To the editor: As part of a review of the literature regarding the use of Povidone iodine (PVI) to perform chemical pleurodesis in the management of congenital chylothorax (CCT), we read with great interest the case reported by Resch et al (1) and their following conclusion: "the risk-benefit assessment of PVI pleurodesis in the treatment of congenital chylothorax does not support its routine use as it may be associated with significant harm". We believe that the current data are certainly insufficient to draw definitive conclusions about the efficacy and safety of this procedure in the neonate. Randomized studies on large neonatal population are required to precise: the risks and benefits of this procedure, the timing and the modalities of its realization (duration of intervention, dilution and dosage of PVI) according to the patient's field (gestational age, weight and associated morbidity). However, we draw attention that significant harms after this procedure were reported in only specific situations. Brissaud O et al (2) reported the case of a newborn dead from end stage renal failure, oliguria, hydrops, and refractory hypotension after PVI pleurodesis. However, this patient had diffuse congenital lymphangectasia in the autopsy. This condition would favorite iodine absorption and could explain the worsening of oligoanuria and precipitation of renal failure in this patient. In another case of CCT reported by Mitanchez et al (3), lymphangiectasis was suspected and even chyle flow resolved within 24 hours, shock and acute renal failure occurred within 12 hours after instillation. Severe chronic failure was persist 6 months later. Mitanchez et al (3) have postulated that the pulmonary lymphangectasia would have favored the massive iodine absorption and thus intoxication in both cases. The case reported by Resch et al (1) combine tow risk factors for developing severe side effects of PVI. First, he has a pulmonary lymphangiectasia who already was jagged as a factor favoring systemic absorption and thus intoxication by the product. Second, he received a high concentration of PVI (10%) as the patient of Mitanchez et al (3). This could also explain the amplification of the risk of major adverse. Scottoni F et al (4) reported another hard situation of an extremely low birth weight and premature infant with extensive deep central veins thrombosis, abnormal renal function before treatment and who has developed multiple organ failure after the procedure. In our opinion, all these serious situations are likely to be either unresponsive to treatment or predictive of major side effects and should be excluded.

References: 1 Resch B, Freidl T, Reiterer F. Povidone-iodine pleurodesis for congenital chylothorax of the newborn. Arch Dis Child Fetal Neonatal Ed Published Online First: 29 September 2015. doi:10.1136/archdischild-2015- 309184 2-Brissaud O, Desfrere L, Mohsen R, Fayon M, Demarquez J. Congenital idiopathic chylothorax in neonates: chemical pleurodesis with povidone- iodine (Betadine). Arch Dis Child Fetal and Neonatal Ed. 2003;88(6):F531- F533. 3-Mitanchez D, Walter-Nicolet E, Salomon R, Bavoux F, Hubert P. Congenital chylothorax: what is the best strategy? Arch Dis Child. Fetal Neonatal Ed. 2006;91(2):F153. 4-Scottoni F, Fusaro F, Conforti A, et al. Pleurodesis with povidone- iodine for refractory chylothorax in newborns: Personal experience and literature review. J Pediatr Surg Published Online First: 28 April 2015. doi:10.1016/j.jpedsurg.2015.03.069

Conflict of Interest: None

Conflict of Interest:

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Dear Editor, I read with interest the article by Dargaville et al (1), about the feasibility and potential effectiveness of MIST, i.e. minimally-invasive surfactant therapy, in preterm infants with respiratory distress syndrome. Similarly to other recent techniques (2,3), the ultimate goal of MIST is that of delivering surfactant while avoiding both "standard" tracheal intubation and mechanical ventilation. The authors have adopted the Horbat method (4), which implies the use of a narrow-bore vascular catheter to intubate briefly the trachea, through which surfactant is then instilled in three-four aliquots. I have some concerns about considering MIST as a "minimally invasive" technique. In fact, some components of the procedure do not appear as marginally invasive as proposed by the authors. First, laryngoscopy with a blade is an invasive manoeuvre, which may injury the upper airways and provoke vagal stimulation. Notably, about 35% of infants suffered bradycardia during the procedure. Second, insertion of a semi-rigid vascular catheter, with its relatively sharp rim, may damage the vocal cords and the trachea. Fortunately, no iatrogenic airway injuries were reported by the authors. However, prior to insertion, some investigators manually fashioned a slight curvature at the tip, possibly to ease the catheter positioning and reduce the risk of perforation. Risk of tearing the trachea could be even higher when dealing with a "fighting" baby (no premedication were used in this study) or when people performing the procedure are relatively inexperienced. In this study, about 20% of the infants required two or more catheterisation attempts, despite the availability of expert neonatologists. I believe the intriguing results reported by the authors are related more to the inherent effect of surfactant, rather than to the delivery method used. More data must be rigorously collected before considering MIST as a safe method for surfactant therapy in preterm infants with RDS. References 1) Dargaville PA, Aiyappan A, De Paoli AG, et al. Minimally-invasive surfactant therapy in preterm infants on continuous positive airway pressure. Arch Dis Child Fetal Neonatal Ed 2012 Jun 9. [Epub ahead of print] 2) G?pel W, Kribs A, Ziegler A, et al. Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial. Lancet 2011;378:1627-34. 3) Finer NN, Merritt TA, Bernstein G, et al. An open label, pilot study of Aerosurf combined with nCPAP to prevent RDS in preterm neonates. J Aerosol Med Pulm Drug Deliv 2010;23:303-9. 4) Dargaville PA, Aiyappan A, Cornelius A, et al. Preliminary evaluation of a new technique of minimally invasive surfactant therapy. Arch Dis Child Fetal Neonatal Ed 2011;96:F243-8

Conflict of Interest:

None declared

Dear Editor, We read with interest the article by Sarkar et al(1) on distribution and severity of hypoxic-ischaemic lesions on brain MRI following therapeutic cooling .It is perhaps one of the very few studies which has attempted to look at the possible differences between the two forms of cooling for hypoxic ischemic encephalopathy(HIE).Brain MRI is increasingly being utilized as a good biomarker of long term neurological outcome when combined with newer advanced techniques such as diffusion weighted imaging (DWI) and proton magnetic resonance spectroscopy (MRS). We agree with the authors regarding the theoretical dangers of differential brain cooling with selective head as compared to whole body hypothermia .This seems to be the reason why many centers are now following whole body cooling(WBC) as opposed to selective head cooling(SHC) in addition to the fact that SHC is more difficult to institute. The initial trials from India too have utilized whole body cooling by indigenous use of ice-gel packs and have shown that therapeutic hypothermia is feasible and useful (2-3). With respect to the current study (1), we have the following observations which might have influenced the findings :

1. As the authors themselves have pointed out in the discussion, the neonates in the SHC group as opposed to WBC were perhaps worse at the outset itself. The data presented shows this to some extent though not statistically significant individually (i) 8/23 babies recovered from APGAR 0-3 in SHC Vs 18/36 in WBC and the details on 4 babies in SHC and 2 in WBC group with respect to APGAR is not there, either they recovered from the poor APGAR score or it was not available (ii) 23% babies in SHC group had pH < 6.7 Vs 12% in WBC (iii) clinical seizures before treatment in SHC group was 50% Vs 37% in WBC group (iv) sentinel events were 56% in SHC Vs 39% in WBC (v) abruptio placenta was 23% in SHC % Vs 12 % in WBC.

2. Other authors have also held a similar opinion regarding the patient group which entered the Cool cap trial which used aEEG as the third entry criteria and hence selected a more severe patient group which was also reflected in the a priori higher prediction of 70% poor outcome in the control group for Cool cap compared with 50% for NICHD trial. Higher incidence of seizures at enrollment in cool cap (59%) vs NICHD trial (43%)( p< 0.05 Fisher exact test ) also suggested that Cool cap population was more severely affected(4-5).

3. Again as the authors agree in the article that SHC was done in the pre-WBC era and hence must have received babies who were sicker. Acute severe asphyxia causes basal ganglia lesions and this was rare as per the authors in their analysis. Instead the injury pattern seemed like a global & prolonged asphyxia in both the groups and thus the neonates enrolled seem to have suffered a prolonged asphyxia. This could also be because both the Cool cap and NICHD babies were not cooled en-route and cooling was started at ~ 4-5 hours and target temperature achieved almost an hour later(4-5).

4. Ultimately we need randomized controlled trials using standard cooling devices/methods encompassing patient population of both the developed and developing world comparing SHC versus WBC with MRI (with DW imaging and MRS) as part of the algorithm to be able to finally address the choice of cooling method.

References:

1.Sarkar S,Donn SM, Bapuraj JR,Bhagat I, Barks JD.Distribution and severity of hypoxic-ischaemic lesions on brain MRI following therapeutic cooling: selective head versus whole body cooling .Arch Dis Child Fetal Neonatal Ed 2012;97:F335-F339

2. Koshy B, Padankatti CS, George KC, Thomas N . Neurodevelopmental outcome following whole body cooling for perinatal asphyxia.Indian Pediatr 2011;48(12):982-3.

3. Bharadwaj SK, Vishnu Bhat B. Therapeutic Hypothermia Using Gel Packs for Term Neonates with Hypoxic Ischaemic Encephalopathy in Resource- limited Settings: a Randomized Controlled Trial. J Trop Pediatr 2012; Mar 6 published online.

4. Azzopardi D, Strohm B, Edwards AD, Halliday H, Juszczak E, Levene M, et al. 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 Neonatal Ed 2009;94:F260-4.

5.Marianne Thoresen. Hypothermia after Perinatal Asphyxia: Selection for Treatment and Cooling Protocol .J Pediatr 2011;158:e45-9

Conflict of Interest:

None declared

1. van Vonderen, J. J. et al. Compressive force applied to a manikin's head during mask ventilation. Arch Dis Child Fetal Neonatal Ed 97, F254-F258 (2012).
2. Svenningsen, L., Lindemann, R. & Eidal, K. Measurements of Fetal Head Compression Pressure During Bearing Down and Their Relationship to the Condition of the Newborn. Acta Obstetricia et Gynecologica Scandinavica 67, 129-133 (1988).

Conflict of Interest:

None declared