The value of the metabolic autopsy in the pediatric hospital setting

OBJECTIVE: To determine the utility of the metabolic autopsy in the hospitalized pediatric patient. STUDY DESIGN: This was a retrospective review of all metabolic autopsies performed at a large pediatric hospital over a 5-year period. Premortem clinical diagnoses were correlated with autopsy findings and results of postmortem testing. RESULTS: Of the 23 metabolic autopsies performed, a metabolic disorder was diagnosed before death in 4 and after death by extensive studies initiated before death in 2. In the remaining 17 cases, postmortem samples were inadequate for subsequent enzymatic analysis in 2, a nonmetabolic explanation for symptoms was identified in 4, and no unifying diagnosis could be defined in 8. A metabolic disorder was diagnosed by postmortem tissue study in 3 of the 17 cases; in all 3 of these cases the patient died in the neonatal period after limited premortem investigation for primary lactic acidosis. For the 8 subjects who had undergone an extensive laboratory workup before death, in each case metabolic autopsy failed to establish a diagnosis. CONCLUSIONS: In a small but significant percentage of cases (18%), the metabolic autopsy successfully identified an undiagnosed metabolic disease. However, metabolic autopsy following an extensive nondiagnostic clinical workup is unlikely to yield a specific metabolic diagnosis.     

High prevalence of renal dysfunction in long-term survivors after pediatric liver transplantation

OBJECTIVE: To determine the prevalence and identify variables associated with renal dysfunction in long-term survivors of pediatric liver transplantation. STUDY DESIGN: Data from 117 patients who survived>or=3 years after liver transplantation were analyzed. Demographic and clinical information was obtained from chart review and from a clinical care database. The dependent variable was renal function as determined by measured glomerular filtration rate (mGFR). Univariate and multivariate analyses were performed to identify independent variables associated with renal dysfunction (mGFR<70 mL/min per 1.73 m2). RESULTS: The average time since liver transplant was 7.6+/-3.4 years (range, 3 to 14.6 years). When the last available mGFR for all patients was analyzed, renal dysfunction was present in 32%. In the univariate analysis, mGFR at 1 year after transplant, cyclosporine immunosuppression, and time since transplant were significant; the second two were strongly collinear. Using multiple logistic regression modeling excluding time since transplant, cyclosporine and mGFR at 1 year after transplant were strongly associated with renal dysfunction. CONCLUSIONS: Renal dysfunction is a common complication in children who survive liver transplantation. Our observations are of critical importance because children may live long enough to move from a stage of renal insufficiency characterized by asymptomatic decreased GFR to symptomatic end-stage renal disease.     

Risk factors for intussusception in infants in Vietnam and Australia: adenovirus implicated, but not rotavirus

OBJECTIVE: This study aimed to investigate risk factors for the development of intussusception in infants in a developing country with a suspected high incidence and in a developed country with a low incidence. STUDY DESIGN: A prospective case-control study of infants <2 years of age with idiopathic intussusception confirmed by air enema or surgery was conducted at the National Hospital of Paediatrics (NHP), Vietnam (n = 533) and the Royal Children's Hospital (RCH), Australia (n = 51). Diagnosis was validated in a subset (84% NHP; 67% RCH) by an independent blinded radiologist. Risk factor assessment was performed using a standardized questionnaire. Stool specimens were assayed for bacterial, viral, and parasitic agents. RESULTS: The incidence of intussusception in Vietnam was 302/100,000 in infants <1 year of age (95% CI: 258-352), substantially higher than in Australia (71/100,000). A strong association with adenovirus infection was observed at both sites (cases positive at NHP: 34%, OR 8.2; cases positive at RCH: 40%, OR 44). No association was identified between intussusception and rotavirus, other enteric pathogens, oral polio vaccine, feeding practices, or living conditions. CONCLUSIONS: The incidence of intussusception in infants was markedly higher in Vietnam than in Australia. A strong association between adenovirus infection and intussusception was identified at both sites suggesting that adenovirus may play a role in the etiology of intussusception.     

The detection of the heterozygous carrier for congenital virilizing adrenal hyperplasia

The response of plasma progesterone, 17 alpha-hydroxyprogesterone (17-OHP), and cortisol to intravenous ACTH was determined in 16 control subjects and seven sets of parents of children with congenital virilizing adrenal hyperplasia. The baseline and poststimulation concentrations of hormones (of each group) were similar except for those of 17-OHP in the parents which were significantly greater following administration of ACTH. When rates of increase were determined, those of progesterone and 17-OHP but not cortisol were significantly greater in the parents. The combined rate of increase of progesterone and 17-OHP was calculated; 10 of the 14 parents had a combined rate of increase greater than the mean plus two standard deviations of the control group. This test provides a simple method for the detection of some heterozygous carriers for CVAH.     

Phenobarbital and diphenylhydantoin levels in neonates with seizures

Little information is available regarding appropriate plasma levels of anticonvulsant drugs in neonates. We determined the plasma levels of phenobarbital and diphenylhydantoin following initial administration and during maintenance therapy in 59 neonates with seizures. Following intravenous administration of 15 to 20 mg/kg, levels of 20.7 +/- 4.4 microgram/ml were achieved for phenobarbital and levels of 14.5 +/- 3 microgram/ml for DPH. Maintenance doses of 5 mg/kg of phenobarbital resulted in initial drug accumulation followed by more rapid elimination of the drug with increasing duration of exposure. Therapeutic plasma levels of DPH could not be achieved by oral administration in the neonate.     

Microbiology of recurrent and chronic otitis media with effusion.

A study was conducted of 274 children who had recurrent acute or chronic otitis media with effusion. Forty-five percent of the ears with effusion were found to contain bacteria, and 11% contained bacteria that were "probable pathogens" (S. pneumoniae, H. influenzae, and S. pyogenes). Bacteria were also found in 40% of the ears without effusions. The type of organism found did not vary with the age of the patient studied or the season of the year. The significance of these bacteria in the etiology of recurrent acute or chronic otitis media with effusion remains to be demonstrated.     

The effect of cyproheptadine and human growth hormone on adrenocortical function in children with hypopituitarism

The cortisol response to insulin hypoglycemia was determined in ten hypopituitary children treated for four months with both growth hormone and cyproheptadine, and in six other children with hypopituitarism treated for four months with hGH alone. All patients had previously normal responses to orally administered metyrapone. There was no demonstrable difference in the F responses to insulin hypoglycemia before and four months following its discontinuation in the patients receiving hGH alone. In the ten patients on combined therapy the F response to insulin hypoglycemia was normal in five and subnormal in five patients. These ten patients were retested at least two months after cessation of CPH therapy. The F response reverted to normal in four of the five patients in whom it had been subnormal. There was no significant change in the five patients with initial normal response. No patients had signs or symptoms of glucocorticoid insufficiency. In some cases, long-term administration of CPH to children with hypopituitarism is associated with decreased F response to insulin hypoglycemia; this may represent decreased adrenocortical reserve in these patients. The previously reported enhancement of growth of hypopituitary children treated with hGH and CPH may in part be a result of decreased F production.