Prenatal diagnosis of familial neonatal hyperinsulinemia

A kindred with familial neonatal hyperinsulinemia is described. Infant A was macrosomatic and stillborn. Infant B was macrosomatic at birth following a pregnancy uncomplicated by maternal diabetes. Following diagnosis of hyperinsulinemic hypoglycemia, this patient was treated with oral diazoxide. Therapy continued until hyperinsulinemia resolved by two years of age. Based on this history, the pregnancy with infant C was intensively monitored using ultrasonography and amniocentesis. Insulin and C-peptide concentrations in amniotic fluid were markedly increased compared to control pregnancies. Based on these results, infant C was delivered immediately upon obtaining evidence of lung maturation. Neonatal hyperinsulinemia was confirmed by a markedly increased cord plasma insulin concentration. Based on our experience, we recommend that insulin concentrations in amniotic fluid be used as an indicator of fetal hyperinsulinemia in kindreds with prior newborn hyperinsulincmic hypoglycemia. This information may be used to direct timing of delivery and therapy in the immediate postnatal period.     

Errors arising through using the Harvard tables and percentage levels of median weight-for-age in assessing nutritional status

A self-selected sample of 417 urban and 379 rural preschool children attending the under-5s clinics was weighed in Sierra Leone. The individual weights were related to the weight-for-age Harvard 3rd centiles and 80% levels of the Harvard medians. In this analysis there were considerable discrepancies between the sexes. Further investigation showed that the distribution of the weight-for-age Harvard centiles for girls is much wider than the distribution of the Harvard centiles for boys. These distributions appear to be unusual when compared with those from London and Hong Kong studies. Accordingly, use of the weight-for-age Harvard centiles may lead to inaccuracy in the assessment of the nutritional status of preschool children. The "percentage method" as suggested by Jelliffe (1966) and Gomez et al. (1956) does not take account of the normal range of distribution of the standards. This study has shown that the 80% levels of sex-specific median weight-for-age occupy positions as much as 600 g below the sex-specific 3rd centiles for Hong Kong Chinese children, while the 80% levels closely follow the 3rd centiles for London children in the preschool age group. Thus the Hong Kong 80% levels are not comparable with the London 80% levels. Therefore, the "percentage method" appears to be misleading in the assessment of nutritional status using weight measurements.     

EPSTEIN-BARR VIRUS PCR CORRELATED WITH VIRAL HISTOLOGY AND SEROLOGY IN PEDIATRIC LIVER TRANSPLANT PATIENTS

Epstein-Barr virus (EBV)-associated illnesses in posttransplant patients are difficult to diagnose. Attempts to aid in the diagnosis of such illnesses using the polymerase chain reaction (PCR) analysis for EBV have met with variable success due to the potential exquisite sensitivity of the assay. We have designed a relatively insensitive EBV PCR assay and compared the results with objective evidence of EBV activity including serologic response and in situ hybridization for the EBV genome. Eighty-five specimens from 65 patients were analyzed by the EBV PCR using DNA from whole blood. EBV serologic evaluation was done on 53 of the samples and in situ hybridization for EBV (EBER-1 mRNA) on 46 paired liver biopsies. Of 85 samples, 25 (29 ) were positive for EBV using the PCR assay. Intensity of amplification was graded 0.5-1 (weak) to 3 (strong). Using these criteria, 19 EBV PCR-positive samples were graded 0.5-1 , 5 were graded 2 , and 1 was graded 3 . Of the moderate to strongly positive samples (2 or 3 ), five of six had two or more EBER-1-positive cells in the liver biopsies. Of the remaining 40 liver biopsies with either negative or weak positive PCR results, 3 had only single cells positive for EBER-1; the remainder were negative. In addition, PCR-positive results correlated with increasing EBV anti-early antigen antibody (P.005) and viral capsid antigen IgG immunoglobulin G VCA (P.05) EBV-positive results using the PCR assay correlated with objective evidence for increased EBV burden in children after liver transplantation. These preliminary data suggest that this PCR test may be useful to help guide immunosuppressive therapy in the posttransplant patient. Further evaluation using larger numbers of patients will be necessary to confirm this.     

Haemodynamic responses and population pharmacokinetics of midazolam following administration to ventilated, preterm neonates

Objective: To evaluate the effects of intravenous midazolam on haemodynamic variables and cerebral blood flow velocity (CBFV) and to determine the pharmacokinetics using a population approach in very low birthweight (VLBW) ventilated infants.
Methodology: Physiological variables were measured at predetermined times in 10 infants with birthweight ≤1500 g following a bolus dose of intravenous midazolam (0.1 mg/kg). Heart rate, mean arterial blood pressure (MAP) and transcutaneous CO₂ (TcPCO₂) were recorded and CBFV was assessed by Doppler ultrasound. Midazolam concentrations were also measured and pharmacokinetic parameters determined using a population modelling package.
Results: No change in heart rate occurred during the study period, while the MAP decreased by 3 mmHg 5 min after midazolam administration compared to baseline values. A non-significant fall in TcPCO₂ was seen at 20 min. Mean CBFV decreased from the baseline by 12% at 5 min, then returning to predose values. Midazolam concentrations were in the range shown to be effective in sedation of paediatric intensive care infants with the elimination being delayed in comparison to older children.
Conclusions: As only minor cerebral and haemodynamic effects were found with the use of midazolam in stable ventilated preterm infants, it appears to be a safe, short-term sedative agent.     

Perinatal outcome following conservative management of mid-trimester pre-labour rupture of the membranes

To assess perinatal outcome and the effect of antenatal steroid use following conservative management of 86 consecutive singleton pregnancies complicated by pre-labour rupture of membranes (ROM) in the mid-trimester (13–26 weeks; mean 22.8 weeks).

Methodology:

Review of obstetric and neonatal case notes between 1 January 1990 and 31 December 1993.

Results:

The duration of ruptured membranes (latent period) ranged from 1.25 to 105 days (mean 23.8 days; median 14 days) and was inversely related to gestational age at ROM. There was clinical evidence of chorioamnionitis in 39.5% with placental histological changes consistent with chorioamnionitis in 76.6%. All infants were delivered before 33 weeks gestation (mean 26 weeks). Overall, the mortality rate was 43.0% but 62.5% in infants with ROM before 24 completed weeks gestation. Adverse outcome (defined as death, severe intraventricular haemorrhage (IVH) or periventricular leucomalacia (PVL)) occurred in 46.5% and was significantly related to both gestation at delivery and gestation at ROM. In the group ( n = 40) with ROM before 24 weeks gestation, adverse outcome occurred in 65% and was inversely related to gestation at ROM independent of gestation at delivery. Antenatal steroid administration resulted in less adverse outcome independent of gestation at delivery (OR 0.31; 95% CI (0.09–0.98; P = 0.046)).

Conclusion:

From the neonatal perspective conservative management is justified for pregnancies with ROM at or after 24 weeks gestation; in this group the use of antenatal steroids prior to delivery may improve perinatal outcome. A poor outcome is associated with ROM that occurs before 24 weeks gestation.     

Intracranial hypertension in Africans with cerebral malaria

The causes of death and neurological sequelae in African children with cerebral malaria are obscure. Intracranial pressure (ICP) was monitored and cerebral perfusion pressure (CPP) calculated in 23 Kenyan children with cerebral malaria. Four children had severe intracranial hypertension (ICP > 40 mm Hg, CPP < 40 mm Hg): two died, one with an ICP of 158 mm Hg and signs of transtentorial herniation, the other one with an ICP of 42 mm Hg and cardiorespiratory arrest. The other two survived with severe neurological sequelae. Nine had intermediate intracranial hypertension (ICP > 20 mm Hg, CPP < 50 mm Hg) and 10 had mild intracranial hypertension (maximum ICP 10-20 mm Hg); all survived without severe sequelae. Mannitol controlled the ICP in children with intermediate intracranial hypertension, but it did not prevent the development of intractable intracranial hypertension in children with severe intracranial hypertension. Intracranial hypertension is a feature of Kenyan children with cerebral malaria and severe intracranial hypertension is associated with a poor outcome.     

Mortality and diabetes from a population based register in Yorkshire 1978-93

OBJECTIVE: To investigate mortality of children diagnosed with insulin dependent diabetes mellitus (IDDM) and to identify common factors before death. DESIGN: Follow up of a population based cohort of children diagnosed with IDDM to ascertain deaths. SETTING: Children were diagnosed in Yorkshire but followed up throughout the United Kingdom. SUBJECTS: From the Yorkshire Children's Diabetes Register details of 1854 children aged 0-16 years (1978-93) were submitted to the NHS Central Register. MAIN OUTCOME MEASURE: Notification and causes of death. RESULTS: 98.3% of cases were traced and 26 deaths identified. Follow up ranged from 1-18 years (median 9.3 years), providing 17,350 person-years of IDDM. Fifteen deaths (58%) were attributed to diabetes or its complications; 11 (42%) were unrelated and included one suicide. For mortality from all causes, the standardised mortality ratio (SMR) of 247 (95% confidence interval (CI) 163 to 362) was significantly increased for those under 34 years. The largest number of deaths (n = 10) occurred in the 15-19 year age range, with an SMR of 442 (95% CI 209 to 802). Case note examination showed a clear tendency towards poor diabetic control, and worries over control were expressed before death by health care professionals. CONCLUSIONS: Despite advances in treatment, IDDM still carries an increased mortality for young people, particularly in the "transition" age range.     

vacA genotypes in Helicobacter pylori strains isolated from children with and without duodenal ulcer in Brazil

Data concerning the association between vacA genotypes and disease in children in both developed and developing countries are scarce, especially because of the small number of children with a duodenal ulcer studied. The vacA genotypes of Helicobacter pylori strains obtained from 65 children (24 with a duodenal ulcer and 41 without a duodenal ulcer; 33 girls; mean age, 10.2 years; age range, 1 to 17 years) were investigated as described by J. C. Atherton et al. (J. Clin. Microbiol. 37:2979-2982, 1999). Ten (15.4%) children were infected with more than one H. pylori strain. None of these patients were included in our analysis of the relationship between gastric disorders and specific vacA genotypes. The s1 allele was detected in all H. pylori strains isolated from patients with a duodenal ulcer and from 21 (58.3%) patients without a duodenal ulcer (P = 0.003). Strains with the s2 allele were found only in patients without ulcer (n = 15; 41.7%). Most s1 strains had the s1b allele (97.5%), a result similar to that reported for adults from the Iberian peninsula, which could reflect the Brazilian population origin. One untypeable s1 strain was isolated. The m1 allele was also more frequently found in strains obtained from duodenal ulcer patients (P = 0.028). The m2 allele was found in strains obtained from 20 (36. 4%) children, 3 (15.8%) with an ulcer and 17 (47.2%) without an ulcer. Only one m hybrid strain (m1 and m2 hybrid) was detected. It was demonstrated for the first time that the frequencies of colonization with strains with the s1 allele (14.3% in children up to 8 years of age and 85.7% in older patients; P = 0.012) and of strains with the m1 allele (11.1% in patients up to the age 8 years and 88.9% in older children; P = 0.013) increase with age.     

Helicobacter species in the intestinal mucosa of patients with ulcerative colitis

In a search for Helicobacter species in the intestinal mucosae of 42 patients with ulcerative colitis (UC) and 74 without UC, only H. pylori was found. Although the bacterium was detected in UC patients by culture (7.1%) and nested PCR (19.0%), its presence was not associated with the disease (P = 0.13).