Risk Factors and Outcomes for Cerebral Palsy With Hypoxic-Ischemic Brain Injury Patterns Without Documented Neonatal Encephalopathy

Background and Objectives Perinatal hypoxic-ischemic brain injury is a leading cause of term-born cerebral palsy, the most common lifelong physical disability. Diagnosis is commonly made in the neonatal period by the combination of neonatal encephalopathy (NE) and typical neuroimaging findings. However, children without a history of neonatal encephalopathy may present later in childhood with motor disability and neuroimaging findings consistent with perinatal hypoxic-ischemic injury. We sought to determine the prevalence of such presentations using the retrospective viewpoint of a large multiregional cerebral palsy registry. Methods Patient cases were extracted from the Canadian Cerebral Palsy Registry with gestational age >36 weeks, an MRI pattern consistent with hypoxic-ischemic injury (HII, acute total, partial prolonged, or combined), and an absence of postnatal cause for HII. Documentation of NE was noted. Maternal-fetal risk factors, labor and delivery, neonatal course, and clinical outcome were extracted. Comparisons were performed using chi 2 tests and multivariable logistic regression with multiple imputation. Propensity scores were used to assess for bias. Results Of the 170 children with MRI findings typical for HII, 140 (82.4%, 95% confidence interval [CI] 75.7%-87.7%) had documented NE and 29 (17.0%, 95% CI 11.7%-23.6%) did not. The group without NE had more abnormalities of amniotic fluid volume (odds ratio [OR] 15.8, 95% CI 1.2-835), had fetal growth restriction (OR 4.7, 95% CI 1.0-19.9), had less resuscitation (OR 0.03, 95% CI 0.007-0.08), had higher 5-minute Apgar scores (OR 2.2, 95% CI 1.6-3.0), were less likely to have neonatal seizures (OR 0.004, 95% CI 0.00009-0.03), and did not receive therapeutic hypothermia. MRI was performed at a median 1.1 months (interquartile range [IQR] 0.67-12.8 months) for those with NE and 12.2 months (IQR 6.6-25.9) for those without (p = 0.011). Patterns of injury on MRI were seen in similar proportions. Hemiplegia was more common in those without documented NE (OR 5.1, 95% CI 1.5-16.1); rates of preserved ambulatory function were similar. Discussion Approximately one-sixth of term-born children with an eventual diagnosis of cerebral palsy and MRI findings consistent with perinatal hypoxic-ischemic brain injury do not have documented neonatal encephalopathy, which was associated with abnormalities of fetal growth and amniotic fluid volume, and a less complex neonatal course. Long-term outcomes seem comparable with their peers with encephalopathy. The absence of documented neonatal encephalopathy does not exclude perinatal hypoxic-ischemic injury, which may have occurred antenatally and must be carefully evaluated with MRI.