Profiling Cytokines According to the Presence or Absence of Small-for-Gestational Age Using Amniotic Fluid Retrieved During Cesarean Section From Pregnant Women With Early-Onset Preeclampsia

Abstract

Background: Preeclampsia (PE) is a hypertensive disorder and a major cause of maternal and fetal mortality. We aimed to investigate the molecular properties of early-onset PE, which requires delivery before 34 weeks’ gestation by analyzing the molecular cytokine profile of amniotic fluid obtained during cesarean section from pregnant women with early-onset PE, based on the presence or absence of small-for-gestational age (SGA).

Methods: This study included 73 pregnant women with early-onset PE among which 21 women had SGA infants, whose birth weight was less than the 10th percentile of the gestational age-specific birth weight. Amniocentesis was performed after exposing the amniotic sac during cesarean delivery. Twenty-five cases of appropriate-for-gestational age (AGA) infants, who had birth weights between the 25th and 75th percentile of the gestational age-specific birth weight, were arbitrarily selected as a control group. Potential protein biomarkers were analyzed using the Olink® Explore 384 Inflammation panel with a Proximity Extension Assay technique. The biological implications of the differentially expressed proteins (DEPs) were assessed using the web-based tool Database for Annotation, Visualization, and Integrated Discovery 2021. Enrichment analysis of hub genes was performed using the Metascape Database.

Results: Although the mean birth weight was significantly lower in the SGA group than that in the AGA group (945.2 ± 302.3 vs. 1,590.0 ± 393.2, respectively; P < 0.001), no difference was observed in the mean gestational age at delivery (P > 0.05). Sixteen DEPs (EPO, WFIKKN2, CLSTN2, CSF3, COL9A1, SCG3, CCL23, SKAP2, CCL20, GZMB, TIMP3, FIS1, IL17C, PON3, VEGFA, and CXCL8) were found to be upregulated in the SGA group compared with the AGA group. Six hub genes (CCL20, CSF3, EPO, VEGFA, IL17C, and GZMB), which are mainly involved in cytokine-cytokine receptor interactions, were overexpressed in the SGA group.

Conclusion: We found six upregulated hub genes with potential as novel biomarkers for early-onset PE with SGA. Although further investigation is warranted to validate our results, our findings may contribute to a better understanding of the pathogenesis of early-onset PE with SGA.