Measurement of the Urinary Lactate:Creatinine Ratio for the Early Identification of Newborn Infants at Risk for Hypoxic-Ischemic Encephalopathy

Abstract

Because increased urinary lactate excretion can be detected by magnetic resonance spectroscopy in hypoxic newborn infants, a study was planned to learn whether the urinary lactate and creatinine levels, measured within hours after birth, are a specific and sensitive means of predicting hypoxic-ischemic encephalopathy (HIE). Forty consecutive neonates with perinatal asphyxia, all born at 36 weeks’ gestation or later, were studied. Urinary proton magnetic resonance spectroscopy was done to determine the lactate:creatinine ratio within 6 hours of birth and again at age 2 to 3 days. Fifty-eight normal infants served as a control group. Real-time ultrasonography was done at intervals up to 10 days after birth to detect increased echogenicity or encephalomalacia. Surviving infants were assessed neurodevelopmentally at age 12 months. HIE developed in 16 of the 40 asphyctic infants but none of the control group. These groups did not differ in birth weight or gestational age. Hyperechogenicity in the basal ganglia and thalamus, as well as diffuse brain edema, were frequent findings in infants who developed HIE. The mean urinary lactate:creatinine ratio within 6 hours of birth was 16.75 in those infants who later developed HIE, 88-fold higher than in asphyctic infants who did not follow this course, and 186 times higher than in normal infants. A ratio of 0.64 or higher was 94 percent sensitive and 100 percent specific in predicting HIE. The ratio tended to increase with the severity of encephalopathy, although not to a significant degree. When they were 2 to 3 days old, infants who developed HIE still had ratios 10 times higher than normal infants and nearly 5-fold higher than asphyctic infants who did not develop HIE. Ten of 16 children who developed HIE neonatally had an adverse outcome; 5 of them had severe neurodevelopmental impairment, and 5 died before age 4 months. Only one of these infants had a postdelivery lactate:creatinine ratio of <1.00, and all but one had a ratio of 3.12 or higher. These ratios were significantly higher than in infants who had a favorable outcome. Estimating the urinary lactate:creatinine ratio by magnetic resonance spectroscopy shortly after birth can help predict which asphyctic infants will develop HIE, and thereby help guide intervention. N Engl J Med 1999;341:328–335