Table 2.
A summary of cited studies regarding neurodevelopmental outcomes and other brain injuries in infants with neonatal hypoglycemia.
| Study | Study type | Cohort year | Study population | Key imaging findings | Key outcome findings |
|---|---|---|---|---|---|
| Caraballo, 2004 (66) | retrospective cohort | 1990–2003 | 15 infants with epilepsy and/or posterior cerebral lesions and NH | 13/15 patients presented parieto-occipital lesions | 1 patient: no seizures; 12 patients: focal seizures and posterior abnormalities on the EEG, the majority with a good outcome; 2 patients: encephalopathy with refractory seizures (after prolonged refractory NH). |
| Filan, 2006 (64) | retrospective cohort | 2004 | 4 term and late-preterm infants with NH | Abnormalities detected in occipital and parietal cortex and white matter, corpus callosum, and optic radiations. | At 1 year of age, one case presented microcephaly, gross motor delay, and visual impairment, while other 3 cases had normal follow-up at 9 months. |
| Burns, 2008 (68) | retrospective cohort | 1992–2006 | 35 term infants with symptomatic NH and 229 controls | White matter abnormalities observed in 94% of infants with NH, with predominantly posterior pattern in 29% of cases. Cortical involvement present in 51% of cases, basal ganglia/thalamic abnormalities in 40%, white matter hemorrhages in 30%, and middle cerebral artery infarctions observed in 3 infants. | At 18 months of age, 65% of infants presented impairments related to the white matter damage. Early MRI findings were more instructive than severity or duration of hypoglycemia in predicting neurodevelopmental outcomes. |
| Tam, 2008 (65) | retrospective cohort | 2000–2005 | 45 neonates of different gestational ages with NH | Diffusion MRI restriction in the mesial occipital poles observed in ½ of term infants with early imaging. | No long-term visual loss in infants with single-day NH. Cortical visual loss in 1/3 of infants with NH lasting ≥2 days. |
| Kerstjens, 2012 (71) | community-based stratified cohort | 2002–2003 | 832 moderately preterm infants | – | Around 4 years of age, NH was found to increase the risk of developmental delay in moderately preterm-born children. |
| Tam, 2012 (8) | prospective cohort | 1994–2010 | 94 term neonates at risk for neonatal encephalopathy | NH associated with a 3.72-fold increased odds of corticospinal tract injury (P=0.047). | At 1 year of age, NH was assosiated with 4.82-fold increased odds of one-point worsened neuromotor score (P=0.038) and a 15-point lower cognitive and language score on the Bayley Scales of Infant Development (P=0.015). |
| Wong, 2013 (83) | cohort | 2004–2010 | 179 term infants with neonatal encephalopathy | Specific imaging features for both NH and HIE can be identified. Selective edema in the posterior white matter, pulvinar, and anterior medial thalamic nuclei were most predictive for NH, while no injury (36%) or a watershed (32%) pattern of injury were seen more often in severe NH. | – |
| van der Aa, 2013 (85) | retrospective | 2000–2012 | 18 infants with perinatal arterial ischemic stroke in the PCA territory | 7/18 patients diagnosed with NH → possible relation between hypoglycemic brain damage and posterior stroke. | – |
| Gataullina, 2013 (67) | retrospective cohort | – | 50 patients with symptomatic metabolic hypoglycaemia at 1 day–5 years | Parieto-occipital white matter lesions were observed in infants with hypoglycaemia occurring from the neonatal period to 6 months of age. | Clinical sequelae were severe (global psychomotor delay, microcephaly, motor deficit, lack of visual contact, and/ or pharmacoresistant epilepsy) in 22 children and mild (speech delay, learning difficulties, and pharmacosensitive epilepsy) in 13 others; 15 children experienced no sequelae. |
| Fong, 2014 (7) | retrospective | 1996–2012 | 11 patients with seizures beyond infancy after NH | All children presented gliosis with or without cortical atrophy in the occipital lobe with or without parietal lobe involvement. | Despite having bilateral occipital brain injury and neurological disability, 6/11 children with epilepsy after NH had infrequent and potentially age-limited focal seizures. |
| McKinlay, 2015 (69) | prospective cohort | 2006–2010 | 404 term and late preterm neonates at risk for NH treated to maintain blood glucose ≥47 mg/dl | – | At 2 years of age, no increased risk of neurosensory impairment or processing difficulty in infants with NH. No correlation between the lowest blood glucose concentration, number of hypoglycemic episodes, or episodes of unrecognized hypoglycemia, and the given outcome. |
| Kaiser, 2015 (74) | retrospective population-based cohort | 1998 | 1943 infants of different gestational ages | – | At 10 years of age, an association was found between early transient hypoglycemia and decreased probability of proficiency on literacy and mathematics achievement tests. |
| Goode, 2016 (72) | secondary analysis of a longitudinal study | 1985 | 743 preterm infants stratified into 4 groups by glucose level | – | No significant differences in cognitive or academic skills at 3, 8, and 18 years of age were observed in preterm-borninfants stratified by glucose level. |
| Basu, 2016 (82) | secondary analysis of a randomized study | 1999–2002 | 214 neonates with HIE | – | A greater risk of unfavorable outcome observed in infants with HIE and NH |
| McKinlay, 2017 (75) | prospective cohort | 2006–2010 | 477 term and late preterm neonates at risk for NH treated to maintain blood glucose ≥47 mg/dl | – | At 4.5 years of age, NH was not assosiated with increased risk of combined neurosensory impairment, but was assosiated with increased risk of poor executive and visual motor functions. Highest risk in children exposed to severe, recurrent, or clinically undetected NH. |
| Basu, 2018 (84) | secondary analysis of a prospective study | 2008–2016 | 178 neonates with HIE | An association observed between early NH in infants with HIE and watershed or focal-multifocal injury on MRI. | – |
NH, neonatal hypoglycemia; HIE, hypoxic-ischemic encephalopathy; PCA, posterior cerebral artery.