Association between Urinary Lactate to Creatinine Ratio and Neurodevelopmental Outcome in Term Infants with Hypoxic-Ischemic Encephalopathy

Abstract

Objective-To assess the association between urinary lactate to creatinine ratio (ULCR) and neurodevelopmental outcome in term infants with hypoxic ischemic encephalopathy and examine the effect of hypothermia on the change in ULCR.Study design-Spot urine samples were collected in 58 term infants (28 hypothermia, 30 control subjects) with hypoxic ischemic encephalopathy. Urinary lactate and creatinine were measured by using 1 H nuclear magnetic resonance spectroscopy and expressed as ULCR. Survivors were examined at 18 months of age.Results-The ULCR was significantly higher in infants who died or had moderate/severe neurodevelopmental disability. Logistic regression analysis controlling for hypothermia and severity of encephalopathy confirmed the association (adjusted odds ratio, 5.52; 95% CI, 1.36, 22.42; P < . 02). Considerable overlap in ULCR was observed between infants with normal/mild disability and those who died or survived with moderate/severe disability. ULCR fell significantly between 6 and 24 hours and 48 and 72 hours of age for all infants. The magnitude of decline did not differ between hypothermia and control groups.Conclusions-High ULCR is associated with death or moderate/severe neurodevelopmental disability. Significant overlap in values between the normal/mild and moderate/severe disability groups limits predictive value of this measure. Whole-body hypothermia did not affect the decline in ULCR.Hypoxic-ischemic encephalopathy is a serious morbidity in newborn infants with high mortality rate and a high rate of poor neurodevelopmental outcome among survivors. METHODSThis study involved a subset of term infants randomly assigned in a controlled trial conducted by the NICHD Neonatal Research Network to evaluate the efficacy and safety of whole-body hypothermia in term infants with hypoxic ischemic encephalopathy. This study was approved by the institutional review board in each site. The subjects and methods of the primary protocol have been published. 9 A set of predetermined criteria was used by trained investigators to establish the diagnosis and severity of hypoxic ischemic encephalopathy. Two hundred eight infants with hypoxic ischemic encephalopathy were enrolled in this trial. Of these infants, 58 were enrolled in the current study, 28 in the hypothermia group, and 30 in the control group.Collection of spot urine was initiated on study infants as soon as consents were obtained. The first urine was collected between 6 and 24 hours and repeated at 48 to 72 hours, using a bag placed over the perineum of girls and a test tube placed over the penis for boys. Urine was aspirated from the bag or test tube using a syringe connected to a catheter. Urine spilled on the diaper was also aspirated. Urine samples were stored at −20°C until shipment in dry ice to the central laboratory (Ralph B. Rogers MR Center, University of Texas-Southwestern Medical Center, Dallas, Texas) for assay.Samples were prepared for nuclear magnetic resonance (NMR) spectroscopy by thawing and removing a 550-μL aliquot...

Evaluation of Urinary S100B Protein Level and Lactate/Creatinine Ratio for Early Diagnosis and Prognostic Prediction of Neonatal Hypoxic-Ischemic Encephalopathy

“…Discussion S100B is predominantly expressed in the nervous system and has been well established as a biochemical marker for brain injuries [8][9][10] . The measurement of urinary S100B may provide an excellent sampling source for the biochemical markers in newborns with HIE [1,2] .…”

“…The urinary lactate/ creatinine ratio may reflect the general metabolic conditions of the perinatal hypoxia and reperfusion damage. The use of the urinary lactate/creatinine ratio in predicting HIE has been established [1,10] . In the present study, the ratio was significantly increased in the newborns with different severity of HIE only on day 1 after birth, with higher ratios representing more severe cases.…”

Neonatal Encephalopathy: Treatment With Hypothermia

“…A secondary analysis involving spot urine samples collected in 58 study participants revealed that a high urinary lactate=creatinine ratio was associated with death or disability (Oh et al, 2008). Lastly, detailed analysis of the randomized controlled trial data revealed safety of hypothermia during the intervention period and during follow-up to 18-22 months .…”

Prevention, Diagnosis, and Treatment of Cerebral Palsy in Near-term and Term Infants

“…19 Finally, a secondary analyses involving spot urine samples collected in 58 study participants, revealed that high urinary lactate to creatinine ratio was associated with death/disability. 20 There are important differences between the Cool Cap and the Whole Body Hypothermia Trial. The 2 trials use different entry criteria distinguished primarily by the use of the aEEG in the Cool Cap trail.…”