Clinical and histological chorioamnionitis, particularly when associated with funisitis, attenuate intrapartum fetal heart rate responses and increase vulnerability to hypoxic-ischemic brain injury at milder degrees of acidemia

BACKGROUND: Animal experimental studies and human observational data suggest that fetal inflammatory response to chorioamnionitis is associated with increased risk of neonatal encephalopathy and attenuation of fetal responses to intrapartum hypoxia-ischemia, but the effects of clinical and/or histological chorioamnionitis and fetal inflammatory response on fetal heart rate patterns during labor in the term human fetus remain undefined. OBJECTIVE: To compare intrapartum fetal heart rate responses to hypoxia, assessed by fetal heart rate deceleration frequency and cumulative deceleration area, in acidemic fetuses in term labor to their peers with and without hypoxic-ischemic encephalopathy and clinical and/or histological chorioamnionitis. STUDY DESIGN: This retrospective cohort study included 317,126 term singleton deliveries from 7 hospitals in the Helsinki University Hospital district, Finland, between 2005 and 2024. Among these, 3487 newborns with umbilical artery acidemia, defined as pH15 seconds) and shallow deceleration (decreases of 10-15 beats per minute lasting >15 seconds) frequencies, cumulative deceleration area (all decelerations of ≥10 beats per minute lasting >15 seconds), and uterine contraction frequency. Neonatal hypoxic-ischemic encephalopathy was diagnosed according to Sarnat staging, and chorioamnionitis based on clinical criteria and/or placental histology. Acidemic cases were categorized into 4 groups: acidemia with hypoxic-ischemic encephalopathy and clinical and/or histological chorioamnionitis (N=133), acidemia with hypoxic-ischemic encephalopathy without chorioamnionitis (N=181), acidemia with clinical and/or histological chorioamnionitis without hypoxic-ischemic encephalopathy (N=436), and acidemia without hypoxic-ischemic encephalopathy or chorioamnionitis (N=2737). RESULTS: Among 3487 term fetuses with umbilical artery acidemia, clinical and/or histological chorioamnionitis was associated with an increased risk of hypoxic-ischemic encephalopathy (adjusted odds ratio, 4.61; 95% confidence interval, 3.60-5.87; P