Recent eLetters

Sir, Alvarez and colleagues1 report a clinically useful metanalysis on the diagnostic value of subependymal pseudocysts and choroid plexus cysts seen on neonatal cerebral ultrasound. It appears that complex subependymal cysts at the caudothalamic groove may be more important clinically than simple cysts here or in the choroid plexus. Their analysis did not expose two other important conditions causing multiple and/or bilateral subependymal pseudocysts in the neonate. Firstly glutaric aciduria type 1(GA1) 2,3, although rare, is important, as it is a potentially treatable autosomal recessive disorder and signs such as macrocephaly may not be present in the neonatal period. In GA1 the subependymal cysts tend to be complex. Screening for this disorder is easy by urine organic analysis, blood spot glutarylcarnitine and plasma total and free carnitine estimations; if abnormal confirmation is by fibroblast glutaryl CoA dehydrogenase activity3 and mutation analysis. The second disorder to consider is in utero exposure to cocaine. While there is debate in the literature, many studies have shown an association with subpendymal cysts4, and subepedymal hemorrhage5. The effect on the foetus may be dose dependent 5 and is likely vascular in basis. In these cases a detailed antenatal history may identify the diagnosis.

1. Fernandez Alvarez JR, Amess PN, Gandhi RS, Rabe H. Diagnostic value of subependymal pseudocysts and choroid plexus cysts on neonatal cerebral ultrasound: a meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2009 ;94(6):F443-F446. 2. Twomey EL,Naughten ER, Donoghue VB ,Ryan S. Neuroimaging findings in glutaric aciduria type 1 .Pediatr Radiol 2003 ;33: 823–830. 3. Hartley L.M, Khwaja O. S, Verity C.M, Glutaric Aciduria Type 1 and Nonaccidental Head Injury. Pediatrics 2001;107(1):174-175 . 4. Smith LM, Qureshi N, Renslo R, Sinow RM. Prenatal cocaine exposure and cranial sonographic findings in preterm infants. J Clin Ultrasound. 2001;29(2):72-77. 5. Frank D.A, McCarten K.M, , Robson C.D, Mirochnick M, Cabral H, Park H, Zuckerman B. Level of In Utero Cocaine Exposure and Neonatal Ultrasound Findings. Pediatrics. 1999;104(5 Pt 1):1101–1105.

Dear Sir

I am writing this letter in reference to the article "Rapid quantitative procalcitonin measurement to diagnose nosocomial infections in newborn infants" by Jacquot et al. [1] The aim of this study was to investigate the diagnostic accuracy of procalcitonin in neonatal nosocomial infections. However, the flawed methodology and the incomplete reporting preclude a reliable conclusion with respect to the diagnostic performance of procalcitonin for ruling out nosocomial sepsis.

With an eye to the study objective, the power calculation should have been based on the expected sensitivity, specificity, predictive accuracy and their minimal acceptable lower confidence limit. [2,3] The authors omitted to report the 95% confidence interval for the estimates of sensitivity and negative predictive value. This prevents the reader of appreciating the range within which the true values are likely to lie [4]. Therefore, I backward calculated the true positive (30), false positive (15), false negative (0), and true negative (28) test results. Using a commercial statistical package (Prism 5.0 GraphPad software, San Diego, CA, USA), the sensitivity (95% CI) can be calculated to be 1 (0.8843 to 1) whereas the accuracy of a negative test is 1 (0.8766 to 1).

As yet, given this (im)precision, procalcitonin cannot be used to rule out nosocomial infection in the NICU at the moment of suspicion.

References:

1. Jacquot A, Labaune JM, Baum TP, Putet G, Picaud JC. Rapid quantitative procalcitonin measurement to diagnose nosocomial infections in newborn infants. Arch Dis Child Fetal Neonatal Ed 2009;94:F345-8.

2. Flahault A, Cadilhac M, Thomas G. Sample size calculation should be performed for design accuracy in diagnostic test studies. J Clin Epidemiol 2005;58:859-62.

3. Buderer NM. Statistical methodology: I. Incorporating the prevalence of disease into the sample size calculation for sensitivity and specificity. Acad Emerg Med 1996;3:895-900.

4. Harper R, Reeves B. Reporting of precision of estimates for diagnostic accuracy: a review. BMJ 1999;318:1322-3.

Competing interests: None

Azzopardi et al (1) report the experience of introducing total body cooling as a standard form of therapy for infants with moderate or severe perinatal asphyxia. It is notable that this publication includes only one level 2 neonatal intensive care unit of the 25 units providing data for the TOBY register (Royal Cornwall Hospital, Truro). The Royal Devon and Exeter Hospital (also a level 2 unit) has since joined the TOBY register having participated in the TOBY trial. Part of the success in recruitment to the TOBY trial was due to the trial being rolled out to many more units in the second phase of the trial (2). The Peninsula Neonatal Network level 3 unit at Derriford Hospital in Plymouth participated in this trial as did the two level 2 units in Exeter and Truro. All the units were very well supported by training days set up at the units by the TOBY trial investigators.

In the Peninsula Neonatal Network this system of care has continued and total body cooling is provided at the three units that participated in the TOBY trial. Since the trial 6 babies have been cooled in Exeter and 9 babies in Truro. The two level 2 units inform the level 3 unit of infants that are being cooled. We believe that there are significant advantages providing total body cooling on a locality basis when the skills are there and the training is continually updated as long as the infant is stable without evidence of multi-system problems. There is close liaison on these issues with the level 3 centre. Early treatment is important and this is best done as soon as possible in the unit in which the infant is born. There are real benefits to not transferring the infant out to another unit particularly when the delivery has been traumatic and there may be a number of questions from parents and vital issues of communication about obstetric management. These can be addressed quickly and locally in these high risk situations. Providing thermal control for infants is part of the everyday management of neonatal units and the level 2 units have had no difficulty in the technical aspects of providing body cooling. This is likely to be made easier with the advent of servo controlled cooling. We all contribute to the TOBY register which provides feedback on our temperature control and all those providing cooling in the units have attended and presented at regional and national meetings on total body cooling.

We believe that there is a strong case to be made for level 2 units who have experience of cooling to continue to provide this. It is important to remember that one of the central tenets of the NHS is to provide appropriate care as close to home as possible for the family. The case for cooling to be provided in level 2 units rests on the support structures and a rigorous approach to case review and quality control/audit both through the TOBY register and by local oversight. The network approach establishes this by ensuring treatment is supported as a network provision, not as a unit provision.

Yours sincerely

Dr Michael Quinn Consultant Neonatal Paediatrician, Neonatal Unit, Royal Devon and Exeter Hospital, Barrack Rd, Exeter EX2 5DW

Dr Paul Munyard Consultant Neonatal Paediatrician, Neonatal Unit, Royal Cornwall Hospital, Treliske, Truro TR1 3LJ.

Correspondence to Dr Michael Quinn.

Competing Interests: None

REFERENCES

1. Azzopardi D, Strohm B, Edwards AD, Halliday H, Juszczak E, Levene M, Thoresen M, Whitelaw A, Brocklehurst P on behalf of the Steering Group and TOBY Cooling Register participants. Treatment of asphyxiated newborns with moderate hypothermia in routine clinical practice: how cooling is managed in the UK outside a clinical trial. Arch Dis Child (Fetal and Neonatal Edition) 2009; 94 (4):F260-F264 2. Azzopardi D, Strohm B, Edwards AD, Dyet L, Halliday H, Juszczak E, Kapellou O, Levene M, Marlow N, Porter E, Thoresen M, Whitelaw A, Brocklehurst P for the TOBY Study Group. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Eng J Med 2009; 361 (14): 1349-1358

Dear Sir, Dr Hawkes is right, if a gas flow meter that will deliver very high flows when turned up to its maximum flow, which may be over 80 L/min, is used with the Neopuff then if the flow is increased about the set level dangerously high levels of PIP and PEEP will be delivered. What is not commonly known is that some flow meters that are marked to deliver a flow from 0 to 15 L/min can deliver these very high flows which will overwhelm the pressure control valves in the Neopuff. A flow meter should never be used with the Neopuff that can deliver a maximum gas flow above 15 L/min. The practical message for all who use the Neopuff is that it should be used according to the manufacturer’s instructions. • The recommended operating gas flow range is 5 to 15 L/min. It specifically says, “Do not attempt to use a flow higher than 15 L/min". • Adjust the gas supply to the desired flow rate between 5 and 15 L/min then set the PIP and PEEP. • If the flow rate increases from 5 to 15L/min, peak pressure typically increases approximately 8 cm H2O/mbar. • The Neopuff should only be used on a baby after checking that correct pressures will be delivered to the baby. If the Neopuff PIP and PEEP are set with a flow of 5 L/min then if the flow is increased to 10 L/min the PEEP will rise to about 15 cm H2O and the PIP will be similar to, or just above the set PIP even when max PIP is set very high. If the flow is increased to 15 L/min the PEEP rises to about 24 cm H2O and PIP is similar to, or just above the set PIP even when max PIP is set very high. The effect of increasing the flow to 15 L/min will be much less if the PIP and PEEP were set at a flow of 10 l/min at the start. The practical clinical messages are simple 1) Pick a flow you are going to use, we suggest 8 L/min should be more than adequate, set the PEEP and PIP and then don’t alter the flow. 2) If the PEEP and PIP are not being delivered this is due to a large leak between the mask and face and that should be remedied by altering mask position and hold and not by increasing the flow. Yours sincerely, Colin Morley, Georg Schmoelzer, Peter Davis

We read with interest the article by K Ganesan et al 1 about using prophylactic oral Nystatin to prevent fungal colonisation and invasive fungaemia. We strongly support this practice especially in preterm babies who are on broad spectrum antibiotics.

It is interesting to know if the authors discovered any other bacterial organisms apart from candida in there routine surveillance swabs. We in our unit in Royal Oldham hospital (large District Hospital 16 neonatal level 2 Cots) not only swab babies but also there microenvironment, toys and religious items left in incubators and cots. In a recent random safety study we found 16 items in 10 cots, surveillance swabs taken form them revealed scanty growth of skin organisms in 7, scanty to moderate growth of coliforms in 3 and scanty growth of staphylococci in 1. It is interesting to note that none of these environmental swabs demonstrated any fungal colonisation. In view of the above study findings we follow a ‘No soft toys or religious items in cots/incubators policy’ along with the enforcement of strict hand washing policy.

Prophylactic nystatin could be the way forward to prevent fungal colonisation but what about colonisation from other bacterial organisms?. The age old saying ‘Prevention is better than cure’ stands true in our fight against infection and hence the need to maintain a clean microenvironment in the neonatal unit.