Hypoxic-ischemic encephalopathy following intrapartum asphyxia: is it avoidable?
AJOG study published this month
Citation
Tarvonen, M., Jernman, R., Stefanovic, V., Tuppurainen, V., Karikoski, R., Haataja, L., & Andersson, S. (2025). Hypoxic-ischemic encephalopathy following intrapartum asphyxia: Is it avoidable? American Journal of Obstetrics and Gynecology. Advance online publication. https://doi.org/10.1016/j.ajog.2025.04.073
This 20-year retrospective cohort study of 317 126 term singleton deliveries evaluated how admission cardiotocography (CTG) distinguishes antepartum from intrapartum hypoxic-ischemic encephalopathy (HIE). A normal admission CTG excluded preexisting fetal hypoxia with 100 % sensitivity and negative predictive value, while abnormal CTG cases showed biochemical markers of chronic hypoxia (median UV erythropoietin 112 U/L vs 29 U/L; p < .001). Among 141 HIE cases with normal admission CTG, 70 (49.6 %) were deemed potentially avoidable, representing 22.3 % of all term HIE instances. These findings underscore the critical role of optimal intrapartum surveillance, timely intervention and structured protocols to prevent a significant proportion of HIE cases.
Study design and population characteristics
This retrospective cohort spanned 2005–2024 across seven Helsinki University Hospital area maternity units. A total of 317 126 term singleton deliveries (≥37 weeks) with admission and continuous intrapartum CTG data were included. Three hundred and fourteen newborns (0.99 per 1000 live births) met Sarnat and ACOG/AAP criteria for HIE. Admission CTG tracings and UA blood gas analyses were available for 99 % of the final cohort, with 92 % undergoing placental histopathology. CTG interpretations were performed prospectively by trained midwives and obstetricians and independently reassessed by study investigators. Logistic regression models incorporated variables with p < .20 in univariate analysis to adjust for confounders.
Admission CTG predictive performance
A normal admission CTG was defined by baseline FHR 110–150 bpm, variability 5–25 bpm, ≥2 accelerations and no decelerations over ≥20 minutes. Normal CTG at admission demonstrated 100 % sensitivity, 100 % negative predictive value and 94.9 % specificity for excluding preexisting fetal neural injury. In 23 467 elective cesarean deliveries without contractions, HIE occurred in 0/22 248 with normal CTG versus 13/1 219 with abnormal CTG (OR 497.89; 95 % CI 29.58–8381). Abnormal admission CTG was observed in 173/314 (55.1 %) HIE cases, indicating chronic antepartum hypoxia. Interpretation followed FIGO guidelines with mandatory training to standardise CTG classification across institutions. Admission CTG performance facilitated accurate timing of hypoxic-ischemic injury.
Classification of HIE onset timing
Normal admission CTG indicated absence of substantial hypoxia before labour, attributing HIE onset to the intrapartum period. Abnormal admission CTG suggested antenatal hypoxic events and more chronic exposure to low oxygen. Among 314 HIE cases, 141 (44.9 %) had normal CTG at admission, designating intrapartum asphyxia as the primary mechanism. Severe acidemia (UA pH < 7.00 and/or BE ≤ −12.0 mmol/L) developed in 127/141 (90.1 %) of normal CTG cases. Moderate acidemia (UA pH 7.09–7.00 and BE −10.0 to −11.9 mmol/L) occurred in 11/141 (7.8 %) of these cases. Biochemical and placental data corroborated CTG-based timing classification in over 97 % of cases.
Acidemia profiles and HIE severity
Overall, 305/314 (97.1 %) HIE cases exhibited moderate or severe UA acidemia at birth. Severe acidemia was more prevalent in normal admission CTG cases (90.1 %) than in abnormal CTG cases (63.6 %; p < .001). Moderate acidemia occurred more often in abnormal CTG cases (32.9 %; UA pH 7.09–7.00; p < .001). Grade 3 HIE affected 48/141 (34.0 %) normal CTG versus 101/173 (58.4 %) abnormal CTG cases (p < .001). Five-minute Apgar <4 was present in 61.7 % of normal CTG and 71.1 % of abnormal CTG cases (p = .034). Continued resuscitation at 10 minutes was required in 87.2 % versus 94.2 % of normal versus abnormal CTG groups (p = .137).
Biochemical markers of hypoxia: EPO and S100β
Median UV erythropoietin concentration was 29 U/L (IQR 7–680) in normal CTG versus 112 U/L (IQR 22–1130) in abnormal CTG HIE cases (p < .001). Elevated UV EPO (>40 U/L) reflects ≥3 hours of fetal hypoxia and differentiates chronic from acute insults. Median serum S100β was 4.72 μg/L (IQR 2.95–7.34) in normal CTG versus 7.59 μg/L (IQR 4.26–11.78) in abnormal CTG cases (p < .001). S100β concentrations positively correlated with HIE severity, with higher median levels in grade 3 versus grade 2 (8.10 vs 5.22 μg/L; p < .001). Strong associations between elevated S100β and UV EPO (>40 U/L) support combined biomarker use for injury timing.
Placental histopathology and its correlation with CTG
Histological examination was completed in 289/314 (92 %) HIE cases without CTG-group differences. Histological chorioamnionitis was more frequent in normal CTG cases (39.7 %) than abnormal CTG cases (16.8 %; p < .001). Maternal vascular malperfusion lesions appeared in 6.4 % of normal CTG versus 22.0 % of abnormal CTG cases (p < .001). Fetal vascular malperfusion was identified in 12.8 % versus 23.7 % of normal versus abnormal CTG groups (p = .020). Combined inflammatory and vascular lesions were less common among potentially avoidable cases (5.7 %) than nonavoidable cases (18.3 %; p = .019). Placental pathology enhances differentiation between acute intrapartum and chronic antepartum hypoxia.
Identification and proportion of potentially avoidable HIE cases
Optimal intrapartum care required decision-to-delivery intervals ≤30 minutes and avoidance of prolonged pathological CTG recordings. Excluding sentinel events and timely interventions, 70/141 (49.6 %) normal CTG HIE cases were classified as potentially avoidable. These 70 cases represent 22.3 % of all 314 term HIE instances, indicating substantial preventability. Delayed responses included cesarean or vacuum-assisted delivery performed after ≥45 minutes of pathological or uninterpretable CTG. Figure 2 outlines the flowchart leading to classification of avoidable HIE based on admission CTG and care timelines. One-fifth of term HIE cases could benefit from strengthened intrapartum monitoring and prompt intervention protocols.
Clinical implications for intrapartum care optimisation
Admission CTG on hospital arrival should be universally applied to detect fetuses at risk before labour escalation. Continuous CTG monitoring demands rigorous training and adherence to FIGO criteria among obstetric teams. Timely decision-to-delivery intervals (<30 minutes) and immediate action on pathological tracings can reduce HIE incidence. Escalation pathways must ensure operative delivery is initiated within recommended intervals when CTG anomalies persist. Integration of biochemical and placental data into real-time assessments may improve intrapartum risk stratification. Quality improvement programmes like Each Baby Counts demonstrate that better intrapartum care can prevent up to 75% of term brain injuries.
Risk factors distinguishing avoidable from nonavoidable HIE cases
Nonavoidable cases showed higher prevalence of meconium-stained amniotic fluid (74.6 % vs 42.9 %; aOR 0.25; p < .001). Histological chorioamnionitis was more frequent in nonavoidable HIE and predicted nonavoidable classification (OR 0.48; p = .078). Placental vascular malperfusion lesions independently predicted nonavoidability (aOR 0.21; 95 % CI 0.08–0.59; p = .003). Perinatal sentinel events occurred exclusively in nonavoidable cases (49.3 %; aOR 0.01; p = .003). No maternal demographic or fetal characteristic independently predicted potentially avoidable HIE. Absence of antepartum risk factors underscores difficulty in anticipating intrapartum compromise in low-risk pregnancies.
Medico-legal considerations and risk management
Failure to implement admission CTG or delayed response to pathological tracings may constitute substandard care and legal liability. Accurate documentation of CTG interpretation, decision-to-delivery intervals and escalation steps is essential for defence in litigation. Informed consent discussions should cover the limitations of intrapartum monitoring, potential HIE risks and intervention thresholds. Risk management protocols must define clear criteria for operative delivery to demonstrate adherence to accepted standards. Regular audits, simulation training and multidisciplinary reviews can strengthen institutional defence and reduce medico-legal exposure. Findings from potentially avoidable HIE cases should guide policy updates, staff education and legal case preparation.
Bibliography
Tarvonen, M., Jernman, R., Stefanovic, V., Tuppurainen, V., Karikoski, R., Haataja, L., & Andersson, S. (2025). Hypoxic-ischemic encephalopathy following intrapartum asphyxia: Is it avoidable? American Journal of Obstetrics and Gynecology. Advance online publication. https://doi.org/10.1016/j.ajog.2025.04.073 Primary source describing admission CTG patterns, biochemical markers, placental pathology and avoidable HIE proportions in a term cohort.
Alfirevic, Z., Devane, D., & Gyte, G. M. (2017). Continuous cardiotocography (CTG) as a form of electronic fetal monitoring for fetal assessment during labour. Cochrane Database of Systematic Reviews, 2, CD006066. https://doi.org/10.1002/14651858.CD006066.pub2 Systematic review evaluating the effectiveness of continuous CTG versus intermittent auscultation for fetal monitoring and its clinical implications.
Knight, H., & Prosser Snelling, E. (2017). Each Baby Counts: National quality improvement programme to reduce intrapartum-related deaths and brain injuries in term babies. Seminars in Fetal & Neonatal Medicine, 22(4), 193–198. https://doi.org/10.1016/j.siny.2017.03.005 Report on a national initiative demonstrating the impact of optimised intrapartum care on reducing term brain injuries and informing medico-legal practice.
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