allopurinol and Developmental-Disabilities

To evaluate the long-term neurodevelopmental and behavioral outcome of antenatal allopurinol treatment during suspected fetal hypoxia.. We studied children born from women who participated in a randomized double-blind placebo controlled multicenter study (ALLO-trial). Labouring women in whom the fetus was suspected to have fetal hypoxia were randomly allocated to receive allopurinol or placebo. At 5 years of age, the children were assessed with 2 parent reported questionnaires, the Ages and Stages Questionnaire (ASQ) and the Child Behavior Checklist (CBCL). A child was marked abnormal for ASQ if it scored below 2 standard deviation under the normative mean of a reference population in at least one domain. For CBCL, a score above the cut-off value (95th percentile for narrowband scale, 85th percentile for broadband scale) in at least one scale was marked as abnormal.. We obtained data from 138 out of the original 222 mildly asphyxiated children included in the ALLO-trial (response rate 62%, allopurinol n = 73, placebo n = 65). At 5 years of age, the number of children that scored abnormal on the ASQ were 11 (15.1%) in the allopurinol group versus 11 (9.2%) in the placebo group (relative risk (RR) 1.64, 95% confidence interval (CI): 0.64 to 4.17, p = 0.30). On CBCL 21 children (30.4%) scored abnormal in de allopurinol group versus 12 children (20.0%) in the placebo group (RR 1.52, 95% CI: 0.82 to 2.83, p = 0.18).. We found no proof that allopurinol administered to labouring women with suspected fetal hypoxia improved long-term developmental and behavioral outcome. These findings are limited due to the fact that the study was potentially underpowered.. NCT00189007 Dutch Trial Register NTR1383.

Topics: Allopurinol; Child Behavior; Child Behavior Disorders; Child Development; Child, Preschool; Developmental Disabilities; Double-Blind Method; Female; Fetal Hypoxia; Follow-Up Studies; Free Radical Scavengers; Humans; Labor, Obstetric; Male; Pregnancy

Free-radical-induced reperfusion injury has been recognised as an important cause of brain tissue damage after birth asphyxia. Allopurinol reduces the formation of free radicals, thereby potentially limiting the amount of hypoxia-reperfusion damage. In this study the long-term outcome of neonatal allopurinol treatment after birth asphyxia was examined.. Follow-up of 4 to 8 years of two earlier performed randomised controlled trials.. Leiden University Medical Center, University Medical Center Groningen and University Medical Center Utrecht, The Netherlands.. Fifty-four term infants were included when suffering from moderate-to-severe birth asphyxia in two previously performed trials.. Infants either received 40 mg/kg allopurinol (with an interval of 12 h) starting within 4 h after birth or served as controls.. Children, who survived, were assessed with the Wechsler Preschool and Primary Scales of Intelligence test or Wechsler Intelligence Scale for Children and underwent a neurological examination. The effect of allopurinol on severe adverse outcome (defined as mortality or severe disability at the age of 4-8 years) was examined in the total group of asphyxiated infants and in a predefined subgroup of moderately asphyxiated infants (based on the amplitude integrated electroencephalogram).. The mean age during follow-up (n=23) was 5 years and 5 months (SD 1 year and 2 months). There were no differences in long-term outcome between the allopurinol-treated infants and controls. However, subgroup analysis of the moderately asphyxiated group showed significantly less severe adverse outcome in the allopurinol-treated infants compared with controls (25% vs 65%; RR 0.40, 95%CI 0.17 to 0.94).. The reported data may suggest a (neuro)protective effect of neonatal allopurinol treatment in moderately asphyxiated infants.

Topics: Allopurinol; Asphyxia Neonatorum; Birth Weight; Developmental Disabilities; Female; Follow-Up Studies; Free Radical Scavengers; Gestational Age; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Intelligence; Male; Neuroprotective Agents; Neuropsychological Tests; Reperfusion Injury; Treatment Outcome

We report on a male patient with Tuberous Sclerosis Complex (TSC), which was prenatally diagnosed. At the age of 3 months the patient developed acute renal failure with excessive hyperuricemia. Kidney function improved after rehydration and application of rasburicase, however without full recovery. Due to the inappropriate high levels of uric acid compared to kidney function, screening of hypoxanthine-guanine phosphoribosyltransferase (HPRT) related diseases was initiated. Mutation analysis revealed a deletion of exon 2 and 3 of the HPRT gene confirming the diagnosis of Lesch-Nyhan Disease (LND). After initiation of allopurinol therapy renal function further improved. In the following months the patient developed clinically a typical neurological phenotype of LND and TSC with seizures, severe dystonia and developmental delay.. Acute renal failure is a rare complication of HPRT related diseases. Combination of two inherited diseases may lead to a delayed diagnosis due to a mixed and maybe misleading phenotype.

Topics: Acute Kidney Injury; Allopurinol; Developmental Disabilities; Dystonia; Exons; Fluid Therapy; Gout Suppressants; Humans; Hyperuricemia; Hypoxanthine Phosphoribosyltransferase; Infant; Lesch-Nyhan Syndrome; Male; Phenotype; Seizures; Tuberous Sclerosis; Urate Oxidase