Impact of peri-intraventricular haemorrhage and periventricular leukomalacia in the neurodevelopment of preterms: A systematic review and meta-analysis

Abstract

ContextWhether all degrees of periventricular leukomalacia (PVL) and peri-intraventricular haemorrhage (PIVH) have a negative impact on neurodevelopment.ObjectiveTo determine the impact of PVL and PIVH in the incidence of cerebral palsy, sensorineural impairment and development scores in preterm neonates. Registered in PROSPERO (CRD42017073113).Data sourcesPubMed, Embase, SciELO, LILACS, and Cochrane databases.Study selectionProspective cohort studies evaluating neurodevelopment in children born preterm which performed brain imaging in the neonatal period.Data extractionTwo independent researchers extracted data using a predesigned data extraction sheet.Statistical methodsA random-effects model was used, with Mantel-Haenszel approach and a Sidik-Jonkman method for the estimation of variances, combined with Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed through the I2 statistic and sensitivity analysis were performed when possible. No funnel plots were generated but publication bias was discussed as a possible limitation.ResultsOur analysis concluded premature children with any degree of PIVH are at increased risk for cerebral palsy (CP) when compared to children with no PIVH (3.4, 95% CI 1.60–7.22; 9 studies), a finding that persisted on subgroup analysis for studies with mean birth weight of less than 1000 grams. Similarly, PVL was associated with CP, both in its cystic (19.12, 95% CI 4.57–79.90; 2 studies) and non-cystic form (9.27, 95% CI 5.93–14.50; 2 studies). We also found children with cystic PVL may be at risk for visual and hearing impairment compared to normal children, but evidence is weak.LimitationsMajor limitations were the lack of data for PVL in general, especially for the outcome of neurodevelopment, the high heterogeneity among methods used to assess neurodevelopment and the small number of studies, which led to meta-analysis with high heterogeneity and wide confidence intervals.ConclusionsThere was no evidence supporting the hypothesis that PIVH causes impairment in neuropsychomotor development in our meta-analysis, but review of newer studies show an increased risk for lower intelligence scores in children with severe lesions, both PIVH and PVL. There is evidence to support the hypothesis that children with any degree of PIVH, especially those born below 1000 grams and those with severe haemorrhage, are at increased risk of developing CP, as well as children with PVL, both cystic and non-cystic.

Maternal-Fetal Inflammation in the Placenta and the Developmental Origins of Health and Disease

“…Intraventricular hemorrhage in preterm is the most common cause of hydrocephalus and increases the risk for poor neurodevelopment outcomes (90). Periventricular leukomalacia is a type of preterm brain injury associated with adverse neurodevelopment (90), including cerebral palsy (91,92). Both intraventricular hemorrhage and periventricular leukomalacia are associated with FIRS (62, 63, 65).…”

Neonatal Adverse Outcomes, Neonatal Birth Risks, and Socioeconomic Status: Combined Influence on Preterm Infants’ Cognitive, Language, and Motor Development in Brazil

“…Mechanical ventilation, periventricular hemorrhage, and periventricular leukomalacia are also risk factors for neurodevelopment impairments. 4,8,9 Brain growth and development inside the uterus are interrupted by preterm birth; infants born with immature brains 7 are more vulnerable to brain damage due to immaturity and possible infections and inflammations. 10 Periventricular hemorrhage and periventricular leukomalacia are common brain injuries in preterm infants.…”

Dexamethasone vs. betamethasone for preterm birth: a systematic review and network meta-analysis

“…46 This posthoc sensitivity analysis, based on the very high risk of attrition bias of this study, provided more consistent results with the indirect evidence. Additionally, a meta-analyses found an increased risk of neurodevelopmental impairment in children with periventricular/intraventricular haemorrhage 88 , mainly driven by cerebral palsy 89 . Since we did not find a differential effect of dexamethasone on neurosensory disability it would be unlikely a favourable effect on IVH.…”