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.

Abstract

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. 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. This retrospective cohort study included 317,126 term singleton deliveries from 7 hospitals in the Helsinki University Hospital district, Finland, between 2005-2024. Among these, 3,487 newborns with umbilical artery acidemia, defined as pH <7.10, and continuous intrapartum cardiotocographic recordings were identified. Fetal heart rate data from the final 9 hours before birth were analyzed, with hourly median values calculated for deep deceleration (decreases of ≥60 beats per minute below baseline lasting >15 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=2,737). Among 3,487 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<.001), despite a shift toward less severe umbilical artery acidemia, with a greater proportion of moderate (pH 7.09-7.00) and a lower proportion of severe (pH <7.00) acidemia (p=.026). Among histological chorioamnionitis cases, funisitis, a histopathologic manifestation of the fetal inflammatory response, remained independently associated with hypoxic-ischemic encephalopathy after adjustment for acidemia severity (adjusted odds ratio, 2.21; 95% confidence interval, 1.32-4.13; p<.001). Consistent with these findings, clinical and/or histological chorioamnionitis was associated with attenuated fetal heart rate responses to intrapartum hypoxic stress. Among fetuses who developed hypoxic-ischemic encephalopathy, those with clinical and/or histological chorioamnionitis exhibited fewer deep decelerations (adjusted ratio of medians, 0.62; 95% confidence interval, 0.49-0.76), a smaller cumulative deceleration area (adjusted ratio of medians, 0.70; 95% confidence interval, 0.59-0.82), and more shallow decelerations (adjusted ratio of medians, 2.45; 95% confidence interval, 2.33-2.63; all p<.001), despite similar uterine contraction frequency, with attenuation most pronounced among fetuses with funisitis. Clinical chorioamnionitis alone remained independently associated with hypoxic-ischemic encephalopathy (adjusted odds ratio, 1.44; 95% confidence interval, 1.02-2.05; p<.001), whereas histological chorioamnionitis was associated with a 2.5-fold higher risk than clinical chorioamnionitis alone (adjusted odds ratio, 2.54; 95% confidence interval, 1.68-3.86; p<.001). Clinical and histological chorioamnionitis, particularly when accompanied by funisitis, are associated with attenuated fetal heart rate responses to intrapartum hypoxic stress and reduced fetal tolerance to hypoxia, thereby increasing the risk of hypoxic-ischemic encephalopathy at milder degrees of acidemia.