Neonatal encephalopathic cerebral injury in South India assessed by perinatal magnetic resonance biomarkers and early childhood neurodevelopmental outcome

Abstract

Although brain injury after neonatal encephalopathy has been characterised well in high-income countries, little is known about such injury in low- and middle-income countries. Such injury accounts for an estimated 1 million neonatal deaths per year. We used magnetic resonance (MR) biomarkers to characterise perinatal brain injury, and examined early childhood outcomes in South India.

Methods: We recruited consecutive term or near term infants with evidence of perinatal asphyxia and a Thompson encephalopathy score ≥6 within 6 h of birth, over 6 months. We performed conventional MR imaging, diffusion tensor MR imaging and thalamic proton MR spectroscopy within 3 weeks of birth. We computed group-wise differences in white matter fractional anisotropy (FA) using tract based spatial statistics. We allocated Sarnat encephalopathy stage aged 3 days, and evaluated neurodevelopmental outcomes aged 3½ years using Bayley III.

Results: Of the 54 neonates recruited, Sarnat staging was mild in 30 (56%); moderate in 15 (28%) and severe in 6 (11%), with no encephalopathy in 3 (6%). Six infants died. Of the 48 survivors, 44 had images available for analysis. In these infants, imaging indicated perinatal rather than established antenatal origins to injury. Abnormalities were frequently observed in white matter (n = 40, 91%) and cortex (n = 31, 70%) while only 12 (27%) had abnormal basal ganglia/thalami. Reduced white matter FA was associated with Sarnat stage, deep grey nuclear injury, and MR spectroscopy N-acetylaspartate/choline, but not early Thompson scores. Outcome data were obtained in 44 infants (81%) with 38 (79%) survivors examined aged 3½ years; of these, 16 (42%) had adverse neurodevelopmental outcomes.

Conclusions: No infants had evidence for established brain lesions, suggesting potentially treatable perinatal origins. White matter injury was more common than deep brain nuclei injury. Our results support the need for rigorous evaluation of the efficacy of rescue hypothermic neuroprotection in low- and middle-income countries.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Study flow chart.

Figure 2. TBSS analysis of whole-brain white matter FA according to conventional MR imaging abnormalities.

In each case FA is compared between the infants classified abnormal (by the criterion given), and the other infants in the cohort. Red-yellow pixels denote regions of white matter where FA values are different between groups with p

Figure 3. Whole-brain white matter FA according to perinatal clinical assessment.

p value maps are displayed as described in Figure 2. Neuro = neurological; Ther. hypotherm. = therapeutic hypothermia.

Figure 4. Whole-brain white matter FA according to outcome assessment aged 3½ years.

p value maps are displayed as described in Figure 2, only using those with 3½ year outcome data for group-wise comparisons. Low Bayley III = infants with scores below predefined cut-offs for Bayley III (2 standard deviations), with otherwise normal neurological examination and Bayley III scores.