Mitochondrial respiratory chain complex IV deficiency presenting as neonatal respiratory distress syndrome.

A term girl infant delivered following foetal distress presented with early respiratory distress syndrome and lactic acidaemia. She subsequently underwent detailed investigation for primary lactic acidaemia and was identified as homozygous for the c.515A>G,p.(Tyr172Cys) missense variant in the LRPPRC gene. Variants in this gene are known to cause French-Canadian type Leigh syndrome. Both parents were confirmed to be heterozygous for this mutation. This is the first case report of mitochondrial respiratory chain complex IV deficiency presenting as foetal distress and neonatal respiratory distress syndrome.

Meconium pseudocyst presenting as massive ascites in a new-born.

Meconium pseudocyst (MPC) is a rare but well-known surgical condition due to prenatal bowel perforation. A case of MPC secondary to prenatal bowel perforation is presented. Massive ascites requiring peritoneal drainage and disappearance of prenatal intraperitoneal calcifications have not been previously reported in MPC. MPC may present at birth with large ascites requiring peritoneal drainage to establish breathing and ventilation. Absence of prenatal intra-abdominal calcifications does not rule out MPC.

Cluster of human parechovirus infections as the predominant cause of sepsis in neonates and infants, Leicester, United Kingdom, 8 May to 2 August 2016.

We report an unusually high number of cases (n = 26) of parechovirus infections in the cerebrospinal fluid (CSF) of neonates and infants admitted with sepsis in the United Kingdom during 8 May to 2 August 2016. Although such infections in neonates and infants are well-documented, parechovirus has not been routinely included in many in-house and commercial PCR assays for CSF testing. Clinicians should consider routine parechovirus testing in young children presenting with sepsis.

Dried blood spots and sparse sampling: a practical approach to estimating pharmacokinetic parameters of caffeine in preterm infants.

AIMS: Dried blood spots (DBS) alongside micro-analytical techniques are a potential solution to the challenges of performing pharmacokinetic (PK) studies in children. However, DBS methods have received little formal evaluation in clinical settings relevant to children. The aim of the present study was to determine a PK model for caffeine using a 'DBS/microvolume platform' in preterm infants. METHODS: DBS samples were collected prospectively from premature babies receiving caffeine for treatment of apnoea of prematurity. A non-linear mixed effects approach was used to develop a population PK model from measured DBS caffeine concentrations. Caffeine PK parameter estimates based on DBS data were then compared with plasma estimates for agreement. RESULTS: Three hundred and thirty-eight DBS cards for caffeine measurement were collected from 67 preterm infants (birth weight 0.6-2.11 kg). 88% of cards obtained were of acceptable quality and no child had more than 10 DBS samples or more than 0.5 ml of blood taken over the study period. There was good agreement between PK parameters estimated using caffeine concentrations from DBS samples (CL = 7.3 ml h⁻¹ kg⁻¹; V = 593 ml kg⁻¹; t(½) = 57 h) and historical caffeine PK parameter estimates based on plasma samples (CL = 4.9-7.9 ml h⁻¹ kg⁻¹; V = 640-970 ml kg⁻¹; t(½) = 101-144 h). We also found that changes in blood haematocrit may significantly confound estimates of caffeine PK parameters based on DBS data. CONCLUSIONS: This study demonstrates that DBS methods can be applied to PK studies in a vulnerable population group and are a practical alternative to wet matrix sampling techniques.

Successful treatment of meticillin-resistant Staphylococcus aureus bacteraemia in a neonate using daptomycin.

Daptomycin is licensed for the management of Staphylococcus aureus infections in adults, including those caused by meticillin-resistant S. aureus (MRSA). Few data exist on paediatric use or dose guidance in neonates. We report the case of a neonate with MRSA bacteraemia successfully managed with daptomycin. Dose requirements were substantially higher than those recommended for adults.

Dexamethasone quantification in dried blood spot samples using LC-MS: The potential for application to neonatal pharmacokinetic studies.

A high-performance liquid chromatography (LC-MS) method has been developed and validated for the determination of dexamethasone in dried blood spot (DBS) samples. For the preparation of DBS samples whole blood spiked with analyte was used to produce 30µl blood spots on specimen collection cards. An 8mm disc was cut from the DBS sample and extracted using a combination of methanol: water (70:30, v/v) containing the internal standard, triamcinolone acetonide. Extracts were centrifuged and chromatographic separation was achieved using a Zorbax Eclipse Plus C18 column using gradient elution with a mobile phase of acetonitrile and water with formic acid at a flow rate of 0.2ml/min. LC-MS detection was conducted with single ion monitoring using target ions at m/z 393.1 for dexamethasone and 435.1 for the internal standard. The developed method was linear within the tested calibration range of 15-800ng/ml. The overall extraction recovery of dexamethasone from DBS samples was 99.3% (94.3-105.7%). The accuracy (relative error) and precision (coefficient of variation) values were within the pre-defined limits of ≤15% at all concentrations. Factors with potential to affect drug quantification measurements such as blood haematocrit, the volume of blood applied onto the collection card and spotting device were investigated. Although a haematocrit related effect was apparent, the assay accuracy and precision values remained within the 15% variability limit with fluctuations in haematocrit of ±5%. Variations in the volume of blood spotted did not appear to affect the performance of the developed assay. Similar observations were made regarding the spotting device used. The methodology has been applied to determine levels of dexamethasone in DBS samples collected from premature neonates. The measured concentrations were successfully evaluated using a simple 1-compartment pharmacokinetic model. Requiring only a microvolume (30µl) blood sample for analysis, the developed assay is particularly suited to pharmacokinetic studies involving paediatric populations.

Iatrogenic malnutrition in neonatal intensive care units: urgent need to modify practice.

BACKGROUND: Extrauterine growth retardation is a major clinical problem in very-low-birth-weight infants. Parenteral nutrition (PN) serves to achieve rapid maximal nutrition in early postnatal life. There is a lack of uniformity with regard to neonatal PN practice. The objective of this study is to ascertain current practice regarding neonatal PN prescription in the early postnatal period in the United Kingdom. METHODS: A study questionnaire was e-mailed to neonatal pharmacists serving level 3 and major level 2 units in the United Kingdom between October 2005 and March 2006. Static numerical information regarding glucose, amino acids, and lipid prescription during the first 10 days of life was collected and compared with current recommendations. RESULTS: Fifty-two (81%) units responded to the questionnaire; 4 units were excluded for incomplete data. Twenty-six units (54%) initiated PN on day 1. Full PN was achieved by the median age of 6 days. Twelve units (25%) achieved full PN only by day 7 or later. Maximum median amino acids were 2.9 g/kg/d. Only 13 units (27%) prescribed >/=3 g/kg/d, and 2 prescribed more than 3.5 g/kg/d. Nineteen units (39%) initiated lipids on day 1. Eleven units (23%) delayed lipids until day 3, and 2 units delayed lipids until day 4. In comparison to the recommended intake of calories and amino acids, the current median prescription would result in a cumulative deficit over the first 10 days of 420 kcal/kg and 11.9 g/kg, respectively. CONCLUSIONS: Our study suggests diverse practice with regard to neonatal PN prescription in the United Kingdom. Current neonatal PN practice entails a significant calorie and protein deficit during early postnatal life and warrants further review.

Tracheal bronchus associated with VACTERL.

UNLABELLED: Tracheal bronchus (TB) associated with VACTERL has not been reported previously. A 5-month-old girl with VACTERL association was ventilator-dependent following surgical closure of a patent ductus arteriosus (PDA). Chest radiographs showed persistent hyperinflation of the right upper lobe. Bronchoscopy showed a laterally displaced right main bronchus with stenosis and malacia of the left main bronchus. Dynamic bronchography revealed a TB associated with tracheal stenosis and malacia below the abnormal bronchus. TB may represent an additional tracheal (T) anomaly in VACTERL association. Dynamic bronchography is a useful diagnostic tool in tracheobronchial anomalies. CONCLUSION: TB may represent an "associated" tracheal (T) anomaly in children with VACTERL association. Bronchoscopy may fail to diagnose an ectopic bronchus. Dynamic bronchography is a useful diagnostic tool in tracheobronchial anomalies.