Congenital - Neurodevelopment
- Mannose-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.
- 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.
- Early last year, Kim and colleagues1 presented a study entitled, “Autosomal Dominant Mannose-Binding Lectin Deficiency Is Associated With Worse Neurodevelopmental Outcomes After Cardiac Surgery in Infants.” The article was published soon after, statistically robust and supported by biologically plausible literature. In brief, the article reported that a common genetic variant in human MBL2 (rs1800450) was associated with increased developmental problems after cardiac surgery. In this issue of the Journal, the same authors examine multiple cohorts for associations of rs1800450 with psychomotor developmental index, mental developmental index, and functional status.
- Wherever a doctor cannot do good, he [or she] must be kept from doing harm. Hippocrates Epidemics (as paraphrased by Auden and Kronenberger1)
- There is considerable variability in anticoagulation use in neonates with transposition of the great arteries (TGA) and single ventricle physiology (SVP) for secondary stroke prevention and primary cardiovascular indications. Leveraging cross-center differences in anticoagulation use, we compared the risk of new postoperative brain injury in neonates with TGA and SVP treated with anticoagulation relative to untreated neonates.
- Neurodevelopmental impairments are common in survivors of complex congenital heart disease.1 Studies with magnetic resonance imaging have identified neonatal brain injury2 and delays in brain development beginning in the third trimester of fetal life.3,4 The etiology of fetal brain immaturity in congenital heart disease (CHD) is an ongoing topic of debate, with many invoking chronic fetal hypoxia as the cause5 and others suggesting that cerebral blood flow or nutrition, specifically glucose delivery to the brain, is impaired.
- Neurodevelopmental disability is the most significant complication for survivors of infant surgery for congenital heart disease. In this study we sought to determine if perioperative circulating brain injury biomarker levels are associated with neurodevelopmental outcomes at 12 months.
- The article by Lawrence and colleagues1 from Children's Hospital of Philadelphia in this issue of the Journal describes an interesting and innovative laboratory study. The authors have applied the “artificial womb” that has been developed by the fetal research group at the Children's Hospital of Philadelphia. This is a closed system that circulates an artificial amniotic fluid and supplies parenteral nutrition to a fetal lamb. It achieves gas transfer using a simple neonatal oxygenator connected to the umbilical vessels with no pump support other than the fetal circulation.
- We tested the hypothesis that chronic fetal hypoxia, at a severity present in many types of congenital heart disease, would lead to abnormal neurodevelopment.