A review on neurodevelopmental abnormalities in congenital heart disease: focus on minimizing the deleterious effects on patients

Figures & data

Table 1. Summarized findings of different interventions on neurodevelopmental abnormalities in children undergoing heart surgery.

S. No	Interventions	Type of study	Results	References
Non-Pharmacological Interventions
1.	Feeding Mode	Retrospective cohort study (n = 208)	Lesser neurodevelopment delay in orally fed children in comparison to enteral tube-fed children	Holst et al. (2019)
2.	Feeding Mode	Retrospective cohort study (n = 194)	Infants on oral feedings developed lesser neurodevelopmental impairment in comparison to infants on G-tube feedings	Jadcherla et al. (2017)
Pharmacological Interventions
3.	Dexmedetomidine	Retrospective cohort study (n = 12,142)	Patients had improved outcomes in patients receiving dexmedetomidine	Schwartz et al. (2016)
		Randomized, single-blind study (n = 80)	Decreased levels of neuron-specific enolase and S-100β protein along with improvement in oxygen metabolism suggesting reduced brain injury	Gong et al. (2019)
		Retrospective study (n = 256)	Significant preservation of intelligence quotient and neurodevelopment undergoing surgery	Huang et al. (2020)
4.	Erythropoietin	Prospective phase I/II clinical trial (n = 42)	No neurological protection from erythropoietin	Andropoulos et al. (2013)
5.	Ketamine	Randomized clinical study (n = 24)	No significant differences in the expression of cytokines, chemokines, S100, and neuron-specific enolase between ketamine-treated and placebo	Bhutta et al. (2012)
6.	Dextromethorphan	Randomized, placebo-controlled trial (n = 13)	Treatment with dextromethorphan exhibited fewer brain abnormalities, however, the effects were not significantly different in comparison to placebo	Schmitt et al. (1997)
7.	Allopurinol	Single centered, randomized, placebo-controlled, blinded trial	Ketamine produced neuroprotection in higher-risk HLHS patients without any significant effect in lower risk, non-HLHS infants	Clancy et al. (2001)
8.	Anticoagulants	Two-center, observational cohort study (n = 118)	No benefit of preventing brain injury with the use of anticoagulation	Leijser et al. (2019)

Holst LM, Serrano F, Shekerdemian L, Ravn HB, Guffey D, Ghanayem NS, Monteiro S. 2019. Impact of feeding mode on neurodevelopmental outcome in infants and children with congenital heart disease. Congenit Heart Dis. 14:1207–1213. doi:10.1111/chd.12827.

 Web of Science ®Google Scholar

Jadcherla SR, Khot T, Moore R, Malkar M, Gulati IK, Slaughter JL. 2017. Feeding methods at discharge predict long-term feeding and neurodevelopmental outcomes in preterm infants referred for gastrostomy evaluation. J. Pediatr. 181:125–130.e1. doi:10.1016/j.jpeds.2016.10.065.

 PubMed Web of Science ®Google Scholar

Schwartz LI, Twite M, Gulack B, Hill K, Kim S, Vener DF. 2016. The perioperative use of dexmedetomidine in pediatric patients with congenital heart disease: an analysis from the congenital cardiac anesthesia society-society of thoracic surgeons congenital heart disease database. Anesth Analg. 123:715–721. doi:10.1213/ANE.0000000000001314.

 Web of Science ®Google Scholar

Gong J, Zhang R, Shen L, Xie Y, Li X. 2019. The brain protective effect of dexmedetomidine during surgery for paediatric patients with congenital heart disease. J Int Med Res. 47:1677–1684. doi:10.1177/0300060518821272.

 Web of Science ®Google Scholar

Huang J, Gou B, Rong F, Wang W. 2020. Dexmedetomidine improves neurodevelopment and cognitive impairment in infants with congenital heart disease. Per Med. 17:33–41. doi:10.2217/pme-2019-0003.

 Web of Science ®Google Scholar

Andropoulos DB, Easley RB, Brady K, McKenzie ED, Heinle JS, Dickerson HA, Shekerdemian LS, Meador M, Eisenman C, Hunter JV, et al. 2013. Neurodevelopmental outcomes after regional cerebral perfusion with neuromonitoring for neonatal aortic arch reconstruction. Ann Thorac Surg. 95:648–655. doi:10.1016/j.athoracsur.2012.04.070.

 Web of Science ®Google Scholar

Bhutta AT, Schmitz ML, Swearingen C, James LP, Wardbegnoche WL, Lindquist DM, Glasier CM, Tuzcu V, Prodhan P, Dyamenahalli U, et al. 2012. Ketamine as a neuroprotective and anti-inflammatory agent in children undergoing surgery on cardiopulmonary bypass: a pilot randomized, double-blind, placebo-controlled trial. Pediatr Crit Care Med. 13:328–337. doi:10.1097/PCC.0b013e31822f18f9.

 Web of Science ®Google Scholar

Schmitt B, Bauersfeld U, Fanconi S, Wohlrab G, Huisman TA, Bandtlow C, Baumann P, Superti-Furga A, Martin E, Arbenz U, et al. 1997. The effect of the N-methyl-D-aspartate receptor antagonist dextromethorphan on perioperative brain injury in children undergoing cardiac surgery with cardiopulmonary bypass: results of a pilot study. Neuropediatrics. 28:191–197. doi:10.1055/s-2007-973699.

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Clancy RR, McGaurn SA, Goin JE, Hirtz DG, Norwood WI, Gaynor JW, Jacobs ML, Wernovsky G, Mahle WT, Murphy JD, et al. 2001. Allopurinol neurocardiac protection trial in infants undergoing heart surgery using deep hypothermic circulatory arrest. Pediatr. 108:61–70. doi:10.1542/peds.108.1.61.

 PubMed Web of Science ®Google Scholar

Leijser LM, Chau V, Seed M, Poskitt KJ, Synnes A, Blaser S, Au-Young SH, Hickey EJ, Campbell A, McQuillen PS, Miller SP. 2019. Anticoagulation therapy and the risk of perioperative brain injury in neonates with congenital heart disease. J Thorac Cardiovasc Surg. 157:2406–2413.e2. doi:10.1016/j.jtcvs.2019.02.029.

 Web of Science ®Google Scholar

Data availability statement

The data will be available on request.