Jump to content

JOIN THE DISCUSSION!

Want to join the discussions?

Sign up for a free membership! 

If you are a member already, log in!

(lost your password? reset it here)

99nicu.org 99nicu.org
  • entries
    125
  • comments
    97
  • views
    29,357

About this blog

I am a Neonatologist trained in Winnipeg, Manitoba and Edmonton, Alberta.  My current position is Section Head of Neonatology in Manitoba and over my career my interests have meandered from time to time.  I have been a past Program Director of Neonatology and Medical Director for a level II Intensive Care Unit prior to relocating to Winnipeg become a Section Head.

Welcome to my blog which I hope will provide a forum for discussion on topics that are of interest to Neonatologists, trainees, all health care professionals and in some cases parents of those we care for.  My intent is to post opinions and analysis on both items from the media and literature that pertain to neonates.  While I have many interests, my particular motivation is to find ways to reduce discomfort for the patients that we care for.  Whether it is through the use of non-invasive testing or finding a way to improve the patient experience this is where I find myself most energized.

I chose the picture for this site as since the inception of this site there is hardly a country that has not had an individual or many people view posts.  Moreover I have received comments from many people from so many different countries that have inspired me to think not just about the impact of these posts in North America but more globally as well.

If you like what you see and would like updates to be sent to you as they are published feel free to follow the site by clicking the follow button on the sidebar to the bottom right.  You can also follow both my Twitter (@NICU_Musings) and Facebook feeds for additional content and discussion by clicking the additional links found there.

My Facebook page serves as a better means of expanding dialogue on a variety of topics and posts

https://www.facebook.com/allthingsneonatal

Please share and like to help expand the circle of knowledge

Entries in this blog

 

Can intranasal application of breastmilk cure severe IVH?

It isn’t often in Neonatology these days that something truly innovative comes along. While the study I will be discussing is certainly small I think it represents the start of something bigger that we will see evolve over the coming years. There is no question that the benefits of mother’s own milk are extensive and include such positive outcomes as improved cognition in preterm infants and reductions in NEC. The benefits come from the immunological properties as well as the microbiome modifying nature of this source of nutrition and have been discussed many times over. Mother’s own milk contains a couple of very special things that form the basis of the reason for the study to be presented. What are neurotrophins and stem cells? Before discussing the study it is important to understand what these two classes of molecules and cells are capable of. Neurotrophins are molecules that have the capability of promoting growth and survival of neural cells. Included in this class are EGF, brain-derived neurotrophic factor, glial derived neurotrophic factor, nerve growth factor, insulin-like growth factor-1, and hepatic growth factor. It turns out that not only are these found in high concentrations in breast milk but that a woman who produces breast milk at early gestational ages has higher amounts of these substances in her milk. Pretty convenient that substances promoting development of the brain and survival of brain cells increase the earlier you deliver! Stem cells are pluripotent cells meaning that they can develop into pretty much any cell type that they need to in the body. This would come in handy for example if you needed some new cells in the brain after a neurological insult. These are also present in mother’s milk and in fact can represent as much as 30% of the population of cells in breast milk. The Nasal Cavity and the Brain Clearly, the distance from the nasal cavity to the brain is relatively short. Without going into exhaustive detail it has been demonstrated in animal models that provision of medications intranasally can reach the brain without traversing the blood stream. This affords the opportunity to provide substances to the neonate through the nasal cavity in the hopes that it will reach the brain and achieve the desired effect.  When you think about it, newborns when feeding have contact between the whole nasopharyngeal cavity and milk (as evidenced by milk occasionally dripping out of the nose when feeding) so using an NG as we do in the NICU bypasses this part of the body.  Is that a good thing? Intranasal application of breast milk Researchers in Germany led by Dr. Kribs published an early experience with this strategy in their article Intranasal breast milk for premature infants with severe intraventricular hemorrhage—an observation. In this paper the strategy;follows; 2 × 0.1 ml of his or her mother’s milk 3 to 8 times a day (0.6 to 1.6 ml total per day). The breast milk was freshly expressed, which means the milk was used within 2 h after expression. The daily application started within the first 5 days of life and was continued for at least 28 days to a maximum of 105 days. The outcome of interest was whether the severe IVH would improve over time compared to a cohort of infants with severe IVH who did not receive this treatment. Importantly this was not a randomized trial and the numbers are small. A total of 31 infants were included with 16 receiving this treatment and 15 not. The two groups were compared with the results as follows. The results don’t reach statistical significance but there is a trend at the bottom of the table above to having less progressive ventricular dilatation and surgery for the same.  Again this is a very small study so take the results with a grain of salt! Is this practice changing?  Not yet but it does beg the question of what a properly designed RCT might look like.  The authors predict what it might look like with a sham nasal application versus fresh mother’s milk. I do wonder though if it may become a study that would be hard to recruit into as when families are approached and the potential benefit explained it may be hard to get them to say anything other than “Just give my baby the breast milk!”  Such is the challenge with RCTs so it may be that a larger retrospective study will have to do first. Regardless, be on the lookout for this research as I suspect we may see more studies such as this coming and soon! * Featured image from the open access paper.  (There couldn’t be a better picture of this out there!)    

AllThingsNeonatal

AllThingsNeonatal

 

Less Invasive Surfactant Administration with High Volume Surfactant

InSurE (Intubate, Surfactant, Extubate) has been the standard approach for some time when it comes to treating RDS.  Less Invasive Surfactant Administration (LISA) or Minimally Invasive Surfactant Administration (MIST) have been growing in popularity as an alternative technique.  More than just popular, the techniques have been shown to reduce some important short term and possibly long term outcomes when used instead of the InSurE approach.  Aldana-Aquirre et al published the most recent systematic review on the topic in  Less invasive surfactant administration versus intubation for surfactant delivery in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis. They demonstrated that when looking at 6 RCTs with 895 infants, the overall results indicate that use of LISA instead of InSurE leads to a lower rate of death or bronchopulmonary dysplasia (BPD) at 36 weeks (risk ratio (RR)=0.75 (95% CI 0.59 to 0.94), p=0.01) and the need for mechanical ventilation within 72 hours of birth (RR=0.71 (0.53 to 0.96), p=0.02) or anytime during the patient stay in the NICU (RR=0.66 (0.47 to 0.93), p=0.02).  This study has been out for two years this month and yet here we are at least in my centre still performing InSurE.   Why is that? One reason likely has something to do with the expression "you can't teach an old dog new tricks".  We know how to do InSurE and we are pretty good at it.  Performing the LISA technique is not just about putting a catheter in the airway and instilling surfactant.  There are several steps that need to be done in order to ensure that the surfactant goes where it is supposed to so there is training required but such training is available in videos posted on the internet or I am sure available from centres willing to share their methods.  Still it takes someone declaring we need to change before anything will happen.  The second reason for this insistence on the status quo has been the availability of only a large volume surfactant in Canada at 5 ml/kg while in European centres the volume administered was half that.  Now a low volume surfactant is available in Canada but some centres have been slow to make a switch due to comfort with the current product.  The drawback to the current product is the concern that you can't use it for LISA techniques since the centres practicing this technique use the low volume form. Can High Volume Be Used For Lisa? Researchers in London, Ontario performed a retrospective cohort study of 43 infants in their institution who underwent the MIST approach for surfactant administration in their study High-volume surfactant administration using a minimally invasive technique: Experience from a Canadian Neonatal Intensive Care Unit. In 2016, London instituted a change in practice to provide MIST for infants born at ≥28 weeks and/or with a birth weight ≥ 1,000 g with respiratory distress syndrome.  Surfactant was provided over 1-3 minutes via a MAC catheter guided through the vocal cords with Magill forceps.  What I like about this study is the reproducibility of it as the authors describe very nicely how the steps were done.   What I also appreciate is the provision of sucrose and atropine prior to the procedure.  Not a rapid sequence induction but it does do something to address the risk of bradycardia and discomfort with cannulation of the trachea.  The results I think speak for themselves that this is indeed possible as 41/43 neonates underwent the procedure with successful instillation of surfactant confirmed by absence of recovered surfactant in aspirated stomach contents.   All of these infants qualified for BLES based on an oxygen requirement on non-invasive support of 40% or more.  These patients are similar to our own in Winnipeg in terms of qualifying criteria for surfactant but perhaps a little higher tolerance of FiO2 before intubating.  Additional evidence that surfactant was indeed received was the reduction to room air in 85% of patients within 24 hours and also the need for a second dose of surfactant in only 10%. Aside from oxygen desaturation in about 50% during BLES administration the adverse effects were fairly limited and similar to what one would see with InSurE. What now? BLES can be administed via MIST despite concerns about the higher volume of surfactant.  What many centres need to address I suspect is that while we think we are practicing InSurE, in many cases we are not.  The goal of that procedure is to provide the surfactant over a few seconds and then get the ETT out right away.  How often does that happen though in reality?  Have you ever found yourself leaving the ETT in till the baby gets to NICU and extubating there?  Seems safer right?  What if in the elevator or hallway on the way to NICU the baby deteriorates and needs intubation?  How long does the ETT stay in? Twenty minutes, 30, 45, 60 or longer?  Thinking about that in a different way, what does that translate into in terms of number of PPV breaths?  Well at a rate of 60 breaths a minute that means 1800,  2700, 3600 and more breaths before the ETT is removed.  I have often wondered if this in itself explains why InSurE seems to be repeatedly identified as being inferior to MIST.  If you intubated, gave the surfactant and pulled the ETT out right away in all cases might the two techniques actually be equivalent. The question now really is how do we get past our tendencies and embrace a change in practice that by design will not allow us to delivery any positive pressure breaths?!  
 

Was resetting the threshold for hypoglycaemia a good thing?

In 2015 the Pediatric Endocrine Society (PES) published new recommendations for defining and managing hypoglycaemia in the newborn. A colleague of mine and I discussed the changes and came to the conclusion that the changes suggested were reasonable with some “tweaks”. The PES suggested a change from 2.6 mmol/L (47 mg/dL) at 48 hours of age as a minimum goal glucose to 3.3 mmol/L (60 mg/dL) as the big change in approach. The arguments for this change was largely based on data from normal preterm and term infants achieving the higher levels by 48-72 hours and some neuroendocrine data suggesting physiologically, the body would respond with counter regulatory hormones below 3.3 mmol/L. As it turned out, we were “early adopters” as we learned in the coming year that no other centre in Canada had paid much attention to the recommendations. The inertia to change was likely centred around a few main arguments. 1. How compelling was the data really that a target of 2.6 and above was a bad idea? 2. Fear! Would using a higher threshold result in many “well newborns” being admitted to NICU for treatment when they were really just experiencing a prolonged period of transitional hypoglycaemia. 3. If its not broken don’t fix it. In other word, people were resistant to change itself after everyone was finally accustomed to algorithms for treatment of hypoglcyemia in their own centres. What effect did it actually have? My colleagues along with one of our residents decided to do a before and after retrospective comparison to answer a few questions since we embraced this change. Their answers to what effect the change brought about are interesting and therefore at least a in my opinion worth sharing. If any of you are wondering what effect such change might have in your centre then read on! Skovrlj R, Marks S and C. Rodd published Frequency and etiology of persistent neonatal hypoglycemia using the more stringent 2015 Pediatric Endocrine Society hypoglycemia guidelines. They had a total of 58 infants in the study with a primary outcome being the number of endocrine consults before and after the change in practice. Not surprisingly as the graph demonstrates the number went up.  Once the protocol was in place we went from arbitrary consults to mandatory so these results are not surprising.  What is surprising though is that the median critical plasma glucose was 2.2 mmol/L, with no significant difference pre or post (2.0 mmol/L pre versus 2.6 mmol/L post, P=0.4)  Ninety percent of the infants who were hypoglycemic beyond 72 hours of age were so in the first 72 hours.  Of these infants, 90% were diagnosed with hyperinsulinemia.  What this tells us is that those who are going to go on to have persistent hypoglycemia will demonstrate similar blood sugars whether you use the cutoff of 2.6 or 3.3 mmol/L.  You will just catch more that present a little later using the higher thresholds.  How would these kids do at home if discharged with true hyperinsulinemia that wasn’t treated?  I can only speculate but that can’t be good for the brain… Now comes the really interesting part! Of the total infants in the study,  thirteen infants or 40% had plasma glucose values of 2.6 to 3.2 mmol/L at the time of consultation after November 2015.  Think about that for a moment.  None of these infants would have been identified using the old protocol.  Nine of these infants went on to require treatment with diazoxide for persistent hyperinsulinemia. All of these infants would have been missed using the old protocol.  You might ask at this point “what about the admission rate?”. Curiously an internal audit of our admission rates for hypoglycemia during this period identified a decline in our admission rates.  Concurrent with this change we also rolled out the use of dextrose gels so the reduction may have been due to that as one would have expected admission rates to rise otherwise.  The other thing you might ask is whether in the end we did the right thing as who says that a plasma blood glucose threshold of 3.3 mmol/L is better than using the tried and true 2.6 mmol/L cutoff? While I don’t have a definitive answer to give you to that last question, I can leave you with something provocative to chew on.  In the sugar babies study the goal glucose threshold for the first 7 days of life was 2.6 mmol/L.  This cohort has been followed up and I have written about these studies before in Dextrose gel for hypoglycemia. Safe in the long run? One of the curious findings in this study was in the following table. Although the majority of the babies in the study had only mild neurosensory impairment detectable using sophisticated testing the question is why should so many have had anything at all? I have often wondered whether the goal of keeping the blood sugar above 2.6 mmol/L as opposed to a higher level of say 3.3 mmol/L may be at play.  Time will tell if we begin to see centres adopt the higher thresholds and then follow these children up.  I don’t know about you but a child with a blood sugar of 2.7 mmol/L at 5 or 6 days of age would raise my eyebrow.  These levels that we have used for some time seem to make sense in the first few days but for discharge something higher seems sensible.
 

Caffeine. Give it and give it early.

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!
 

At 22 weeks of gestation does your faith matter most to outcome?

Recent statements by the American Academy of Pediatric’s, NICHD, the American College of Obstetricians and Gynecologists (ACOG), the Society for Maternal-Fetal Medicine (SMFM), and recommend selective approaches to mothers presenting between 22 0/7 to 22 6/7 weeks. The decision to provide antenatal steroids is only recommended if delivery is expected after 23 weeks. Furthermore the decision to resuscitate is based on an examination of a number of factors including a shared decision with the family. In practice this leads to those centres believing this is mostly futile generally not resuscitating or offering steroids while other more optimistic hospitals having higher rates of proactive (steroids and resuscitation) rates. Then there are other centres where the standard approach is proactive such as one in Uppsala, Sweden where this approach is used almost exclusively. What would happen then if one compared the outcome for infants born at 22 weeks between this hospital and another where a selective approach is generally offered. In this case you would have a lot of experience with resuscitating infants at 22 weeks and the other a fraction of all presenting as a few to many would receive compassionate care. This is exactly what has now happened. A Tale of Two Cities The University Children’s Hospital, Uppsala, Sweden has been compared retrospectively to Nationwide Children’s Hospital, Columbus, Ohio, USA (NCH) with respect to survival and outcomes for their infants born at 22 weeks. The paper by Backes CH et al entitled Outcomes following a comprehensive versus a selective approach for infants born at 22 weeks of gestation tells a very interesting story about the power of belief or faith that one can accomplish something if they set their mind to it. The authors examined a period from 2006-2015, dividing this time into two epochs with the first being 2006-2010 to account for differing practices and resources over time. Given that Uppsala took a proactive approach to all of their 40 live born infants during this time, it provided an opportunity to look at the 72 infants who were live born in the Ohio and examine their differences. In Ohio the approach was as follows; 16 (22%) received proactive care, 18 (25%) received inconsistent care (steroids but no resuscitation), and 38 (53%) received comfort care. In other words, although the total number of infants live born in Ohio was almost double that of Uppsala, only 16 were proactively treated in Ohio compared to all 40 in Uppsala. The differences in outcome are striking Survival in delivery room: (38/40, 95% vs 12/16, 75%; P = 0.049) Provision of delivery room surfactant: (40/40, 100% vs 9/16, 56%; P<0.01) Survival at 24 h (37/40, 93% vs. 9/16, 56%; P < 0.01). Survival to 1 year (21/40, 53% vs. 3/16, 19%; P < 0.05). Among the infants treated proactively, median age of death (17 postnatal days at range 0 h–226 days vs. 3 postnatal hours at NCH, range 0 h–10 days; P < 0.01). All surviving infants had BPD All infants surviving to initial hospital discharge were alive at 18 months’ postnatal age. With respect to long term outcome the authors note: “Outpatient follow-up (qualitative or non-qualitative neurodevelopmental testing) was available in 26 out of 27 infants (96%) Eleven of the 26 (42%) were unimpaired, and all unimpaired infants were in the UUCH cohort. Among the 15 infants with impairment at UUCH, 3 had mild impairment and 12 had moderate or severe impairment. All surviving infants at NCH had moderate or severe impairment.” A word about antenatal steroids as well. In Uppsala 85% of mothers received 2 doses of antenatal steroids vs 25% in Ohio. People sometimes question whether ANS at this age are effective. It is interesting to note that 44% of babies in the Ohio group vs 3% p<0.01 received chest compressions +/- epinephrine in the delivery room. Might this explain the better state of some of these infants at birth? The Power of Belief When I do rounds I often remark that try as we might we can’t will babies to do better. I also commonly say however that we need to be optimistic and although I am accused of seeing the world through rose coloured glasses I think there is an important lesson to be learned from this study. This comparison is really a contrast between a system that believes they can do a good thing for these families by actively promoting a proactive approach vs a system in which I imagine a reluctant approach exists even for those infants where a proactive plan is enacted. One sign of this might be that in Sweden 100% of these deliveries had a Neonatologist present vs 75% in the US. It could be due to other factors such as ability of the Neo to get in within time of the delivery however rather than a sign they didn’t feel they were needed due to futility. There is evidence as well that the aggressiveness of the proactive approach also differs between the two sites based on a couple observations. The first is the rate of surfactant provision in the delivery room which was 100% in Sweden but only 56% in the US. The other thing of note is the time of death for those who did not survive. The median time of death in the US was 3 hours vs 17 days in Uppsala. What does this tell us about the approaches? I would imagine (although the numbers are small) that the teams in the US were much more likely to lose hope (or faith) and withdraw early while the other centre possibility motivated by their past successes pushed forward. Remarkably, although one might think that the teams in Uppsala were simply creating significantly impaired survivors, 42% of the survivors were unimpaired from a developmental standpoint in follow-up. All surviving infants though from Ohio had moderate to severe impairment. What this story may also really be about is practice. The reality is that the team in Sweden had over twice the exposure to such infants over time. Although the number presenting at this GA was higher, the ones that actually were resuscitated and given steroids was less than half. One cannot take away though that Uppsala in the end demonstrated that a proactive approach is definitely not futile. Not only can these children survive but almost half will be developmentally intact. We must acknowledge as well though that since this is a retrospective study there may be factors that may have affected the results. As the saying goes “Individual results may vary”. Are the teams the same in both centres in terms of number of Neonatologists? Are there more residents caring for these infants vs fellows? Are the resources the same? What about proximity of the Neonatologist to the hospital? There are other factors such as cohesiveness of the team and communication between team members that may be influencing the results. In the end though, this is a story of a team that believed it could and did. Perhaps seeing the world through rose coloured glasses is not such a bad thing in the end.

AllThingsNeonatal

AllThingsNeonatal

 

Does size really matter when weaning from an incubator?

Look around an NICU and you will see many infants living in incubators. All will eventually graduate to a bassinet or crib but the question always is when should that happen? The decision is usually left to nursing but I find myself often asking if a baby can be taken out. My motivation is fairly simple. Parents can more easily see and interact with their baby when they are out of the incubator. Removing the sense of “don’t touch” that exists for babies in the incubators might have the psychological benefit of encouraging more breastfeeding and kangaroo care. Both good things. Making the leap For ELBW and VLBW infants humidity is required then of course they need this climate controlled environment. Typically once this is no longer needed units will generally try infants out of the incubator when the temperature in the “house” is reduced to 28 degrees. Still though, it is not uncommon to hear that an infant is “too small”. Where is the threshold though that defines being too small? Past research studies have looked at two points of 1600 vs 1800g for the smallest of infants. One of these studies was a Cochrane review by New K, Flenady V, Davies MW. Transfer of preterm infants for incubator to open cot at lower versus higher body weight. Cochrane Database Syst Rev 2011;(9). This concluded that early transition was safe for former ELBWs at the 1600g weight cut off. What about the majority of our babies? While the ELBW group takes up a considerable amount of energy and resources the later preterm infants from 29 to 33 6/7 weeks are a much larger group of babies. How safe is this transition for this group at these weights? Shankaran et al from the NICHD published an RCT on this topic recently; Weaning of Moderately Preterm Infants from the Incubator to the Crib: A Randomized Clinical Trial. The study enrolled Infants in this gestational age range with a birth weight <1600g were randomly assigned to a weaning weight of 1600 or 1800 g. Within 60 to 100 g of weaning weight, the incubator temperature was decreased by 1.0°C to 1.5°C every 24 hours until 28.0°C. Weaning to the crib occurred when axillary temperatures were maintained 36.5°C to 37.4°C for 8 to 12 hours. Clothing and bedcoverings were standardized. The primary outcome was LOS from birth to discharge. What did they find? A total of 366 babies were enrolled (187 at 1600g and 179 at 1800g. Baseline characteristics of the two groups revealed no statistical differences. Mean LOPS was a median of 43 days in the lower and 41 days in the higher weight group (P = .12). After transition to a crib weight gain was better in the lower weight group, 13.7 g/kg/day vs 12.8 g/kg/ day (P = .005). Tracking of adverse events such as the incidence of severe hypothermia did not differ between groups. The only real significant difference was a better likelihood of weaning from the incubator in the higher group at 98% success vs 92% on the first attempt. Putting. That in perspective though, a 92% success rate by my standards is high enough to make an attempt worthwhile!   Concluding thoughts The authors have essentially shown that whether you wean at the higher or lower weight threshold your chances of success are pretty much the same. Curiously, weight gain after weaning was improved which seems counter intuitive. I would have thought that these infants would have to work extra hard metabolically to maintain their temperature and have a lower weight gain but that was not the case. Interestingly, this finding has been shown in another study as well; New K, Flint A, Bogossian F, East C, Davies MW. Transferring preterm infants from incubators to open cots at 1600 g: a multicentre randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2012;97:F88-92. Metabolic rate has been shown to increase in these infants but skin fold thickness has been shown to increase as well in infants moved to a crib. How these two things go together is a little beyond me as I would have thought that as metabolic rate increases storage of tissue would slow. Not apparently the case but perhaps just another example of the bodies ability to overcome challenges when put in difficult situations. A case maybe of “what doesn’t kill you makes you stronger?” The authors do point out that the intervention was unmasked but the standardization of weaning procedure and garments used in the cribs should have overcome that. There were 36% of parents who did not consent to the study so their inclusion could have swayed the results perhaps but the sample size here was large despite that. That the final results agree with findings in ELBW infants suggests that the results are plausible. What I think this study does though is tell us overall that weaning at a smaller weight is at least alright to try once one is at minimal settings in an incubator. Will this change your units practice? It is something that at least merits discussion.  

AllThingsNeonatal

AllThingsNeonatal

 

Every drop counts

As a Neonatologist, there is no question that I am supportive of breast milk for preterm infants.  When I first meet a family I ask the question “are you planning on breastfeeding” and know that other members of our team do the same.  Before I get into the rest of this post, I realize that while breast milk may be optimal for these infants there are mother’s who can’t or won’t for a variety of reasons produce enough breast milk for their infants.  Fortunately in Manitoba and many other places in the world breast milk banks have been developed to provide donor milk for supporting these families.  Avoidance of formula in the early days to weeks of a ELBWs life carries benefits such as a reduction in NEC which is something we all want to see. Mother’s own milk though is known to have additional benefits compared to donor milk which requires processing and in so doing removes some important qualities.  Mother’s own milk contains more immunologic properties than donor including increased amounts of lactoferrin and contains bioactive cells.  Growth on donor human milk is also reduced compared to mothers’ own milk and lastly since donor milk is obtained from mothers producing term milk there will be properties that differ from that of mothers producing fresh breast milk in the preterm period.  I have no doubt there are many more detailed differences but for basic differences are these and form the basis for what is to come. The Dose Response Effect of Mother’s Own Milk Breast milk is a powerful thing.  Previous studies on the impact of mother’s own milk (MOM) have shown that with every increment of 10 mL/kg/d of average intake, the risk of such outcomes as BPD and adverse developmental outcomes are decreased. In the case of BPD the effect is considerable with a 9.5% reduction in the odds of BPD for every 10% increase in MOM dose.  With respect to developmental outcome ach 10 mL/kg/day increase in MOM was associated with a 0.35 increase in cognitive index score. One of the best names for a study has to be the LOVE MOM study which enrolled 430 VLBW infants from 2008-2012.    The results of this study Impact of early human milk on sepsis and health-care costs in very low birth weight infants.indicated that with incremental increases of 10 mL/kg of MOM reductions in sepsis of 19% were achieved and in addition overall costs were reduced. The same group just published another paper on this cohort looking at a different angle. NICU human milk dose and health care use after NICU discharge in very low birth weight infants.  This study is as described and again looked at the impact of every 10 mL/kg increase in MOM at two time points; the first 14 and the first 28 days of life.  Although the data for the LOVE MOM trial was collected prospectively it is important to recognize how the data for this study was procured. At the first visit after NICU discharge the caregiver was asked about hospitalizations, ED visits and specialized therapies and specialist appointments. These were all tracked at 4 and 8 months of corrected age were added to yield health care utilization in the first year, and the number of visits or provider types at 4, 8, and 20 months of corrected age provided health care utilization through 2 years. What were the results? “Each 10 mL/kg/day increase in HM in the first 14 days of life was associated with 0.26 fewer hospitalizations (p =
0.04) at 1 year and 0.21 fewer pediatric subspecialist types (p = 0.04) and 0.20 fewer specialized therapy types (p = 0.04) at 2 years.” The results at 28 days were not statistically significant.  The authors reported both unadjusted and adjusted results controlling for many factors such as gestational age, completion of appointments and maternal education to name a few which may have influenced the results.  The message therefore is that the more of MOM a VLBW is provided in the first 14 days of life, the better off they are in the first two years of life with respect to health care utilization.   That even makes some sense to me.  The highest acuity typically for such infants is the first couple of weeks when they are dealing with RDS, PDA, higher oxygen requirements etc.  Could the protective effects of MOM have the greatest bang for your buck during this time.  By the time you reach 28 days is the effect less pronounced as you have selected out a different group of infants at that time point? What is the weakness here though?  The biggest risk I see in a study like this is recall bias. Many VLBW infants who leave the NICU have multiple issues requiring many different care providers and services.  Some families might keep rigorous records of all appointments in a book while others might document some and not others.  The big risk here in this study is that it is possible that some parents overstated the utilization rates and others under-reported.  Not intentionally but if you have had 20 appointments in the first eight months could the number really by 18 or 22? Another possibility is that infants receiving higher doses of MOM were healthier at the outset.  Maternal stress may decrease milk production so might mothers who had healthier infants have been able to produce more milk?  Are healthier infants in the first 14 days of life less likely to require more health care needs in the long term? How do we use this information? In spite of the caveats that I mentioned above there are multiple papers now showing the same thing.  With each increment of 10 mL/kg of MOM benefits will be seen.  It is not a binary effect meaning breastfed vs not.  Rather much like the medications we use to treat a myriad of conditions there appears to be a dose response.  It is not enough to ask the question “Are you intending to breastfeed?”.  Rather it is incumbent on all of us to ask the follow-up question when a mother says yes; “How can we help you increase your production?” if that is what the family wants>

AllThingsNeonatal

AllThingsNeonatal

 

Delayed cord clamping may get replaced. Time for physiological-based cord clamping?

Much has been written on the topic of cord clamping.  There is delayed cord clamping of course but institutions differ on the recommended duration.  Thirty seconds, one minute or two or even sometimes three have been advocated for but in the end do we really know what is right?  Then there is also the possibility of cord milking which has gained variable traction over the years.  A recent review was published here. Take the Guessing Out of the Picture? Up until the time of birth there is very little pulmonary blood flow.  Typically, about 10% of the cardiac output passes through the lungs and the remained either moves up the ascending aorta or bypasses the lungs via the ductus arteriosus.  After birth as the lung expands, pulmonary vascular resistance rapidly decreases allowing cardiac output to take on the familiar pattern which we all live with.  Blood returning from the systemic venous circulation no longer bypasses the lung but instead flows through pulmonary capillaries picking up oxygen along the way.  One can imagine then that if a baby is born and the cord is clamped right away, blood returning from the systemic circulation continues to bypass the lung which could lead to hypoxemia and reflexive bradycardia.  This has been described previously by Blank et al in their paper Haemodynamic effects of umbilical cord milking in premature sheep during the neonatal transition. A group of researchers from the Netherlands published a very interesting paper Physiological-based cord clamping in preterm infants using a new purpose-built resuscitation table: a feasibility study this month.  The study centres around a resuscitation table called the Concord that is brought to the mother for resuscitation after birth.  The intervention here was applied to infants 26 to 35 weeks gestational age.  The cord was clamped after each of the following was achieved for an infant indicating successful transition with opening of the lung and establishment of an FRC. 1. Establishment of adequate breathing (average tidal volume ≥4 mL/kg) on CPAP.  They used a mask capable of measuring expired tidal volumes. 2. HR above 100 bpm 3. SpO2 above 25th percentile using FiO2 <0.4 In this way, the cord was only clamped once the baby appeared to have physiologically made the transition from dependence on umbilical cord blood flow to ventilation perfusion matching in the lung.  Although 82 mothers consented only 37 preterm infants were included in the end.  Exclusion criteria were signs of placental abruption or placenta praevia, signs of severe fetal distress determined by the clinician and the necessity for an emergency caesarean section ordered to be executed within 15 min.  This really was a proof of concept study but the results are definitely worth looking at. How Did These Babies Do? There are many interesting findings from this study. The mean time of cord clamping was 4 minutes and 23 seconds (IQR 3:00 – 5:11).  Heart rate was 113 (81–143) and 144 (129–155) bpm at 1 min and 5 min
after birth.  Only one patient developed bradycardia to <60 BPM but this was during a mask readjustement.  The main issue noted as far as adverse events was hypothermia with a mean temperature of 36.0 degrees at NICU admission.  Almost 50% of infants had a temperature below 36 degrees.  Although the authors clearly indicate that they took measures to prevent heat loss it would appear that this could be improved upon! What stands out most to me is the lengthy duration of cord clamping.  This study which used a physiologic basis to determine when to clamp a cord has demonstrated that even at 1 minute of waiting that is likely only 1/4 of the time needed to wait for lung expansion to occur to any significant degree.  I can’t help but wonder how many of the patients we see between 26-35 weeks who have a low heart rate after delivery might have a higher heart rate if they were given far more time than we currently provide for cord clamping. I can also see why cord milking may be less effective.  Yes, you will increase circulating blood volume which may help with hemodynamic stability but perhaps the key here is lung expansion.  You can transfuse all the blood you want but if it has nowhere to go just how effective is it? As we do more work in this area I have to believe that as a Neonatal community we need to prepare ourselves for the coming of the longer delay for cord clamping.  Do we need to really have the “Concord” in every delivery or perhaps it is time to truly look at durations of 3-4 minutes before the team clamps the cord. Stay tuned!

AllThingsNeonatal

AllThingsNeonatal

 

Using the printed word to treat apnea of prematurity

As the saying goes, sometimes less is more.  In recent years there has been a move towards this in NICUs as the benefits of family centred care have been shown time and time again.  Hi tech and new pharmaceutical products continue to develop but getting back to the basics of skin to skin care for many hours and presence of families as an integral team member have become promoted for their benefits.  The fetus is a captive audience and hears the mother's heart beat and voice after the development of hearing sometime between 24-26 weeks gestational age.  This is a normal part of development so it would stand to reason that there could be a benefit to hearing this voice especially after hearing has developed and the fetus has grown accustomed to it.  Hospital including my own have developed reading programs for our patients and some companies have developed speakers in isolettes designed to limit the maximum decibel to 45 but allowing parents to make recordings of their voices.  Music may be played through these speakers as well but today we will focus on the benefit of voice. Could reading to your baby reduce apnea of prematurity? This is the question that Scala M et al sought to answer in their paper Effect of reading to preterm infants on measures of cardiorespiratory stability in the neonatal intensive care unit.  This was a small prospective study of the impact of parental reading on cardiorespiratory stability in preterm NICU infants. Eighteen patients were enrolled who were born between 23-31 weeks gestation.  The study was carried out when the babies were between 8-56 days old at a mean postnatal age of 30 weeks. Each patient served as their own control by comparing episodes of oxygen desaturation to <85% during pre-reading periods (3 hours and 1 hour before) to during reading and then 1 hour post reading.  Parents were asked to read or create a recording lasting a minimum of 15 min but up to 60 min of recorded reading.  The parents were offered a standard set of books that had a certain rhythm to the text or could choose their own.  Recorded reading was played for infants up to twice per day by the bedside nurse. While it was small in number of patients the authors point out that the total exposure was large with 1934 min of parental bedside reading analyzed (range 30–270 min per infant, mean 123, median 94 min).  Patients could be on respiratory support ranging from ventilators to nasal cannulae. Was it effective? It certainly was. I should mention though that the authors excluded one patient in the end when it was found that they failed their hearing screen.  Arguably, since the infant could not have benefited from the intervention effect this makes sense to me.  As shown from table 3 there was a statistical reduction in desaturation events during the reading period which was sustained in terms of a downward trend for one hour after the intervention was completed.  In case you are asking was the difference related to oxygen use the answer is no.  There was no difference in the amount of oxygen provided to patients.  While the events were not eliminated they were certainly reduced.  The other point worth mentioning is that there appears to be a difference between live (through open portholes) vs prerecorded reading (through a speaker in the isolette). Now for a little controversy Does source of the reading matter?  The authors found that maternal had a greater effect than paternal voice.  As a father who has read countless books to his children I found this a little off-putting.  As a more objective critic though I suppose I can buy the biologic plausibility here.  I suspect there is an independent effect of voice having a positive impact on development.  If we buy the argument though that the voice that the fetus has most been accustomed to is the mothers, then the findings of an augmented effect of the maternal voice over fathers makes some sense.  I will have to put my ego aside for a moment and acknowledge that the effect here could be real. There will no doubt need to be larger studies done to drill down a number of questions such as what is the ideal type of reading, duration, rhythmic or non etc but this is a great start.  I also think this falls into the category of "could this really be a bad thing?".  Even if in the end no benefit is shown to this type of intervention, the potential for family bonding with their preterm infant alone I think is cause for embracing this intervention. Lastly, with the move to single patient rooms there is one study that demonstrated the isolation encountered from infrequent contact with their newborn can have a long lasting effect on development.  The article by Pineda RG et al Alterations in brain structure and neurodevelopmental outcome in preterm infants hospitalized in different neonatal intensive care unit environments. had a mean parental visitation of 19 +/- 19 hours a week or a little over 2 hours a day but with a very large standard deviation meaning many infants had almost no visitation.  The message here is that while quiet is good for infant development, too much can be a bad thing.  Maybe live reading or even recordings are a way around that.

AllThingsNeonatal

AllThingsNeonatal

 

Don’t let the cord gas fool you

It has to be one of the most common questions you will hear uttered in the NICU.  What were the cord gases?  You have a sick infant in front of you and because we are human and like everything to fit into a nicely packaged box we feel a sense of relief when we are told the cord gases are indeed poor.  The congruence fits with our expectation and that makes us feel as if we understand how this baby in front of us looks the way they do. Take the following case though and think about how you feel after reading it.  A term infant is born after fetal distress (late deceleration to as low as 50 BPM) is noted on the fetal monitor.  The infant is born flat with no heart rate and after five minutes one is detected.  By this point the infant has received chest compressions and epinephrine twice via the endotracheal tube.  The cord gases are run as the baby is heading off to the NICU for admission and low and behold you get the following results back; pH 7.21, pCO2 61, HCO3 23, lactate 3.5.   You find yourself looking at the infant and scratching your head wondering how the baby in front of you that has left you moist with perspiration looks as bad as they do when the tried and true cord gas seems to be betraying you.  To make matters worse at one hour of age you get the following result back; pH 6.99, pCO2 55, HCO3 5, lactate 15.  Which do you believe?  Is there something wrong with the blood gas analyzer? How Common Is This Situation You seem to have an asphyxiated infant but the cord gas isn’t following what you expect as shouldn’t it be low due to the fetal distress that was clearly present?  It turns out, a normal or mildly abnormal cord gas may be found in asphyxiated infants just as commonly as what you might expect.  In 2012 Yeh P et al looked at this issue in their paper The relationship between umbilical cord arterial pH and serious adverse neonatal outcome: analysis of 51,519 consecutive validated samples. The authors sampled a very large number of babies over a near 20 year period to come up with a sample of 51519 babies and sought to pair the results with what they knew of the outcome for each baby. This is where things get interesting.  When looking at the outcome of encephalopathy with seizures and/or death you will note that only 21.71% of the babies with this outcome had a gas under 7.00.  If you include those under 7.10 as still being significantly distressed then this percentage rises to 34.21%.  In other words almost 66% of babies who have HIE with seizures and/or death have a arterial cord pH above 7.1!  The authors did not look at encephalopathy without seizures but these are the worst infants and almost 2/3 have a cord gas that you wouldn’t much as glance at and say “looks fine” How do we reconcile this? The answer lies in the fetal circulation.  When an fetus is severely stressed, anaerobic metabolism takes over and produces lactic acid and the metabolic acidosis that we come to expect.  For the metabolites to get to the umbilcal artery they must leave the fetal tissues and enter the circulation.  If the flow of blood through these tissues is quite poor in the setting of compromised myocardial contractility the acids sit in the tissues.  The blood that is therefore sitting in the cord at the time of sampling actually represents blood that was sent to the placenta “when times were good”.  When the baby is delivered and we do our job of resuscitating the circulation that is restored then drives the lactic acid into the blood stream and consumes the buffering HCO3 leading to the more typical gases we are accustomed to seeing and reestablishing the congruence our brains so desire.  This in fact forms the basis for most HIE protocols which includes a requirement of a cord gas OR arterial blood gas in the first hour of life with a pH < 7.00. Acidosis May Be Good For the Fetus To bend your mind just a little further, animal evidence suggests that those fetuses who develop acidosis may benefit from the same and be at an advantage over those infants who don’t get acidemia.  Laptook AR et al published Effects of lactic acid infusions and pH on cerebral blood flow and metabolism.  In this study of piglets, infusion of lactic acid improved cerebral blood flow.  I would suggest improvement in cerebral blood flow of the stressed fetus would be a good thing.  Additionally we know that lactate may be used by the fetus as additional metabolic fuel for the brain which under stress would be another benefit.  Finally the acidemic fetus is able to offload O2 to the tissues via the Bohr effect.  In case you have forgotten this phenomenon, it is the tendency for oxygen to more readily sever its tie to hemoglobin and move into the tissues. I hope you have found this as interesting as I have in writing it.  The next time you see a good cord gas in a depressed infant, pause for a few seconds and ask yourself is this really a good or a bad thing?

AllThingsNeonatal

AllThingsNeonatal

 

The days of the Apgar score may be numbered

One of the first things a student of any discipline caring for newborns is how to calculate the apgar score at birth.  Over 60 years ago Virginia Apgar created this score as a means of giving care providers a consistent snapshot of what an infant was like in the first minute then fifth and if needed 10, 15 and so on if resuscitation was ongoing.  For sure it has served a useful purpose as an apgar score of 0 and 0 gives one cause for real worry.  What about a baby with an apgar of 3 and 7 or 4 and 8?  There are certainly infants who have done very well who initially had low apgar scores and conversely those who had higher apgar scores who have had very significant deleterious outcomes including death.  I don’t mean to suggest that the apgar scores don’t provide any useful predictive value as they are used as part of the criteria to determine if a baby merits whole body cooling or not.  The question is though after 60+ years, has another score been created to provide similar information but enhance the predictive value derived from a score? The Neonatal Resuscitation and Adaptation Score (NRAS) Back in 2015 Jurdi et al published  Evaluation of a Comprehensive Delivery Room Neonatal Resuscitation and Adaptation Score (NRAS) Compared to the Apgar Score.  This new score added into a ten point score resuscitative actions taken at the 1 and 5 minute time points to create a more functional score that included interventions.  The other thing this new score addressed was more recent data that indicated a blue baby at birth is normal (which is why we have eliminated asking the question “is the baby pink?” in NRP.  Knowing that, the colour of the baby in the apgar score may not really be that relevant.  Take for example a baby with an apgar score of 3 at one minute who could have a HR over 100 and be limp, blue and with shallow breathing.  Such a baby might get a few positive pressure breaths and then within 10 seconds be breathing quite well and crying.  Conversely, they might be getting ongoing PPV for several minutes and need oxygen.  Were they also getting chest compressions?  If I only told you the apgar score you wouldn’t have much to go on.  Now look at the NRAS and compare the information gathered using two cardiovascular (C1&2), one neurological test (N1) and two respiratory assessments (R1&2).   The authors in this study performed a pilot study on only on 17 patients really as a proof of concept that the score could be taught and implemented.  Providers reported both scores and found “superior interrater reliability (P < .001) and respiratory component reliability (P < .001) for all gestational ages compared to the Apgar score.”   A Bigger Study Was Needed The same group in 2018 this time led by Witcher published Neonatal Resuscitation and Adaptation Score vs Apgar: newborn assessment and predictive ability.  The primary outcome was the ability of a low score to predict mortality with a study design that was a non-inferiority trial.  All attended deliveries were meant to have both scores done but due to limited numbers of trained personnel who could appropriately administer both scores just under 90% of the total deliveries were assigned scores for comparison.  The authors sought to recruit 450 infants to show that a low NRAS score (0–3) would not be inferior to a similar Apgar at predicting death.  Interestingly an interim analysis found the NRAS to be superior to Apgar when 75.5% of the 450 were enrolled, so the study was stopped.  What led the apgar score to perform poorly in predicting mortality (there were only 12 deaths though in the cohort) was the fact that 49 patients with a 1 minute apgar score of 0-3 survived compared to only 7 infants with a low NRAS score. The other interesting finding was the ability of the NRAS to predict the need for respiratory support at 48 hours with a one minute apgar score of 0-3 being found in 39% of those on support compared to 100% of those with a low NRAS.  Also at 5 minutes a score of 4-6 for the apgar was found in 48% of those with respiratory support at 48 hours vs 87% of those with a similar range NRAS.  These findings were statistically significant while a host of other conditions such as sepsis, hypoglycemia, hypothermia and others were no different in terms of predictive ability of the scores. An Even Bigger Study is Needed To be sure, this study is still small and missed just over 90% of all deliveries so it is possible there is some bias that is not being detected here.  I do think there is something here though which a bigger study that has an army of people equipped to provide the scoring will add to this ongoing story.  Every practitioner who resuscitates an infant is asked at some point in those first minutes to hour “will my baby be ok?”.  The truth is that the apgar score has never lived up to the hope that it would help us provide an accurate clairvoyant picture of what lies ahead for an infant.   Where this score gives me hope is that a score which would at the very least help me predict whether an infant would likely still be needing respiratory support in 48 hours provides the basic answer to the most common question we get in the unit once admitted; “when can I take my baby home”.  Using this score I could respond with some greater confidence in saying “I think your infant will be on support for at least 48 hours”.  The bigger question though which thankfully we don’t have to address too often for the sickest babies at birth is “will my baby survive?”.  If a larger study demonstrates this score to provide a greater degree of accuracy then the “Tipping Point” might just be that to switching over to the NRAS and leaving the apgar score behind.  That will never happen overnight but medicine is always evolving and with time you the reader may find yourself becoming very familiar with this score!

AllThingsNeonatal

AllThingsNeonatal

 

This Vitamin Could Save A Babies Life

It has been a few months now that I have been serving as Chair of the Fetus and Newborn Committee for the Canadian Pediatric Society. Certain statements that we release resonate strongly with me and the one just released this week is certainly one of them. Guidelines for vitamin K prophylaxis in newborns is an important statement about a condition that thankfully so few people ever experience.  To read the statement on the CPS website click here. Similar story to vaccinations Prior to the American Academy of Pediatrics in 1961 proclaiming that all newborns should receive IM Vitamin K at birth the incidence of Vitamin K deficient bleeding was 0.25 – 1.7%. Think about that for a moment. A new parent could expect that 1/100 babies roughly might have intestinal bleeding or worse an intracranial hemorrhage due to an insufficient amount of vitamin K levels in the newborn. The types of bleeding could be categorized into three different time epochs. Early onset (occurring in the first 24 hours post-birth), classic (occurring at days 2 to 7) and late onset (at 2 to 12 weeks and up to 6 months of age). With a rate that high detractors of providing Vitamin K at birth would say “why should we give it; I haven’t heard of any baby getting such bleeding?” Looking at it another way though, why don’t you see congenital rubella or kids with measles much these days? It’s due to vaccination. Thankfully as a Neonatologist, I don’t see Vitamin K deficient bleeding since most parents provide Vitamin K to their babies at birth.  If you went back to the era prior to 1961 when widespread supplementation of Vitamin K began in the US, I imagine it would not have been too uncommon to hear about a baby who had bleeding issues after birth.  Just because we don’t hear about German Measles much anymore doesn’t mean the virus causing it doesn’t still exist! How Effective is Vitamin K? How effective is Vitamin K administration at birth in preventing hemorrhagic disease of the newborn (HDNB)? Studies estimate an incidence of 0.25 per 100000 live births or 1 in 400000 babies vs the 1/100 risk without any vitamin K. That is one effective intervention! At this point I would ask those families that are still concerned about giving Vitamin K to their infants if this is a risk they can accept? If they refuse Vitamin K and there is a significant bleed how will they react? The Change in this CPS Statement From the Past In the last statement on Vitamin K, the authors suggested that the oral route was a reasonable option. Instead of giving 1 mg of Vitamin K IM one would dose it as 2 mg orally and then repeat at 2-4 weeks and then 6-8 weeks. In looking at the effectiveness though it is worth noting that while we can assure that families will get the first dose, as with any medication that needs repeat dosing there is the risk of forgetfulness leading to missed dosing down the road. In fact when the authors looked at the risk of late HDNB they found the following “The relative risk for VKDB, when comparing PO versus IM vitamin K administration in these two studies, was 28.75 (95% CI 1.64 to 503.45) and 5.97 (95% CI 0.54 to 65.82), respectively [19][20].” The outcome of course remains rare but the risk based on two studies was almost 30 times higher than if IM dosing was given. On this basis IM is recommended. Having said all this I recognize that despite all this information, some families will choose for a number of reasons to still opt for the oral dose. As the statement suggests we need to encourage such use when a family refuses IM vitamin K. The 30 fold risk compared to IM administration is magnitudes lower than the approximate 1/100 risk of giving nothing at all! In the end I believe that one case of intracranial hemorrhage from inadequate vitamin K is too much. This one vitamin indeed could save a life.

AllThingsNeonatal

AllThingsNeonatal

 

Intubating to give surfactant is so 2017!

A catchy title for sure and also an exaggeration as I don’t see us abandoning the endotracheal tube just yet.  There has been a lot of talk about less invasive means of giving surfactant and the last few years have seen several papers relating to giving surfactant via a catheter placed in the trachea (MIST or LISA techniques as examples).  There may be a new kid on the block so to speak and that is aerosolized surfactant.  This has been talked about for some time as well but the challenge had been figuring out how to aerosolize the fluid in such a way that a significant amount of the surfactant would actually enter the trachea.  This was really a dream of many Neonatologists and based on a recently published paper the time may be now for this technique to take off. A Randomized Trial of Aerosolized Surfacant Minocchieri et al as part of the CureNeb study team published Nebulised surfactant to reduce severity of respiratory distress: a blinded, parallel, randomised controlled trial. This trial set out to obtain a sample size of 70 patients between 29 0/7 to 33 6/7 weeks to demonstrate a difference in need for intubation from 30% down to 5% in patients treated with CPAP (30% was based on the historical average).  The authors recognizing that the babies in this GA bracket might behave differently, further stratified the randomization into two groups being 29 0/7 – 31 6/7 weeks and 32 0/7 to 33 6/7 weeks.  Those babies who were on CPAP and met the following criteria for intubation were either intubated in the control group and given surfactant (curosurf) using the same protocol as those nebulized or had surfactant delivered via nebulisation (200 mg/kg: poractant alfa) using a customised vibrating membrane nebuliser (eFlow neonatal). Surfactant nebulisation(100 mg/kg) was repeated after 12 hours if oxygen was still required.  The primary dichotomous outcome was the need for intubation within 72 hours of life, and the primary continuous outcome was the mean duration of mechanical ventilation at 72 hours of age. Criteria for intubation 1. FiO2 >0.35 over more than 30 min OR FiO2 >0.45 at
anytime.
2. More than four apnea/hour OR two apnea requiring BVM
3. Two cap gases with pH <7.2 and PaCO2 >65 mm Hg (or) >60 mm Hg if arterial blood gas sample).
4. Intubation deemed necessary by the attending physician. Did It Work? Eureka! It seemed to work as 11 of 32 infants were intubated in the surfactant nebulisation group within 72 hours of birth vs.22 out of 32 infants receiving CPAP alone (RR (95% CI)=0.526 (0.292 to 0.950)). The reduction though was accounted for by the bigger babies in the 32 0/7 to 33 6/7 weeks group as only 1 of 11 was intubated when given nebulized surfactant compared to 10 of 13 managed with CPAP.  The duration of ventilation in the first 72 hours was not different between the groups: the median (range) 0 (0–62) hour for the nebulization group and 9 (0–64) hours for the control group (p=0.220).  It is important in seeing these results that the clinicians deciding whether infants should be intubated for surfactant administration were blind to the arm the infants were in.  All administration of curosurf via nebulization or sham procedures were done behind a screen. The total number of infants randomized were 66 so they did fall shy of the necessary recruitment but since they did find a difference the results seem valid.  Importantly, there were no differences in complications although I can’t be totally confident there really is no risk as this study was grossly underpowered to look at rarer outcomes. Breaking down the results This study has me excited as what it shows is that “it kind of works“.  Why would larger babies be the ones to benefit the most?  My guess is that some but not a lot of surfactant administered via nebulization reaches the alveoli.  Infants with lesser degrees of surfactant deficiency (32 0/7 to 33 6/7) weeks might get just enough to manage without an endotracheal tube.  Those infants (in particular less than 32 0/7 weeks) who have more significant surfactant deficiency don’t get enough and therefore are intubated.  Supporting this notion is the overall delay in time to intubation in those who were intubated despite nebulization (11.6 hours in the nebulization group vs 4.9 hours in the control arm).  They likely received some deposition in the distal alveoli but not enough to completely stave off an endotracheal tube. One concerning point from the study though had to do with the group of infants who were intubated despite nebulization of surfactant.  When you look at total duration of ventilation (hours) it was 14.6 (9.0–24.8) in the control arm vs 25.4 (14.6–42.2) p= 0.029*.  In other words infants who were intubated in the end spent about twice as long intubated as those who were intubated straight away.  Not a huge concern if you are born at 32 weeks or more but those additional thousands of positive pressure breaths are more worrisome as a risk for CLD down the road. As it stands, if you had an infant who was 33 weeks and grunting with an FiO2 of 35% might you try this if you could get your hands on the nebulizer?  It appears to work so the only question is whether you are confident enough that the risk of such things as pneumothorax or IVH isn’t higher if intubation is delayed.  It will be interesting to see if this gets adopted at this point. The future no doubt will see a refinement of the nebulizer and an attempt to see how well this technique works in infants below 29 weeks.  It is in this group though that prolonging time intubated would be more worrisome.  I don’t want to dismiss this outright as I see this as a pilot study that will lead the way for future work that will refine this technique.  If we get this right this would be really transformative to Neonatology and just might be the next big leap.

AllThingsNeonatal

AllThingsNeonatal

 

Can video laryngoscopes reduce risk of harm from intubation?

The modern NICU is one that is full of patients on CPAP these days. As I have mentioned before, the opportunity to intubate is therefore becoming more and more rare is non-invasive pressure support becomes the mainstay of therapy. Even for those with established skills in placing an endotracheal tube, the number of times one gets to do this per year is certainly becoming fewer and fewer. Coming to the rescue is the promise of easier intubations by being able to visualize an airway on a screen using a video laryngoscope. The advantage to the user is that anyone who is watching can give you some great tips and armed with this knowledge you may be better able to determine how to adjust your approach. For those of you who have followed the blog for some time, you will recall this is not the first time video laryngoscopy has come up. I have spoken about this before in Can Video Laryngoscopy Improve Trainee Success in Intubation.  In that piece, the case was made that training residents how to intubate using a video laryngoscope (VL) improves their success rate. An additional question that one might ask though has to do with the quality of the intubation.  What if you can place a tube using a video laryngoscope but the patient suffers in some way from having that piece of equipment in the mouth?  Lucky for us some researchers from the Children's Hospital of Philadelphia have completed a study that can help answer this additional question. Video Laryngoscopy may work but does it cause more harm than good? Using a video laryngoscope requires purchasing one first and they aren't necessarily cheap.  If they were to provide a better patient experience though the added cost might well be worth it.  Pouppirt NR et al published Association Between Video Laryngoscopy and Adverse Tracheal Intubation-Associated Events in the Neonatal Care Unit.  This study was a retrospective comparison of two groups; one having an intubation performed with a VL (n=161 or 20% of the group) and the other with a standard laryngoscope (644 or 80% of the group).  The study relied on the use of the National Emergency Airway Registry for Neonates (NEAR4NEOs), which records all intubations from a number of centres using an online database and allows for analysis of many different aspects of intubations in neonates.  In this case the data utilized though was from their centre only to minimize variation in premedication and practitioner experience. Tracheal intubation adverse events (TIAEs) were subdivided into severe (cardiac arrest, esophageal intubation with delayed recognition, emesis with witnessed aspiration, hypotension requiring intervention (fluid and/or vasopressors), laryngospasm, malignant hyperthermia, pneumothorax/pneumomediastinum, or direct airway injury) vs non-severe (mainstem bronchial intubation, esophageal intubation with immediate recognition, emesis without aspiration, hypertension requiring therapy, epistaxis, lip trauma, gum or oral trauma, dysrhythmia, and pain and/or agitation requiring additional medication and causing a delay in intubation. Looking at the patient characteristics and outcomes, some interesting findings emerge. Patients who had the use of the VL were older and weighed more.  They were more likely to have the VL used for airway obstruction than respiratory failure and importantly were also more likely to receive sedation/analgesia and paralysis.  These researchers have also recently shown that the use of paralysis is associated with less TIAEs so one needs to bear this in mind when looking at the rates of TIAEs.  There were a statistically significant difference in TIAEs of any type of 6% in the VL group to 19% in the traditional laryngoscopy arm but severe TIAEs showed not difference. Given that several of the baseline characteristics might play a role in explaining why VL seemed superior in terms of minimizing risk of TIAEs by two thirds, the authors performed a multivariable analysis in which they took all factors that were different into account and then looked to see if there was still an effect of the VL despite these seemingly important differences.  Interestingly, us of VL showed an Odds ratio of 0.43 (0.21,0.87 95% CI) in spite of these differences. What does it mean? Video laryngoscopy appears to make a difference to reducing the risk on TIAEs as an independent factor.  The most common TIAE was esophageal intubation at 10% and reducing that is a good thing as it leads to fewer intubation attempts.  This was also sen as the first attempt success was 63% in the VL group vs 44% in the other. Now we need to acknowledge that this was not a randomized controlled trial so it could indeed be that there are other factors that the authors have not identified that led to improvements in TIAEs as well.  What makes this study so robust though is the rigour with which the centre documents all of their intubations using such a detailed registry.  By using one centre much of the variability in practice between units is eliminated so perhaps these results can be trusted.  Would your centre achieve these same results? Maybe not but it would certainly be interesting to test drive one of these for a period of time see how it performs.

AllThingsNeonatal

AllThingsNeonatal

 

Was adding placement of EKG leads to NRP a good idea after all?

It is hard to believe but it has been almost 3 years since I wrote a piece entitled A 200 year old invention that remains king of all tech in newborn resuscitation. In the post I shared a recent story of a situation in which the EKG leads told a different story that what our ears and fingers would want us to believe. The concept of the piece was that in the setting of pulseless electrical activity (where there is electrical conductance in the myocardium but lack of contraction leaves no blood flow to the body) one could pick up a signal from the EKG leads when there is in fact no pulse or perfusion to vital organs. This single experience led me to postulate that this situation may be more common than we think and the application of EKG leads routinely could lead to errors in decision making during resuscitation of the newborn. It is easy to see how that could occur when you think about the racing pulses of our own in such situations and once chest compressions start one might watch the monitor and forget when they see a heart rate of 70 BPM to check for a corresponding pulse or listen with the stethoscope. I could see for example someone stopping chest compressions and continuing to provide BVM ventilation despite no palpable pulse when they see the QRS complex clearly on the monitor. I didn’t really have much evidence to support this concern but perhaps there is a little more to present now. A Crafty Animal Study Provides The Evidence I haven’t presented many animal studies but this one is fairly simple and serves to illustrate the concern in a research model. For those of you who haven’t done animal research, my apologies in advance as you read what happened to this group of piglets. Although it may sound awful, the study has demonstrated that the concern I and others have has is real. For this study 54 newborn piglets (equivalent to 36-38 weeks GA in humans) were anesthetized and had a flow sensor surgically placed around the carotid artery.  ECG leads were placed as well and then after achieving stabilization, hypoxia was induced with an FiO2 of 0.1 and then asphyxia by disconnecting the ventilator and clamping the ETT.  By having a flow probe around the carotid artery the researchers were able to determine the point of no cardiac output and simultaneously monitor for electrical activity via the EKG leads.  Auscultation for heart sounds was performed as well. The results essentially confirm why I have been concerned with an over reliance on EKG leads.   Of the 57 piglets, 14 had asystole and no carotid flow but in 23 there was still a heart rate present on the EKG with no detectable carotid flow. This yields a sensitivity of only 37%.  Moreover, the overall accuracy of the ECG was only 56%. Meanwhile the stethoscope which I have referred to previously as the “king” in these situations had 100% sensitivity so remains deserving of that title. What do we do with such information? I think the results give us reason to pause and remember that faster isn’t always better.  Previous research has shown that signal acquisition with EKG leads is faster than with oximetry.  While a low heart rate detected quickly is helpful to know what the state of the infant is and begin the NRP pathway, we simply can’t rely on the EKG to tell us the whole story.  We work in interdisciplinary teams and need to support one another in resuscitations and provide the team with the necessary information to perform well.  The next time you are in such a situation remember that the EKG is only one part of the story and that auscultation for heart sounds and palpation of the umbilical cord for pulsation are necessary steps to demonstrate conclusively that you don’t just have a rhythm but a perfusing one. I would like to thank the Edmonton group for continuing to put out such important work in the field of resuscitation!

AllThingsNeonatal

AllThingsNeonatal

 

Is paralysis for intubation really needed?

A few weeks back I wrote about the topic of intubations and whether premedication is really needed (Still performing awake intubations in newborns? Maybe this will change your mind.) I was clear in my belief that it is and offered reasons why. There is another group of practitioners though that generally agree that premedication is beneficial but have a different question. Many believe that analgesia or sedation is needed but question the need for paralysis. The usual argument is that if the intubation doesn’t go well and the patient can’t spontaneously ventilate could we be worse off if the patient loses their muscle tone. Neonatal Intubation Registry At the CPS meeting last month in Quebec City. I had the pleasure of listening to a talk by Dr. Elizabeth Foglia on the findings from a Neonatal intubation registry that many centres have been contributing to. The National Emergency Airway Registry for Neonates (NEAR4NEOs), records all intubations from a number of centres using an online database and allows for analysis of many different aspects of intubations in neonates. This year, J. Krick et al published Premedication with paralysis improves intubation success and decreases adverse events in very low birth weight infants: a prospective cohort study. This study compared results from the registry of two centres, the University of Washington Medical Center (UWMC) and Seattle Children’s Hospital where the former rarely uses paralysis and the latter in almost all instances of non-emergent intubation. In all, 237 encounters were analyzed in the NICU for babies < 1500g with the majority of encounters (181) being from UWMC. The median PMA at intubation was 28 completed weeks (IQR: 27, 30), chronological age was 9 days (IQR: 2, 26) and weight was 953 g (IQR: 742,1200). The babies were compared based on the following groups. Premedication with a paralytic 21%, without a paralytic 46% and no premedication 31%. This was an observational study that examined the rates of adverse events and subdivided into severe (cardiac arrest, esophageal intubation with delayed recognition, emesis with witnessed aspiration, hypotension requiring intervention (fluid and/or vasopressors), laryngospasm, malignant hyperthermia, pneumothorax/pneumomediastinum, or direct airway injury) vs non-severe (mainstem bronchial intuba- tion, esophageal intubation with immediate recognition, emesis without aspiration, hypertension requiring therapy, epistaxis, lip trauma, gum or oral trauma, dysrhythmia, and pain and/or agitation requiring additional medication and causing a delay in intubation.). How did the groups compare? It turns out paralysis seems to be a big deal (at least in this group of infants). Use of paralysis resulted in less attempts to intubate (median 1 attempt; IQR: 1, 2.25 vs. 2; IQR: 1, 3, p < 0.05)). In fact success was no different between the groups with no paralysis or no premedication at all! When it comes to  tracheal intubation adverse events the impact of using paralysis becomes more evident.   Paralysis does make a difference in reducing the incidence of such events and moreover when only looking at the rate of severe adverse events as defined above the finding was that none occurred when paralysis was used vs 9 when no paralysis was employed and 5 when no premedication was used at all.  The rate of bradycardic events was less in the paralytic group but rates of oxygen desaturation between the three arms were no different. How do we interpret the results? Based on the results from the registry it looks like paralysis is a good thing here when electively intubating infants.   If we try to determine the reason for it I suspect it may have much to do with the higher likelihood of success on the first attempt at placing an ETT. The longer it takes to place the ETT or the more number of attempts requiring intermittent PPV in a patient who truly needs a tube the greater the likelihood that you will see adverse events including bradycardia.  It may simply be that a calm and still patient is an easier intubation and getting the tube in faster yields a more stable patient. I am biased though and I think it is worth pointing out another possible reason for the differing results.  One hospital in this study routinely used premedication and the other did not.  Almost 3/4 of the patients came from one hospital which raises the possibility that skill set could be playing a role.  If the skill of providers at the two hospitals differed, the results could reflect the variable skill in the practitioners versus the difference in the medications used themselves.  What I don’t know though is whether the two share the same training program or not.  Are the trainees the same at both sites (google maps says the two sites are 11 minutes away by car)?  The difference still might be in local respiratory therapists or Neonatologists intubating as well.  Regardless, the study provides evidence that paralysis makes a difference.  To convince those out there though who remain skeptical I think we are going to need the registry to take part in a prospective trial using many centres.  A format in which several centres that don’t use paralysis are compared to several who do routinely would help to sort out the concern in skill when looking only at two centres.  This wouldn’t be randomized of course but I think it would be very difficult at this point to get a centre that strongly believes in using paralysis to randomize so a prospective study using groups chosen by the individual centre might be the next best thing.  If anyone using the registry is reading this let me know what you think?

AllThingsNeonatal

AllThingsNeonatal

 

Hospital or Home Based Therapy For Neonatal Abstinence?

This post is very timely as the CPS Fetus and Newborn committee has just released a new practice point: Managing infants born to mothers who have used opioids during pregnancy Have a look at discharge considerations as that section in the statement speaks to this topic as well! As bed pressures mount seemingly everywhere and “patient flow” becomes the catch-word of the day, wouldn’t it be nice to manage NAS patients in their homes?  In many centres, such patients if hospitalized can take up to 3 weeks on average to discharge home off medications.  Although done sporadically in our own centre, the question remains is one approach better than the another?  Nothing is ever simple though and no doubt there are many factors to consider depending on where you live and what resources are available to you.  Do you have outpatient follow-up at your disposal with practitioners well versed in the symptoms of NAS and moreover know what to do about them?  Is there comfort in the first place with sending babies home on an opioid or phenobarbital with potential side effects of sedation and poor feeding?  Nonetheless, the temptation to shift therapy from an inpatient to outpatient approach is very tempting. The Tennessee Experience Maalouf Fl et al have published an interesting account of the experience with outpatient therapy in their paper Outpatient Pharmacotherapy for Neonatal Abstinence Syndrome.  The authors were able to take advantage of the Tennessee Medicaid program using administrative
and vital records data from 2009 to 2011 to capture a cohort of 736 patients who were treated for NAS.  Forty five percent or 242 patients were treated as outpatients vs 290 cared for in hospital for the duration of treatment.  It is worth mentioning at this point that when the authors say they were cared for as outpatients it really is a hybrid model as the duration of hospitalization for the inpatients was a median of 23 days (IQR 14-35) versus 11 days (IQR 7-18) for inpatients (P < .001).  This practice isn’t much different than my own in which I start therapy in hospital and then discharge home with a period of home therapy. The strength of the study is the volume of patients and the ability to follow-up with these babies for the first 6 months of life to determine what happened to them after discharge.  In terms of duration of treatment, the differences are significant but perhaps not surprising. The median length of treatment for outpatients was 60 days (IQR 38-92) compared with 19 days (IQR 10-31) for inpatients (P < .001).  What was interesting as well is that 82% of babies were discharged home on phenobarbital and 9.1% on methadone and 7.4% with both.  A very small minority was discharged home on something else such as morphine or clonidine.  That there was a tripling of medication wean is not surprising as once the patients are out of the watchful eye of the medical team in hospital it is likely that practitioners would use a very slow wean out of hospital to minimize the risk of withdrawal. An Unintended Consequence This study found a statistically significant increase in risk for presenting to the emergency department for those patients treated as outpatients. What this graph demonstrates is that there was no increase risk in the first month but there was for the first 6 months.  Despite the increased risk of presentation to the ED the rate of hospitalization was not different.  Drilling down the data further, the reason for coming to the ED was not for withdrawal which was 10% in the outpatient and 11% in the inpatient group.  The other major reason was The most common diagnoses were upper respiratory infections; 80% outpatient vs 71% inpatient.  So while there was a significant difference (which was not by much) my take on it is that it was most likely by chance as I can’t think of how infections in the first 6 months could be linked to choice of medication wean. What about phenobarbital? Phenobarbital has been used for many years in Neonatology for control of seizures, sedation (taking advantage of a side effect) and management of NAS.  The problem with a median use of phenobarbital for 2 months is its potential to affect development. An animal study by Diaz in 1999 in which rat pups were given two weeks of phenobarbital starting on day 5 of life and then euthanized demonstrated the following weight reductions when high dose phenobarbital was utilized.  In human data, children with febrile seizures treated with phenobarbital in the paper Late cognitive effects of early treatment with phenobarbital. had decreased intelligence than those not exposed to phenobarbital. The issue here for me is not necessarily whether babies can be treated successfully as outpatients for NAS.  The concern is at what cost if the choice of drug is phenobarbital.  The reason phenobarbital was chosen is likely due to compliance.  We know that the more frequently a drug is dose the less likely compliance will be achieved.  Phenobarbital being dosed either q12h or q24h is an ideal drug from a compliance point of view but the ramifications of this treatment deserve reconsideration. I look forward to seeing further studies on this topic and hope that we see the results of an opioid outpatient treatment program.  I know these exist and would welcome any information you as the readers of this blog can offer.  Treating patients in the home makes great sense to me but we need to do it with the right drugs!

AllThingsNeonatal

AllThingsNeonatal

 

How long should we treat preterm infants with caffeine?

Much has been written about methylxanthines over the years with the main questions initially being, “should we use them?”, “how big a dose should we use” and of course “theophylline vs caffeine”. At least in our units and in most others I know of caffeine seems to reign supreme and while there remains some discussion about whether dosing for maintenance of 2.5 -5 mg/kg/d of caffeine base or 5 – 10 mg/kg/d is the right way to go I think most favour the lower dose. We also know from the CAP study that not only does caffeine work to treat apnea of prematurity but it also appears to reduce the risk of BPD, PDA and duration of oxygen therapy to name a few benefits. Although initially promising as providing a benefit by improving neurodevelopmental outcomes in those who received it, by 5 and 11 years these benefits seem to disappear with only mild motor differences being seen. Turning to a new question The new query though is how long to treat? Many units will typically stop caffeine somewhere between 33-35 weeks PMA on the grounds that most babies by then should have outgrown their irregular respiration patterns and have enough pulmonary reserve to withstand a little periodic breathing. Certainly there are those who prove that they truly still need their caffeine and on occasion I have sent some babies home with caffeine when they are fully fed and otherwise able to go home but just can’t seem to stabilize their breathing enough to be off a monitor without caffeine. Then there is also more recent data suggesting that due to intermittent hypoxic episodes in the smallest of infants at term equivalent age, a longer duration of therapy might be advisable for these ELBWs. What really hasn’t been looked at well though is what duration of caffeine might be associated with the best neurodevelopmental outcomes. While I would love to see a prospective study to tackle this question for now we will have to do with one that while retrospective does an admirable job of searching for an answer. The Calgary Neonatal Group May Have The Answer Lodha A et al recently published the paper Does duration of caffeine therapy in preterm infants born ≤1250 g at birth influence neurodevelopmental (ND) outcomes at 3 years of
age? This retrospective study looked at infants under 1250g at birth who were treated within one week of age with caffeine and divided them into three categories based on duration of caffeine therapy. The groups were as follows, early cessation of caffeine ≤ 14 days (ECC), intermediate cessation of caffeine 15–30 days (ICC), and late cessation of
caffeine >30 days (LCC).  In total there were 508 eligible infants with 448 (88%)  seen at 3 years CA at follow-up. ECC (n = 139), ICC (n = 122) and LCC (n = 187).  The primary outcome here was ND at 3 years of age while a host of secondary outcomes were also examined such as RDS, PDA, BPD, ROP as typical morbidities.  It made sense to look at these since provision of caffeine had previously been shown to modify such outcomes. Did they find a benefit? Sadly there did not appear to be any benefit regardless of which group infants fell in with respect to duration of caffeine when it came to ND. When looking at secondary outcomes there were a few key differences found which favoured the ICC group.  These infants had the lowest days of supplemental oxygen, hospital stay ROP and total days of ventilation.  This middle group also had a median GA 1 week older at 27 weeks than the other two groups.  The authors however did a logistic regression and ruled out the improvement based on the advanced GA.  The group with the lowest use of caffeine had higher number of days on supplemental oxygen and higher days of ventilation on average than the middle but not the high caffeine group.  It is tempting to blame the result for the longer caffeine group on these being babies that were just sicker and therefore needed caffeine longer.  On the other hand the babies that were treated with caffeine for less than two weeks appear to have likely needed it longer as they needed longer durations of oxygen and were ventilated longer so perhaps were under treated. What is fair to say though is that the short and long groups having longer median days of ventilation were more likey to have morbidities associated with that being worse ROP and need for O2.  In short they likely had more lung damage.  What is really puzzling to me is that with a median GA of 27-28 weeks some of these kids were off caffeine before 30 weeks PMA and in the middle group for the most part before 32 weeks!  If they were in need of O2 and ventilation for at least two weeks maybe they needed more caffeine or perhaps the babies in these groups were just less sick? What is missing? There is another potential answer to why the middle group did the best.  In the methods section the authors acknowledge that for each infant caffeine was loaded at 10 mg/kg/d.  What we don’t know though is what the cumulative dose was for the different groups.  The range of dosing was from 2.5-5 mg/kg/d for maintenance.  Lets say there was an over representation of babies on 2.5 mg/kg/d in the short and long duration groups compared to the middle group.  Could this actually be the reason behind the difference in outcomes?  If for example the dosing on average was lower in these two groups might it be that with less respiratory drive the babies in those groups needed faster ventilator rates with longer durations of support leading to more lung damage and with it the rest of the morbidities that followed? It would be interesting to see such data to determine if the two groups were indeed dosed on average lower by looking at median doses and total cumulative doses including miniloads along the way.  We know that duration may need to be prolonged in some patients but we also know that dose matters and without knowing this piece of information it is tough to come to a conclusion about how long exactly to treat. What this study does though is beg for a prospective study to determine when one should stop caffeine as that answer eludes us!

AllThingsNeonatal

AllThingsNeonatal

 

Still performing awake intubations in newborns? Maybe this will change your mind.

If I look back on my career there have been many things I have been passionate about but the one that sticks out as the most longstanding is premedicating newborns prior to non-emergent intubation.  The bolded words in the last sentence are meant to reinforce that in the setting of a newborn who is deteriorating rapidly it would be inappropriate to wait for medications to be drawn up if the infant is already experiencing severe oxygen desaturation and/or bradycardia.  The CPS Fetus and Newborn committee of which I am a member has a statement on the use of premedication which seems as relevant today as when it was first developed.  In this statement the suggested cocktail of atropine, fentanyl and succinylcholine is recommended and having used it in our centre I can confirm that it is effective.  In spite of this recommendation by our national organization there remain those who are skeptical of the need for this altogether and then there are others who continue to search for a better cocktail.  Since I am at the annual conference for the CPS in Quebec city  I thought it would be appropriate to provide a few comments on this topic. Three concerns with rapid sequence induction (RSI) for premedication before intubation 1. "I don't need it.  I don't have any trouble intubating a newborn" - This is perhaps the most common reason I hear naysayers raise.  There is no question that an 60-90 kg practitioner can overpower a < 5kg infant and in particular an ELBW infant weighing < 1 kg.  This misses the point though.  Premedicating has been shown to increase success on the first attempt and shorten times to intubation. Dempsey 2006, Roberts 2006, Carbajal 2007, Lemyre 2009 2.  "I usually get in on the first attempt and am very slick so risk of injury is less." Not really true overall.  No doubt there are those individuals who are highly successful but overall the risk of adverse events is reduced with premedication. (Marshall 1984, Lemyre 2009). I would also proudly add another Canadian study from Edmonton by Dr. Byrne and Dr. Barrington who performed 249 consecutive intubations with predication and noted minimal side effects but high success rates at first pass. 3. "Intubation is not a painful procedure".  This one is somewhat tough to obtain a true answer for as the neonate of course cannot speak to this.  There is evidence available again from Canadian colleagues in 1984 and 1989 that would suggest that infants at the very least experience discomfort or show physiologic signs of stress when intubated using an "awake" approach.  In 1984 Kelly and Finer in Edmonton published Nasotracheal intubation in the neonate: physiologic responses and effects of atropine and pancuronium. This randomized study of atropine with or without pancuronium vs control demonstrated intracranial hypertension only in those infants in the control arm with premedication ameliorating this finding.  Similarly, in 1989 Barrington, Finer and the late Phil Etches also in Edmonton published Succinylcholine and atropine for premedication of the newborn infant before nasotracheal intubation: a randomized, controlled trial. This small study of 20 infants demonstrated the same finding of elimination of intracranial hypertension with premedication.  At the very least I would suggest that having a laryngoscope blade put in your oral cavity while awake must be uncomfortable.  If you still doubt that statement ask yourself whether you would want sedation if you needed to be intubated?  Still feel the same way about babies not needing any? 4.  What if I sedate and paralyze and there is a critical airway?  Well this one may be something to consider.  If one knows there is a large mass such as a cystic hygroma it may be best to leave the sedation or at least the paralysis out.  The concern though that there might be an internal mass or obstruction that we just don't know about seems a little unfounded as a justification for avoiding medications though. Do we have the right cocktail? The short answer is "I don't know".  What I do know is that the use of atropine, an opioid and a muscle relaxant seems to provide good conditions for intubating newborns.  We are in the era of refinement though and as a recent paper suggests, there could be alternatives to consider;Effect of Atropine With Propofol vs Atropine With Atracurium and Sufentanil on Oxygen Desaturation in Neonates Requiring Nonemergency IntubationA Randomized Clinical Trial.  I personally like the idea of a two drug combination for intubating vs.. three as it leaves one less drug to worry about a medication error with.  There are many papers out there looking at different drug combinations.  This one though didn't find a difference between the two combinations in terms of prolonged desaturations between the two groups which was the primary outcome. Interestingly though the process of intubating was longer with atropine and propofol.  Given some peoples reluctance to use RSI at all, any drug combination which adds time to the the procedure is unlikely to go over well.  Stay tuned though as I am sure there will be many other combinations over the next few years to try out!    

AllThingsNeonatal

AllThingsNeonatal

 

It’s time to approach nutrition in extreme preemies as if it were a drug

One of the benefits of operating this site is that I often learn from the people reading these posts as they share their perspectives.  On a recent trip I was reunited with Boubou Halberg a Neonatologist from Sweden whom I hadn’t seen in many years. I missed him on my last trip to Stockholm as I couldn’t make it to Karolinska  University but we managed to meet each other in the end.  As we caught up and he learned that I operated this site he passed along a paper of his that left an impact on me and I thought I would share with you. When we think about treating an infant with a medicinal product, we often think about getting the right drug, right dose and right administration (IV, IM or oral) for maximum benefit to the patient.  When it comes to nutrition we have certainly come a long way and have come to rely on registered dieticians where I work to handle a lot of the planning when it comes to getting the right prescription for our patients.  We seem comfortable though making some assumptions when it comes to nutrition that we would never make with respect to their drug counterparts.  More on that later… A Swedish Journey to Ponder Westin R and colleagues (one of whom is my above acquaintance) published a seven year retrospective nutritional journey in 2017 from Stockholm entitled Improved nutrition for extremely preterm infants: A population based observational study.  After recognizing that over this seven year period they had made some significant changes to the way they approached nutrition, they chose to see what effect this had on growth of their infants from 22 0/7 to 26 6/7 weeks over this time by examining four epochs (2004-5, 2006-7, 2008-9 and 2010-11.  What were these changes?  They are summarized beautifully in the following figure. Not included in the figure was a progressive change as well to a more aggressive position of early nutrition in the first few days of life using higher protein, fat and calories as well as changes to the type of lipid provided being initially soy based and then changing to one primarily derived from olive oil.  Protein targets in the first days to weeks climbed from the low 2s to the mid 3s in gram/kg/d while provision of lipid as an example doubled from the first epoch to the last ending with a median lipid provision in the first three days of just over 2 g/kg/d. While figure 3 from the paper demonstrates that regardless of time period there were declines in growth across all three measurements compared to expected growth patterns, when one compares the first epoch in 2004-2005 with the last 2010-11 there were significant protective effects of the nutritional strategy in place.  The anticipated growth used as a standard was based on the Fenton growth curves. What this tells us of course is that we have improved but still have work to do.  Some of the nutritional sources as well were donor breast milk and based on comments coming back from this years Pediatric Academic Society meeting we may need to improve how that is prepared as growth failure is being noted in babies who are receiving donated rather than fresh mother’s own milk.  I suspect there will be more on that as time goes by. Knowing where you started is likely critical! One advantage they have in Sweden is that they know what is actually in the breast milk they provide.  Since 1998 the babies represented in this paper have had their nutritional support directed by analyzing what is in the milk provided by an analyzer.  Knowing the caloric density and content of protein, carbohydrates and fats goes a long way to providing a nutritional prescription for individual infants.  This is very much personalized medicine and it would appear the Swedes are ahead of the curve when it comes to this.  in our units we have long assumed a caloric density of about 68 cal/100mL.  What if a mother is producing milk akin to “skim milk” while another is producing a “milkshake”.  This likely explains why some babies despite us being told they should be getting enough calories just seem to fail to thrive.  I can only speculate what the growth curves shown above would look like if we did the same study in units that actually take a best guess as to the nutritional content of the milk they provide. This paper gives me hope that when it comes to nutrition we are indeed moving in the right direction as most units become more aggressive with time.  What we need to do though is think about nutrition no different than writing prescriptions for the drugs we use and use as much information as we can to get the dosing right for the individual patient!

AllThingsNeonatal

AllThingsNeonatal

 

Part 2: Does prophylactic dextrose gel really work?

In the first part of this series of posts called Can prophylactic dextrose gel prevent babies from becoming hypoglycemic? the results appeared to be a little lackluster.  The study that this blog post was based on was not perfect and the lack of a randomized design left the study open to criticism and an unbalancing of risks for hypoglycemia.  Given these faults it is no doubt that you likely didn’t run anywhere to suggest we should start using this right away as a protocol in your unit. Another Study Though May Raise Some Eyebrows New Zealand researchers who have been at the forefront of publications on the use of dextrose gel recently published another article on the topic Prophylactic Oral Dextrose Gel for Newborn Babies at Risk of Neonatal Hypoglycaemia: A Randomised Controlled Dose-Finding Trial (the Pre-hPOD Study).  As the short study name suggests “Pre-hPOD” this was a preliminary study to determine which dosing of dextrose gel would provide the greatest benefit to prevent neonatal hypoglycemia.  The study is a little complex in design in that there were eight groups (4 dextrose gel vs 4 placebo) with the following breakdown. Dosing was given either once at 1 h of age (0.5 ml/kg or 1 ml/kg) or three more times (0.5 ml/kg) before feeds in the first 12 h, but not more frequently than every 3 h. Each dose of gel was followed by a breastfeed. The groups given prophylaxis fell into the following risk categories; IDM (any type of diabetes), late preterm (35 or 36 wk gestation), SGA (BW < 10th centile or < 2.5 kg), LBW (birthweight > 90th centile or > 4.5 kg), maternal use of β-blockers. Blood glucose was measured at 2 h of age and then AC feeds every 2 to 4 h for at least the first 12 h.  This was continued until an infant had 3 consecutive blood glucose concentrations of 2.6 mmmol/L.  With a primary outcome of hypoglycemia in the first 48 hours their power calculation dictated that a total sample size of 415 babies (66 in each treatment arm, 33 in each placebo arm) was needed which thankfully they achieved which means we can believe the results if they found no difference! What did they find? One might think that multiple doses and/or higher doses of glucose gel would be better than one dose but curiously they found that the tried and true single dose of 0.5 mL/kg X 1 offered the best result.  “Babies randomised to any dose of dextrose gel were less likely to develop hypoglycaemia than those randomised to placebo (RR 0.79, 95% CI 0.64–0.98, p = 0.03; number needed to 10.” Looking at the different cumulative doses, the only dosing with a 95% confidence interval that does not cross 1 was the single dosing.  Higher and longer dosing showed no statistical difference in the likelihood of becoming hypoglycemic in the first 48 hours.  As was found in the sugar babies study, admission to NICU was no different between groups and in this study as with the sugar baby study if one looked at hypoglycemia as a cause for admission there was a slight benefit.  Curiously, while the previous study suggested a benefit to the rate of breastfeeding after discharge this was not noted here. How might we interpret these results? The randomized nature of this study compared to the one reviewed in part I leads me to trust these findings a little more than the previous paper.  What this confirms in my mind is that giving glucose gel prophylaxis to at risk infants likely prevents hypoglycemia in some at risk infants and given that there were no significant adverse events (other than messiness of administration), this may be a strategy that some units wish to try out.  When a low blood glucose did occur it was later in the group randomized to glucose gel at a little over 3 hours instead of 2 hours.  The fact that higher or multiple dosing of glucose gel given prophylactically didn’t work leads me to speculate this may be due to a surge of insulin.  Giving multiple doses or higher doses may trigger a normal response of insulin in a baby not at risk of hypoglycemia but in others who might already have a high baseline production of insulin such as in IDMs this surge might lead to hypoglycemia.  This also reinforces the thought that multiple doses of glucose gel in babies with hypoglycemia should be avoided as one may just drive insulin production and the treatment may become counterproductive. In the end, I think these two papers provide some food for thought.  Does it make sense to provide glucose gel before a problem occurs?  We already try and feed at risk babies before 2 hours so would the glucose gel provide an added kick or just delay the finding of hypoglycemia to a later point. One dose may do the trick though. A reader of my Facebook page sent me a picture of the hPOD trial which is underway which I hope will definitively put this question to rest.  For more on the trial you can watch Dr. Harding speak about the trial here.        

AllThingsNeonatal

AllThingsNeonatal

 

Can prophylactic dextrose gel prevent babies from becoming hypoglycemic?

I have written a number of times already on the topic of dextrose gels. Previous posts have largely focused on the positive impacts of reduction in NICU admissions, better breastfeeding rates and comparable outcomes for development into childhood when these gels are used. The papers thus far have looked at the effectiveness of gel in patients who have become hypoglycemic and are in need of treatment. The question then remains as to whether it would be possible to provide dextrose gel to infants who are deemed to be at risk of hypoglycemia to see if we could reduce the number of patients who ultimately do become so and require admission. Answering that question Recently, Coors et al published Prophylactic Dextrose Gel Does Not Prevent Neonatal Hypoglycemia: A Quasi-Experimental Pilot Study. What they mean by Quasi-Experimental is that due to availability of researchers at off hours to obtain consent they were unable to produce a randomized controlled trial. What they were able to do was compare a group that had the following risk factors (late preterm, birth weight <2500 or >4000 g, and infants of mothers with diabetes) that they obtained consent for giving dextrose gel following a feed to a control group that had the same risk factors but no consent for participation. The protocol was that each infant would be offered a breastfeed or formula feed after birth followed by 40% dextrose gel (instaglucose) and then get a POC glucose measurement 30 minutes later. A protocol was then used based on different glucose results to determine whether the next step would be a repeat attempt with feeding and gel or if an IV was needed to resolve the issue. To be sure, there was big hope in this study as imagine if you could prevent a patient from becoming hypoglycemic and requiring IV dextrose followed by admission to a unit.  Sadly though what they found was absolutely no impact of such a strategy.  Compared with the control group there was no difference in capillary glucose after provision of dextrose gel (52.1 ± 17.1 vs 50.5 ± 15.3 mg/dL, P = .69).   One might speculate that this is because there are differing driving forces for hypoglycemia and indeed that was the case here where there were more IDMs and earlier GA in the prophylactic group.  On the other hand there were more LGA infants in the control group which might put them at higher risk.  When these factors were analyzed though to determine whether they played a role in the lack of results they were found not to. Moreover, looking at rates of admission to the NICU for hypoglycemia there were also no benefits shown.  Some benefits were seen in breastfeeding duration and a reduction in formula volumes consistent with previous studies examining the effect of glucose gel on both which is a win I suppose. It may also be that when you take a large group of babies with risks for hypoglycemia but many were never going to become hypoglycemic, those who would have had a normal sugar anyway dilute out any effect.  These infants have a retained ability to produce insulin in response to a rising blood glucose and to limit the upward movement of their glucose levels.  As such what if the following example is at work? Let’s say there are 200 babies who have risk factors for hypoglycemia and half get glucose gel.  Of the 100 about 20% will actually go on to have a low blood sugar after birth.  What if there is a 50% reduction in this group of low blood sugars so that only 10 develop low blood glucose instead of 20.  When you look at the results you would find in the prophylaxis group 10/100 babies have a low blood sugar vs 20/100.  This might not be enough of a sample size to demonstrate a difference as the babies who were destined not to have hypoglycemia dilute out the effect.  A crude example for sure but when the incidence of the problem is low, such effects may be lost. A Tale of Two Papers This post is actually part of a series with this being part 1.  Part 2 will look at a study that came up with a different conclusion.  How can two papers asking the same question come up with different answers?  That is the story of medicine but in the next part we will look at a paper that suggests this strategy does work and look at possible reasons why.

AllThingsNeonatal

AllThingsNeonatal

 

Screening for congenital heart disease; will early discharge be its ruin?

In 2017 the Canadian Pediatric Society published the practice point Pulse oximetry screening in newborns to enhance detection of critical congenital heart disease.  In this document we recommended universal screening for CCHDs but stressed the following: “Recognizing that delivery and time of discharge practices vary across Canada, the timing of testing should be individualized for each centre and (ideally) occur after 24 hours postbirth to lower FP results. And because the intent is to screen newborns before they develop symptoms, the goal should be to perform screening before they reach 36 hours of age.” This recommendation was put in place to minimize the number of false positive results and prevent Pediatricians and Cardiologists nationwide from being inundated with requests to rule out CCHD as earlier testing may pick up other causes for low oxygen saturation such as TTN.  The issue remains though that many patients are indeed discharged before 24 hours and in the case of midwife deliveries either in centres or in the home what do we do? A Population Study From the Netherlands May Be of Help Here Researchers in the Netherlands had a golden opportunity to answer this question as a significant proportion of births occur there in the home under the care of a midwife. Accuracy of Pulse Oximetry Screening for Critical Congenital Heart Defects after Home Birth and Early Postnatal Discharge by Ilona C. Narayen et al was published this month in J Peds. About 30% of births are cared for by a midwife with about 20% occurring in the home. The authors chose to study this population of infants who were all above 35 weeks gestation and not admitted to an intensive care nor had suspicion of CCHD prior to delivery. The timing of the screening was altered from the typical 24-48 hours to be two time points to be more reflective of midwives practice. All patients were recruited after birth with the use of information pamphlets. The prospective protocol was screening on 2 separate moments: on day 1, at least 1 hour after birth, and on day 2 or 3 of life. The criteria for passing or failing the test are the same as those outlined in the CPS practice point. As part of the study, patients with known CCHDs were also screened separately as a different group to determine the accuracy of the screening test in patients with known CCHD. Results There were nearly 24000 patients born during this period. Only 49 cases of CCHD were identified by screening and of these 36 had been picked up antenatally giving a detection rate of 73%. Out of 10 patients without prenatal diagnosis who also had saturation results available the detection rate was 50%. Three of the misses were coarctation of the aorta (most likely diagnosis to be missed in other studies), pulmonary stenosis (this one surprises me) and TGA (really surprises me). The false-positive rate of pulse oximetry screening (no CCHD) was 0.92%. The specificity was over 99% meaning that if you didn’t have CCHD you were very likely to have a negative test. Not surprisingly, most false- positives occurred on day 1 (190 on day 1 vs 31 infants on day 2 or 3). There were five patients missed who were not detected either by antenatal ultrasound. These 5 negatives ultimately presented with symptoms at later time points and all but one survived (TGA) so out of 24000 births the system for detecting CCHD did reasonably well in enhancing detection as they picked up another 5 babies that had been missed antenatally narrowing the undetected from 10 down to 5. Perhaps the most interesting thing about the study though is what they also found. As the authors state: “Importantly, 61% (134/221) of the infants with false-positive screenings proved to have significant noncardiac illnesses re- quiring intervention and medical follow-up, including infection/ sepsis (n = 31) and PPHN or transient tachypnea of the newborn (n = 88)” There are certainly detractors of this screening approach but remember these infants were all thought to be asymptomatic. By implementing the screening program there was opportunity to potentially address infants care needs before they went on to develop more significant illness. Under appreciated TTN could lead to hypoxia and worsen and PPHN could become significantly worse as well. I think it is time to think of screening in this way as being more general and not just about finding CCHD. It is a means to identify children with CCHD OR RESPIRATORY illnesses earlier in their course and do something about it!

AllThingsNeonatal

AllThingsNeonatal

 

Capnography or colorimetric detection of CO2 in the delivery suite. What to choose?

For almost a decade now confirmation of intubation is to be done using detection of exhaled CO2. The 7th Edition of NRP has the following to say about confirmation of ETT placement “The primary methods of confirming endotracheal tube placement within the trachea are detecting exhaled CO2 and a rapidly rising heart rate.” They further acknowledge that there are two options for determining the presence of CO2 “There are 2 types of CO2 detectors available. Colorimetric devices change color in the presence of CO2. These are the most commonly used devices in the delivery room. Capnographs are electronic monitors that display the CO2 concentration with each breath.” The NRP program stops short of recommending one versus the other. I don’t have access to the costs of the colorimetric detectors but I would imagine they are MUCH cheaper than the equipment and sensors required to perform capnography using the NM3 monitor as an example. The real question though is if capnography is truly better and might change practice and create a safer resuscitation, is it the way to go? Fast but not fast enough? So we have a direct comparison to look at. Hunt KA st al published Detection of exhaled carbon dioxide following intubation during resuscitation at delivery this month. They started from the standpoint of knowing from the manufacturer of the Pedicap that it takes a partial pressure of CO2 of 4 mm Hg to begin seeing a colour change from purple to yellow but only when the CO2 reaches 15 mm Hg do you see a consistent colour change with that device. The capnograph from the NM3 monitor on the other hand is quantitative so is able to accurately display when those two thresholds are reached. This allowed the group to compare how long it took to see the first colour change compared to any detection of CO2 and then at the 4 and 15 mm Hg levels to see which is the quicker method of detection. It is an interesting question as what would happen if you were in a resuscitation and the person intubates and swears that they are in but there is no colour change for 5, 10 or 15 seconds or longer? At what point do you pull the ETT? Compare that with a quantitative method in which there is CO2 present but it is lower than 4. Would you leave the tube in and use more pressure (either PIP/PEEP or both?)? Before looking at the results, it will not shock you that ANY CO2 should be detected faster than two thresholds but does it make a difference to your resuscitation? The Head to Head Comparison The study was done retrospectively for 64 infants with a confirmed intubation using the NM3 monitor and capnography.  Notably the centre did not use a colorimetric detector as a comparison group but rather relied on the manufacturers data indicating the 4 and 15 mm Hg thresholds for colour changes.  The mean age of patients intubated was 27 weeks with a range of 23 – 34 weeks.  The results I believe show something quite interesting and informative.   Median time secs (range) Earliest CO2 detection 3.7 (0 – 44s) 4 mm Hg 5.3 (0 – 727) 15 mm Hg 8.1 (0 – 727) I wouldn’t worry too much about a difference of 1.6 seconds to start getting a colour change but it is the range that has me a little worried.  The vast majority of the patients demonstrated a level of 4 or 15 mm Hg within 50 seconds although many were found to take 25-50 seconds.  When compared to a highest level of 44 seconds in the first detection of CO2 group it leads one to scratch their head.  How many times have you been in a resuscitation and with no CO2 change you keep the ETT in past 25 seconds?  Looking closer at the patients, there were 12 patients that took more than 30 seconds to reach a threshold of 4 mm Hg.  All but one of the patients had a heart rate in between 60-85.  Additionally there was an inverse relationship found between gestational age and time to detection.  In other words, the smallest of the babies in the study took the longest to establish the threshold of 4 and 15 mm Hg. Putting it into context? What this study tells me is that the most fragile of infants may take the longest time to register a colour change using the colorimetric devices.  It may well be that these infants take longer to open up their pulmonary vasculature and deliver CO2 to the alveoli.  As well these same infants may take longer to open the lung and exhale the CO2.  I suppose I worry that when a resuscitation is not going well and an infant at 25 weeks is bradycardic and being given PPV through an ETT without colour change, are they really not intubated?  In our own centre we use capnometry in these infants (looks for a wave form of CO2) which may be the best option if you are looking to avoid purchasing equipment for quantitative CO2 measurements.  I do worry though that in places where the colorimetric devices are used for all there will be patients who are extubated due to the thought that they in fact have an esophageal intubation when the truth is they just need time to get the CO2 high enough to register a change in colour. Anyways, this is food for thought and a chance to look at your own practice and see if it is in need of a tweak…

AllThingsNeonatal

AllThingsNeonatal

 

Should all babies be screened for hypoglycemia?

Hypoglycemia has to be one of the most common conditions that we screen for or treat in the NICU and moreover in newborn care in general. The Canadian Pediatric Society identifies small for gestational age infants (weight <10th percentile), large for gestational age (LGA; weight > 90th percentile) infants, infants of diabetic mothers (IDMs) and preterm infants as being high risk for hypoglycemia. It is advised then to screen such babies in the absence of symptoms for hypoglycemia 2 hours after birth after a feed has been provided (whether by breast or bottle). I am sure though if you ask just about any practitioner out there, they will tell you a story about a baby with “no risk factors” who had hypoglycemia. These one-off cases have the effect though of making us want to test everyone for fear that we will miss one. If that is the case though should we be recommending that all babies get at least one check? The Canadian Pediatric Surveillance Program (CPSP) The CPSP is a branch of the Canadian Pediatric Society that “provides an innovative means to undertake active paediatric surveillance and increase awareness of childhood disorders that are high in disability, morbidity, mortality and economic cost to society, despite their low frequency. I submit my surveys each month as i hope other Canadian Pediatricians do and help to determine the impact of these rare conditions in our Canadian population.  Like with any survey we rely on people taking the time to submit but there is always the risk that what is being sent in under represents the true burden of illness as some cases may not be identified.  Having said that, it is the best we have! Turning our attention to hypoglycemia in low risk newborns From April 2014 to March 2016 the CPSP searched for these types of patients and just published the results of their findings in Hypoglycemia in unmonitored full-term newborns—a surveillance study by Flavin MP et al.  What I like about the study is that they have been able to look at a group of babies that fall outside those identified as being at risk in the CPS statement Screening guidelines for newborns at risk for low blood glucose.  They were looking for severe hypoglycemia by using a threshold of < 2.0 mmol/L (36 mg/dl) and all infants must have received IV dextrose.  In the end after excluding ineligible cases they had 93 babies who met criteria.  Based on the Canadian birth rate this translates to an incidence of 1 in every 8378 births. These babies were all supposed to be low risk but there were in fact clues that while not strictly identified as risks in the CPS statement could have increased the likelihood of a low blood glucose.  Twenty three percent of mothers had maternal hypertension and another 23% were obese while 47% had excessive weight gain during pregnancy.  Furthermore, 8% of mothers were treated with a beta blocker (most likely labetalol I would think) during pregnancy which is a risk factor for hypoglycemia although not specifically cited in the current CPS statement. A concerning finding as well was the likelihood of severe symptoms in this group on presentation. Twenty percent presented with major clinical signs (seizure, apnea or cyanosis). Median glucose levels at presentation were much lower than those without major signs (median = 0.8 mmol/L, interquartile range [IQR] = 0.5 versus 1.6 mmol/L, IQR = 0.7; P < 0.001).  Lastly, providers were asked about neurodevelopmental concerns at discharge approximately 20% were thought to have issues. Are these patients really low risk though? Twenty five percent of the patients submitted had a birth weight less than the 10%ile for GA.  These patients as per the CPS guideline recommendations are actually considered at risk and should have been screened.  The second issue to address has to do with the way we diagnose diabetes in pregnancy.  All women are provided with the oral glucose tolerance test around 28 weeks of pregnancy. No test is perfect but it is the best we have.  Women who have excessive weight gain in pregnancy (almost 50% of the cohort) are at higher risk of developing diabetes or some degree of insulin resistance as are those who are classified as obese.  I have long suspected and think it may be the case here that some babies who do not meet the criteria for screening as their mothers do not have a diagnosis of GDM actually are at risk due to some degree of insulin resistance or perhaps their mothers develop GDM later.  The evidence for this are the occasional LGA babies who are born to mothers without a GDM diagnosis but who clearly have been exposed to high insulin levels as they behave like such affected infants with poor feeding and low sugars in the newborn period.  The authors here comment on those that were SGA but how many in this cohort were LGA? The effect of hypertension can also not be minimized which was present in about a quarter of patients.  These babies while not being officially SGA may have experienced a deceleration in weight gain in the last few weeks but remained above the 10%ile.  These infants would not have the glycogen stores to transition successfully but would not be targeted as being at risk by the current definitions. Should we be screening everyone then? If we acknowledge that about 25% were IUGR in this study (<10%ile) and should have been screened, the expected rate would be 1:1170 births alone.  In Manitoba with our 17000 births a year we would capture about two extra babies a year which translates into a low of pokes for a lot of healthy babies.  Given the further information that 1:5 babies who are identified may have neurodevelopmental concerns it would take about 2-3 years of testing to prevent one concern.  That pick up rate for me is far too low to subject so many babies to testing.  What this study though does highlight is the need to view risk factors a little less strictly.  Babies who are almost meeting the criteria for being LGA or those whose mother’s have taken lebetalol should have a low threshold for screening.  Should hypertension on medications, excessive maternal weight gain or obesity in the mother be considered a risk?  What I didn’t see in the end of this study were patients who truly were AGA, being born to healthy non overweight mothers presenting as high risk. Maybe what is really needed based on this study is to re-evaluate what we consider at risk.  In the meantime, maybe we should be testing a few extra babies who fall into these “lesser” risk categories.  Better yet a study isolating such patients and looking at the frequency of hypoglycemia in these patients is warranted to get a better idea of whether they are indeed risks.

AllThingsNeonatal

AllThingsNeonatal

×