Impaired cognitive performance in premature newborns with two or more surgeries prior to term-equivalent age.

BACKGROUND: Anesthesia in early childhood is associated with adverse neurodevelopmental outcome; however, it is not known if age at exposure affects the risk of adverse outcome. Our objective was to evaluate the association of the number and timing of anesthetic exposures for surgery with cognitive outcome in a cohort of premature newborns. METHODS: A cohort study of exposure to anesthesia for surgery in premature newborns (<33 wk gestation) prospectively evaluated with neonatal magnetic resonance imaging (MRI) and neurodevelopmental testing at 3-6 y was employed. Exposure to anesthesia for surgery was classified as before term-equivalent age (TEA, <42 wk postmenstrual age) or after (≥42 wk). Multivariate regression was performed to analyze the association of composite IQ scores with the number of surgeries before and after TEA. RESULTS: Among 137 newborns, 25 (18.2%) had one surgery before TEA and 18 (13.1%) had ≥2 surgeries. Two or more surgeries before TEA were associated with significantly reduced composite IQ scores at 4.6 ± 0.6 y after adjusting for gestational age and illness severity. Neither the number of surgeries after TEA nor sedation for MRI was associated with cognitive outcome. CONCLUSIONS: More than one surgery prior to TEA is independently associated with impaired cognitive performance in premature newborns.

Diminished white matter injury over time in a cohort of premature newborns.

OBJECTIVES: To determine the rate of magnetic resonance imaging (MRI)-detected noncystic white matter injury (WMI) in a prospective cohort of premature newborns, and to evaluate its associations with changes in clinical predictors of WMI over the study period. STUDY DESIGN: A prospective cohort of premature newborns (<33 weeks gestational age) was studied with MRI within 4 weeks of birth and near term-equivalent age. A pediatric neuroradiologist scored the severity of WMI on T1-weighted MRI according to published criteria. WMI was classified as none/mild or moderate/severe. Subjects with severe cystic WMI, periventricular hemorrhagic infarction, or motion artifact on MRI were excluded. Changes in clinical characteristics and predictors of WMI over the study period (1998-2011) were evaluated. Predictors of moderate/severe WMI, including birth year, were evaluated using multivariate logistic regression. RESULTS: Among 267 newborns, 45 (17%) had moderate/severe WMI. The rate of moderate/severe WMI decreased over the study period (P = .002, χ(2) test for trends). On multivariate logistic regression, the odds of moderate/severe WMI decreased by 11% for each birth year of the cohort (OR, 0.89; 95% CI, 0.81-0.98; P = .02). Prolonged exposure to indomethacin also was independently associated with reduced odds of moderate/severe WMI. CONCLUSION: The decreasing burden of MRI-detected moderate/severe noncystic WMI in our cohort of premature newborns is independent over time of changes in the known clinical predictors of WMI. Prolonged exposure to indomethacin is associated with reduced WMI.

Infection and white matter injury in infants with congenital cardiac disease.

More than 60% of newborns with severe congenital cardiac disease develop perioperative brain injuries. Known risk factors include: pre-operative hypoxemia, cardiopulmonary bypass characteristics, and post-operative hypotension. Infection is an established risk factor for white matter injury in premature newborns. In this study, we examined term infants with congenital cardiac disease requiring surgical repair to determine whether infection is associated with white matter injury. Acquired infection was specified by site - bloodstream, pneumonia, or surgical site infection - according to strict definitions. Infection was present in 23 of 127 infants. Pre- and post-operative imaging was evaluated for acquired injury by a paediatric neuroradiologist. Overall, there was no difference in newly acquired post-operative white matter injury in infants with infection (30%), compared to those without (31%). When stratified by anatomy, infants with transposition of the great arteries, and bloodstream infection had an estimated doubling of risk of white matter injury that was not significant, whereas those with single ventricle anatomy had no apparent added risk. When considering only infants without stroke, the estimated association was higher, and became significant after adjusting for duration of inotrope therapy. In this study, nosocomial infection was not associated with white matter injury. Nonetheless, when controlling for risk factors, there was an association between bloodstream infection and white matter injury in selected sub-populations. Infection prevention may have the potential to mitigate long-term neurologic impairment as a consequence of white matter injury, which underscores the importance of attention to infection control for these patients.

Recurrent postnatal infections are associated with progressive white matter injury in premature infants.

OBJECTIVE: Our objective was to identify clinical predictors of progressive white matter injury. METHODS: We evaluated 133 infants of <34 weeks of gestation at birth from 2 university hospitals. Infants underwent MRI twice, initially when in stable condition for transport and again at term-equivalent age or before transfer or discharge. Two neuroradiologists who were blinded to the clinical course graded MRI white matter injury severity by using a validated scale. Potential risk factors were extracted from medical charts. RESULTS: Twelve neonates (9.0%) had progressive white matter injury. In the unadjusted analysis of 10 newborns without Candida meningoencephalitis, recurrent culture-positive postnatal infection and chronic lung disease were associated with progressive white matter injury. Exposure to multiple episodes of culture-positive infection significantly increased the risk of progressive white matter injury. Of the 11 neonates with >1 infection, 36.4% (4 infants) had progressive injury, compared with 5.0% (6 infants) of those with

White-matter injury is associated with impaired gaze in premature infants.

Periventricular leukomalacia is a risk factor for visual impairment in children born prematurely. The impact of diffuse white-matter injury, as detected on magnetic resonance imaging, on early visual function is unknown. We developed two 5-point visual-gaze scores to analyze the association between this clinical assessment and white-matter injury in 93 premature neonates <34 weeks of gestational age at birth. Older postmenstrual age was associated with higher values of the two gaze scores. Infants with moderate or severe white-matter injury had lower scores than their peers without white-matter injury (0.41 points, 95% confidence interval of 0.13-0.69 for visual fixation score; and 0.70 points, 95% confidence interval of 0.30-1.10 for conjugate score, P < 0.005). Using the results from both scales, a score of >or=9 in an infant examined at >or=36 weeks postmenstrual age predicted normal white matter on magnetic resonance examination, with a sensitivity of 84% and a specificity of 100%. These preliminary findings suggest that white-matter injury affects visual function even before term equivalent postmenstrual age.