Supplementary Material for: Urinary lactate-to-creatinine ratio during the first days of life correlates with the degree of brain damage in premature infants

Introduction
This study aimed to assess the association between the urinary lactate-to-creatinine ratio (ULCR) and brain spectroscopy (1H-MRS) findings in very-low-gestational-age (VLGA) infants with and without preterm brain injury.
Methods
Urine samples were collected from 54 VLGA infants during the first week of life, after one month of life, and at term-equivalent age (TEA). Urinary lactate was measured via highly selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a quantitative Organic Acid Analysis Kit and expressed as the ULCR. MRI and 1H-MRS were performed at TEA. The Kidokoro grading system was used to assess the Global Brain Abnormality Score (GBAS).
Results
VLGA infants with a GBAS moderate+severe had higher ULCRs on the 2nd and 3rd days of life (DOLs) than those with a GBAS normal or mild. Only the GBAS moderate+severe subgroup presented with a secondary increase in the ULCR on the 3rd DOL, whereas in the GBAS normal or mild, the ULCR oscillated around similar values or gradually decreased. Significant positive correlations were detected between the ULCR on the 3rd DOL and the lactate/creatinine and lactate/N-acetyl aspartate ratios measured via 1H-MRS at TEA (r=0.308; p=0.022 and r=0.334; p=0.013, respectively).
Conclusions
An increased ULCR during the first three DOLs in patients with a GBAS moderate+severe suggest an energy catastrophe that may play a role in the development of premature brain injury. Serial measurement of the ULCR during the first days of life may help in the early identification of premature infants at risk for moderate+severe brain damage.