Impact of Chronic Hypoxia on Neurodevelopment of Children with Cyanotic Congenital Heart Disease

Document Type: Original article

Authors

1 Children’s Medical Centre, Paediatric Centre of Excellence, Tehran University of Medical Sciences (TUMS), Tehran, Iran

2 Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran

Abstract

Background: Children with cyanotic Congenital Heart Disease (CHD) are at higher risk for delay in their growth and development due to more energy consumption during their activities. In addition, they are more prone to respiratory infection and hospitalization. Due to the nature of disease, these patients suffer from a chronic hypoxia and its impact on growth and development is not well investigated. This study was designed to find out which physical growth and neurodevelopmental parameters of these patients are affected by chronic hypoxia in comparison with acyanotic disease.
Methods: 81 children with CHD (34 cyanotic and 47 acyanotic), aged between 6 months to 3 years from Children’s Medical Center affiliated to Tehran University of Medical Sciences in Tehran were recruited from January 2013 to January 2014. Growth parameters including weight, height, and head circumference were checked and then these indices were categorized into three groups of Failure To Thrive (FTT). Functional development was assessed by using modified Denver Developmental Screening Test (DDST II).
Results: In acyanotic group, Ventricular Septal Defect (VSD) and in the cyanotic group, tetralogy of fallot (TOF) were the most prevalent disorders. Growth indices were low in 52% of patients (70% of cyanotic and 38.2% acyanotic), and also weight and height parameters were significantly lower in the cyanotic group (p= 0.009 and p= 0.05).
62% of cyanotic patients and 17% of acyanotic patients had delay at least in one of their neurological development indices (Gross motor, fine motor, speech or psychosocial behavior). This study also demonstrates an association between neurodevelopment delay and FTT in cyanotic patients, but not in acyanotic ones.
Conclusion: Results in this study suggest that children with cyanotic CHD are more prone to delay in their development besides their growth possibly due to the nature of their disease. Therefore, chronic hypoxia can be a risk factor influencing neurodevelopment of the patients and appropriate intervention is required to gain better outcome.

Keywords


1. Botto LD. Epidemiology and prevention of congenital heart defects. Congenital Heart Disease: Karger Publishers 2015.p.28-45.
2. Hoffman J. The global burden of congenital heart disease. Cardiovasc J Afr 2013;24(4):141-5.
3. Rahim F, Ebadi A, Saki G, Remazani A. Prevalence of congenital heart disease in Iran: a clinical study. J Med Sci 2008;8(6):547-52.
4. McKenzie ED, Andropoulos DB, DiBardino D, Fraser CD, Jr. Congenital heart surgery 2005: the brain: it’s the heart of the matter. Am J Surg 2005;190(2):289-94.
5. Jerrell JM, Shuler CO, Tripathi A, Black GB, Park YM. Long-term neurodevelopmental outcomes in children and adolescents with congenital heart disease. Prim Care Companion CNS Disord 2015;17(5).
6. Snookes SH, Gunn JK, Eldridge BJ, Donath SM, Hunt RW, Galea MP, et al. A systematic review of motor and cognitive outcomes after early surgery for congenital heart disease. Pediatrics 2010;125(4):e818-27.
7. Donofrio MT, Duplessis AJ, Limperopoulos C. Impact of congenital heart disease on fetal brain development and injury. Curr Opin Pediatr 2011;23(5):502-11.
8. Majnemer A, Limperopoulos C, Shevell MI, Rohlicek C, Rosenblatt B, Tchervenkov C. A new look at outcomes of infants with congenital heart disease. Pediatr Neurol 2009;40(3):197-204.
9. Miller SP, McQuillen PS, Vigneron DB, Glidden DV, Barkovich AJ, Ferriero DM, et al. Preoperative brain injury in newborns with transposition of the great arteries. Ann Thorac Surg 2004;77(5):1698-706.
10. Limperopoulos C, Majnemer A, Shevell MI, Rosenblatt B, Rohlicek C, Tchervenkov C. Neurodevelopmental status of newborns and infants with congenital heart defects before and after open heart surgery. J Pediatr 2000;137(5):638-45.
11. Limperopoulos C, Majnemer A, Shevell MI, Rohlicek C, Rosenblatt B, Tchervenkov C, et al. Predictors of developmental disabilities after open heart surgery in young children with congenital heart defects. J Pediatr 2002;141(1):51-8.
12. Limperopoulos C, Majnemer A, Shevell MI, Rosenblatt B, Rohlicek C, Tchervenkov C. Neurologic status of newborns with congenital heart defects before open heart surgery. Pediatrics 1999;103(2):402-8.
13. Khalil A, Suff N, Thilaganathan B, Hurrell A, Cooper D, Carvalho JS. Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2014;43(1):14-24.
14. Marino BS, Lipkin PH, Newburger JW, Peacock G, Gerdes M, Gaynor JW, et al. Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association. Circulation 2012;126(9):1143-72.
15. Dinleyici EC, Kilic Z, Buyukkaragoz B, Ucar B, Alatas O, Aydogdu SD, et al. Serum IGF-1, IGFBP-3 and growth hormone levels in children with congenital heart disease: relationship with nutritional status, cyanosis and left ventricular functions. Neuro Endocrinol Lett 2007;28(3):279-83.
16. Varan B, Tokel K, Yilmaz G. Malnutrition and growth failure in cyanotic and acyanotic congenital heart disease with and without pulmonary hypertension. Arch Dis Child 1999;81(1):49-52.
17. Zechel JL, Gamboa JL, Peterson AG, Puchowicz MA, Selman WR, Lust WD. Neuronal migration is transiently delayed by prenatal exposure to intermittent hypoxia. Birth Defects Res B Dev Reprod Toxicol 2005;74(4):287-99.
18. Dalili M, Meraji SM, Davari P, Moghaddam MY, Abkenar HB, Vahidi A, et al. Growth status of Iranian children with hemodynamically important congenital heart disease. Acta Med Iran 2011;49(2):103-8.
19. Hosseini F, Borzouei B, Vahabian M. Failure to thrive severity determination by new design curves in standard growth charts. Acta Med Iran 2011;49(12):795-800.
20. Shahshahani S, Vameghi R, Azari N, Sajedi F, Kazemnejad A. Validity and Reliability Determination of Denver Developmental Screening Test-II in 0-6 Year-Olds in Tehran. Iran J Pediatr 2010;20(3):313-22.
21. Anderson JB, Beekman III RH. Addressing Nutrition and Growth in Children with Congenital Heart Disease. Pediatric and Congenital Cardiac Care: Springer 2015.p.153-63.
22. Daymont C, Neal A, Prosnitz A, Cohen MS. Growth in children with congenital heart disease. Pediatrics 2013;131(1):e236-42.
23. Lata K, Mishra D, Mehta V, Juneja M. Neurodevelopmental Status of Children Aged 6-30 Months With Congenital Heart Disease. Indian Pediatr 2015;52(11):957-60.
24. Costello CL, Gellatly M, Daniel J, Justo RN, Weir K. Growth Restriction in Infants and Young Children with Congenital Heart Disease. Congenit Heart Dis. 2015;10(5):447-56.
25. Medoff-Cooper B, Ravishankar C. Nutrition and growth in congenital heart disease: a challenge in children. Curr Opin Cardiol 2013;28(2):122-9.
26. van Houten JP, Rothman A, Bejar R. High incidence of cranial ultrasound abnormalities in full-term infants with congenital heart disease. Am J Perinatol 1996;13(1):47-53.
27. Sun L, Macgowan CK, Sled JG, Yoo SJ, Manlhiot C, Porayette P, et al. Reduced fetal cerebral oxygen consumption is associated with smaller brain size in fetuses with congenital heart disease. Circulation 2015;131(15):1313-23.
28. Polat S, Okuyaz C, Hallioglu O, Mert E, Makharoblidze K. Evaluation of growth and neurodevelopment in children with congenital heart disease. Pediatr Int 2011;53(3):345-9.
29. Stieh J, Kramer HH, Harding P, Fischer G. Gross and fine motor development is impaired in children with cyanotic congenital heart disease. Neuropediatrics 1999;30(2):77-82.
30. Yilmaz IZ, Erdur BC, Ozbek E, Mese T, Karaarslan U, Genel F. Neurodevelopmental evaluation of children with cyanotic congenital heart disease. Minerva Pediatr 2018 Aug;70(4):365-70.