Hypoglycaemia is the most common metabolic disorder in newborns. It affects up to 15% of all babies and is the only known common preventable cause of brain damage in infancy. However, the relationship between the frequency and severity of neonatal hypoglycaemia and later performance is not known.
CHYLD (Children with Hypoglycaemia and their Later Development) is a large multi-disciplinary cohort study following the development of children who were identified as being at risk of developing neonatal hypoglycaemia. Babies in the study were managed according to standard clinical guidelines. They were assessed at 2, 4.5 and 9 years of age to understand how neonatal hypoglycaemia relates to later development, learning-related skills and academic achievements.
CHYLD 2 year study findings
At 2 years, 37% of these children had some evidence of neurosensory impairment, but there was no relationship between the occurrence, severity or frequency of neonatal low glucose concentrations and developmental outcome. Interestingly, high glucose concentrations and less glucose stability in the first 48 hours was associated with relatively large increases (40-70%) in the risk of impairment, particularly cognitive delay.
CHYLD 4.5 years study findings
At 4.5 years, neonatal hypoglycaemia was associated with a 2-3 fold increased risk of poor executive function and visual-motor integration, with greater impairment in children with severe or recurrent hypoglycaemia. There was a 4-fold increase in the risk of executive function difficulty in children who had experienced undetected and therefore untreated low neonatal glucose concentrations.
CHYLD 9-10 study
At 9-10 years of age, children who had and had not experienced neonatal hypoglycaemia had similar levels of academic achievement, executive function, visual-motor function, behaviour, growth and health. Overall this group of children who were born at risk of hypoglycaemia had a high rate of low academic achievement (47%). These findings suggest that babies born at risk of hypoglycaemia are at increased risk of later academic difficulties, but hypoglycaemia does not make these worse if babies are screened and treated as in this study, with the intention of maintaining their blood glucose concentrations above 2.6 mmol/L.
In a subgroup of children who underwent brain MRI as part of this study, those who had experienced neonatal hypoglycaemia had slightly reduced size of some deep grey matter structures and occipital cortical thickness compared with those who did not.
Ongoing work will explore how different aspects of child development have changed over time in this cohort, and how the MRI findings relate to child behaviour.
For more information about the study, or to make an enquiry, email the study team at CHYLD@auckland.ac.nz
Shah R, Dai DWT, Alsweiler JM, Brown GTL, Chase JG, Gamble GD, Harris DL, Keegan P, Nivins S, Wouldes TA, Thompson B, Turuwhenua J, Harding JE, McKinlay CJD for the Children with HYpoglycaemia and Their Later Development (CHYLD) Study team. Association of neonatal hypoglycemia with academic performance in mid-childhood. JAMA 327: 1158-1170, 2022. DOI:10.1001/jama.2022.0992
Nivins S, Kennedy E, Thompson B, Gamble GD, Alsweiler JM, Metcalfe R, McKinlay CJD, Harding JE for the Children with Hypoglycemia and their Later Development (CHYLD) Study Group. Associations between neonatal hypoglycaemia and brain volumes, cortical thickness and white matter microstructure in mid-childhood: An MRI study. Neuroimage: Clinical 33: 102943, 2022. https://doi.org/10.1016/j.nicl.2022.102943
Shah R, Brown GTL, Keegan P, Harding JE, McKinlay CJD on behalf of the CHYLD Study Group. School readiness screening and educational achievement at 9-10 years of age. Journal of Paediatrics and Child Health 57: 1929-1935, 2021. DOI:10.1111/jpc.15616
Paudel N, Thompson B, Chakraborty A, Harding JE, Jacobs RJ, Wouldes TA, Yu STY, Anstice NS on behalf of the CHYLD Study Team. Relationship between visual and neurodevelopmental measures at two years with visual acuity and stereopsis at 4.5 years in children born at risk of neonatal hypoglycaemia. Opthalmic and Physiological Optics 42: 195-204, 2021. DOI: 10.1111/opo.12910
Shah R, Harding JE, Brown J, McKinlay CJD. Neonatal glycemia and neurodevelopmental outcomes: A systematic review and meta-analysis. Neonatology 115:116–126, 2019. DOI:10.1159/000492859
McKinlay, C.J.D., Alsweiler, J.M., Anstice, N.S., Burakevych, N., Chakraborty, A., Chase, J.G., Gamble, G.D., Harris, D.L., Jacobs, R.J., Jiang, Y., Paudel, N., San Diego, R.J., Thompson, B., Wouldes, T.A., Harding, J.E. (2017). Association of neonatal glycemia with neurodevelopmental outcomes at 4.5 years. JAMA Pediatrics, 171 (10), 972-983. DOI: 10.1001/jamapediatrics.2017.1579
McKinlay, C.J.D., Alsweiler, J.M., Ansell, J.M., Anstice, N.S., Chase, J.G., Gamble, G.D., Harris, D.L., Jacobs, R.J., Jiang, Y., Paudel, N., Signal, M., Thompson, B., Wouldes, T.A., Yu, T.-Y., Harding, J.E. (2015). Neonatal glycemia and neurodevelopmental outcomes at 2 years. New England Journal of Medicine, 373 (16), 1507-1518. DOI:10.1056/NEJMoa1504909
Burakevych N, McKinlay CJD, Alsweiler JM, Wouldes TA, Harding JE for the CHYLD Study team. Pre-school screening for developmental and emotional health: Comparison with neurodevelopmental assessment. Journal of Paediatrics and Child Health 52, 600-607, 2016. doi:10.1111/jpc.13169
Burakevych N, McKinlay CJD, Alsweiler JM, Wouldes TA, Harding JE for the CHYLD Study team. BAYLEY-III motor scale and neurological examination at 2 years do not predict motor skills at 4.5 years. Developmental Medicine and Child Neurology 59: 216-223, 2017. DOI: 10.1111/dmcn.13232.
Harris, D. L., Weston, P. J., Harding, J. E., Signal, M., & Chase, J. G. (2013). Dextrose gel for neonatal hypoglycaemia (the Sugar Babies Study): A randomised, double-blind, placebo-controlled trial. The Lancet, 382 (9910), 2077-208310.1016/S0140-6736(13)61645-1