ABSTRACT
BACKGROUND: Neurodevelopmental impairment is an important consequence for survivors of surgery for critical congenital heart disease. This study sought to determine whether intraoperative methylprednisolone during neonatal cardiac surgery is associated with neurodevelopmental outcomes at 12 months of age and to identify early prognostic variables associated with neurodevelopmental outcomes. METHODS: We performed a planned secondary analysis of a 2-center, double-blind, randomized, placebo-controlled trial of intraoperative methylprednisolone in neonates undergoing cardiac surgery. A brain injury biomarker was measured during surgery. Bayley Scales of Infant and Toddler Development-III (BSID-III) were performed at 12 months of age. Two-sample t tests and generalized linear models were used. RESULTS: There were 129 participants (n = 61 methylprednisolone; n = 68 placebo). There were no significant differences in BSID-III scores and brain injury biomarker levels between treatment groups. Participants who underwent a palliative (versus corrective) procedure had lower mean BSID-III cognitive (101 ± 15 versus 106 ± 14; P = .03) and motor scores (85 ± 18 versus 94 ± 16; P < .01). Longer ventilation time was associated with lower motor scores. Longer cardiac intensive care unit stay was associated with lower cognitive, language, and motor scores. Cardiopulmonary bypass time, aortic cross-clamp time, and deep hypothermic circulatory arrest were not associated with BSID-III scores. CONCLUSIONS: Neurodevelopmental outcomes were not associated with intraoperative methylprednisolone or intraoperative variables. Participants who underwent a neonatal palliative (versus corrective) procedure had longer cardiac intensive care unit stays and worse neurodevelopmental outcomes at 1 year. This work suggests that interventions focused solely on the operative period may not be associated with a long-term neurodevelopmental benefit.
Subject(s)
Brain Injuries , Cardiac Surgical Procedures , Neurodevelopmental Disorders , Biomarkers , Cardiac Surgical Procedures/adverse effects , Humans , Infant , Infant, Newborn , Methylprednisolone/therapeutic use , Neurodevelopmental Disorders/epidemiology , Neurodevelopmental Disorders/etiology , PrognosisABSTRACT
BACKGROUND: 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. METHODS: A secondary analysis of a randomized controlled trial of neonates who underwent cardiac surgery was performed. Glial fibrillary acidic protein (GFAP) was measured: (1) before skin incision; (2) immediately after bypass; (3) 4 and (4) 24 hours postoperatively. Linear regression models were used to determine an association with the highest levels of GFAP and Bayley Scales of Infant and Toddler Development third edition (BSID) composite scores. RESULTS: There were 97 subjects who had cardiac surgery at a mean age of 9 ± 6 days and completed a BSID at 12.5 ± 0.6 months of age. Median (25th-75th percentile) levels of GFAP were 0.01 (0.01-0.02), 0.85 (0.40-1.55), 0.07 (0.05-0.11), and 0.03 (0.02-0.04) ng/mL at the 4 time points, respectively. In univariate analysis GFAP was negatively associated with cognitive, language, and motor composite scores. GFAP levels immediately after bypass differed between institutions; 1.57 (0.92-2.48) versus 0.77 (0.36-1.21) ng/mL (P = .01). After adjusting for center and potential confounders, GFAP was independently associated with BSID motor score (P = .04). CONCLUSIONS: Higher GFAP levels at the time of neonatal cardiac operations were independently associated with decreased BSID motor scores at 12 months. GFAP might serve as a diagnostic means to acutely identify perioperative brain-specific injury and serve as a benchmark of therapeutic efficacy for investigational treatments, discriminate center-specific effects, and provide early prognostic information for intervention.
Subject(s)
Cardiac Surgical Procedures/adverse effects , Child Development , Glial Fibrillary Acidic Protein/blood , Heart Defects, Congenital/surgery , Neurodevelopmental Disorders/etiology , Age Factors , Biomarkers/blood , Child Language , Cognition , Heart Defects, Congenital/blood , Heart Defects, Congenital/complications , Heart Defects, Congenital/diagnostic imaging , Humans , Infant , Infant Behavior , Infant, Newborn , Motor Activity , Neurodevelopmental Disorders/diagnosis , Neurodevelopmental Disorders/physiopathology , Neurodevelopmental Disorders/psychology , Predictive Value of Tests , Randomized Controlled Trials as Topic , Time Factors , Treatment Outcome , Up-RegulationABSTRACT
When predicting child developmental outcomes, reliance on children's scores on measures of developmental functioning alone might mask more subtle behavioral difficulties especially in children with developmental risk factors. The current study examined predictors and stability of examiner behavior ratings and their association with concurrent and subsequent mental and motor performance in toddlers born at extremely low birth weight. Toddlers were evaluated using the Behavior Rating scale (BRS) and the mental and psychomotor indexes of the Bayley-II at 18 and 30 months corrected age. BRS total and factor scores showed moderate stability between 18 and 30 months. These scores also predicted 30-month Mental Scale and Psychomotor Scale scores above and beyond prior mental and motor performance. Our findings suggest that early behavior ratings are associated with child mental and motor performance; therefore, behavior ratings might be useful in identifying toddlers at developmental risk and who might benefit from early intervention.
