript editing. KNL: data collection or management, data analysis. YMK: data collection or management, data analysis, ELISA assay.

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Correspondence to Kyo Hoon Park.

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Song, J.S., Woo, S.J., Park, K.H. et al. Association of inflammatory and angiogenic biomarkers in maternal plasma with retinopathy of prematurity in preterm infants. Eye 37, 1802–1809 (2023). https://doi.org/10.1038/s41433-022-02234-9

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