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UOG Journal Club: Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis
 

UOG Journal Club: Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis

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Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis ...

Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis

A. Khalil, N. Suff, B. Thilaganathan, A. Hurrell, D. Cooper and J.S. Carvalho

Link to free access article: http://onlinelibrary.wiley.com/doi/10.1002/uog.12526/abstract

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    UOG Journal Club: Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis UOG Journal Club: Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis Presentation Transcript

    • UOG Journal Club: January 2014 Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis A. Khalil, N. Suff, B. Thilaganathan, A. Hurrell, D. Cooper and J.S. Carvalho Volume 43, Issue 1, Date: January 2014, pages 14-24 Journal Club slides prepared by Dr. Katherine Goetzinger (UOG Editor for Trainees)
    • Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis Khalil et al., UOG 2014 • Congenital heart disease (CHD) is the leading cause of infant mortality, secondary to birth defects • As CHD mortality rates have decreased, more attention has turned to neurologic morbidities in surviving CHD neonates • While neurologic injury in CHD patients previously has been attributed to brain injury during cardiac surgery, recent studies have suggested a high incidence of abnormal neuroimaging and neurodevelopmental delay in the pre-operative setting
    • Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis Khalil et al., UOG 2014 Objective 1. To perform a systematic review to quantify the nonsurgical risk of neurodevelopmental delay and brain abnormalities in newborns and infants with CHD
    • Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis Khalil et al., UOG 2014 Methodology Systematic Review & Meta-Analysis Search Strategy: Medline, EMBASE and The Cochrane Library Study Type: Prospective/retrospective cohort studies, case-control studies and case series Inclusion Criteria: Studies reporting brain lesions on neuroimaging and/or neurodevelopmental outcomes in newborns and infants with CHD before heart surgery Outcomes: 1.Structural brain abnormalities revealed by neuroimaging 2.Abnormalities detected on neurologic assessment
    • Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis Khalil et al., UOG 2014 Methodology Systematic Review & Meta-Analysis Analysis: •Forest plots: fixed and random effects models •Between-study heterogeneity: Higgin’s I2 •Publication bias: Funnel plots, Begg and Mazumdar’s rank correlation test and the Egger test •Subgroup analysis based on lesion type •Transposition of the great vessels (TGA) •Left-sided heart lesions •Unspecified/mixed cardiac lesions
    • Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis Khalil et al., UOG 2014 Results Potentially appropriate studies identified from search (n=9129) Citations excluded based on title or abstract (n=9010) Citations retrieved for detailed evaluation of full manuscript (n=119) Studies excluded (n=100) Studies included in systematic review (n=19) Outcome: Brain abnormalities (n=13) 425 CHD cases Outcome: Neurological developmental abnormality (n=9) 512 CHD cases
    • Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis Khalil et al., UOG 2014 Results: Brain Abnormalities on Neuroimaging n/N Prevalence (95% CI) I2 p Transposition of great arteries (TGA) 21/71 34% (24-46) 0.0% 0.47 Left-sided lesions 31/46 66% (53-79) 0.0% 0.06 Mixed/unspecified lesions 292/589 46% (42-52) 18.1% 0.28 Lesion Type There was no evidence of significant publication bias Begg and Mazumdar’s rank correlation test: p=0.66 Egger test: p=0.24
    • Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis Khalil et al., UOG 2014 Results: Neurodevelopmental delay Study Newburger 1993 n/N 55/152 0.36 (0.29, 0.44) Limperopoulos 1999 28/50 0.56 (0.41, 0.70) Rufo-Campos 2003 21/83 0.25 (0.16, 0.36) Tavani 2003 7/17 0.41 (0.18, 0.67) Miller 2004 7/10 0.70 (0.35, 0.93) Dent 2006 11/17 0.65 (0.38, 0.86) Da Rocha 2009 5/20 0.25 (0.09, 0.49) Gessler 2009 12/32 0.38 (0.21, 0.56) Majnemer 2009 60/131 0.46 (0.37, 0.55) The prevalence of neurodevelopmental delay was 206/512 Combined (random) 0.42 (0.34, 0.51) 0.2 0.4 0.6 0.8 1.0 I² = 68.9% (95% CI = 22.3 to 0.0 82.8%) proportion (95% confidence interval) 42% [95% CI (34-51)] I2=68.9% There was no evidence of significant publication bias
    • Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis Khalil et al., UOG 2014 Results: Study Quality Studies Reporting Data on Neuroimaging* Studies Reporting Data on Neurodevelopmental Outcomes* Study Design 100% 78% Eligibility Criteria 100% 89% Sample Size 69% 44% Follow Up 69% 78% Efforts to Reduce Bias 92% 89% Quality Measure *Percentage of studies reporting on each quality measure
    • Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis Khalil et al., UOG 2014 Conclusions • There is a high prevalence of brain lesions on neuroimaging as well as a significant risk of pre-operative neurodevelopmental delay in CDH infants • The prevalence of brain lesions appears to be dependent on the type of CHD, with a higher prevalence noted with left-sided cardiac lesions Implications for Practice • This study highlights the importance of diagnosis of fetal CHD to allow identification of newborns at increased risk for neurodevelopmental delay • Providers may consider close periodic developmental surveillance as part of medical follow up for infants with CHD, especially left-sided lesions
    • Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis Khalil et al., UOG 2014 Strengths • Meta-analysis used to overcome small sample size issues from prior studies, allowing quantification of risk Limitations • All included studies were observational • Variable study quality • Timing of CHD diagnosis is unclear in many of the included studies • Stratified analysis based on type of lesion • No evidence of significant publication bias • No information available on prenatal neuroimaging • Strict inclusion criteria to determine eligible studies • Brain lesions on imaging do not always correlate with neurodevelopmental delay
    • Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis Khalil et al., UOG 2014 Discussion Points • • • • • • What is the biological basis for the hypothesis that CHD predisposes to brain abnormalities and neurodevelopmental delay in the newborn? Why do babies with left-sided cardiac lesions appear to be at greatest risk? How would over- or under-reporting of brain abnormalities and developmental delay affect the results of this meta-analysis? Is there a role for more detailed neuroimaging with sonography and/or MRI in fetuses with CHD? At what point in gestation should this occur? How do brain abnormalities observed on neuroimaging correlate to degree of neurodevelopmental handicap? Should pediatric providers routinely incorporate neurodevelopmental screening into their postnatal follow up of infants with CHD?