title: Neurodevelopmental delay with critical congenital heart disease is mainly from prenatal injury not infant cardiac surgery: current evidence based on a meta-analysis of functional magnetic resonance imaging.
abstract: OBJECTIVE
  No consensus has been reached regarding whether brain injury related to congenital heart disease (CHD) is caused by infant cardiac surgery and/or prenatal injury resulting from the CHD. We performed this meta-analysis to identify the likely cause of neurodevelopmental delay in CHD patients.
  
  
  METHODS
  We carried out a literature search without language restriction in December 2013, retrieving records from PubMed, EMBASE, the Cochrane Library and the World Health Organization trials center, to identify studies applying functional magnetic resonance imaging (fMRI) evaluation of brain function before surgery and, in some cases, after surgery (both immediate term and short term postoperatively). The preoperative and postoperative fMRI results were extracted, and meta-analysis was performed using Revman 5.1.1 and STATA 11.0, according to the guidelines from the Cochrane review and MOOSE groups.
  
  
  RESULTS
  The electronic search yielded 937 citations. Full text was retrieved for 15 articles and eight articles (nine studies) were eligible for inclusion: six studies (n = 312 cases) with fMRI analysis before surgery and three (n = 36 cases) with complete perioperative fMRI analysis. The overall average diffusivity of CHD cases was significantly higher than that of controls, with a summarized standard (std) mean difference of 1.39 (95% CI, 0.70-2.08), and the fractional anisotropy was lower in CHD cases, with a summarized mean difference of -1.43 (95% CI, -1.95 to -0.91). N-acetylaspartate (NAA)/choline (Cho) for the whole brain was significantly lower in CHD cases compared with healthy ones, while lactate/Cho was significantly higher in CHD cases. Immediate term postoperatively, significant changes in NAA/creatine and NAA/Cho, relative to preoperative values, were found. However, the difference did not persist at the short-term follow-up.
  
  
  CONCLUSIONS
  This meta-analysis suggests that the delay in neurological development in newborns with CHD is due mainly to prenatal injury, and cardiac surgery might lead to mild brain injuries postoperatively, but fMRI shows recovery within a short period.
authors.affiliation: Department of Pediatric Cardiovascular Disease, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.|Ministry of Education Key Laboratory of Women and Children's Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.|West China Medical School, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: West China Medical School, Sichuan University, Chengdu, Sichuan, China.
authors.forename: S
authors.initials: S
authors.lastname: Yin
authors.affiliation: West China Stomatology School, Sichuan University, Chengdu, Sichuan, China.
authors.forename: J
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Pediatric Cardiovascular Disease, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.|Ministry of Education Key Laboratory of Women and Children's Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.|Program for Changjiang Scholars and Innovative Research Team in University, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Hua
authors.affiliation: Department of Pediatric Cardiovascular Disease, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.|Ministry of Education Key Laboratory of Women and Children's Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.|West China Medical School, Sichuan University, Chengdu, Sichuan, China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pediatric Cardiovascular Disease, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.|Ministry of Education Key Laboratory of Women and Children's Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.|Program for Changjiang Scholars and Innovative Research Team in University, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: D
authors.initials: D
authors.lastname: Mu
authors.affiliation: Department of Pediatric Cardiovascular Disease, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.|Ministry of Education Key Laboratory of Women and Children's Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.|Program for Changjiang Scholars and Innovative Research Team in University, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: K
authors.initials: K
authors.lastname: Zhou
mesh_terms: D001930:Brain Injuries / Q000209:etiology* / Q000473:pathology; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D005260:Female; D006330:Heart Defects, Congenital / Q000150:complications* / Q000601:surgery; D006801:Humans; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D065886:Neurodevelopmental Disorders / Q000209:etiology* / Q000473:pathology; D011247:Pregnancy; D049188:Prenatal Injuries
keywords: cardiac surgery; congenital; heart defects; magnetic resonance imaging; meta-analysis; neurological development