We read Hsieh et al's paper with much interest. In an experimental study of ethanol introduction in an empty isolette, they conclude that neonates in isolettes are at risk of of inadvertent exposure to ethanol from hands cleaned with ethanol-based hand sanitiser.
We would like to share with the readers of Arch Dis Child Fetal Neonatal, the results of a similar study conducted in 2011. Measurements of isopropanol/ethanol exposure were conducted for 9 neonates nursed in incubators1. We found very variable exposure profiles with peak isopropanol/ethanol value of 1982, respectively 906 ppm. A wide range of possible exposure situations were also investigated using a one-box dispersion model2. Both our clinical and experimental papers offered different approaches to reduce the potential isopropanol/ethanol exposure for neonates nursed in isolettes.
We were delighted to read that the results from Hsieh et al. were concordant with our findings. We believe that this new publication gives further evidence and emphasis on the, unfortunately often underestimated, issue of neonatal exposure to gaseous pollutants.
1 Paccaud et al. Hand-disinfectant alcoholic vapors in incubators. JNPM 4(1):15-19, 2011
2 Vernez et al. Solvent vapours in incubators: a source of exposure among neonates? Gefahrstoffe -Reinhaltung der Luft 71 (5):209-214, 2011
We thank you very much for your question and we would appreciate having the opportunity to share the full results of the regression analyses for our 3 outcomes: neurodevelopmental impairment, significant neurodevelopmental impairment and significant neurodevelopmental impairment or death. The omission of this information was due solely to the manuscript restrictions on words and tables. We agree with you that this information is useful. As we are not able to provide tables in an e-letter, we would be happy to share this information via e-mail with any interested reader.
Sincerely,
Anne Synnes, MDCM, MHSC, FRCPC
Neonatologist, BC Women’s Hospital and Health Centre,
Clinical Professor, Department of Pediatrics, University of British Columbia
Director, Canadian Neonatal Follow-Up Network
Vancouver, Canada
We are delighted that our work received the attention of the neonatal community. The protocol in the study was exactly as stated in our paper, oral feeds were offered at least once in 72 hours, more often if cues were evident. As cue-based feeding depends on individual infants’ physiological wellbeing and readiness to feed a traditional feeding guideline based on volume and time would be contradictory. The cue based feeding might have some effect on earlier achievement of the full oral feeding.(1) Usual total feeding volume in our unit is between 120 ml/kg/day to 180 ml/kg/day and this depends on several factors: co-morbidity (e.g. patent ductus arteriosus, chronic lung disease), type of milk (maternal breast milk, donor breast milk, different type of formulas), weight gain. The total enteral intake would not be feasible to protocolize. The volume taken orally (volume per feed and hike of feeds) was determined by the effort and energy of each individual baby as opposed to following any particular schedule (as mentioned earlier cue-based or infant-led feeding). As our cohort consisted of infants on full enteral feeding, there was no specific definition of feeding intolerance and indeed we did not identify any problems with feeding intolerance in the trial.
The first oral feed in our trial was 9.3 ± 6.5 days after randomization in High Flow (HF) group and 10.9 ± 4.8 days in nasal Continuous Positive Airway Pressure (CPAP) group, that is 33.3 ± 0.9 weeks of postmenstru...
We are delighted that our work received the attention of the neonatal community. The protocol in the study was exactly as stated in our paper, oral feeds were offered at least once in 72 hours, more often if cues were evident. As cue-based feeding depends on individual infants’ physiological wellbeing and readiness to feed a traditional feeding guideline based on volume and time would be contradictory. The cue based feeding might have some effect on earlier achievement of the full oral feeding.(1) Usual total feeding volume in our unit is between 120 ml/kg/day to 180 ml/kg/day and this depends on several factors: co-morbidity (e.g. patent ductus arteriosus, chronic lung disease), type of milk (maternal breast milk, donor breast milk, different type of formulas), weight gain. The total enteral intake would not be feasible to protocolize. The volume taken orally (volume per feed and hike of feeds) was determined by the effort and energy of each individual baby as opposed to following any particular schedule (as mentioned earlier cue-based or infant-led feeding). As our cohort consisted of infants on full enteral feeding, there was no specific definition of feeding intolerance and indeed we did not identify any problems with feeding intolerance in the trial.
The first oral feed in our trial was 9.3 ± 6.5 days after randomization in High Flow (HF) group and 10.9 ± 4.8 days in nasal Continuous Positive Airway Pressure (CPAP) group, that is 33.3 ± 0.9 weeks of postmenstrual age and 33.6 ± 0.7 weeks respectively. This would be in keeping with premature newborn physiology, when efficient coordination of suck, swallow and breathing occurring between 32 and 36 weeks of gestation.(2, 3) In fact this result compares favorably to previous reports. Hwang et al. in their cohort of infants born below 32 weeks of gestation reported first oral feed at 33.9 ± 1.7 weeks of postmenstrual age. Their group included all infants born below 32 weeks who achieved full oral feeding before discharge.(4) The infants included in our cohort were more premature (born below 30 weeks of gestation). We also excluded the ‘healthiest’ infants who were off respiratory support (63 in total, which would be over 40% of eligible infants). On the other hand we excluded also the ‘sickest’ infants with high respiratory support (19 infants) and infants who were not established on full enteral feeds at 32 weeks of gestation (5 infants). Shetty et al. in their cohort of infants similar in profile to our population reported first oral feed at median of 35 weeks of postmenstrual age (range 33 to 44 weeks) in CPAP group and 34.4 (range 33 to 37.86) in HF/CPAP group.(3) A physiological study undertaken by Amaizu et al. showed ability of infants born between 26 and 29 weeks of gestation to tolerate 1 to 2 oral feeds in 24 hours at 34.0 ± 1.0 weeks of postmenstrual age, this ability improved with gestational age at birth (34.4 ± 1.2 weeks at 26 to 27 weeks of gestation versus 33.6 ± 0.6 weeks at 28 to 29 weeks of gestation). It is worth noting that these were stable infants without chronic lung disease.(5) We would therefore believe that our results fully reflect the physiology of oral feeding in preterm newborns and would be fully justifiable for clinical practice.
We are using non-nutritive sucking in our unit as a standard practice.
We would like to thank you for the correction of our terminology used in reference to the important work of Shetty et al., however we believe that their work was a retrospective cohort study (retrospectively comparing two cohorts of infants managed differently in different time epochs).(3)
We firmly believe that our conclusion was justified that there was no difference in the duration to reach full oral feeds between stable preterm infants managed on HF Nasal Cannula and those managed on nasal CPAP, and that oral feeding was feasible and safe regardless of the method used for non-invasive respiratory support.(6)
1. Watson J, McGuire W. Responsive versus scheduled feeding for preterm infants. Cochrane database of systematic reviews (Online). 2016(8):CD005255. Epub 2016/09/01.
2. Foster JP, Psaila K, Patterson T. Non-nutritive sucking for increasing physiologic stability and nutrition in preterm infants. Cochrane database of systematic reviews (Online). 2016;10:CD001071. Epub 2016/11/02.
3. Shetty S, Hunt K, Douthwaite A, Athanasiou M, Hickey A, Greenough A. High-flow nasal cannula oxygen and nasal continuous positive airway pressure and full oral feeding in infants with bronchopulmonary dysplasia. Archives of disease in childhood Fetal and neonatal edition. 2016;101(5):F408-11. Epub 2016/02/18.
4. Hwang YS, Ma MC, Tseng YM, Tsai WH. Associations among perinatal factors and age of achievement of full oral feeding in very preterm infants. Pediatrics and neonatology. 2013;54(5):309-14. Epub 2013/05/11.
5. Amaizu N, Shulman R, Schanler R, Lau C. Maturation of oral feeding skills in preterm infants. Acta paediatrica. 2008;97(1):61-7. Epub 2007/12/07.
6. Glackin SJ, O'Sullivan A, George S, Semberova J, Miletin J. High flow nasal cannula versus NCPAP, duration to full oral feeds in preterm infants: a randomised controlled trial. Archives of disease in childhood Fetal and neonatal edition. 2017;102(4):F329-F32. Epub 2016/12/25.
We thank dr. Kumar and dr. Yadav for their interest in our study. We hope that by stating ‘delayed cord clamping may not be advisable in second-born MC twins after vaginal birth’, we expressed that gynecologists could consider to deviate from the international guidelines in some cases. It is possible that not all babies will benefit from placental transfusion in a similar way. However, we certainly agree with dr. Kumar and dr. Yadav that the optimal timing of umbilical cord clamping in twins warrants further investigation.
Thank you for your interest in our study and your comment. When you read the 6th paragraph of the discussion of the article, you will find that we completely agree that Oxytocin could have influenced the observations. This was an observational study and moment of oxytocin was given to the discretion of the midwife. Nevertheless, we still observed umbilical circulation much longer than previously described. This study was performed in 2015, but our local guideline has recently been changed to administering oxytocin after cord clamping. A new study is currently undertaken using the same methodology.
Thank you for this interesting and highly needed piece of knowledge on physiological umbilical bllod flow. Just one remark: uterotonics were given to all women directly after birth. Oxytocin may alter umbilical blood flow due to modifications in timing and strength of contractions, and influence timing of placental disattachment. Possibly, true physiological blood flow may be still different (and continue for even longer), if medication were administered after clamping (quite possibly with no significant disadvantage for the parturient).
Dear Editor
We genuinely appreciate the readers keen interest in our paper and critical comments.1 Here are our clarifications regarding their comments.
1. The readers have perhaps misunderstood the concept of “intention to treat analysis” and “per protocol analysis”.2 Infants were analysed as they were randomized in their respective groups (intention to treat analysis). Per protocol analysis excludes the patients who deviate from the protocol. In our study, we needed to exclude the infants who were lost to follow-up and therefore their outcomes were not known. We did not exclude them because there was a protocol deviation or violation.
2. Blood dextrose levels were monitored as per unit protocol and once stable on full enteral feeds they were done once a week along with weekly routine blood evaluations up to discharge. No additional testing for blood sugars was done for the study.
3. We believe that propranolol at lower doses of 0.5mg/kg/dose 12 hourly is unlikely to affect the normal vascularization in other organs. This drug has been previously used in newborns including preterm newborns for different indications. Till date there have been no reports of deranged neuro-developmental outcome attributed to propranolol. However, we agree with the readers thoughts that long term neuro-developmental outcome would have been useful but this was beyond the scope of this study.
4. In our study, for babies born at 31-32 weeks post menstrual age the...
Dear Editor
We genuinely appreciate the readers keen interest in our paper and critical comments.1 Here are our clarifications regarding their comments.
1. The readers have perhaps misunderstood the concept of “intention to treat analysis” and “per protocol analysis”.2 Infants were analysed as they were randomized in their respective groups (intention to treat analysis). Per protocol analysis excludes the patients who deviate from the protocol. In our study, we needed to exclude the infants who were lost to follow-up and therefore their outcomes were not known. We did not exclude them because there was a protocol deviation or violation.
2. Blood dextrose levels were monitored as per unit protocol and once stable on full enteral feeds they were done once a week along with weekly routine blood evaluations up to discharge. No additional testing for blood sugars was done for the study.
3. We believe that propranolol at lower doses of 0.5mg/kg/dose 12 hourly is unlikely to affect the normal vascularization in other organs. This drug has been previously used in newborns including preterm newborns for different indications. Till date there have been no reports of deranged neuro-developmental outcome attributed to propranolol. However, we agree with the readers thoughts that long term neuro-developmental outcome would have been useful but this was beyond the scope of this study.
4. In our study, for babies born at 31-32 weeks post menstrual age the first evaluation was done by 34 weeks corrected gestational age. This is our unit protocol based on our experience (as we have seen ROP even at earlier gestation in our country). This protocol also ensures a ROP evaluation before discharge in babies who get discharged early. It does not matter whether ROP screening starts (for infants born at 31 to 32 weeks of post menstrual age) at 2 weeks or 4 weeks, as long as there is a regular periodical follow up until full vascularization of retina.
We hope that this clarifies all the concerns raised by readers.
REFERENCES:
1. Sanghvi KP, Kabra NS, Padhi P, Singh U, Dash SK, Avasthi BS. Prophylactic propranolol for prevention of ROP and visual outcome at 1 year (PreROP trial). Arch Dis Child Fetal Neonatal Ed. 2017 Jan 13. pii: fetalneonatal-2016-311548. doi: 10.1136/archdischild-2016-311548. [Epub ahead of print]
2. Intention to treat analysis and per protocol analysis: complementary information. Prescrire Int. 2012 Dec; 21(133):304-6.
Dear Sir/Madam,
We read with great interest the article by Sanghvi et al1 titled “Sanghvi KP, Kabra NS, Padhi P, Singh U, Dash SK, Avasthi BS. Prophylactic propranolol for prevention of ROP and visual outcome at 1 year (PreROP trial). Arch Dis Child Fetal Neonatal Ed. 2017 Jan 13. pii: fetalneonatal-2016-311548. doi: 10.1136/archdischild-2016-311548. [Epub ahead of print]” published in your journal which concluded that prophylactic propranolol in the prescribed dose of 1 mg/kg/day showed a decreasing trend in all outcomes of ROP though statistically not significant. We appreciate that it was a double blinded study which tried to see the effect of propranolol prophylaxis on ROP prevention in lower doses without any serious adverse events.
This trial was need based and addressed a very important and clinically relevant issue. However, we would like to address a few important concerns which came to our notice while reading through the article.
The authors state that the analysis was planned according to intention to treat(ITT) analysis, but if we see the final analysis in flow diagram, the babies which were lost to follow up are not included in the analysis. Thus, it is not a ITT but a per protocol analysis.2
The babies received study drug till 37 weeks or till complete vasularization of retina. Were blood dextrose levels monitored till this time? If the response is yes, then this would expose these tiny neonates to unnecessary daily pricks and pa...
Dear Sir/Madam,
We read with great interest the article by Sanghvi et al1 titled “Sanghvi KP, Kabra NS, Padhi P, Singh U, Dash SK, Avasthi BS. Prophylactic propranolol for prevention of ROP and visual outcome at 1 year (PreROP trial). Arch Dis Child Fetal Neonatal Ed. 2017 Jan 13. pii: fetalneonatal-2016-311548. doi: 10.1136/archdischild-2016-311548. [Epub ahead of print]” published in your journal which concluded that prophylactic propranolol in the prescribed dose of 1 mg/kg/day showed a decreasing trend in all outcomes of ROP though statistically not significant. We appreciate that it was a double blinded study which tried to see the effect of propranolol prophylaxis on ROP prevention in lower doses without any serious adverse events.
This trial was need based and addressed a very important and clinically relevant issue. However, we would like to address a few important concerns which came to our notice while reading through the article.
The authors state that the analysis was planned according to intention to treat(ITT) analysis, but if we see the final analysis in flow diagram, the babies which were lost to follow up are not included in the analysis. Thus, it is not a ITT but a per protocol analysis.2
The babies received study drug till 37 weeks or till complete vasularization of retina. Were blood dextrose levels monitored till this time? If the response is yes, then this would expose these tiny neonates to unnecessary daily pricks and pain which could lead to adverse neurological outcome.3
In this study propranolol was used to prevent ROP with the hypothesis of decreasing VEGF expression. However, this could also affect the vascularization in many other organs in preterm babies, especially the CNS.4 This study would have been more meaningful if the authors, a priori, had planned neurological assessment at 1 year.
The first examination for ROP was done at least 2 weeks and /or 31 – 32 weeks of post menstrual age. But this does not hold true for babies born at 31 or 32 weeks in whom AAP5 recommend screening at 4weeks of age and not at 2weeks as done by the authors.
1. Sanghvi KP, Kabra NS, Padhi P, Singh U, Dash SK, Avasthi BS. Prophylactic propranolol for prevention of ROP and visual outcome at 1 year (PreROP trial). Arch Dis Child Fetal Neonatal Ed. 2017 Jan 13. pii: fetalneonatal-2016-311548. doi: 10.1136/archdischild-2016-311548. [Epub ahead of print]
2. Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Devereaux PJ, Elbourne D, Egger M, Altman DG; CONSORT. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. Int J Surg. 2012;10(1):28-55. doi: 10.1016/j.ijsu.2011.10.001. Epub 2011 Oct 12
3. Ranger M, Grunau RE. Early repetitive pain in preterm infants in relation to the developing brain. Pain Manag. 2014 Jan;4(1):57-67. doi: 10.2217/pmt.13.61
4. Haigh JJ. Role of VEGF in organogenesis. Organogenesis. 2008 Oct;4(4):247-56.
5. American Academy of Pediatrics, Section on Ophthalmology; American Academy of Ophthalmology; American Association for Pediatric Ophthalmology and Strabismus. Screening examination of premature infants for retinopathy of prematurity. Pediatrics 2006; 117:572–6.
We read with great interest the article by Van Zanten HA et al., published in this journal and found it very useful.1 The author rightly stated that the results reflect the real situation as data were collected for the duration infants were admitted, while nurses taking care of them and where workload varied. It will be very relevant for developing countries where nurse patient ratio is poor. But; at the same time would like to offer following comments, clarification to which would benefit the readers of this journal and will help in replication of these results in different settings also.
It is not very clear whether it was a prospective study or retrospective. In Introduction section, in the end, the author mentioned that we performed a retrospective study in preterm infants to evaluate automated fraction of inspired oxygen (FiO2) control when it was used as standard care and thus for a longer period. While in “Methods” section it is mentioned that it was a prospective observational study. These contradictory statements create confusion to the reader.
The author mentioned that during the manual period, the nurses manually titrated the supplemental oxygen following local guidelines. However; these guidelines are not given in the current paper. It would be better if clear guidelines would have been described like other studies to improve the external validity and generalizability.2
In the present study, FiO2 and pulse oximeter saturation (SpO2) were sa...
We read with great interest the article by Van Zanten HA et al., published in this journal and found it very useful.1 The author rightly stated that the results reflect the real situation as data were collected for the duration infants were admitted, while nurses taking care of them and where workload varied. It will be very relevant for developing countries where nurse patient ratio is poor. But; at the same time would like to offer following comments, clarification to which would benefit the readers of this journal and will help in replication of these results in different settings also.
It is not very clear whether it was a prospective study or retrospective. In Introduction section, in the end, the author mentioned that we performed a retrospective study in preterm infants to evaluate automated fraction of inspired oxygen (FiO2) control when it was used as standard care and thus for a longer period. While in “Methods” section it is mentioned that it was a prospective observational study. These contradictory statements create confusion to the reader.
The author mentioned that during the manual period, the nurses manually titrated the supplemental oxygen following local guidelines. However; these guidelines are not given in the current paper. It would be better if clear guidelines would have been described like other studies to improve the external validity and generalizability.2
In the present study, FiO2 and pulse oximeter saturation (SpO2) were sampled every minute, and it is quite common to have fluctuations within a period of one minute which will get missed if we have a data point of one-minute intervals and hence might give fallacious results. In this interval one might have done rapid intervention during hypoxemia in the manual group, hence that hypoxemia episode might get masked with intervention. A study by Van Kaam et al using the same technology and lesser interval (5 seconds) found that automated control reduced hypoxemia.2
The author didn’t mention about sickness status of babies enrolled in the study. Babies with persistent pulmonary arterial hypertension and patent ductus arteriosus may have a difference in pre and postductal saturation. So, in such cases probe site will have implication. What was probe site chosen in babies in this study? Also; the author should mention whether sickness levels in both groups were similar or not.
The study concludes that with the implementation of automated oxygen control there was a significant reduction in hypoxemia, but not hypoxemia. It seems to be oversimplification of results. Carefully looking at the results there will be concern that more babies were having SpO2<90%, (median (IQR) 8.6 (7.2–11.7) 15.1 (14.0–21.1) <0.0001) in the automated group. And this finding is consistent with most of the studies done on automated oxygen control.3 Possible reason for this finding may be the human behavior to accept high saturation or an inherent problem with the design of automated algorithm which tends to keep saturation on the lower side of target range and hence more prone to hypoxemia.4 The cumulative effect of preventing hyperoxemia (>95%) and allowing lower saturations (85-89%) in automated group, on clinical outcomes needs to be evaluated.
As of now from various studies done using this algorithm, it seems that automated oxygenation control systems cannot prevent the occurrence of episodes of hypoxemia. Although studies have shown that it reduces the duration or severity and severity of hypoxemia episodes by increasing Fio2 but still there is need of development in an algorithm to prevent these episodes.
Competing interests: None
Source of funding: None
References:
1 Van Zanten H, Kuypers K, Stenson B et al. The effect of implementing an automated oxygen control on oxygen saturation in preterm infants. Archives of Disease in Childhood - Fetal and Neonatal Edition 2017;:fetalneonatal-2016-312172. doi:10.1136/archdischild-2016-312172
2 van Kaam A, Hummler H, Wilinska M et al. Automated versus Manual Oxygen Control with Different Saturation Targets and Modes of Respiratory Support in Preterm Infants. The Journal of Pediatrics 2015;167:545-550.e2. doi:10.1016/j.jpeds.2015.06.012
3 Claure NBancalari E. Oxygen Saturation Targeting by Automatic Control of Inspired Oxygen in Premature Infants. NeoReviews 2015;16:e406-e412. doi:10.1542/neo.16-7-e406
4 Bancalari EClaure N. Control of Oxygenation During Mechanical Ventilation in the Premature Infant. Clinics in Perinatology 2012;39:563-572. doi:10.1016/j.clp.2012.06.013
We read with great interest the article by Van Zanten HA et al., published in this journal and found the results impressive.[1] However, we have certain observations about the conduct of the study
Even though the authors state that this report was part of a quality improvement initiative in their NICU, the authors have neither reported the results in the format suitable for a quality improvement study nor have clearly stated the design; at the end of introduction they seem to mention that this was a retrospective data analysis; whereas, in the first line of the methods they state the design as a prospective observational study. Even though the automatic oxygen controller group would not have been affected much by any one of the design, the impact would have been in the manual group, keeping especially the training of the NICU staff in mind. It’s also worth emphasizing here that the authors mention about the local guidelines practiced for manual titration of supplemental oxygen based on the saturations, for the sake of external validity.[2]
Minute wise data points used in this study may have significantly underestimated the hypoxemic episodes and thereby the proportion of times an infant remained in the ‘below target range’ saturations. In a logical sense, manual titration would have happened sooner than expected for a hypoxemic event and hence would not have been captured if more frequent data points are not considered. Using the same technology and a lesser in...
We read with great interest the article by Van Zanten HA et al., published in this journal and found the results impressive.[1] However, we have certain observations about the conduct of the study
Even though the authors state that this report was part of a quality improvement initiative in their NICU, the authors have neither reported the results in the format suitable for a quality improvement study nor have clearly stated the design; at the end of introduction they seem to mention that this was a retrospective data analysis; whereas, in the first line of the methods they state the design as a prospective observational study. Even though the automatic oxygen controller group would not have been affected much by any one of the design, the impact would have been in the manual group, keeping especially the training of the NICU staff in mind. It’s also worth emphasizing here that the authors mention about the local guidelines practiced for manual titration of supplemental oxygen based on the saturations, for the sake of external validity.[2]
Minute wise data points used in this study may have significantly underestimated the hypoxemic episodes and thereby the proportion of times an infant remained in the ‘below target range’ saturations. In a logical sense, manual titration would have happened sooner than expected for a hypoxemic event and hence would not have been captured if more frequent data points are not considered. Using the same technology and a lesser interval (5 seconds) Van Kaam et al had shown aptly that automated control reduced hypoxemia.[2]
Comparative data on the clinical morbidities such as pulmonary artery hypertension and patent ductus arteriosus would be important as these morbidities if differentially distributed in the comparison groups, would have affected the hypoxemic episodes and proportion of time below the target range.
While concluding, the authors seem to have conveniently avoided describing the significant time spent below the target range in the automated control group. Even though this could have been due to the inherent human behavioral pattern of responding faster to lower saturations, an inbuilt error in the closed loop algorithm with a differential sensitivity towards lower saturations could have also played a role in such phenomenon.[3] For a reader, a strong message would be that even though the control is automated, a close look into the algorithm of the manufacturer is immediately required to avoid spending more time below the target range, especially when one does not know the impact of such ‘below target range’ saturations on long-term neurodevelopmental and pulmonary outcomes.
Competing interests: None
Source of funding: None
References:
1 Van Zanten H, Kuypers K, Stenson B et al. The effect of implementing an automated oxygen control on oxygen saturation in preterm infants. Archives of Disease in Childhood - Fetal and Neonatal Edition 2017fetalneonatal-2016-312172. doi:10.1136/archdischild-2016-312172
2 van Kaam A, Hummler H, Wilinska M et al. Automated versus Manual Oxygen Control with Different Saturation Targets and Modes of Respiratory Support in Preterm Infants. The Journal of Pediatrics 2015;167:545-550.e2. doi:10.1016/j.jpeds.2015.06.012
3 Bancalari E, Claure N. Control of Oxygenation During Mechanical Ventilation in the Premature Infant. Clinics in Perinatology 2012;39:563-572. doi:10.1016/j.clp.2012.06.013
Sir,
We read Hsieh et al's paper with much interest. In an experimental study of ethanol introduction in an empty isolette, they conclude that neonates in isolettes are at risk of of inadvertent exposure to ethanol from hands cleaned with ethanol-based hand sanitiser.
We would like to share with the readers of Arch Dis Child Fetal Neonatal, the results of a similar study conducted in 2011. Measurements of isopropanol/ethanol exposure were conducted for 9 neonates nursed in incubators1. We found very variable exposure profiles with peak isopropanol/ethanol value of 1982, respectively 906 ppm. A wide range of possible exposure situations were also investigated using a one-box dispersion model2. Both our clinical and experimental papers offered different approaches to reduce the potential isopropanol/ethanol exposure for neonates nursed in isolettes.
We were delighted to read that the results from Hsieh et al. were concordant with our findings. We believe that this new publication gives further evidence and emphasis on the, unfortunately often underestimated, issue of neonatal exposure to gaseous pollutants.
1 Paccaud et al. Hand-disinfectant alcoholic vapors in incubators. JNPM 4(1):15-19, 2011
2 Vernez et al. Solvent vapours in incubators: a source of exposure among neonates? Gefahrstoffe -Reinhaltung der Luft 71 (5):209-214, 2011
Dear Dr. Degraeuwe,
We thank you very much for your question and we would appreciate having the opportunity to share the full results of the regression analyses for our 3 outcomes: neurodevelopmental impairment, significant neurodevelopmental impairment and significant neurodevelopmental impairment or death. The omission of this information was due solely to the manuscript restrictions on words and tables. We agree with you that this information is useful. As we are not able to provide tables in an e-letter, we would be happy to share this information via e-mail with any interested reader.
Sincerely,
Anne Synnes, MDCM, MHSC, FRCPC
Neonatologist, BC Women’s Hospital and Health Centre,
Clinical Professor, Department of Pediatrics, University of British Columbia
Director, Canadian Neonatal Follow-Up Network
Vancouver, Canada
We are delighted that our work received the attention of the neonatal community. The protocol in the study was exactly as stated in our paper, oral feeds were offered at least once in 72 hours, more often if cues were evident. As cue-based feeding depends on individual infants’ physiological wellbeing and readiness to feed a traditional feeding guideline based on volume and time would be contradictory. The cue based feeding might have some effect on earlier achievement of the full oral feeding.(1) Usual total feeding volume in our unit is between 120 ml/kg/day to 180 ml/kg/day and this depends on several factors: co-morbidity (e.g. patent ductus arteriosus, chronic lung disease), type of milk (maternal breast milk, donor breast milk, different type of formulas), weight gain. The total enteral intake would not be feasible to protocolize. The volume taken orally (volume per feed and hike of feeds) was determined by the effort and energy of each individual baby as opposed to following any particular schedule (as mentioned earlier cue-based or infant-led feeding). As our cohort consisted of infants on full enteral feeding, there was no specific definition of feeding intolerance and indeed we did not identify any problems with feeding intolerance in the trial.
Show MoreThe first oral feed in our trial was 9.3 ± 6.5 days after randomization in High Flow (HF) group and 10.9 ± 4.8 days in nasal Continuous Positive Airway Pressure (CPAP) group, that is 33.3 ± 0.9 weeks of postmenstru...
We thank dr. Kumar and dr. Yadav for their interest in our study. We hope that by stating ‘delayed cord clamping may not be advisable in second-born MC twins after vaginal birth’, we expressed that gynecologists could consider to deviate from the international guidelines in some cases. It is possible that not all babies will benefit from placental transfusion in a similar way. However, we certainly agree with dr. Kumar and dr. Yadav that the optimal timing of umbilical cord clamping in twins warrants further investigation.
Thank you for your interest in our study and your comment. When you read the 6th paragraph of the discussion of the article, you will find that we completely agree that Oxytocin could have influenced the observations. This was an observational study and moment of oxytocin was given to the discretion of the midwife. Nevertheless, we still observed umbilical circulation much longer than previously described. This study was performed in 2015, but our local guideline has recently been changed to administering oxytocin after cord clamping. A new study is currently undertaken using the same methodology.
Thank you for this interesting and highly needed piece of knowledge on physiological umbilical bllod flow. Just one remark: uterotonics were given to all women directly after birth. Oxytocin may alter umbilical blood flow due to modifications in timing and strength of contractions, and influence timing of placental disattachment. Possibly, true physiological blood flow may be still different (and continue for even longer), if medication were administered after clamping (quite possibly with no significant disadvantage for the parturient).
Dear Editor
Show MoreWe genuinely appreciate the readers keen interest in our paper and critical comments.1 Here are our clarifications regarding their comments.
1. The readers have perhaps misunderstood the concept of “intention to treat analysis” and “per protocol analysis”.2 Infants were analysed as they were randomized in their respective groups (intention to treat analysis). Per protocol analysis excludes the patients who deviate from the protocol. In our study, we needed to exclude the infants who were lost to follow-up and therefore their outcomes were not known. We did not exclude them because there was a protocol deviation or violation.
2. Blood dextrose levels were monitored as per unit protocol and once stable on full enteral feeds they were done once a week along with weekly routine blood evaluations up to discharge. No additional testing for blood sugars was done for the study.
3. We believe that propranolol at lower doses of 0.5mg/kg/dose 12 hourly is unlikely to affect the normal vascularization in other organs. This drug has been previously used in newborns including preterm newborns for different indications. Till date there have been no reports of deranged neuro-developmental outcome attributed to propranolol. However, we agree with the readers thoughts that long term neuro-developmental outcome would have been useful but this was beyond the scope of this study.
4. In our study, for babies born at 31-32 weeks post menstrual age the...
Dear Sir/Madam,
We read with great interest the article by Sanghvi et al1 titled “Sanghvi KP, Kabra NS, Padhi P, Singh U, Dash SK, Avasthi BS. Prophylactic propranolol for prevention of ROP and visual outcome at 1 year (PreROP trial). Arch Dis Child Fetal Neonatal Ed. 2017 Jan 13. pii: fetalneonatal-2016-311548. doi: 10.1136/archdischild-2016-311548. [Epub ahead of print]” published in your journal which concluded that prophylactic propranolol in the prescribed dose of 1 mg/kg/day showed a decreasing trend in all outcomes of ROP though statistically not significant. We appreciate that it was a double blinded study which tried to see the effect of propranolol prophylaxis on ROP prevention in lower doses without any serious adverse events.
This trial was need based and addressed a very important and clinically relevant issue. However, we would like to address a few important concerns which came to our notice while reading through the article.
The authors state that the analysis was planned according to intention to treat(ITT) analysis, but if we see the final analysis in flow diagram, the babies which were lost to follow up are not included in the analysis. Thus, it is not a ITT but a per protocol analysis.2
The babies received study drug till 37 weeks or till complete vasularization of retina. Were blood dextrose levels monitored till this time? If the response is yes, then this would expose these tiny neonates to unnecessary daily pricks and pa...
Show MoreWe read with great interest the article by Van Zanten HA et al., published in this journal and found it very useful.1 The author rightly stated that the results reflect the real situation as data were collected for the duration infants were admitted, while nurses taking care of them and where workload varied. It will be very relevant for developing countries where nurse patient ratio is poor. But; at the same time would like to offer following comments, clarification to which would benefit the readers of this journal and will help in replication of these results in different settings also.
Show MoreIt is not very clear whether it was a prospective study or retrospective. In Introduction section, in the end, the author mentioned that we performed a retrospective study in preterm infants to evaluate automated fraction of inspired oxygen (FiO2) control when it was used as standard care and thus for a longer period. While in “Methods” section it is mentioned that it was a prospective observational study. These contradictory statements create confusion to the reader.
The author mentioned that during the manual period, the nurses manually titrated the supplemental oxygen following local guidelines. However; these guidelines are not given in the current paper. It would be better if clear guidelines would have been described like other studies to improve the external validity and generalizability.2
In the present study, FiO2 and pulse oximeter saturation (SpO2) were sa...
We read with great interest the article by Van Zanten HA et al., published in this journal and found the results impressive.[1] However, we have certain observations about the conduct of the study
Show MoreEven though the authors state that this report was part of a quality improvement initiative in their NICU, the authors have neither reported the results in the format suitable for a quality improvement study nor have clearly stated the design; at the end of introduction they seem to mention that this was a retrospective data analysis; whereas, in the first line of the methods they state the design as a prospective observational study. Even though the automatic oxygen controller group would not have been affected much by any one of the design, the impact would have been in the manual group, keeping especially the training of the NICU staff in mind. It’s also worth emphasizing here that the authors mention about the local guidelines practiced for manual titration of supplemental oxygen based on the saturations, for the sake of external validity.[2]
Minute wise data points used in this study may have significantly underestimated the hypoxemic episodes and thereby the proportion of times an infant remained in the ‘below target range’ saturations. In a logical sense, manual titration would have happened sooner than expected for a hypoxemic event and hence would not have been captured if more frequent data points are not considered. Using the same technology and a lesser in...
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