We read with interest the meta-analysis evaluating vitamin E for intraventricular haemorrhage (IVH) prevention in preterm neonates.1 Across five randomised trials involving 554 infants, vitamin E supplementation reduced any-grade IVH (risk ratio 0.57, 95% confidence interval CI 0.35–0.92), prompting the authors to suggest vitamin E as a potential adjunct to contemporary neuroprotective care. We commend the authors for revisiting a difficult but clinically relevant preventive strategy. The applicability of these findings to contemporary practice may, however, be limited. The included trials span several decades and largely predate widespread use of antenatal corticosteroids, magnesium sulfate, standardised haemodynamic bundles and modern parenteral lipid formulations. A recent systematic review of vitamin supplementation in very low birth weight (VLBW) and very preterm infants reported substantial heterogeneity and mainly low or very low certainty of evidence for vitamin-based interventions, including vitamin E.2 In addition, a comprehensive narrative review of vitamin E neuroprotection highlights mixed translational success and suggests that encouraging clinical signals may be linked to specific formulations and dosing schedules rather than uniform benefit with routine higher-dose systemic supplementation.3 We would therefore welcome additional analyses, where data permit, stratified by study era and key clinical context, and by route, dose and baseline IVH risk; sensitivity analyses focused on severe (grade III–IV) IVH or excluding older/high-risk-of-bias trials could further clarify robustness and clinical relevance. Safety and outcome selection also merit further exploration. The present meta-analysis focuses on short-term IVH incidence, yet contemporary population-based data show that both low- and high-grade IVH are associated with multimorbidity and reduced survival without severe neurodevelopmental impairment (NDI) at 2 years' corrected age.4 In parallel, a multi-year quality-improvement project has reported IVH reduction through care bundles targeting haemodynamic stability and delivery-room management, complementing pharmacologic approaches.5 A more detailed synthesis of adverse events in the vitamin E trials (including sepsis, necrotising enterocolitis, mortality and, where available, longer-term neurodevelopmental outcomes), together with composite outcomes such as survival without severe NDI, would help clinicians balance potential benefits and harms. Overall, further clarification of the influence of study era, formulation/dosing strategy, and safety and longer-term outcomes would strengthen interpretation of the pooled estimate and better guide clinicians considering vitamin E prophylaxis in extremely preterm infants. We congratulate the authors on bringing renewed attention to micronutrient-based neuroprotection and for providing a timely synthesis that will inform future analyses and research in this field (Table 1). Prashant R. Kokiwar: Conceptualization (equal); data curation (equal); formal analysis (equal); funding acquisition (equal); investigation (equal); methodology (equal); project administration (equal); resources (equal); software (equal); supervision (equal); validation (equal); visualization (equal); writing—original draft (equal); writing—review and editing (equal). Ambreen S. Chauhan: Conceptualization (equal); data curation (equal); formal analysis (equal); funding acquisition (equal); investigation (equal); methodology (equal); project administration (equal); resources (equal); software (equal); supervision (equal); validation (equal); visualization (equal); writing—original draft (equal); writing—review and editing (equal). A. Kavya: Conceptualization (equal); data curation (equal); formal analysis (equal); funding acquisition (equal); investigation (equal); methodology (equal); project administration (equal); resources (equal); software (equal); supervision (equal); validation (equal); visualization (equal); writing—original draft (equal); writing—review and editing (equal). Archana Dhyani: Conceptualization (equal); data curation (equal); formal analysis (equal); funding acquisition (equal); investigation (equal); methodology (equal); project administration (equal); resources (equal); software (equal); supervision (equal); validation (equal); visualization (equal); writing—original draft (equal); writing—review and editing (equal). The authors have nothing to report. The authors declare no conflicts of interest. None. Not applicable. All data are incorporated into the article.
Kokiwar et al. (Wed,) studied this question.