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

Juliana Wendling Gotardo,Guilherme Pucci Stangler,Clarissa Gutierrez Carvalho,Nathalia De Freitas Valle Volkmer,Alícia Dorneles Dornelles,Betânia Barreto De Athayde Bohrer,Umberto Simeoni

doi:10.1371/journal.pone.0223427

Juliana Wendling Gotardo, Guilherme Pucci Stangler + Show 5 more

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https://doi.org/10.1371/journal.pone.0223427

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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.

Highlights

The incidence of preterm births worldwide varies significantly, being as low as 5% in some European countries and as high as 18% in some places in Africa [1]
Our analysis concluded premature children with any degree of peri-intraventricular haemorrhage (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
periventricular leukomalacia (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)

Summary

Introduction

The incidence of preterm births worldwide varies significantly, being as low as 5% in some European countries and as high as 18% in some places in Africa [1]. In the United States, preterm birth delivery rates have remained somewhat stable over the last years, varying from 10.4% in 2007 to 9.8% in 2016 and 10.0% in 2017 [4]. Incidence of complications such as peri-intraventricular haemorrhage (PIVH) is considered high in preterm infants, especially those born with less than 32 weeks gestational age (GA) [5]. In these early preterm infants, a recent cohort study found an overall incidence of 36.2% of any PIVH, with Papile grade III and IV affecting around 7.1% of these newborns [5]. A recent systematic review described a high incidence of white matter abnormalities in preterm infants, estimated at 39.6% for infants

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