Prognostic significance of interleukin-6, hypoxia-inducible factor-1 and ferritin in the development of placental insufficiency in pregnant women with COVID-19 and anaemia

Evidence indicates that COVID-19 adversely affects the course of pregnancy; however, the mechanisms underlying the associated placental insufficiency and anaemia remain inadequately explored. Aim . To assess the prognostic value of serum interleukin-6 (IL-6), hypoxia-inducible factor-1α (HIF-1α) and ferritin for the development of placental insufficiency in pregnant women with moderate COVID-19 and anaemia. Materials and methods . Seventy-eight pregnant women were followed prospectively at predefined control points. Baseline (12–14 weeks’ gestation): all participants had experienced moderate COVID-19 (community-acquired pneumonia). Second control point (19–20 weeks): women were allocated to two groups according to the presence of anaemia: group 1 –COVID-19 with mild anaemia (n = 54); group 2 – COVID-19 without anaemia (n = 24). Third control point (30–32 weeks): group 1 was subdivided into subgroup 1A – placental insufficiency present (n = 34) and subgroup 1B –placental insufficiency absent (n = 20). COVID-19 was confirmed by SARS-CoV-2 RNA detection in oropharyngeal and nasopharyngeal swabs using polymerase chain reaction and, where indicated, by radiological criteria of viral lung injury. Serum IL-6 (pg/mL), HIF-1α (ng/mL) and ferritin (μg/L) were measured by solid-phase enzyme-linked immunosorbent assay with Vector-Best (Russia) and BCM Diagnostics (Austria) kits. Red-blood indices (haemoglobin, erythrocyte count) were obtained on a Medonic M haematology analyser (Switzerland). Results . Women with COVID-19 and anaemia exhibited significantly higher IL-6 (p < 0.001), HIF-1α (p < 0.001) and ferritin (p < 0.001) concentrations than those without anaemia. Placental insufficiency was diagnosed in 63 % of the affected group. Strong positive correlations were found between placental insufficiency and HIF-1α (r = 0.76; p < 0.05), IL-6 (r = 0.82; p < 0.05) and ferritin (r = 0.72; p < 0.05). A prognostic index of placental insufficiency (PIPI) was derived: PIPI = –12.84 + 2.486 × HIF-1α – 0.921 × IL-6 + 0.380 × ferritin, where variables represent serum concentrations. The threshold value was 1.204: PIPI ≥ 1.204 indicated a high risk of placental insufficiency, whereas PIPI < 1.204 indicated no risk. Absolute PIPI values were directly proportional to risk magnitude. Conclusion . Elevated serum IL-6, HIF-1α and ferritin are informative predictors of placental insufficiency in pregnant women with moderate COVID-19 and anaemia.