Presented at the Neonatal Society 2003 Spring Meeting.
Counsell S2, Saraswatula A1, Allsop J2, Kapellou O1, Harrison M1, Rutherford M2, Modi N1
1 Section of Paediatrics & Neonatal Medicine, Division of Paediatrics, Obstetrics & Gynaecology
2 Robert Steiner MR Unit, Imaging Sciences Department, Imperial College, Faculty of Medicine, Hammersmith Hospital, Du Cane Road London W12 OHS
Introduction: Accumulating evidence points to the fetal inflammatory response to intrauterine infection as a major determinant of neurodisability, through damage to white matter and other brain injury (1). It is plausible that postnatal infection, remote from the brain, is also a major determinant of inflammatory white matter damage, though evidence in support of this hypothesis is lacking.
Aim: The aim of this study was to explore the effect of postnatal systemic infection in babies born preterm, upon an MR imaging index of white matter development, the apparent diffusion coefficient (ADC) (2).
Methods: We compared the ADC at age term equivalent in infants who had experienced at least one episode of systemic postnatal infection with those who had not. A robust diagnosis of systemic infection was made utilising predefined criteria comprising alteration in laboratory indices (C-reactive protein and blood film), and clinical signs suggestive of infection, in addition to a positive blood culture. Magnetic resonance images were obtained in 52 infants with median gestational age at birth of 29 weeks (range 25-34). Diffusion weighted imaging was acquired using single shot echo planar imaging (EPI) at multiple levels. Fifteen slices of 5mm thickness were obtained (TR 6000ms, TE 110ms, FOV 24cm, single b values of 0 and 1000 mm²/s). Data were analysed using SPSS version 11. Parametric or non-parametric procedures were employed as appropriate. Multiple regression analysis was used to explore the relative contributions of postnatal infection, prolonged rupture of membranes, antenatal steroid exposure, associated focal cerebral pathology (parenchymal lesions), disease severity and actual postmenstrual age at the time of imaging. All imaging analyses were carried out without knowledge of infection status. Approval was received from the Imperial College Faculty of Medicine and Hammersmith Hospitals Trust Research Ethics Committee.
Results: Eighteen infants had at least 1 episode of systemic postnatal infection and 34 infants had no episodes of infection. There was a significant difference in ADC between the groups (median (range): infection 1.577 (1.287, 1.804); no-infection 1.451(1.163, 1.707); difference 0.092, 95% confidence interval for difference 0.005 to 0.179) (p = 0.039). This difference persisted after adjusting for duration of full (level 1) intensive care, postmenstrual age at time of imaging, antenatal steroid exposure, disease severity, prolonged rupture of membranes and presence of focal cerebral pathology (adjusted difference 0.102; 95% confidence interval for difference 0.005 to 0.200;p=0.040).
Conclusion: These novel data represent the first evidence that postnatal infection may affect brain development in preterm infants. It will be important to establish if these observations have implications for later neurocognitive performance.
References
1. Dammann O, Kuban KC, Leviton A. Mental Retardation and Developmental Disabilities Research Reviews 2002; 8:46-50
2. Counsell SJ, Allsop JM, Harrison MC et al. Pediatrics, in press