Preterm Brain Injury and Neurodevelopmental Outcomes: A Meta-analysis

Abstract

CONTEXT: Preterm brain injuries are common; neurodevelopmental outcomes following contemporary neonatal care are continually evolving. OBJECTIVE: To systematically review and meta-analyze neurodevelopmental outcomes among preterm infants after intraventricular hemorrhage (IVH) and white matter injury (WMI). DATA SOURCES: Published and gray literature were searched across 10 databases between 2000 and 2021. STUDY SELECTION: Observational studies reporting 3-year neurodevelopmental outcomes for preterm infants with IVH or WMI compared with preterm infants without injury. DATA EXTRACTION: Study characteristics, population characteristics, and outcome data were extracted. RESULTS: Thirty eight studies were included. There was an increased adjusted risk of moderate-severe neurodevelopmental impairment after IVH grade 1 to 2 (adjusted odds ratio 1.35 [95% confidence interval 1.05–1.75]) and IVH grade 3 to 4 (adjusted odds ratio 4.26 [3.25–5.59]). Children with IVH grade 1 to 2 had higher risks of cerebral palsy (odds ratio [OR] 1.76 [1.39–2.24]), cognitive (OR 1.79 [1.09–2.95]), hearing (OR 1.83 [1.03–3.24]), and visual impairment (OR 1.77 [1.08–2.9]). Children with IVH grade 3 to 4 had markedly higher risks of cerebral palsy (OR 4.98 [4.13–6.00]), motor (OR 2.7 [1.52–4.8]), cognitive (OR 2.3 [1.67–3.15]), hearing (OR 2.44 [1.42–4.2]), and visual impairment (OR 5.42 [2.77–10.58]). Children with WMI had much higher risks of cerebral palsy (OR 14.91 [7.3–30.46]), motor (OR 5.3 [3–9.36]), and cognitive impairment (OR 3.48 [2.18–5.53]). LIMITATIONS: Heterogeneity of outcome data. CONCLUSIONS: Mild IVH, severe IVH, and WMI are associated with adverse neurodevelopmental outcomes. Utilization of core outcome sets and availability of open-access study data would improve our understanding of the nuances of these outcomes.

Perspectives : Understanding the Pathophysiology of Intraventricular Hemorrhage in Preterm Infants and Considering of the Future Direction for Treatment

“…IVH Grade 3 and 4 had significantly higher risks of cerebral palsy (OR, 4.98) and motor (OR, 10 2.7), cognitive (OR, 2.3), and visual (OR, 5.42) impairement 44) .…”

“…IVH grade 4 is known to be caused by venous drainage obstruction and bleeding into surrounding tissues after venous infarction and is not an extension of the original bleeding. IVH grade 3 and 4 are serious and followed by hydrocephalus, often requiring multiple neurosurgical interventions and inevitably resulting in poor neurodevelopmental outcomes [ 7 , 37 , 44 ].…”

“…An updated meta-analysis, published in 2022, comparing 3-year neurodevelopmental outcomes in preterm infants with IVH with those in preterm infants without IVH reported that the adjusted risk for moderate to severe neurodevelopmental disability was indicated by an odds ratio (OR) of 1.35 for IVH grade 1 and 2 and 4.26 for IVH grade 3 and 4. IVH grade 3 and 4 had significantly higher risks of cerebral palsy (OR, 4.98) and motor (OR, 2.7), cognitive (OR, 2.3), and visual (OR, 5.42) impairement [ 44 ].…”

“…Although survival rates for extremely low birth weight (ELBW) infants have remarkably improved in recent years owing to technological and scientific advances in neonatal care, intraventricular hemorrhage (IVH) continues to be a major complication of prematurity that can affect long-term neurodevelopmental outcomes [ 1 , 7 , 20 , 30 , 38 , 44 ]. Severe types of IVH (grade 3 and 4 according to Volpe classification) continue to occur in up to 15% of ELBW infants, and more than half of these infants develop post-hemorrhagic ventricular dilatation (PHVD) resulting in periventricular white matter injury (WMI) [ 1 , 38 , 52 ].…”

Neuroimaging of Germinal Matrix and Intraventricular Hemorrhage in Premature Infants

“…Severe GM-IVH (grades III and IV) and PHVD are known to be associated with adverse neurodevelopmental outcomes in premature infants [ 9 , 24 ]. Even mild GM-IVH (grades I and II) could be a risk factor for cerebral palsy and cognitive, hearing, and visual impairment [ 28 ].…”