Supplementary Material for: Isolated Cystic Periventricular Leukomalacia Differs from Cystic Periventricular Leukomalacia with Intraventricular Hemorrhage in Prevalence, Risk Factors and Outcomes in Preterm Infants

Background: Cystic periventricular leukomalacia (cPVL) is the most severe white matter injury and is often associated with intraventricular hemorrhage (IVH) in preterm infants. Objective: The aim of this study was to investigate the prevalence, risk factors and neurodevelopmental outcomes of isolated cPVL and cPVL with low-grade and high-grade IVH in premature infants. Methods: From 2001 to 2012, 9,964 infants with <31 weeks' gestational age (GA) admitted to Taiwan hospitals were enrolled. cPVL was classified into three groups: isolated cPVL, cPVL with low-grade (I/II) IVH, and cPVL with high-grade (III) IVH. Results: Of 7,805 infants with complete ultrasound data, 286 (3.7%) had cPVL. Among the cPVL infants, 93 (32.5%) were isolated, 118 (41.3%) had low-grade IVH and 75 (26.2%) had high-grade IVH. The risk of cPVL with IVH was significantly higher among infants with <27 weeks' GA than those with ≥27 weeks' GA, in contrast to that of isolated cPVL. Using infants without cPVL and IVH as the reference group, the most significant predictor of isolated cPVL was neonatal sepsis (odds ratio 2.39; 95% confidence interval 1.52-3.77), while 5-min Apgar score <5 (2.50; 1.48-4.21) and prolonged mechanical ventilation (2.19; 1.42-3.42) were associated with cPVL with low-grade IVH, and GA <27 weeks (2.63; 1.56-4.42), pneumothorax (3.04; 1.40-6.65) and prolonged mechanical ventilation (3.36; 1.88-6.01) contributed to cPVL with high-grade IVH. cPVL infants with low-grade and high-grade IVH had a higher risk of abnormal neurodevelopmental outcomes than infants with isolated cPVL at the age of 24 months. Conclusions: Isolated cPVL, cPVL with low-grade IVH and cPVL with high-grade IVH had different risk factors and neurodevelopmental outcomes, suggestive of different causal pathways.