Interventions to Reduce Severe Brain Injury Risk in Preterm Neonates

Abstract

ImportanceInterventions to reduce severe brain injury risk are the prime focus in neonatal clinical trials.ObjectiveTo evaluate multiple perinatal interventions across clinical settings for reducing the risk of severe intraventricular hemorrhage (sIVH) and cystic periventricular leukomalacia (cPVL) in preterm neonates.Data SourcesMEDLINE, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases were searched from inception until September 8, 2022, using prespecified search terms and no language restrictions.Study SelectionRandomized clinical trials (RCTs) that evaluated perinatal interventions, chosen a priori, and reported 1 or more outcomes (sIVH, cPVL, and severe brain injury) were included.Data Extraction and SynthesisTwo co-authors independently extracted the data, assessed the quality of the trials, and evaluated the certainty of the evidence using the Cochrane GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Fixed-effects pairwise meta-analysis was used for data synthesis.Main Outcomes and MeasuresThe 3 prespecified outcomes were sIVH, cPVL, and severe brain injury.ResultsA total of 221 RCTs that assessed 44 perinatal interventions (6 antenatal, 6 delivery room, and 32 neonatal) were included. Meta-analysis showed with moderate certainty that antenatal corticosteroids were associated with small reduction in sIVH risk (risk ratio [RR], 0.54 [95% CI, 0.35-0.82]; absolute risk difference [ARD], −1% [95% CI, −2% to 0%]; number needed to treat [NNT], 80 [95% CI, 48-232]), whereas indomethacin prophylaxis was associated with moderate reduction in sIVH risk (RR, 0.64 [95% CI, 0.52-0.79]; ARD, −5% [95% CI, −8% to −3%]; NNT, 20 [95% CI, 13-39]). Similarly, the meta-analysis showed with low certainty that volume-targeted ventilation was associated with large reduction in risk of sIVH (RR, 0.51 [95% CI, 0.36-0.72]; ARD, −9% [95% CI, −13% to −5%]; NNT, 11 [95% CI, 7-23]). Additionally, early erythropoiesis-stimulating agents (RR, 0.68 [95% CI, 0.57-0.83]; ARD, −3% [95% CI, −4% to −1%]; NNT, 34 [95% CI, 22-67]) and prophylactic ethamsylate (RR, 0.68 [95% CI, 0.48-0.97]; ARD, −4% [95% CI, −7% to 0%]; NNT, 26 [95% CI, 13-372]) were associated with moderate reduction in sIVH risk (low certainty). The meta-analysis also showed with low certainty that compared with delayed cord clamping, umbilical cord milking was associated with a moderate increase in sIVH risk (RR, 1.82 [95% CI, 1.03-3.21]; ARD, 3% [95% CI, 0%-6%]; NNT, −30 [95% CI, −368 to −16]).Conclusions and RelevanceResults of this study suggest that a few interventions, including antenatal corticosteroids and indomethacin prophylaxis, were associated with reduction in sIVH risk (moderate certainty), and volume-targeted ventilation, early erythropoiesis-stimulating agents, and prophylactic ethamsylate were associated with reduction in sIVH risk (low certainty) in preterm neonates. However, clinicians should carefully consider all of the critical factors that may affect applicability in these interventions, including certainty of the evidence, before applying them to clinical practice.

The performance of the practices associated with the occurrence of severe intraventricular hemorrhage in the very premature infants: data analysis from the Chinese neonatal network

“…However, there are few studies to systemically investigate the associations between the practices and the occurrences of sIVH in detail. Different from the study [ 33 ], we did not find the practices of the antenatal corticosteroids and MgSO4 therapy were associated with the lower rate of sIVH. However, another systematic review indicated that although the antenatal MgSO4 could decreased the rate of IVH in preterm infant, this effect was not statistically significant.…”

Risk factors for brain injury in premature infants with twin-to-twin transfusion syndrome: a retrospective cohort study

“…Moreover, selection of suitable ventilator parameters tailored to the infant’s condition may help minimize the use of invasive ventilation. Volume-targeted ventilation and appropriate oxygen saturation target (85–89%) after birth could reduce the duration of mechanical ventilation, stabilize cerebral blood flow and reduce the incidence of BI ( 19 , 20 ).…”

Early Neurodevelopmental Assessments for Predicting Long-Term Outcomes in Infants at High Risk of Cerebral Palsy

“…Prematurity affects approximately 1 in 10 births globally, whereas HIE affects 1.6 per 1000 live births in high-income countries and 12.1 per 1000 in low- or middle-income countries . Interventions to mitigate the risk of morbidities linked to prematurity and HIE are limited, leaving affected infants at an elevated risk of neurodevelopmental complications that adversely affect motor skills and cognitive abilities. While various neurodevelopmental concerns exist, cognitive impairment and cerebral palsy stand out as primary concerns, affecting approximately 16.9% and 6.9% of very preterm infants, respectively .…”