Early Metabolic Alterations are Associated with Intraventricular Hemorrhage and Its Complications in Very Preterm Infants

INTRODUCTION: To identify early metabolic alterations associated with intraventricular hemorrhage (IVH) and its complications, periventricular hemorrhagic infarction (PVHI), and Post-hemorrhagic ventricular dilatation (PHVD), in very preterm infants. METHODS: This population-based observational cohort included 7,313 preterm infants born at 24-32 weeks' gestation between 2009 and 2019. Twenty-one analytes were quantified from dried blood samples collected within the first 96 hours of life using tandem mass spectrometry. Multivariable logistic regression models were used to examine the association between analyte concentration quartiles and IVH, including analysis stratified by IVH-related complications. RESULTS: IVH was diagnosed in 882 infants, while 6,431 had normal neurosonography. Compared with infants in the lowest quartile, those in the highest quartile of methionine and proline concentrations had increased odds of IVH (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.21-1.86 and OR 1.74, 95% CI 1.40-2.17, respectively). In contrast, infants in the highest quartile of free carnitine concentrations had significantly lower odds of IVH (OR 0.53, 95% CI 0.42-0.67). These associations were more pronounced among infants with PVHI (n=149) and PHVD (n=152) (P<0.001). CONCLUSION: Among very preterm infants, higher methionine and proline concentrations within the first 96 hours of life were associated with increased risks of IVH and its complications, whereas higher free carnitine concentrations were associated with lower risks. Whether these metabolic alterations reflect secondary responses to ischemic-hemorrhagic brain injury or act as modulators of germinal matrix vulnerability warrants further investigation.