Recent eLetters
Displaying 1-10 letters out of 541 published
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Re:Procalcitonin for early diagnosis of neonatal nosocomial sepsis
Submit responseDear Editor, Thank you for the opportunity of answering to the comments of Chiesa (1) about our paper (2). First, the assay: Procalcitonin (PCT) was measured with an immunoluminometric, quantitative method, as in studies cited by us and by Chiesa. We used reagents Brahms and Berthold LB9507 luminometer (Dasit). The analytical signal, proportional to the concentration of the PCT in the sample, was converted into continuous concentration values. The definitive results were available in 5-6 hours from the blood collection, that we considered as "fast".
Second: the first blood sample was taken on admission of all patients to NICU (time 0), in the absence of clinical and laboratory signs of infection, to check the increase of PCT during the subsequent infection, when it would be manifested. These results were never included in the calculation of the maximum value of PCT during infection. Infants with maternal-fetal infections were excluded from the study. In neonates who developed signs of nosocomial sepsis at least 48 h after the admission in NICU, PCT levels were further measured, as stated in the methods, at least within 24 and 48 h after the onset of the infection. These data only were used to calculate the median value of the highest PCT levels during the infection. PCT was also measured in 762 (GA 34+/-4 weeks, BW 2130+/-863 g) critically ill, but uninfected, patients; 205 of them were VLBW (29+/-3 weeks, BW 1123+/-258g), admitted to NICU in the first three days of life. Our unpublished data confirm a physiologic increase in PCT levels during the first days of life (3-5). Considering all uninfected neonates, the median values of PCT by day of life were: 0.40 ng/ml (IQR 0.21-1.20), in the first , 2.38 ng/ml (IQR 0.77-8.76), in the second and 0.52 ng/ml (IQR 0.28 -1.37), in the third. We obtained similar results in VLBW infants. Stratifying for BW (collinear with gestational and postnatal age), the accuracy of PCT did not differ significantly in neonates with a BW 1500- 2500 gr from that of heavier BW: a cut-off of 2.4 ng/ml. yielded a sensitivity of 55%, a specificity of 84% and a positive Likelihood Ratio of 3.4. Finally, in the first study of Chiesa, cited in his letter, (3) PCT was measured in healthy neonates, and a nomogram was established with statistical cut-offs. Despite this, when the problem of late-onset sepsis was investigated, a matched case-control design was adopted. (4) In this study cases and controls were defined, on clinical grounds, as we did, apparently ignoring statistical cut-offs and postnatal age, that was one of the variables of matching. Turner introduced as well a nomogram by gestational age in the first 4 days of life (5). However he has published results about PCT accuracy in another study (6), with the current, evidence-based approach, where different cut-offs were explored to establish the most appropriate for clinical application in a given context,. A number of biological or clinical reasons (e.g. concomitant diseases, age, labour, drugs etc.) can lead to misdiagnosis, measured by sensitivity, specificity and the other values of accuracy, that we hold as meaningful with our approach.
Dr.ssa Cinzia Auriti Dr. Vincenzo M. Di Ciommo
1). Chiesa C, Pacifico L, Osborn JF, Natale F, De Curtis M Procalcitonin for early diagnosis of neonatal nosocomial sepsis Arch Dis Child Fetal Neaonatal Ed Published 31 March 2011 2). Auriti C, Fiscarelli E, Ronchetti MP, at al. Procalcitonin in detecting neoanatal nosocomial sepsis. Arch Dis Child Fetal Neaonatal Ed 2011.Published online First: 15 March 2011 doi:10.1136/adc.2010.194100 3) Chiesa C, Panero A, Rossi N, et al. Reliability of procalcitonin concentrations for the diagnosis of sepsis in critically ill neonates. Clin Infect Dis 1998;26:664-72. 4) Chiesa C, Natale F, Pascone R, et al. C reactive protein and procalcitonin: Reference intervals for preterm and term newborns during the early neonatal period. Clin Chim Acta 2011; 412: 1053-59 5) Turner D, Hammerman C, Rudensky B, et al. Procalcitonin in preterm infants during the first few days of life: introducing an age related nomogram. Arch Dis Child Fetal Neonatal Ed 2006;91:F283-6 6) Turner D, Hammerman C, Rudensky B, et al. The role of procalcitonin as a predictor of nosocomial sepsis in preterm infants. Acta Paediatr 2006;95:1571-6
Conflict of Interest:
None declared
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Survey of management of patent ductus arteriosus in neonatal units across England
Submit responseWe read with great interest the review "Patent ductus arteriosus-time to grasp the nettle" (Smith, Kissack, ADC F&N 2013; 98) which highlighted the controversies in PDA management and variation in management. Evidence to support the routine closure of the ductus arteriosus to improve neonatal morbidity remains inconclusive1. We recently conducted a survey on PDA management in neonatal units across England to understand current clinical practice. A structured questionnaire was emailed with an online hyperlink to consultant neonatologists working in tertiary neonatal units in England.Fourteen questions addressed work load, management strategies, fluid management, drugs used, threshold for treatment of PDA, cardiology service available in their unit. The survey was conducted from August 2012 to November 2012. The response rate was 75%.The majority (68%) of neonatologists felt that a symptomatic strategy best describes their practice for treating PDA, while 25% felt that they practised a presymptomatic/ echo directed targeted strategy. Only two neonatologists (at the same unit) practice a prophylactic treatment strategy and two neonatologists felt that their practice does not fit in any of above categories. Significant variation was observed when percentage of preterm babies treated for PDA/year was compared within different units practising same symptomatic strategy (7% to 75%).The drug of choice for treating PDA was ibuprofen for 74% of neonatologists, with only 26% using indomethacin. Fluid intake is restricted in PDA by18 neonatologists out of 63 (28%); 16 of these restrict fluids only in symptomatic babies while two restrict fluid in all babies with PDA. Most neonatologists continue feeds during medical treatment of a PDA with only 6 (10%) stopping. Just over half of neonatologists restrict fluids while treating baby for PDA (53%). We asked clinical questions to all the neonatologists to understand the threshold for treatment. Previously a similar question was asked to neonatologists in the United States of America2. Neonatologists from UK are much more conservative when compared to neonatologists from United States when it comes to treating PDAs in preterm babies. Interestingly 18% neonatologists from England said that they would treat a moderately large PDA in a preterm baby, even if the baby is extubated and on CPAP with 5% going on to surgical ligation if medical treatment fails or is contraindicated. No neonatologists from the UK would treat a moderate to large PDA in a baby who is self-ventilating in air as opposed to one third of Neonatologists from United States. A second course of medical treatment is given by 80% neonatologists before ligating PDA while 11% would give only one course of treatment before ligating the duct if baby hasn't responded. Of those that responded, only one neonatologist would give three courses of medical treatment before ligating while 5 neonatologists felt that they would very rarely ligate a PDA in preterm babies (1-5/every 5 years). Echocardiography was performed by 79% of neonatologists themselves to diagnose and treat PDA. In 46% of units there is no cardiology service and the decision to treat PDA is made based on echocardiography findings of the neonatologists. In these units babies require transfer to cardiology centre for cardiology input. Onsite cardiology services are available in 18% of the units, with 20% of units having a paediatric cardiologist visiting twice a week. Two units get cardiology input within 24 hrs of request and a further two units have a paediatric cardiology visiting twice a month. In conclusion, significant variations exist in practice amongst neonatologists when it comes to management of PDA in preterm babies. There are significant variations in the number of babies treated on different units by neonatologists claiming to follow same treatment strategy suggesting different thresholds for treatment. The use of a prophylactic treatment strategy is becoming rare. Most of neonatologists do echocardiography themselves to make a decision regarding treatment of PDA, with a half of units responding not having access to specialist cardiology services on site. Reference: 1. Bose CL, Laughon MM (2007) Patent ductus arteriosus: lack of evidence for common treatments. Arch Dis Child Fetal Neonatal Ed 92:F498-F502 2. Jhaveri N et al: Feeding practices and patent ductus arteriosus ligation preferences-are they related? Am J Perinatol 27: 667-674, 2009
Conflict of Interest:
None declared
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This may due to Low Maternal DHEA
Submit responseIt is my hypothesis that evolution selected dehydroepiandrosterone(DHEA) because it optimizes replication and transcription of DNA. Therefore DHEA levels affect all tissues and life span. (I think selection for DHEA produced mammalia. "Hormones in Mammalian Evolution," Rivista di Biologia / Biology Forum 2001; 94: 177- 184).
A case may be made that sufficient maternal DHEA is necessary both for conception and full term pregnancy. A mother must produce sufficient DHEA for herself as well as a fetus, until such time that the fetus starts to produce DHEA sufficient to initiate birth and support for itself.
A mother who has difficulty initiating and supporting conception and pregnancy may be low DHEA. If DHEA levels do affect all tissues, growth and development of the child may be impaired, especially for the brain. This may explain the findings of Seggers, et al.
Conflict of Interest:
None declared
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End of life decision making
Submit responseEnd of Life Decision Making (EoL DM) in NICU is an extremely sensitive issue. In our unit we have practiced shared DM for a long time however as the authors write we did not come across any large studies looking into parents perceptions of EoL DM in the long term.
1. We appreciate that telephonic interviews were discarded in this paper to ensure accurate assessment of parent's self-perceived role. Also interviews were conducted by three skilled interviewers and to ensure reliability of themes extracted, however it is not clear if each parent was interviewed three times, which if it did appeared a bit excessive. Also it was not clear where the interview happened. 2. We noted that only 145 out of 258 eligible families were contacted. We wonder whether inclusion of non-French speaking families would improve the sample size? 3. As noted by the authors there were limitations in the sample with overrepresentation of certain categories leading to limited possibility of generalization of results. Overall we appreciate the large amount of work into this study and hope that such studies will prompt further large projects to improve our strategies of decision making for these babies and families in times of extreme grief.
Conflict of Interest:
None declared
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Positioning of neonates for lumbar puncture
Submit responseLumbar puncture is a blind procedure (no guidance about the path of the lumbar puncture needle except for the sensory information that the performer obtains about interspinous distance before inserting the needle and upon puncturing the duramater). 1. We feel that the for a successful procedure, besides ensuring adequate interspinous space to insert the needle by ensuring optimum position of the patient it is very important to ensure that the patient is as calm and comfortable as possible so that we donot have to chase a moving target with a sharp needle. In our unit we use a few drops of 24% sucrose just before positioning in lateral recumbent position. The observation in the study that heart rate increases the most in sitting position (with or without flexed hips) in itself suggests that the baby is far from calm at that point. 2. The authors have concluded that 'Sitting flexed position of hips, which seems to be suffciently safe and serve to enhance the success rate of a LP' appears to be misrepresented as the authors have themselves recognized that one of the limitations of this study is that there is absence of performed lumbar puncture so success of the procedure cannot be gauged in this study. 3. Sitting position may not be practically feasible in preterm and sick ventilated neonates who have cardiovascular instability
Conflict of Interest:
None declared
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Re:Minimally-invasive (and painful?) surfactant therapy.
Submit responseSir, we read with interest the article by Dargaville et al., entitled "Minimally-invasive surfactant therapy in preterm infants on continuous positive airway pressure", in which the authors describe significant results using a semirigid vascular catheter inserted into the trachea by direct laringoscopy for surfactant administration, without analgesia and sedation(1). However, direct laringoscopy and tracheal manipulation, is an extremely distressing and painful procedure, with potential for airway and systemic injury. It is well established that direct laringoscopy and tracheal intubation without analgesia should be performed only for urgent resuscitations. Neonatal pain may result in altered systemic and cerebral blood pressure, intracranial hemorrhage, hypersensitive pain perception and long-term sequelaes(2). In their study 36% of the neonates had bradycardia sustained for more than 10s during laryngoscopy or vocal cord manipulation. It is now evident that initial stabilization with CPAP and rescue surfactant administration if necessary, is not worse than intubation, mechanical ventilation and surfactant administration immediately after birth. INSURE procedure is an alternative, combining early surfactant and CPAP. Welzing et al. have shown that INSURE can be performed using remifentanil as premedication for tracheal intubation with excellent neonatal outcome(3). In the same way, our group have shown that remifentanil as premedication allows early awakening and extubation(4). However, the short period of positive pressure ventilation required for INSURE, even if an ultra short acting opioid is used, could compromise the benefit of early surfactant. In this way, some reports have shown that a laryngeal mask airway (LMA) as a conduit for surfactant administration could be a simple and painless procedure(5). Trials of surfactant administration through the LMA are now being conducted. So, finding a noninvasive and painless method of surfactant administration, without laryngoscopy, tracheal manipulation and positive pressure ventilation, will be one of the most important subjects for neonatology research in upcoming years.
References 1.Dargaville PA, et al. Minimally-invasive surfactant therapy in preterm infants on continuous positive airway pressure. Arch Dis Child Fetal Neonatal Ed 2013;98:F122-F126. 2.Carbajal R, Eble B, Anand KJ. Premedication for tracheal intubation in neonates: confusion or controversy? Semin Perinatol 2007;3:309-17. 3.Welzing L, Kribs A, Huenseler C, Eifinger F, Mehler K, Roth B. Remifentanil for INSURE in preterm infants: a pilot study for evaluation of efficacy and safety aspects. Acta Paediatr 2009;98:1416-20. 4.e Silva YP, Gomez RS, Marcatto JdeO, Maximo TA, Barbosa RF, Silva AC. Early awakening and extubation with remifentanil in ventilated premature neonates. Paediatr Anaesth 2008;18:176-83. 5.Trevisanuto D, Grazzina N, Ferrarese P, Micaglio M, Verghese C, Zanardo V. Laryngeal mask airway used as a delivery conduit for the administration of surfactant to preterm infants with respiratory distress syndrome. Biol Neonate 2005;87:217-20.
Conflict of Interest:
None declared
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Born just a few weeks early: does it matter?
Submit responseSarah J Kotecha1, John Henderson2, Sailesh Kotecha1.
1Department of Child Health, Cardiff University, Cardiff. 2School of Social and Community Medicine, University of Bristol, Bristol.
Re: Born just a few weeks early: does it matter? Boyle et al. 98:F85- 88. Doi:10.1136/archdischild-2011-300535.
We read with interest the review by Boyle and Boyle on early and late morbidity in late preterm born children (1). Clearly there is increasing interest in late preterm born infants who have both increased short- and importantly long-term mortality and morbidity as we reviewed recently (2). Of interest to readers of Archives of Diseases of Childhood, will be recent publications using data from the Avon Longitudinal Study of Parents and Children cohort on longer term respiratory function and neurodevelopmental outcomes. Like Abe et al (3), we did not find strong evidence of an association between asthma and late preterm birth but we have reported decrements in FEV1 in late preterm infants, (born at 33-34 weeks gestation), at 8-9 years of age of the same magnitude as extremely preterm infants, (born at 25-32 weeks gestation), (4), recently highlighted in a Thorax editorial (5). Encouragingly, we did see improvements in FEV1 when the late preterm born infants were studied again at 14-17 years of age but clearly further studies are required to assess if these children are candidates for chronic pulmonary obstructive disease in adulthood especially if exposed to noxious substances such as tobacco smoke and environmental pollution. Furthermore, children born late-preterm are less likely to be successful in early school assessments than those born at term (6). In addition to those mentioned by Boyle and Boyle there is increasing literature in this field in particular reporting the longer term outcomes of this population; despite these observations, a recent survey by the British Thoracic Society of respiratory physicians noted that little consideration is given to early life factors when patients with respiratory disease are seen in their clinical practice (7). We are sure readers of Archives of Diseases of Childhood will be as concerned as we are about the potential public health impact of these effects if they are carried through the life course from 8-9 years into adulthood, especially as late preterm infants are a growing population.
1. Boyle JD, Boyle EM. Born just a few weeks early: does it matter? Arch Dis Child Fetal Neonatal Ed 2013;98:F85-88. Doi:10.1136/archdischild- 2011-300535. 2. Kotecha SJ, Dunstan FD, Kotecha S. Long term respiratory outcomes of late preterm-born infants. Semin Fetal Neonatal Med 2012 Apr;17(2):77-81. 3. Abe K, Shapiro-Mendoza CK, Hall LR, et al. Late preterm birth and risk of developing asthma. J Pediatr 2010;157:74-8. 4. Kotecha SJ, Watkins WJ, Paranjothy S, Dunstan FD, Henderson AJ, Kotecha S. Effect of late preterm birth on longitudinal lung spirometry in school age children and adolescents. Thorax 2012 Jan;67(1):54-61. 5. Bush A, Pavord ID. Thorax: the Cappuccino years. 2013 Jan;68(1): 1-4. 6. Peacock PJ, Henderson J, Odd D, Edmond A. Early school attainment in late-preterm infants. Arch Dis Child 2012;97:118-120. doi:10.1136/118 adc.2011.300925 7. Bolton CE, Bush A, Hurst JR, Kotecha S, McGarvey L, Stocks J, Walshaw M. Are Early Life Factors Considered when Managing Respiratory Disease? A British Thoracic Society (BTS) Survey of Current Practice. Thorax 2012 Dec;67(12):1110 (Research Letter)
Conflicts of interest
None to declare
Conflict of Interest: None declared
Conflict of Interest:
None declared
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Should air insufflation to aid location of gastric feeding tube tip location in neonates become standard practice?
Submit responseQuandt et al (1) have emphasised stomach insufflation as a means to improve neonatal feeding tube location rates. Experience in our neonatal unit indicates that other measures may be more important.
It is a practice standard in our neonatal unit for a gastric tube to be placed prior to performing the first chest radiograph. We retrospectively audited all first chest radiographs taken during the six month period from August 2011 to February 2012. We excluded infants who were born in another hospital or if there was no gastric tube present on first radiograph. Eighty-eight neonates fulfilled the inclusion criteria. Images were viewed on PACS (online digital radiograph viewing system). We scored the tube position as per Quandt et al (1) and images were viewed independently by two individuals (RB and LS) and results correlated. Tube tip was locatable in 90% of radiographs with sixty-seven in the stomach and thirteen outside the stomach. Of the eight radiographs with an unlocatable tip, all were explainable by truncation of the radiograph.
In summary, we did not find that prior air insufflation would have aided location. We did however identify a requirement to specify in the radiology request that the stomach be included in the radiographic field and also that the procedure for measuring estimated gastric tube length needed to be reviewed.
1. Quandt D, Brons E, Schiffer PM, et al. Improved radiological assessment of neonatal feeding tubes. Arch Dis Child Fetal Neonatal Ed 2013;98:F78-F80.
Conflict of Interest:
None declared
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Delay in identification of oesophageal atresia in a preterm neonate with radial club hand due to coiling of 5F nasogastric tube
Submit responseWe had a 29 weeks/1.29kg/male neonate born with left radial club hand deformity. The resident attending the resuscitation had 'passed' a 5F nasogastric tube and certified the orifices patent. Baby was admitted in NICU, had no respiratory distress and was started on trophic feeds of 2ml 2 hourly by 5F nasogastric tube passed via the nostril which the baby 'accepted'. After 12 hours baby developed worsening respiratory distress and had to be ventilated. Chest X ray taken without a nasogastric tube showed right upper lobe pneumonia. With a diagnosis of aspiration pneumonia, repeat Xray with 5F tube showed its tip to be coiled upwards in the thorax and absent gastric bubble and a gasless abdomen. The diagnosis of oesophageal atresia without fistula was confirmed by a 10F tube and contrast studies. With the additional finding of vertebral segmentation defects, the baby was labelled with a diagnosis of VACTERL association. This case illustrates the need for using a large size feeding tube to rule out oesophageal atresia. Patient Consent Obtained.
Conflict of Interest:
None declared
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Etiology of perinatal stroke; a role for prothrombotic coagulation factors?
Submit responseWe read with grat interest the article on perinatal stroke of J Harteman and co-workers. In our experience in perinatal stroke, multiple, often coexisting, risk factors are involved, varying from maternal and fetal risk factors during pregnancy and delivery, to infectious causes and cardiac diseases as well as medical interventions and congenital prothrombotic coagulation factors. We have performed a retrospective study to explore the prevalence of different predisposing conditions in perinatal stroke patients we evaluated 96 patients (43 males; 53 females), including subjects with ischemic and hemorrhagic stroke subtypes. Baseline investigations included complete blood count, total cholesterol, triglycerides, lipoprotein (a), prothrombin, activated thromboplastin, plasma fibrinogen level, activity of protein C sensitivity ratio, total plasma homocysteine, lupus anticoagulant, anticardiolipin, and anti-beta2 glycoprotein1 antibodies. DNA analysis was performed for the Factor V Leiden mutation, Factor II G20219A variant, and the thermolabile variant of MTHFR. We have oberved that the major genetic risk factor in our series of patients was heterozygosity and homozigosity for the MTHFR C677T mutation (39/96 patients; 40%) in 5 patients was associated with the Factor V Leiden mutation, in 6 with deficiency of activity of protein C. Acquired predisposing conditions were present in 18/96 (18%) patients and included Threatened abortion, oligohydramnios, intra uterine growth retardation, gestosis, chorioamniositis. In 7 patients both genetic and aquired predisposing factors were present. Our results emphasize that prothrombotic coagulation risk factors, especially MTHFR mutation, can predispose to perinatal stroke, alone or in combination with other genetic or acquired factors (1,2). References 1)Muwakkit SA, Majdalani M, Hourani R, Mahfouz RA, Otrock ZK, Bilalian C, Chan AK, Abboud M, Mikati MA. Inherited thrombophilia in childhood arterial stroke: data from Lebanon.Pediatr Neurol. 2011 Sep;45(3):155-8. 2)Darmency-Stamboul V, Chantegret C, Ferdynus C, Mejean N, Durand C, Sagot P, Giroud M, Bejot Y, Gouyon JB.Antenatal factors associated with perinatal arterial ischemic stroke.Stroke. 2012 Sep;43(9):2307-12.
Conflict of Interest:
None declared
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