Association between urinary lactate to creatinine ratio and neurodevelopmental outcome in term infants with hypoxic-ischemic encephalopathy.

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.

Assay of D-lactate in urine of infants and children with reference values taking into account data below detection limit.

Accumulation of D-lactic acid produced by intestinal bacteria such as streptococci and lactobacilli has been extensively studied in ruminants [1-4]. In humans an increased production of D-lactate by intestinal bacteria under pathological conditions such as the short bowel syndrome can cause metabolic acidosis [5-8]. Since the lactate assays routinely used only measure L-lactate we developed a sensitive method of D-lactate quantification and established reference values in spot urines of infants and children (0 to 4 years of age). The enzymatic method with fluorimetric quantification of NADH is linear up to 2 mmol/l. It has a detection limit of 3.4 micromol/l. Among structurally related organic acids an interference was found only for L-lactate and DL-2-hydroxybutyrate at concentrations which are way beyond their physiological excretion. One hundred and sixty five spot urines of healthy Swiss (S), Austrian (A), German (G) and Chilean (CHI) infants aged from 0 to 4 years were analyzed. The distribution of the data is close to a lognormal one. Values below the detection limit were simulated and age groups were formed. In all populations D-lactate excretion was found highest during the first year of life; it declines with age during infancy and remains stable from 2.5 to 4 years of age. We show that D-lactate is excreted physiologically by healthy infants and children below 4 years of age and present reference values for D-lactate excretion which show some differences between the populations tested.