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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.




© 2014 Lally et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Figure_S1.tif (703 kB)
Blood glucose, oxygen saturation (SaO2) and blood pressure (mean and standard deviation error bar) in all infants in the first 4 days after birth. Norm/Mild = normal/mild Sarnat encephalopathy stage at 3 days after birth; Mod/Sev = moderate/severe Sarnat encephalopathy stage at 3 days after birth. doi:10.1371/journal.pone.0087874.s001

Figure_S2.tif (747 kB)
Individual blood glucose measurements in the 4 hypoglycaemic infants in the first 4 days after birth according to 3½ year outcome (Unknown = unpresented for 3½ year assessment). doi:10.1371/journal.pone.0087874.s002

Figure_S3.tif (138 kB)
Mean (standard deviation) Thompson scores at ages up to 4 days in infants grouped according to Sarnat neonatal encephalopathy (NE) stage assessed at 3 days after birth. doi:10.1371/journal.pone.0087874.s003

Figure_S4.tif (1203 kB)
Use of the 6-hour Thompson score as an inclusion criterion for cooling therapy compared to the Sarnat encephalopathy stage (normal, mild, moderate or severe) at 3 days after birth. Sensitivity and specificity: infants with moderate/severe Sarnat stage treated as disease positive, normal/mild stage as disease negative. doi:10.1371/journal.pone.0087874.s004

Figure_S5.tif (436 kB)
Whole-brain white matter FA according to MR spectroscopy assessment. p value maps are displayed as described in Figure 2, only using those with MR spectroscopy data for group-wise comparisons. NAA = N-acetylaspartate; Lac = lactate; Cho = choline-containing compounds; Cr = total creatine. doi:10.1371/journal.pone.0087874.s005

Figure_S6.tif (609 kB)
Conventional MR imaging (MRI) scores across infants with different 3½ year outcomes. doi:10.1371/journal.pone.0087874.s006

Table_S1.docx (21 kB)
Clinical characteristics. Values are mean (standard deviation) or proportion (%) unless otherwise indicated. †Clinical sepsis with elevated C-reactive protein with or without positive blood culture, requiring antibiotic treatment, within three days of birth; CI = confidence interval. *Indicates difference between groups with p<0.05. doi:10.1371/journal.pone.0087874.s007

Table_S2.docx (22 kB)
Biochemical characteristics. Values are mean (standard deviation) unless otherwise indicated. †Denotes skewed distributions where median (IQR) is reported, along with the difference in medians (p value of Mann-Whitney U test). *Indicates difference between group means with p<0.05. CI = confidence interval; WBC = white blood cells; SGPT = serum glutamic-pyruvic transaminase; PT = prothrombin time; APTT = activated partial thromboplastin time. doi:10.1371/journal.pone.0087874.s008

Table_S3.docx (20 kB)
Clinical features and brain injury of surviving infants who attended 3½ year follow-up or were lost to follow-up. Values are proportion (%) unless otherwise indicated. CI = confidence interval; WM = white matter; BGT = basal ganglia and thalami; PLIC = posterior limb of the internal capsule. doi:10.1371/journal.pone.0087874.s009

Table_S4.docx (20 kB)
Characteristics and outcomes of neonatal encephalopathy for infants undergoing whole-body therapeutic hypothermia or normothermia. Values are mean (standard deviation) or proportion (%). †Sepsis = Clinical sepsis with elevated C-reactive protein with or without positive blood culture within three days of birth. ‡Abnormal outcome = cerebral palsy; visual or hearing impairment; evidence of seizures or use of anti-epileptic medication at age 3½ years; slowed head growth; or a composite motor score <82 or composite cognitive score <85 on Bayley III. doi:10.1371/journal.pone.0087874.s010

Table_S5.docx (20 kB)
Sensitivity and specificity of conventional MR imaging in identifying infants with cerebral palsy or low Bayley III scores (<82 for composite motor, <85 for composite cognitive) at 3½ years. doi:10.1371/journal.pone.0087874.s011

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