Genetic and Congenital Anomalies in Infants With Hypoxic-Ischemic Encephalopathy

Abstract

Background: Infants with hypoxic ischemic encephalopathy (HIE) may have underlying conditions predisposing them to hypoxic-ischemic injury during labor and delivery. It is unclear how genetic and congenital anomalies impact outcomes of HIE.

Methods: Infants with HIE enrolled in a phase III trial underwent genetic testing when clinically indicated. Infants with known genetic or congenital anomalies were excluded. The primary outcome, i.e., death or neurodevelopmental impairment (NDI), was determined at age two years by a standardized neurological examination, Bayley Scales of Infant Development, Third Edition (BSID-III), and the Gross Motor Function Classification Scales. Secondary outcomes included cerebral palsy and BSID-III motor, cognitive, and language scores at age two years.

Results: Of 500 infants with HIE, 24 (5%, 95% confidence interval 3% to 7%) were diagnosed with a genetic (n = 15) or congenital (n = 14) anomaly. Infants with and without genetic or congenital anomalies had similar rates of severe encephalopathy and findings on brain magnetic resonance imaging. However, infants with genetic or congenital anomalies were more likely to have death or NDI (75% vs 50%, P = 0.02). Among survivors, those with a genetic or congenital anomaly were more likely to be diagnosed with cerebral palsy (32% vs 13%, P = 0.02), and had lower BSID-III scores in all three domains than HIE survivors without such anomalies.

Conclusions: Among infants with HIE, 5% were diagnosed with a genetic or congenital anomaly. Despite similar clinical markers of HIE severity, infants with HIE and a genetic or congenital anomaly had worse neurodevelopmental outcomes than infants with HIE alone.

Keywords: Congenital anomaly; Genetic anomaly; Hypoxic-ischemic encephalopathy; Neonatal.

FIGURE.

Brain developmental abnormalities in children with moderate to severe hypoxic-ischemic encephalopathy. (A) Sagittal T1-weighted image demonstrates dysgenesis of the corpus callosum, with early termination of the corpus callosum (white arrow) due to absent posterior body and splenium. (B) Axial T2-weighted imaging demonstrates white matter hypoplasia as evidenced by diminished periatrial white matter volume (black arrows) and wide sylvian fissures (black asterisks) in an infant who was born at 40.5 weeks gestational age.