Association of Congenital Heart Disease and Neurodevelopmental Disorders: an Observational and Mendelian Randomization Study

Overview

Journal Ital J Pediatr

Publisher Biomed Central

Specialty Pediatrics

Date 2024 Apr 8

PMID 38589916

Authors

Zhi-Yuan Liu

Qiong-Qiong Wang

Xian-Yong Pang

Xiao-Bi Huang

Gui-Ming Yang

Sheng Zhao

Affiliations

Soon will be listed here.

Abstract

Background: This study aims to thoroughly study the connection between congenital heart disease (CHD) and neurodevelopmental disorders (NDDs) through observational and Mendelian randomization (MR) designs.

Methods: This observational study uses data from the National Survey of Children's Health (2020-2021). Multivariable logistic regression and propensity score matching (PSM) were performed to analyze the association. PSM was used to minimize bias for covariates such as age, race, gender, maternal age, birth weight, concussion or brain injury, preterm birth, cerebral palsy, Down syndrome, and other inherited conditions. In MR analyses, inverse variance-weighted measures, weighted median, and MR-Egger were employed to calculate causal effects.

Results: A total of 85,314 children aged 0-17 were analyzed in this study. In regression analysis, CHD (p = 0.04), the current heart condition (p = 0.03), and the severity of current heart condition (p < 0.05) had a suggestive association with speech or language disorders. The severity of current heart condition (p = 0.08) has a potential statistically significant association with attention deficit hyperactivity disorder(ADHD). In PSM samples, ADHD(p = 0.003), intellectual disability(p = 0.012), and speech or language disorders(p < 0.001) were all significantly associated with CHD. The severity of current heart condition (p < 0.001) also had a significant association with autism. MR analysis did not find causality between genetically proxied congenital cardiac malformations and the risk of NDDs.

Conclusions: Our study shows that children with CHD have an increased risk of developing NDDs. Heart conditions currently and severity of current heart conditions were also significantly associated with these NDDs. In the future, we need to try more methods to clarify the causal relationship between CHD and NDDs.

Citing Articles

A case report of spastic diplegic cerebral palsy in a late preterm child with hypoplastic left heart syndrome.

Escapita A, Thomas J, Johnson T Transl Pediatr. 2024; 13(7):1258-1265.

PMID: 39144425 PMC: 11320016. DOI: 10.21037/tp-24-57.

References

McQuillen P, Goff D, Licht D . Effects of congenital heart disease on brain development. Prog Pediatr Cardiol. 2010; 29(2):79-85. PMC: 2927012. DOI: 10.1016/j.ppedcard.2010.06.011. View

von Rhein M, Dimitropoulos A, Valsangiacomo Buechel E, Landolt M, Latal B . Risk factors for neurodevelopmental impairments in school-age children after cardiac surgery with full-flow cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2012; 144(3):577-83. DOI: 10.1016/j.jtcvs.2012.02.005. View

Grove J, Ripke S, Als T, Mattheisen M, Walters R, Won H . Identification of common genetic risk variants for autism spectrum disorder. Nat Genet. 2019; 51(3):431-444. PMC: 6454898. DOI: 10.1038/s41588-019-0344-8. View

Sananes R, Manlhiot C, Kelly E, Hornberger L, Williams W, MacGregor D . Neurodevelopmental outcomes after open heart operations before 3 months of age. Ann Thorac Surg. 2012; 93(5):1577-83. DOI: 10.1016/j.athoracsur.2012.02.011. View

Demontis D, Walters R, Martin J, Mattheisen M, Als T, Agerbo E . Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nat Genet. 2018; 51(1):63-75. PMC: 6481311. DOI: 10.1038/s41588-018-0269-7. View

Sigmon E, Kelleman M, Susi A, Nylund C, Oster M . Congenital Heart Disease and Autism: A Case-Control Study. Pediatrics. 2019; 144(5). DOI: 10.1542/peds.2018-4114. View

Paternoster L, Tilling K, Davey Smith G . Genetic epidemiology and Mendelian randomization for informing disease therapeutics: Conceptual and methodological challenges. PLoS Genet. 2017; 13(10):e1006944. PMC: 5628782. DOI: 10.1371/journal.pgen.1006944. View

Gilboa S, Salemi J, Nembhard W, Fixler D, Correa A . Mortality resulting from congenital heart disease among children and adults in the United States, 1999 to 2006. Circulation. 2010; 122(22):2254-63. PMC: 4911018. DOI: 10.1161/CIRCULATIONAHA.110.947002. View

Wier M, Yoshida C, Odouli R, Grether J, Croen L . Congenital anomalies associated with autism spectrum disorders. Dev Med Child Neurol. 2006; 48(6):500-7. DOI: 10.1017/S001216220600106X. View

10.

Davies N, Holmes M, Davey Smith G . Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. 2018; 362:k601. PMC: 6041728. DOI: 10.1136/bmj.k601. View

11.

Tsao P, Lee Y, Jeng M, Hsu J, Huang K, Tsai S . Additive effect of congenital heart disease and early developmental disorders on attention-deficit/hyperactivity disorder and autism spectrum disorder: a nationwide population-based longitudinal study. Eur Child Adolesc Psychiatry. 2017; 26(11):1351-1359. DOI: 10.1007/s00787-017-0989-8. View

12.

Dent C, Spaeth J, Jones B, Schwartz S, Glauser T, Hallinan B . Brain magnetic resonance imaging abnormalities after the Norwood procedure using regional cerebral perfusion. J Thorac Cardiovasc Surg. 2005; 130(6):1523-30. DOI: 10.1016/j.jtcvs.2005.07.051. View

13.

Burgess S, Thompson S . Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017; 32(5):377-389. PMC: 5506233. DOI: 10.1007/s10654-017-0255-x. View

14.

Bergemann A, Hansen J, Rotermann I, Voges I, Scheewe J, Otto-Morris C . Neuropsychological performance of school-aged children after staged surgical palliation of hypoplastic left heart syndrome. Eur J Cardiothorac Surg. 2014; 47(5):803-11. DOI: 10.1093/ejcts/ezu299. View

15.

Davey Smith G, Ebrahim S . 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease?. Int J Epidemiol. 2003; 32(1):1-22. DOI: 10.1093/ije/dyg070. View

16.

Cassidy A, Newburger J, Bellinger D . Learning and Memory in Adolescents With Critical Biventricular Congenital Heart Disease. J Int Neuropsychol Soc. 2017; 23(8):627-639. DOI: 10.1017/S1355617717000443. View

17.

Brosig C, Bear L, Allen S, Simpson P, Zhang L, Frommelt M . Neurodevelopmental outcomes at 2 and 4 years in children with congenital heart disease. Congenit Heart Dis. 2018; 13(5):700-705. PMC: 6289798. DOI: 10.1111/chd.12632. View

18.

Sanderson E . Multivariable Mendelian Randomization and Mediation. Cold Spring Harb Perspect Med. 2020; 11(2). PMC: 7849347. DOI: 10.1101/cshperspect.a038984. View

19.

Jin S, Homsy J, Zaidi S, Lu Q, Morton S, DePalma S . Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands. Nat Genet. 2017; 49(11):1593-1601. PMC: 5675000. DOI: 10.1038/ng.3970. View

20.

Benyamin B, Pourcain B, Davis O, Davies G, Hansell N, Brion M . Childhood intelligence is heritable, highly polygenic and associated with FNBP1L. Mol Psychiatry. 2013; 19(2):253-8. PMC: 3935975. DOI: 10.1038/mp.2012.184. View