AbstractAimThis study aimed to clarify the diagnostic accuracy of amniotic fluid interleukin‐6 for fetal inflammatory response syndrome (FIRS).MethodsThis retrospective cohort study was conducted in a single institution and targeted cases of preterm birth within 24 h after amniocentesis among singleton cases that underwent amniocentesis at our hospital for suspected intraamniotic inflammation (IAI) from gestational ages of 22–36 weeks between August 2014 and March 2020. FIRS was defined as >11.0 pg/mL of umbilical cord blood interleukin‐6.ResultsThe analysis included 158 pregnant women. There was a strong correlation between amniotic fluid interleukin‐6 and umbilical cord blood interleukin‐6 (r = 0.70, p < 0.001). The area under the receiver operating characteristic curve of amniotic fluid interleukin‐6 for FIRS was 0.93, with a cutoff value of 15.5 ng/mL, and showed high sensitivity and specificity (0.91 and 0.88, respectively). An amniotic fluid interleukin‐6 cutoff value of ≥15.5 ng/mL was associated with a significant risk of FIRS (adjusted odds ratio: 27.9; 95% confidence interval: 6.3–123.0; p < 0.001).ConclusionsThe results of this study show that amniotic interleukin 6 alone can be used to diagnose FIRS prenatally. While there is a need for validation, it may be possible to treat IAI while preventing damage to the central nervous and respiratory systems in the uterus by keeping the amniotic fluid interleukin‐6 below the cutoff value.