Characteristics, Genetic Testing, and Diagnoses of Infants with Neonatal Encephalopathy Not Due to Hypoxic Ischemic Encephalopathy: A Cohort Study

J Pediatr. 2023 Sep;260:113533. doi: 10.1016/j.jpeds.2023.113533. Epub 2023 Jun 1.


Objective: To characterize the presentation and evaluation of infants with neonatal encephalopathy (NE) not due to hypoxic-ischemic encephalopathy (non-HIE NE) and to describe the genetic abnormalities identified.

Study design: Retrospective cohort study of 193 non-HIE NE neonates admitted to a level IV NICU from 2015 through 2019. For changes in testing over time, Cochrane-Armitage test for trend was used with a Bonferroni-corrected P-value, and comparison between groups was performed using Fisher exact test.

Result: The most common symptom of non-HIE NE was abnormal tone in 47% (90/193). Ten percent (19/193) died prior to discharge, and 48% of survivors (83/174) required medical equipment at discharge. Forty percent (77/193) underwent genetic testing as an inpatient. Of 52 chromosomal studies, 54 targeted tests, and 16 exome sequences, 10%, 41%, and 69% were diagnostic, respectively, with no difference in diagnostic rates between infants with and without an associated congenital anomaly and/or dysmorphic feature. Twenty-eight genetic diagnoses were identified.

Conclusions: Neonates with non-HIE NE have high rates of morbidity and mortality and may benefit from early genetic testing, even in the absence of other exam findings. This study broadens our knowledge of genetic conditions underlying non-HIE NE, which may enable families and care teams to anticipate the needs of the individual, allow early initiation of targeted therapies, and facilitate decisions surrounding goals of care.

Keywords: encephalopathic; exome; infant; neonate; newborn.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cohort Studies
  • Genetic Testing
  • Humans
  • Hypothermia, Induced*
  • Hypoxia-Ischemia, Brain* / complications
  • Hypoxia-Ischemia, Brain* / diagnosis
  • Hypoxia-Ischemia, Brain* / genetics
  • Infant
  • Infant, Newborn
  • Infant, Newborn, Diseases* / therapy
  • Retrospective Studies