Abstract
In this retrospective nationwide population-based case–control study, we investigated the impact of congenital heart disease (CHD) on the development of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), which remains unclear. Children aged <18 years that were diagnosed with CHD (n = 3552) between January 1, 1997 and December 31, 2009 were identified from the National Health Insurance Research Database in Taiwan. Non-CHD controls (n = 14,208) matched for age and sex (1:4) were selected from the same dataset. All subjects were observed until December 31, 2011 or their death. Comorbid perinatal conditions and early developmental disorders (EDD) that were diagnosed before ADHD and ASD diagnosis were also analyzed. The incidence rates of perinatal comorbidities, EDD, ADHD, and ASD were higher in the CHD group than in the control group. Multivariate Cox regression analysis revealed that the CHD group had an increased risk of developing ADHD (adjusted hazard ratio [aHR] 2.52, 95% confidence interval CI 1.96–3.25) and ASD (aHR 1.97, 95% CI 1.11–3.52) after adjusting for confounding comorbidities. EDD, but not perinatal comorbidities were also independent risk factors for ADHD and ASD after adjustment. Subgroup analysis indicated that the risk for ADHD (HR 16.59, 95% CI 12.17–22.60) and ASD (HR 80.68, 95% CI 39.96–176.12) was greatly increased in CHD subjects with EDD than in non-CHD subjects without EDD. These findings suggested that CHD at birth and EDD during early childhood were two independent risk factors for ADHD and ASD and that concurrent CHD and EDD might additively increase these risks.
Similar content being viewed by others
References
van der Linde D, Konings EE, Slager MA, Witsenburg M, Helbing WA, Takkenberg JJ, Roos-Hesselink JW (2011) Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol 58:2241–2247
Wu MH, Chen HC, Lu CW, Wang JK, Huang SC, Huang SK (2010) Prevalence of congenital heart disease at live birth in Taiwan. J Pediatr 156:782–785
Yeh SJ, Chen HC, Lu CW, Wang JK, Huang LM, Huang SC, Huang SK, Wu MH (2013) Prevalence, mortality, and the disease burden of pediatric congenital heart disease in Taiwan. Pediatr Neonatol 54:113–118
Marino BS, Lipkin PH, Newburger JW, Peacock G, Gerdes M, Gaynor JW, Mussatto KA, Uzark K, Goldberg CS, Johnson Jr WH, Li J, Smith SE, Bellinger DC, Mahle WT, American Heart Association Congenital Heart Defects Committee, Council on Cardiovascular Disease in the Young, Council on Cardiovascular Nursing, and Stroke Council (2012) Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association. Circulation 126:1143–1172
Ozmen A, Terlemez S, Tunaoglu FS, Soysal S, Pektas A, Cilsal E, Koca U, Kula S, Deniz Oguz A (2016) Evaluation of neurodevelopment and factors affecting it in children with acyanotic congenital cardiac disease. Iran J Pediatr 26:e3278
Hallioglu O, Gurer G, Bozlu G, Karpuz D, Makharoblidze K, Okuyaz C (2015) Evaluation of neurodevelopment using Bayley-III in children with cyanotic or hemodynamically impaired congenital heart disease. Congenit Heart Dis 10:537–541
Jortveit J, Oyen N, Leirgul E, Fomina T, Tell GS, Vollset SE, Eskedal L, Døhlen G, Birkeland S, Holmstrøm H (2016) Trends in mortality of congenital heart defects. Congenit Heart Dis 11:160–168
Siffel C, Riehle-Colarusso T, Oster ME, Correa A (2015) Survival of children with hypoplastic left heart syndrome. Pediatrics 136:e864–e870
Boyle CA, Boulet S, Schieve LA, Cohen RA, Blumberg SJ, Yeargin-Allsopp M, Visser S, Kogan MD (2011) Trends in the prevalence of developmental disabilities in US children, 1997–2008. Pediatrics 127:1034–1042
Fayyad J, Sampson NA, Hwang I, Adamowski T, Aguilar-Gaxiola S, Al-Hamzawi A, Andrade LH, Borges G, de Girolamo G, Florescu S, Gureje O, Haro JM, Hu C, Karam EG, Lee S, Navarro-Mateu F, O’Neill S, Pennell BE, Piazza M, Posada-Villa J, Ten Have M, Torres Y, Xavier M, Zaslavsky AM, Kessler RC, WHO World Mental Health Survey Collaborators (2017) The descriptive epidemiology of DSM-IV Adult ADHD in the World Health Organization World Mental Health Surveys. Atten Defic Hyperact Disord 9:47–65
Wang LJ, Lee SY, Yuan SS, Yang CJ, Yang KC, Huang TS, Chou WJ, Chou MC, Lee MJ, Lee TL, Shyu YC (2016) Prevalence rates of youths diagnosed with and medicated for ADHD in a nationwide survey in Taiwan from 2000 to 2011. Epidemiol Psychiatr Sci 20:1–11
Lung FW, Chiang TL, Lin SJ, Shu BC (2017) Urban and education disparity for autism spectrum disorders in Taiwan birth cohort study. J Autism Dev Disord 47:599–606
Barkley RA (2002) International consensus statement on ADHD. Clin Child Fam Psych 5:89–111
Dawson G (2008) Early behavioral intervention, brain plasticity, and the prevention of autism spectrum disorder. Dev Psychopathol 20:775–803
Rappaport GC, Ornoy A, Tenenbaum A (1998) Is early intervention effective in preventing ADHD? Isr J Psychiatry Relat Sci 35:271–279
Hansen E, Poole TA, Nguyen V, Lerner M, Wigal T, Shannon K, Wigal SB, Batra AS (2012) Prevalence of ADHD symptoms in patients with congenital heart disease. Pediatr Int 54:838–843
Shillingford AJ, Glanzman MM, Ittenbach RF, Clancy RR, Gaynor JW, Wernovsky G (2008) Inattention, hyperactivity, and school performance in a population of school-age children with complex congenital heart disease. Pediatrics 121:e759–e767
Razzaghi H, Oster M, Reefhuis J (2015) Long-term outcomes in children with congenital heart disease: National Health Interview Survey. J Pediatr 166:119–124
Mari MA, Cascudo MM, Alchieri JC (2016) Congenital heart disease and impacts on child development. Braz J Cardiovasc Surg 31:31–37
Mahle WT, Wernovsky G (2001) Long-term developmental outcome of children with complex congenital heart disease. Clin Perinatol 28:235–247
Lata K, Mishra D, Mehta V, Juneja M (2015) Neurodevelopmental status of children aged 6–30 months with congenital heart disease. Indian Pediatr 52:957–960
Sterken C, Lemiere J, Van den Berghe G, Mesotten D (2016) Neurocognitive development after pediatric heart surgery. Pediatrics. doi:10.1542/peds.2015-4675
Sterken C, Lemiere J, Vanhorebeek I, Van den Berghe G, Mesotten D (2015) Neurocognition after pediatric heart surgery: a systematic review and meta-analysis. Open Heart 2:e000255
Flanagan JE, Landa R, Bhat A, Bauman M (2012) Head lag in infants at risk for autism: a preliminary study. Am J Occup Ther 66:577–585
Hatakenaka Y, Kotani H, Yasumitsu-Lovell K, Suzuki K, Fernell E, Gillberg C (2016) Infant motor delay and early symptomatic syndromes eliciting neurodevelopmental clinical examinations in Japan. Pediatr Neurol 54:55–63
Gillberg C, Steffenburg S (1987) Outcome and prognostic factors in infantile autism and similar conditions: a population-based study of 46 cases followed through puberty. J Autism Dev Disord 17:273–287
Perna R, Loughan A (2012) Early developmental delays: neuropsychological sequelae and subsequent diagnoses. Appl Neuropsychol Child 1:57–62
Chan MC, Lin CH, Kou YR (2016) Hyperlipidemia in COPD is associated with decreased incidence of pneumonia and mortality: a nationwide health insurance data-based retrospective cohort study. Int J Chron Obstr Pulm Dis 11:1053–1059
Chen CH, Xirasagar S, Lin CC, Wang LH, Kou YR, Lin HC (2011) Risk of adverse perinatal outcomes with antithyroid treatment during pregnancy: a nationwide population-based study. BJOG 118:1365–1373
Chen CH, Huang MC, Liu HC, Huang CJ, Lin HC, Kou YR (2011) Increased risk of preterm birth among women with mitral valve prolapse: a nationwide, population-based study. Ann Epidemiol 21:391–398
Rosenthal GL (1996) Patterns of prenatal growth among infants with cardiovascular malformations: possible fetal hemodynamic effects. Am J Epidemiol 143:505–513
Donofrio MT, Bremer YA, Schieken RM, Gennings C, Morton LD, Eidem BW, Cetta F, Falkensammer CB, Huhta JC, Kleinman CS (2003) Autoregulation of cerebral blood flow in fetuses with congenital heart disease: the brain sparing effect. Pediatr Cardiol 24:436–443
Rollins CK, Watson CG, Asaro LA, Wypij D, Vajapeyam S, Bellinger DC, DeMaso DR, Robertson Jr RL, Newburger JW, Rivkin MJ (2014) White matter microstructure and cognition in adolescents with congenital heart disease. J Pediatr 165:936–944, 944.e1–944.e2
Khalil A, Bennet S, Thilaganathan B, Paladini D, Griffiths P, Carvalho JS (2016) Prevalence of prenatal brain abnormalities in fetuses with congenital heart disease: systematic review. Ultrasound Obstet Gynecol 48:296–307
Donofrio MT, Massaro AN (2010) Impact of congenital heart disease on brain development and neurodevelopmental outcome. Int J Pediatr. doi:10.1155/2010/359390
Madhok AB, Ojamaa K, Haridas V, Parnell VA, Pahwa S, Chowdhury D (2006) Cytokine response in children undergoing surgery for congenital heart disease. Pediatr Cardiol 27:408–413
Sharma R, Bolger AP, Li W, Davlouros PA, Volk HD, Poole-Wilson PA, Coats AJ, Gatzoulis MA, Anker SD (2003) Elevated circulating levels of inflammatory cytokines and bacterial endotoxin in adults with congenital heart disease. Am J Cardiol 92:188–193
Oades RD, Dauvermann MR, Schimmelmann BG, Schwarz MJ, Myint AM (2010) Attention-deficit hyperactivity disorder (ADHD) and glial integrity: S100B, cytokines and kynurenine metabolism–effects of medication. Behav Brain Funct 28(6):29
Wei H, Zou H, Sheikh AM, Malik M, Dobkin C, Brown WT, Li X (2011) IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation. J Neuroinflammation 8:52
Almeida LF, Araujo Junior E, Crott GC, Okido MM, Berezowski AT, Duarte G, Maarcolin AC (2016) Epidemiological risk factors and perinatal outcomes of congenital anomalies. Rev Bras Ginecol Obstet 38:348–355
Story L, Pasupathy D, Sankaran S, Sharland G, Kyle P (2015) Influence of birthweight on perinatal outcome in fetuses with antenatal diagnosis of congenital heart disease. J Obstet Gynaecol Res 41:896–903
Pringsheim T, Sandor P, Lang A, Shah P, O’Connor P (2009) Prenatal and perinatal morbidity in children with Tourette syndrome and attention-deficit hyperactivity disorder. J Dev Behav Pediatr 30:115–121
Kim HW, Cho SC, Kim BN, Kim JW, Shin MS, Kim Y (2009) Perinatal and familial risk factors are associated with full syndrome and subthreshold attention-deficit hyperactivity disorder in a korean community sample. Psychiatry Investig 6:278–285
Say GN, Karabekiroglu K, Babadagi Z, Yuce M (2016) Maternal stress and perinatal features in autism and attention deficit/hyperactivity disorder. Pediatr Int 58:265–269
Nath S, Roy R, Mukherjee S (2012) Perinatal complications associated with autism–a case control study in a neurodevelopment and early intervention clinic. J Indian Med Assoc 110:526–529
Joseph RM, O’Shea TM, Allred EN, Heeren T, Hirtz D, Paneth N, Leviton A, Kuban KC (2017) Prevalence and associated features of autism spectrum disorder in extremely low gestational age newborns at age 10 years. Autism Res 10:224–232
Gardener H, Spiegelman D, Buka SL (2011) Perinatal and neonatal risk factors for autism: a comprehensive meta-analysis. Pediatrics 128:344–355
Acknowledgements
The authors are grateful to the Enago Editing Service for their help with language editing. This study was supported by a Grant MOST 104-2320-B-010-014-MY3 from the Ministry of Science and Technology, Taiwan.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
All authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Tsao, PC., Lee, YS., Jeng, MJ. et al. 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 26, 1351–1359 (2017). https://doi.org/10.1007/s00787-017-0989-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00787-017-0989-8