Risk Factors for Term-Born Periventricular White Matter Injury in Children With Cerebral Palsy
A Case-Control Study
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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 and controls from Alberta Pregnancy Outcomes and Nutrition (APrON) study. A diagnosis of PVWMI was performed 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% CIs.
Results A total of 160 cases (7.06% of the registry sample) were compared with 1,950 controls. Of the term-born PVWMI participants, 59.4% were male 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 male participants were not more likely to experience PVWMI compared with female participants (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).
Discussion Risk factors such as pregnancy complications, antenatal toxin exposure, perinatal infection, and 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.
Glossary
- APrON=
- Alberta Pregnancy Outcomes and Nutrition;
- CCPR=
- Canadian Cerebral Palsy Registry;
- CP=
- cerebral palsy;
- GMFCS=
- gross motor function classification system;
- MACS=
- manual ability classification system;
- OR=
- odds ratio;
- PVWMI=
- periventricular white matter injury
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Canadian Cerebral Palsy Registry (CCPR) coinvestigators are listed in the appendix at the end of the article.
Submitted and externally peer reviewed. The handling editor was Renee Shellhaas, MD, MS.
- Received February 10, 2022.
- Accepted in final form August 5, 2022.
- © 2022 American Academy of Neurology
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