Performance of a Novel Molecular Method in the Diagnosis of Late-Onset Sepsis in Very Low Birth Weight Infants.

OBJECTIVE: To compare the use of a generic molecular assay to 'standard' investigations used to assist the diagnosis of late onset bacterial sepsis in very low birth weight infants (VLBW, <1500 g). METHODS: VLBW infants, greater than 48 hours of age, who were clinically suspected to have sepsis were investigated using standard tests (full blood count, C-reactive protein (at presentation) and blood culture), in addition, blood was taken for a universal molecular assay (16S rRNA reverse transcriptase PCR) for comparison. Clinical data were recorded during the suspected infection episode. A validated sepsis score (NEO-KISS) was used to retrospectively determine the presence of sepsis (independent of blood culture). The performance of each of the tests were compared by sensitivity, specificity, positive/negative likihood ratios (+/-LR) and postive/negative predictive values (PPV/NPV). RESULTS: Sixty-five babies with suspected clinical sepsis were prospectively included. The performance indicators are presented with 95% confidence limits. For the detection of bacteria, blood culture had sensitivity of 0.57 (0.34-0.78), specificity of 0.45 (0.30-0.61); +LR of 1.05 (0.66-1.66) and-LR of 0.94 (0.52-1.7); PPV of 33.3 (18.56-50.97) and NPV of 68.97 (49.17-87.72). Serum CRP had sensitivity of 0.92 (0.64-1) and specificity of 0.36 (0.17-0.59); +LR of 1.45 (1-2.1) and-LR of 0.21 (0.03-1.5); PPV of 44.46 (26.6-66.6) and NPV of 88.9 (51.8-99.7). The universal molecular assay had sensitivity of 0.76 (0.53-0.92), specificity of 0.95 (0.85-0.99); +LR of 16.8 (4.2-66.3) and-LR of 0.25 (0.1-0.5); PPV of 88.9 (65.3-98.6) and NPV of 89.4 (76.9-96.5). CONCLUSIONS: In VLBW infants this universal molecular assay performed better in the diagnosis of late onset sepsis (LOS) than blood culture and CRP. Further development is required to explore and improve the performance of the assay in real-time diagnosis.

Human parechovirus infection in neonatal intensive care.

BACKGROUND: Approximately 5-6% of all infective episodes in neonatal intensive care unit (NICU) are of viral origin. Previous studies suggest that human parechovirus (HPeV) infection presents most commonly in term infants, as a sepsis-like syndrome in which meningoencephalitis is prominent. Our aim was to study the infection rate and associated features of HPeV. METHODS: Blood samples were taken from NICU babies older than 48 hours, who were being investigated for late onset sepsis. Clinical and laboratory data were collected at the time of the suspected sepsis episode. Samples were tested using universal primers and probe directed at the 5'-untranslated region of the HPeV genome by reverse transcriptase polymerase chain reaction (RT-PCR). Results were confirmed by electrophoresis and DNA sequencing. RESULTS: HPeV was detected in 11 of 84 samples (13%). These infants had a mean [interquartile range (IQR)] gestational age of 28.9 (26.9-30.6) weeks and mean birth weight of 1.26 (SD = 0.72) kg. The median day of presentation was 16 (IQR: 11-27). These characteristics were similar to the infants without positive viral detection. Six infants presented with respiratory signs. One infant presented with signs of meningitis. Six of the 11 episodes of HPeV infection occurred during the winter months (December to February). No HPeV positive infants had abnormal findings on their 28-day cranial ultrasound examination. CONCLUSIONS: We found an HPeV infection rate of 13% in infants being tested for late onset sepsis. HPeV should be considered as a possible cause of sepsis-like symptoms in preterm infants.

ABCA3 Deficiency: an unusual cause of respiratory distress in the newborn.

Respiratory Distress Syndrome (RDS) is due to deficiency of surfactant and commonly occurs in preterm babies. We report the first confirmed case in Northern Ireland of ABCA3 transporter deficiency which is a rare but important cause of RDS in term babies.A 38 week gestation female infant developed respiratory distress at four hours of age. Chest radiography was consistent with RDS. The baby required repeated doses of surfactant, each resulting in transient periods of decreased ventilatory requirement and improvement in blood gases, but unfortunately she did not survive.DNA sequencing demonstrated two different mutations in the ABCA3 gene, one inherited from each parent. The baby was therefore a compound heterozygote, and both mutations were thought to be functionally significant.ABCA3 transporter deficiency is a genetic disorder that is increasingly recognized as a cause of RDS in term babies in whom congenital deficiency of surfactant B and abnormalities of surfactant protein C have been excluded. It should be considered in mature babies who develop severe RDS.

Variation in [U-13C] alpha linolenic acid absorption, beta-oxidation and conversion to docosahexaenoic acid in the pre-term infant fed a DHA-enriched formula.

Docosahexaenoic acid (DHA) is an integral component of neural cell membranes and is critical to the development and function of the CNS. A premature delivery interrupts normal placental supply of DHA such that the infant is dependent on the nature of the nutritional support offered. The most abundant omega-3 fatty acid in pre-term formulas is alpha linolenic acid (ALNA), the precursor of DHA. This project studied the absorption, beta-oxidation and conversion of ALNA to DHA by pre-term infants ranging from 30-37 wk of corrected gestation. [U-(13)C] ALNA was administered emulsified with a pre-term formula to 20 well pre-term infants on full enteral feeds. Enrichment of (13)C in stool and as (13)CO(2) in breath was used to estimate absorption across the gut and partitioning toward beta-oxidation respectively. Excretion of the administered dose of (13)C in stool ranged from 2.0 to 26.2%; excretion decreased with increasing birth gestation. Appearance as (13)CO(2) on breath ranged from 7.6 to 19.0%. All infants synthesised eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and DHA with the least mature having the highest cumulative plasma DHA. These results show considerable variation suggesting that the worst absorption of ALNA and the greatest production of DHA occur in infants born at the earliest gestation.

Readmission with respiratory syncytial virus (RSV) infection among graduates from a neonatal intensive care unit.

We evaluated the incidence of readmission with respiratory syncytial virus (RSV) infection among the graduates of a regional Neonatal Intensive Care Unit (NICU), and characterized those who were rehospitalized. These data were used as a predictive tool to estimate the number of babies likely to suffer readmission with RSV for the year 2000 cohort. Using the published efficacies of palivizumab, the costs and benefits of protecting this cohort were assessed. Retrospective analysis of 2,507 NICU inpatient records from January 1, 1994-December 31, 1999 from the Royal Maternity Hospital, Belfast, were compared with data on positive RSV samples from 1,790 patients between January 1, 1995-December 31, 1999 from the Northern Ireland Regional Virus Laboratory. The analysis yielded 136 (7.6%) ex-NICU patients among the positive RSV samples over this 5-year period. Characteristic seasonal peaks of RSV infection with interseasonal variability were observed. Of those readmitted, 86.9% were hospitalized with RSV before their first birthday. A calculated readmission rate of 5.4% for all NICU graduates, and 6.4% for those