The role of placental and cardiotocography analysis in the assessment of fetal risk for neonatal hypoxic ischaemic encephalopathy and their relationship to perinatal brain injury

<p dir="ltr"><b>Introduction: </b>Hypoxic ischaemic encephalopathy (HIE) of the newborn relates to neurological dysfunction caused by perinatal asphyxia. HIE is associated with a high risk for mortality and long-term adverse neurodevelopment. Newborns with HIE are often born to women who have had a seemingly uneventful pregnancy, and up to two-thirds have no obvious antecedent intrapartum sentinel event. Recent research provides evidence that deficiencies within the maternal-placental-fetal (MPF) triad contributes to the pathogenesis of HIE.</p><p dir="ltr"><b>Aim and Hypothesis: </b>This study aimed to determine the role of the MPF triad in the pathogenesis of HIE through analyses of the placenta and intrapartum fetal heart rate characteristics (cardiotocography, CTG) in near-term and term-born infants with moderate or severe HIE compared with healthy newborn infants. These findings were then related to brain injury assessed by neonatal neuroimaging as a surrogate outcome measure of disease severity. This study hypothesised that the MPF triad has a role in the pathogenesis of HIE and the severity of associated brain injury as assessed by neonatal neuroimaging.</p><p dir="ltr"><b>Methods:</b> Retrospective observational case-control study of newborn infants with moderate or severe HIE (cases, n=140) and healthy newborn infants (controls, n=98) with placental and intrapartum CTG analyses. A retrospective observational cohort sub-study comprising the same newborn infants with moderate or severe HIE was conducted to evaluate the relationships between the placenta, intrapartum CTG and severity of brain injury assessed on neonatal neuroimaging. Placental pathology, intrapartum CTG and neonatal neuroimaging were reviewed using up-to-date guidelines for reporting and/or validated scoring systems, with all reviewers blinded to the clinical history of participants.</p><p dir="ltr"><b>Results: </b>Associations were found between the presence of 1) placental pathology and 2) CTG abnormality and HIE. There was an association between placental pathology and duration of CTG abnormalities. Placental pathology and abnormal CTG had limited impact on the location/severity of brain injury.</p><p dir="ltr"><b>Conclusion: </b>This study adds important information to the unanswered research question of what is the cause of HIE in the absence of an intrapartum sentinel event (ISE). This research study demonstrates the importance of placental pathology and prolonged, consecutive durations of CTG abnormality contributing to the development of HIE.</p>