Back to the drawing board

Abstract

Authors have nothing to disclose with regard to commercial support. Authors have nothing to disclose with regard to commercial support. Neonates and infants with complex congenital heart disease are at increased risk for adverse neurodevelopmental outcomes relative to children without heart disease. If risk factors for such adverse outcomes could be identified, alternative treatment approaches tailored to different phenotypes might be developed. Further, insights about the mechanistic explanation for adverse outcomes associated with certain risk factors may suggest strategies to mitigate the potential deleterious impact of the risk factor. In this context, a recent report describing worse neurodevelopmental outcomes after congenital heart surgery in patients with mannose-binding lectin (MBL) deficiency was particularly intriguing.1Kim D.S. Li Y.K. Kim J.H. Bergquist C.S. Gerdes M. Bernbaum J.C. et al.Autosomal dominant mannose-binding lectin deficiency is associated with worse neurodevelopmental outcomes after cardiac surgery in infants.J Thorac Cardiovasc Surg. 2018; 155: 1139-1147Abstract Full Text Full Text PDF Scopus (10) Google Scholar Interestingly, there was also a suggestion in the report that this association may be age related, in that the association was greatest in younger patients. As with any novel observation, the findings must be validated and confirmed; unfortunately, however, the same investigators were unable to do so when they studied mannose-binding lectin deficiency in 2 similar populations.2Kim D.S. Newberger J.W. Bellinger D.C. et al.Failure to validate association of mannose-binding lectin (MBL) deficiency with adverse outcomes after cardiac surgery in infants.J Thorac Cardiovasc Surg. 2019; 157: e397-e398Abstract Full Text Full Text PDF Scopus (2) Google Scholar Indeed, mannose-binding lectin deficiency actually appeared to be neuroprotective in certain subpopulations. Although the original observation was not confirmed in the validation study, we believe that the follow-up report by Kim and colleagues2Kim D.S. Newberger J.W. Bellinger D.C. et al.Failure to validate association of mannose-binding lectin (MBL) deficiency with adverse outcomes after cardiac surgery in infants.J Thorac Cardiovasc Surg. 2019; 157: e397-e398Abstract Full Text Full Text PDF Scopus (2) Google Scholar is nonetheless very valuable. Most fundamentally, investigators interested in neurodevelopment can be confident that they have the most current information available. Perhaps even more importantly, the community must acknowledge the intellectual rigor of Kim and colleagues2Kim D.S. Newberger J.W. Bellinger D.C. et al.Failure to validate association of mannose-binding lectin (MBL) deficiency with adverse outcomes after cardiac surgery in infants.J Thorac Cardiovasc Surg. 2019; 157: e397-e398Abstract Full Text Full Text PDF Scopus (2) Google Scholar in “correcting” the record. All too often, a promising initial report appears in the literature, but no confirmatory (or contradictory) sequel is available. Is this because no validation study was done? Or is it because the attempt at replication was unsuccessful, and a negative study was less attractive to both investigators and editors? In an era in which trust in the scientific community can no longer be taken for granted (if it ever was), Kim and colleagues2Kim D.S. Newberger J.W. Bellinger D.C. et al.Failure to validate association of mannose-binding lectin (MBL) deficiency with adverse outcomes after cardiac surgery in infants.J Thorac Cardiovasc Surg. 2019; 157: e397-e398Abstract Full Text Full Text PDF Scopus (2) Google Scholar have provided both first-class science and an example of how to “do it right.” They are to be applauded for providing what the noted sage Paul Harvey might have called “the rest of the story.” Failure to validate association of mannose-binding lectin deficiency with adverse neurodevelopmental outcomes after cardiac surgery in infantsThe Journal of Thoracic and Cardiovascular SurgeryVol. 157Issue 6PreviewMannose-binding lectin (MBL) is an acute-phase reactant that activates the complement system. A genetic variant of MBL2, rs1800450, with a minor allele frequency of approximately 14%, is associated with the protein change MBL2Gly54Asp and causes autosomal dominant MBL deficiency. We recently reported in this Journal that rs1800450 was associated with increased pervasive developmental problems after cardiac surgery at 4-year follow-up.1 Most initial reports of genotype-phenotype associations are not subsequently validated. Full-Text PDF Open Archive