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  • Blog Entries

    • By AllThingsNeonatal in All Things Neonatal
      Choosing to provide postnatal systemic steroids to preterm infants for treatment of evolving BPD has given many to pause before choosing to administer them. Ever since K Barrington published his systematic review The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs. and found a 186% increase in risk of CP among those who received these treatments, efforts have been made to minimize risk when these are given.  Such efforts have included shortening the exposure from the length 42 day courses and also decreasing the cumulative dose of dexamethasone.  Fortunately these efforts have led to findings that these two approaches have not been associated with adverse neurodevelopmental outcomes.  Having said that, I doubt there is a Neonatologist that still doesn’t at least think about long term outcome when deciding to give dexamethasone.  The systemic application certainly will have effects on the lung but the circulating steroid in the brain is what occupies our thoughts.
      What About Applying it Directly to the Lung
      If you wanted to prevent BPD the way to do it would be to minimize the time infants are exposed to positive pressure ventilation.  Rather than giving steroids after a week or two maybe it would be best to give them early.  Recent evidence supports this for systemic steroids and has been written about recently. Hydrocortisone after birth may benefit the smallest preemies the most! This still involves providing steroid systemically.  Over the years, inhaled steroids have been tried as have intratracheal instillation of steroid with and without surfactant as a vehicle for distribution to the lung.  This month colleagues of mine anchored by Dr. G. t’Jong (a founding member of the “Tall Men of Pediatrics #TMOP) published a systematic review and meta-analysis of all such RCTs in their paper Efficacy and safety of pulmonary application of corticosteroids in preterm infants with respiratory distress syndrome: a systematic review and metaanalysis.  The results of the study suggest that there may well be a role for this approach.
      All of the included studies used a prophylactic approach of giving between the first 4 hours and the 14th day of postnatal age doses of pulmonary steroids with the goal of preventing death or BPD. The GA of enrolled infants ranged from 26 to 34 weeks, and the birth weight ranged from 801 to 1591 g. Out of 870 possible articles only 12 made the cut and compromised the data for the analysis.
      Routes of steroid were by inhalation, liquid instillation though the endotracheal tube or by mixing in surfactant and administering through the ETT.
      What Did They Find?
      Using 36 weeks corrected age as a time point for BPD or death, the forrest plot demonstrated the following.  A reduction in risk of BPD or death of 15% with a range of 24% to only a 4% reduction.

      Looking at the method of administration though is where I find things get particularly interesting.

      What this demonstrates is that how you give the steroids matters.  If you use the inhalational or intratracheal instillation (without a vehicle to distribute the steroids) there is no benefit in reduction of BPD or death.  If however you use a vehicle (in both Yeh studies it was surfactant) you find a significant reduction in this outcome.  In fact if you just look at the studies by Yeh the reduction is 36% (CI 34 – 47%).  In terms of reduction of risk these are big numbers.  So big one needs to question if the numbers are real in the long run.
      Why might this work though?
      In the larger study by Yeh, budesonide was mixed with surfactant and delivered to intubated infants every 8 hours until FiO2 was less than 30%, they were extubated or a maximum of 6 doses were reached.  We know that surfactant spreads throughout the lung very nicely so it stands to reason that the budesonide could have been delivered evenly throughout the lung.  Compare this with inhalational steroid that most likely winds up on the plastic tubing or proximal airway.  The anti-inflammatory nature of steroids should decrease damage in the distal airways offsetting the effects of positive pressure ventilation.
      Future Directions
      I am excited by these findings (if you couldn’t tell).  What we don’t know though is whether the belief that the steroid stays in the lung is true. Are we just making ourselves feel better by believing that the steroid won’t be absorbed and move systemically.  This needs to be tested and I believe results of such testing will be along in the near future.
      Secondly, we need a bigger study or at least another to add to the body of research being done.  Such a study will also need long term follow-up to determine if this strategy does at least have equal neurodevelopmental outcomes to the children who don’t receive steroid.  The meta-analysis above does show in a handful of studies that long term outcome was no different but given the history of steroids here I suspect we will need exceptionally strong evidence to see this practice go mainstream.
      What I do believe is whether you choose to use steroids prophylactically using hydrocortisone or using intratracheal surfactant delivered budesonide, we will see one or both of these strategies eventually utilized in NICUs before long.
    • By AllThingsNeonatal in All Things Neonatal
      The medical term for this is placentophagy and it is a real thing. If you follow the lay press you may have seen that originally this was promoted by Kourtney Kardashian who did this herself and then by Kim who planned on doing the same after delivery. See Did Kourtney Kardashian Eat Her Placenta?
      This is not completely without basis as many readers will be thinking already that they have heard about the health benefits of doing the same. Reports of improved mood and reductions in the baby blues following ingestion of placenta as well as improvements in breast milk production have led to this growing practice. The evidence for this up until recently though was quite old and fraught with poorly design of such studies. The bigger driver however has been word of mouth as many women having heard about the promises of better mood at the very least have thought “why not? Can’t hurt.”
      What I will do in this post is run through a little background and a few recent studies that have shed some light on how likely this is to actually work.
      Where did the idea come from?
      Animals eat their placentas after delivery. It turns out that unprocessed placenta is quite high in the hormone prolactin which is instrumental for breastfeeding. Given the large amount of this hormone as well as the number of other hormones present in such tissue it was thought that the same benefits would be found in humans. Eating unprocessed human tissue whether it is put in a capsule or not is unwise as unwanted bacteria can be consumed. In fact, a case of GBS sepsis has been linked to such a practice in which the source of the GBS was thought to be due to contaminated unprocessed maternal placenta that had been ingested. Buser GL, Mat´o S, Zhang AY, Metcalf BJ, Beall B, Thomas AR. Notes from the field: Late-onset infant group B streptococcus infection associated
      with maternal consumption of capsules containing dehydrated placenta.
      What happens when you process placenta by steaming and drying?
      This would be the most common way of getting it into capsules. This process which renders it safe to consume may have significant effects on reducing hormonal levels.This was found in a recent study that measured oxytocin and human placental lactogen (both involved positively in lactation) and found reductions in both of 99.5% and 89.2%, respectively compared versus raw placenta. I would assume that other hormones would be similarly affected so how much prolactin might actually wind up in these capsules after all?
      Clinical Randomized Double Blind Controlled Trial
      Twenty seven women from Las Vegas were recruited into a pilot trial (12 beef placebo vs 15 steamed and dried placenta) with the authors examining three different outcomes across three studies. The first study Effects of placentophagy on maternal salivary hormones: A pilot trial, part 1 looked at a large number of salivary hormones at four time points. Plasma samples were taken as well to determine the volume of distribution of the same. First samples were at week 36 of gestation then within 4 days (96 h) of birth followed by days 5–7 (120–168 h) postpartum and finally Days 21–27 (504–648 h) postpartum. All consumption of capsules was done in the home as was collection of samples. As per the authors in terms of consumption it was as follows “two 550 mg capsules three times daily for the first 4 days; two 550 mg capsules twice daily on days 5 through 12, and then to decrease the dose to two 550 mg capsules once daily for the remainder of the study (days 13 through approximately day 20 of supplementation).
      No difference was found between salivary concentrations of hormones at any time point other than that with time they declined following birth. Curiously the volume of distribution of the hormones in serum was slightly higher in the placenta capsule groups but not enough to influence the salivary concentrations. It was felt moreover that the amount of incremental hormone level found in the serum was unlikely to lead to any clinical response.
      The second study was on mood Placentophagy’s effects on mood, bonding, and fatigue: A pilot trial, part 2. Overall there were no differences for the groups but they did find “some evidence of a decrease in depressive symptoms within the placenta group but not the placebo group, and reduced fatigue in placenta group participants at the end of the study compared to the placebo group.”
      The last paper published from the same cohort is Ingestion of Steamed and Dehydrated Placenta Capsules Does Not Affect Postpartum Plasma Prolactin Levels or Neonatal Weight Gain: Results from a Randomized, Double-Bind, Placebo-Controlled Pilot Study. This study specifically addressed the issue of prolactin levels and found no difference between the groups. Neonatal weight gain was used as a proxy for breastmilk production as it was thought that if there was an effect on breastmilk you would see better weight gain. About 80% in both groups exclusively breastfed so the influence of formula one can’t take out of the equation. In the end weight gain was no different between groups although a trend to better weight gain was seen in the placebo group.
      To eat or not to eat that is the question?
      What is clear to me is that the answer to this question remains unclear! What is clear is that I don’t think it is wise to consume raw placenta due to the risks of bacterial contamination. Secondly, the levels of hormones left in the placental preparation and the most common preparation of steaming and drying leave hormone levels that are unlikely to influence much at all from a biochemical standpoint. It also seems that breastmilk production and neonatal weight gain aren’t influenced much by consumption of these pills.
      The issue though in all of this is that while the previous research was of low quality, the current research while of better quality is at a low volume. These were pilot trials and not powered to find a difference likely. The finding in the subgroup of some effect on mood at the end of the study does leave some hope to those that believe in the power of the placenta to help. Would a larger study find benefit to this practice? My suspicion from a biochemical standpoint is not but that one may feel a benefit from a placebo response.
      Should you go out and have your placenta prepared for consumption? If you have Kardashian like wealth then go for it if you think it will help. If you don’t then I would suggest waiting for something more definitive before spending your money on placentophagy.
    • By Jelli KA in Bubbly Girl in NICU
      Several tweet posted on the subject of music therap­y, namely by Fiona Lawson and Dr. Michae­l Narvey. It prompted me to share  paper on the on the Music therapy(MT) in NICU as I was abl­e to research for my posgrad as a way of­ humanizing NICU experience. I had a top­ic on my mind for a while since I used t­o work in the NICU. I First heard of this kind of therapy  from a french television TV5. Here I saw how music was used in a neurological ward for its appeasing edge.    Music therapy i­n Medicine has been around since ancient time.­es.In the NICU it has been used as a therapeutic tool for more than 25 year The US is a pioneer in the field ­, a good example is a Florida University where Dr.Jayne Stanley [1] developed the Lullaby dummy­  -©PALS - by the company Power Devices.      There are many initiative­ exploring the benefits of music therapy around the World. Most i­nitiatives center their studies using the *NIDCAP* Neon­atal framework. The location spans from Spain to Brazil passing by Canada back to Sweden.For example, I found 5 Spanish initiatives, like "Música en­ vena"  which is still on going in the NICU-La­ Paz Hospital-. Together with research studies I also used testimonials of professionals  (music therapist and clinicians), such as the o­ne described in the blog *the amia musica* .      
           Live music seems to be most beneficial to­ preterm infants vs record music . They also established that the n­oise level should be under 55dB.Music therapy has been shown to pro­vides several benefits.To summ up they are as follows :
      #-Firstly,  🎶therapy provides a reduction ­of heart and breathing rate proving the ­ calming effect.of therapy.
      #-Secondly, ­addition 🎶 therapy can help form mother-­baby bond especially when done in conjun­ction with kangaroo care,as well reducing parental stress #-Third and fina­l, studies suggests that the cumulative effe­ct in preterm belongings to the music therapy group­ where discharged earlier compared to­ the control group.     
       .   . .This conclusion are ­backed up by research studies reviewed. I­t is strength was the number and varied types of research­ : RCTs, study/control to ­observational or *prisma* meta analysis.All studies reported on or more positive results.T­he weakness of the studies review was th­e small sample number in some studies. T­he other was some quality sta­ndards were not ideal. Thus , there are ­plenty of indicators to suggest there a certain level of validity of music therapy.    
           . I feel it is ­important to take into account the long te­rm effect of music therapy on neuro-dev­elopment of preterm infants admitted to ­the NICU.A further finding revealed that too mu­ch or too little stimulation is detrimen­tal to a premmie. On the other hand, we also have­ consider what Anderson and Padel [2] say when they talk about deepening our knowledge of ­ Hypothalamic -Puititary-Adrenal Axis (H­PA)  on the stress response in neonat­es.   
         In this posgrad assignment were ­asked to propose a specific proposal .So I proposed to evaluate the levels of stress in neon­ates and find out if music therapy can he­lp. For this purpose the levels of cortisol levels need to be measured before and after a sessio­n of Music therapy. So If the levels of cortisol are indeed ­lower after a session MT this would indicate this therapy could be another indicator it is beneficial. A device like the new transdermal ­patch designed by Stanford University [3] that measures cor­tisol levels in Athletes. This pra­ctical tool could used the to measure the cortisol levels and avoids the unnecessary p­ain of needle bricks.
      [1]Tom Butler: FLORIDA STATE UNIVERSITY.New musical pacifier helps premature babies get healthy.Eureka Alerta , Florida [ Internet] May 2012 . Disponible en: https://www.eurekalert.org/pub_releases/2012-05/fsu-nmp052112.php
      [2]Anderson DE1 and Patel AD2. Infants born preterm, stress, and neurodevelopment in the neonatal intensive care unit: might music have an impact? Dev Med Child Neurol. [Internet] 2018 [Consultado 27 de Julio 2018 ] Mar;60(3):256-266. Disponible en: https://onlinelibrary.wiley.com/doi/abs/10.1111/dmcn

      *.Loewy, J et al.The effects of music therapy on vital signs, feeding, and sleep in premature infants. Pediatrics. [Internet] 2013 [ Consultado 24 de Julio 2018] May;131(5):902-18. Disponible en: http://www.pediatrics.org/cgi/doi/10.1542/peds.2012-1367
      [3]Kubota,T .Wearable device from Stanford measures cortisol in sweat.Stanford News. [ Internet] Julio 2018 [ Consultado 20 Julio 2018] Stanford University, Stanford, California. Disponible en: https://news.stanford. edu/2018/07/20/wearable-device-measures-cortisol-sweat/
    • By AllThingsNeonatal in All Things Neonatal
      Use of caffeine in the NICU as a treatment for apnea of prematurity is a topic that has certainly seen it’s fair share of coverage on this blog. Just when you think there is an aspect of treatment with caffeine that hasn’t been covered before, along comes a new paper to change my mind.
      The Caffeine for Apnea of Prematurity study or CAP, demonstrated that caffeine given between 3-10 days of age reduced the incidence of BPD in those treated compared to those receiving placebo. As an added benefit, in follow-up studies of these patients there appeared to be a benefit to neurodevelopmental outcomes as well at 18-21 months but this was lost by school age with groups being equivalent. In recent years evidence has mounted that starting caffeine earlier in the time course (<3 days and in many cases in the first hour after birth) has led to less need for intubation and BPD. What has really not been known though is whether the use of caffeine in this way might have any long term benefits aside from these short term outcomes.
      Dr. Abhay Lodha from Calgary and a group of researchers led by Prakesh Shah from the Canadian Neonatal Network using our robust Canadian network data have tried to answer this with their paper Early Caffeine Administration and Neurodevelopmental Outcomes in Preterm Infants
      The group studied were <29 weeks’ gestation born between April 2009 and September 2011 and admitted to Canadian Neonatal Network centres. As defined in the paper “Neonates who received caffeine were divided into early- (received within 2 days of birth) and late-caffeine (received after 2 days of birth) groups. The primary outcome was significant neurodevelopmental impairment, defined as cerebral palsy, or a Bayley Scales of Infant and Toddler Development, Third Edition composite score of <70 on any component, hearing aid or cochlear implant, or bilateral visual impairment at 18 to 24 months’ corrected age.”
      There were 2018 neonates included in the analysis with 1545 in the early group and 563 in the late. It is worth noting that there were 473 infants lost to follow-up meaning that there was about an 80% follow-up rate. Looking at the characteristics of those infants lost to follow-up there were no striking differences that one would expect between them and the group followed.
      What did they find?

      The odds of BPD (aOR 0.61; 95% CI 0.45–0.81), PDA (aOR 0.46; 95% CI 0.34–0.62), and Severe Neurologic Injury – parenchymal injury or GR III/IV IVH or PVL (aOR 0.66; 95% CI 0.45–0.97) were reduced in the early- caffeine group. The primary outcome was also found to be significantly different as per the table below demonstrating the odds after logistic regression analysis.
      So early caffeine seems to be good. Is that all then?
      I am very happy to see these results but a few questions remain. Before we get too enthusiastic, I find myself thinking back to the early 2000s after the initial CAP results showed an apparent difference in outcome. The question is whether the reduction in odds seen here for the primary outcome will persist as these children age. Will we see a tendency for the differences to vanish as these children enter school age? I suspect we might but that doesn’t mean all is lost here. What the authors have demonstrated clearly is that early caffeine is not harmful as there is no suggestion of those infants exposed to caffeine so shortly after birth fare worse than those treated later.
      Also as the authors state, what isn’t clear is how caffeine works to decrease the risk of developmental impairment. In the discussion they offer some insightful thoughts as to what may be at play and I agree that certainly an anti-inflammatory effect may be responsible for some of the effect. I do wonder though if one could tie the reductions to the lower likelihood of BPD. Development of BPD has been shown many times over to be associated with worse developmental outcomes. Aside from the anti-inflammatory effect mentioned, could the avoidance of early intubation and therefore reduced risk of BPD from positive pressure ventilation be the reason?
      In the end if the results persistent into school age, the reason won’t really matter and I hope it does. Will see what happens when we revisit this cohort in a few years but in the meantime I think this paper certainly confirms in my mind the need to give caffeine and make sure it’s provided early!
    • By AllThingsNeonatal in All Things Neonatal
      This post is very exciting to me.  All of us in the field of Neonatology are used to staring at patient monitors.  With each version of whatever product we are using there seems to be a new feature that is added to soothe our appetites for more data.  The real estate on the screen is becoming more and more precious as various devices such as ventilators, NIRS and other machines become capable of displaying their information in a centralized place.  The issue though is that there is only so much space available to display all of this information but underneath the hood so to speak is so much more!
      Come Along For The Ride
      One of our Neonatologists Dr. Yasser Elsayed has been very aware of these features embedded in the patient monitor. 
      Through teaching on rounds, some of our staff have become aware of these features but delivering this content to the masses has been an issue.  That is where this post and it’s linked content come into play.  I have created a new Youtube playlist where all of this great content can be found.  Each video is very watchable with most being 5-7 minutes long with the longest being 14:16.  Each video starts with a demonstration on the patient monitor of the lesson being taught and how to access the data using the patient monitor (in this case a Phillips but I have no doubt many other monitors have the same tech – just ask your rep how to get it) followed by a brief voice-over powerpoint to deliver the essential concepts.
      However you wish to digest the information is up to you but as they are short we hope that you will be able to find the content you need quickly and apply the knowledge to patient care.  How can you use the information?  The next time a patient is giving you cause to worry try looking into some of the deeper trends that the monitor is hiding from plain sight. Is there a trend towards becoming hypotensive for the patient that can be revealed in their blood pressure histogram?  Maybe the issue lies with the way the patient is being ventilated and examining trends in the pleth waveforms may reveal where the underlying problem lies.
      The Topics (click the links to go to Youtube)
      Complete List of Videos
      Part 1 – Using Histograms
      Part 2 – How to interpret blood pressure histograms
      Part 3 – Using vital signs as trends
      Part 4 – Impact of ventilation on pleth waveforms
      Part 5 – How to interpret arterial pressure waveforms
      Part 6 – Near Infrared Spectroscopy
  • Upcoming Events

    • 05 May 2019 12:00 AM Until 07 May 2019 12:00 PM
      Council of International Neonatal Nurses Conference 2019 to be held in Auckland, New Zealand from 5th to the 8th May.  www.coinn2019.com 
    • 01 July 2019 06:00 AM Until 30 September 2019 05:00 AM
      It is an online course which lasts 3 months, starting in July, 2019. 28 topics avilable 24/24 and 7/7. 22 mexican professors and 8 international ones. 

    • 05 September 2019 06:00 AM Until 09:00 PM
      After (another) successful meeting with NAVA enthusiast from several countries, we are ready to announce the date of the next workshop!
      The goal of this event is to increase skills on the use of NAVA ventilation in the NICUs, which already have some experience with NAVA and they have a Servo-i or Servo-n ventilator.
      Date: 05-06.09.2019
      Location: Turku, Finland
      Registration fee: 600€ + taxes (incl. lunches and refreshments during the workshops) 
      How to register: contact Hanna Soukka (hanna.soukka@utu.fi or NAVA@tyks.fi before June 30, 2019)
      The preliminary program is attached below.  In case of any questions, don't hesitate to ask here or email!
      We've received approval from Ethical MedTech.
      On behalf of Hanna Soukka and Baby Friendly Ventilation Study Group,
      NAVA workshop September 2019 invitation letter and preliminary program.pdf
    • 17 September 2019 Until 21 September 2019
    • 18 September 2019 Until 22 September 2019
      the 3rd Congress of Joint European Neonatal Societies (jENS)
      18. Sep 2019 – 22. Sep 2019
      Maastricht, Netherlands
      URL will be posted later.

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