Perinatal arterial ischemic stroke and periventricular venous infarction in infants with unilateral cerebral palsy

Abstract

AIM To explore clinical factors associated with perinatal arterial ischemic stroke (AIS) and periventricular venous infarction (PVI) in infants who develop unilateral cerebral palsy (CP).METHOD This was a case-control study. Data current to 2019 was extracted from the Canadian Cerebral Palsy Registry (CCPR). Cases were infants born at term with confirmed unilateral CP. Magnetic resonance images were stratified by expert review of reports as definitive perinatal stroke (AIS or PVI). Controls with common data elements were recruited from a population-based study in Alberta. Multivariable regression analyses were performed to estimate associations expressed as odds ratios with 95% confidence intervals. RESULTSOf 2093 cases from the CCPR, 662 had unilateral CP, of whom 299 (45%) had perinatal stroke: AIS 169 (57%) and PVI 130 (43%). Median age at diagnosis for AIS was 11.9 months (interquartile range: 6.2-25.7mo; range 0.17-104.1mo), and 58.6% were male. Median age at diagnosis for PVI was 25.3 months (interquartile range: 14.5-38mo, range 0.7-114.7mo) and 57.7% were male. Independent associations for both AIS and PVI on multivariable analysis were chorioamnionitis, illicit drug exposure, diabetes, gestational age, and maternal age. Variables associated with AIS alone were low Apgar score and prolonged rupture of membranes. Variables associated with PVI alone were small for gestational age and primigravida.INTERPRETATION Controlled analysis of disease-specific unilateral CP may offer unique perspectives on its pathophysiology. Acute intrapartum factors are mainly associated with AIS, while in utero factors are associated with PVI.disease-specific mechanisms of unilateral cerebral palsy.• Periventricular venous inaction may be associated with chorioamnionitis, substance use, and gestational diabetes.• Intrapartum factors are significantly associated with arterial ischemic stroke.

Development and Validation of a Prediction Model for Perinatal Arterial Ischemic Stroke in Term Neonates

“…Preliminary univariable analyses were done to show possible associations between each individual predictor and outcome ( Table 2 ). Of the 18 study variables identified in Table 2 , the 9 following factors were selected as candidate predictors for the model because existing literature and biological plausibility with regard to the placental hypothesis of PAIS supported that these factors were associated with a higher pretest probability of PAIS ( Table 3 ) 9 , 10 , 13 , 14 , 15 , 16 , 17 , 18 , 20 , 21 , 22 , 34 , 38 , 39 , 40 , 41 , 42 , 45 , 46 : maternal age, tobacco exposure in pregnancy, recreational drug (substance) exposure in pregnancy, preeclampsia, chorioamnionitis, maternal fever intrapartum, emergency cesarean delivery, low Apgar score (<7) at 5 minutes, and male sex. All 9 variables selected as candidate predictors were significantly associated with the outcome in univariable analyses, and no further variable selection was undertaken; all 9 variables were included in the final model.…”

“… 33 A system for confirming and classifying perinatal stroke (arterial and venous) in participants with hemiparetic cerebral palsy was recently validated in this registry. 34 The International Pediatric Stroke Study, established in 2006, is a clinical research registry of pediatric stroke that stores medical and imaging data for international collaborative research. 23 These data are collected using standardized procedures from International Pediatric Stroke Study investigators in more than 15 countries, with approximately 70% of participants residing in Canada and the US.…”

“…The Alberta Pregnancy Outcomes and Nutrition common data elements have previously been used as control variables in studies of factors associated with PAIS. 34 …”

“…Descriptive statistics were used to evaluate data for completeness and to identify the prevalence of each study variable among cases and controls. Candidate predictors for the model were identified a priori based on peer-reviewed research literature 10 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 34 , 38 , 39 , 40 , 41 , 42 that previously showed them to be associated with PAIS and/or to have biological plausibility in placental pathology. Thus, the selection of candidate predictors was based on known associations (higher pretest probability) rather than prompted by the current data.…”

“…Previous association with PAIS 13,34 and placental disease (maternal and fetal vascular malperfusion) 21,40 2.36 (0.99-5.58)…”