Risk Factors for Term-Born Periventricular White Matter Injury in Children With Cerebral Palsy: A Case-Control Study

Abstract

Objective:The aim of this study was to identify possible risk factors associated with term born children with cerebral palsy (CP) and periventricular white matter injury (PVWMI) on imaging.Methods:This is a case-controlled study restricted to term born children with CP with the cases extracted from the Canadian Cerebral Palsy Registry (CCPR) and controls from Alberta Pregnancy Outcomes and Nutrition (APrON) Study. A diagnosis of PVWMI was made based on expert categorization of MRI reports. Risk factor variables were selected a priori; these included pregnancy complications, antenatal toxin exposure, perinatal infection, sex, small for gestational age, and perinatal adversity (i.e. neonatal encephalopathy presumably on the basis of intrapartum hypoxia-ischemia). We used multivariable analyses to calculate odds ratios (ORs) and their 95% confidence intervals (CIs).Results:A total of 160 cases (7.06% of the registry sample) were compared to 1950 controls. Of the term born PVWMI participants, 59.4% were males and 13.5 % were born to mothers of extreme maternal age. Multivariable analysis of each risk factor controlled for weight showed PVWMI is associated with pregnancy complications (OR=3.35; 95% CI=2.23-4.94), antenatal toxin exposure (OR=2.45; 95% CI=1.67-3.55), perinatal infection (OR=3.61; 95% CI=1.96-6.29) and perinatal adversity (OR=2.03; 95% CI=1.42-2.94). Term born males were not more likely to have PVWMI compared to females (OR=1.37; 95% CI=0.98-1.93). Multiple regression analyses suggested independent associations between PVWMI and pregnancy complications (OR=3.75; 95% CI 2.46-5.62), antenatal toxin exposure (OR=2.80; 95% CI 1.88-4.12), perinatal infection (OR=4.62; 95% CI 2.46-8.42) and perinatal adversity (OR=2.49; 95% CI= 1.71-3.69).Conclusions:Risk factors such as pregnancy complications, antenatal toxin exposure, perinatal infection as well as perinatal adversity are associated with PVWMI in term born children, suggesting perhaps variable interactions between antenatal and perinatal factors to yield this under-recognized CP phenotype.