Association Between Endotype of Prematurity and Cystic Periventricular Leukomalacia: A Bayesian Model-Averaged Meta-Analysis

Pathophysiological pathways-or endotypes-leading to prematurity can be clustered into two groups: infection/inflammation and dysfunctional placentation. We aimed to perform a systematic review and meta-analysis of studies exploring the association between these endotypes and cystic periventricular leukomalacia (cPVL). PubMed and Embase were searched for observational studies examining preterm infants and reporting data on the association between endotype of prematurity and cPVL. Chorioamnionitis represented the infectious-inflammatory endotype, while dysfunctional placentation proxies were hypertensive disorders of pregnancy (HDPs) and small for gestational age (SGA)/intrauterine growth restriction (IUGR). Bayesian model-averaged (BMA) meta-analysis was used to calculate Bayes factors (BFs). The BF is the ratio of the probability of the data under the alternative hypothesis (H presence of association) over the probability of the data under the null hypothesis (H absence of association). Of 1141 potentially relevant studies; 67 (108,571 infants) were included. The BMA analysis showed strong evidence in favor of a positive association between chorioamnionitis and cPVL (OR 1.58; 95% CrI 1.12 to 2.20; BF = 20.5) and extreme evidence in favor of a negative association between HDPs and cPVL (OR 0.63; 95% CrI 0.54 to 0.75; BF = 2937). The evidence for the SGA/IUGR group was inconclusive (OR 0.87; 95% CrI 0.75 to 1.01; BF = 1.41). This Bayesian meta-analysis provides evidence indicative of an association between antenatal infection-inflammation and an increased risk of developing cPVL in preterm infants. Conversely, infants exposed to HDPs are less likely to develop cPVL.