Developmental outcomes for extreme preemies after delivery room CPR.

Developmental outcomes for extreme preemies after delivery room CPR.

We have all been there.  After an uneventful pregnancy a mother presents to the labour floor in active labour.  The families world is turned upside down and she goes on to deliver an infant at 27 weeks.  If the infant is well and receives minimal resuscitation and is on CPAP we provide reassurance and have an optimistic tone.  If however their infant is born apneic and bradycardic and goes on to receive chest compressions +/- epinephrine what do we tell them?  This infant obviously is much sicker after delivery and when the family asks you “will my baby be ok?” what do you tell them?  It is a human tendency to want to reassure and support but if they ask you what the chances are of a good outcome it has always been hard to estimate.  What many of us would default to is making an assumption that the need for CPR at a time when the brain is so fragile may lead to bleeding or ischemia would lead to worse outcomes.  You would mostly be right. One study by Finer et al  entitled Intact survival in extremely low birth weight infants after delivery room resuscitation.demonstrated that survival for infants under 750g was better if they had a history of CPR after delivery.  The thought here is that more aggressive resusctiation might be responsible for the better outcome by I would presume establishing adequate circulation sooner even if the neonates did not appear to need it immediately.

The Canadian Neonatal Network

In Canada we are fortunate to have a wonderful network called the Canadian Neonatal Network.  So many questions have been answered by examining this rich database of NICUs across the county.  Using this database the following paper was just published by Dr. A. Lodha and others; Extensive cardiopulmonary resuscitation of preterm neonates at birth and mortality and developmental outcomes. The paper asked a very specific and answerable question from the database.  For infants born at <29 weeks gestational age who require extensive resuscitation (chest compressions, epinephrine or both) what is the likelihood of survival and/or neurodevelopmental impairment (NDI) at 18-24 months of age vs those that did not undergo such resuscitation?  For NDI, the authors used a fairly standard definition as “any cerebral palsy (GMFCS1), Bayley-III score <85 on one or more of the cognitive, motor or language composite scores, sensorineural or mixed hearing impairment or unilateral or bilateral visual impairment.”  Their secondary outcomes were significant neurodevelopmental impairment (sNDI), mortality, a Bayley-III score of <85 on any one of the components (cognitive, language, motor), sensorineural or mixed hearing loss,or visual impairment.sNDI was defined as the presence of one or more of the following: cerebral palsy with GMFCS 3, Bayley-III cognitive, language or motor composite score <70, hearing impairment requiring hearing aids or cochlear implant, or bilateral visual impairment”

What did they discover?

It is a fortunate thing that the database is so large as when you are looking at something like this the number of infants requiring extensive resuscitation is expected to be small.  The authors collected data from January 1, 2010 and September 30, 2011 and had a total number of infants born at less than 29 weeks of 2760.  After excluding those with congenital anomalies and those who were born moribund they were left with 2587.  From these 80% had follow-up data and when applying the final filter of extensive resuscitation they were left with 190 (9.2%) who received delivery room CPR (DR-CPR) vs 1545 who did not receive this.

Before delving into the actual outcomes it is important to note that neonates who did not receive DR-CPR were more likely to be born to mothers with hypertension and to have received antenatal steroids (89 vs 75%).  With these caveats it is pretty clear that as opposed to the earlier study showing better outcomes after DR-CPR this was not the case here.

 

 

 

 

 

 

 

The results are interesting in that it is pretty clear that receiving DR-CPR is not without consequence (higher rate of seizures, severe neurological injury, BPD).  Looking at the longer term outcomes though is where things get a little more interesting.  Mortality and mortality or neurodevelopmental impairment are statistically significant with respect to increased risk.  When you take out NDI alone however the CI crosses one and is no longer significant.  Neither is CP for that matter with the only statistically significant difference being the Bayley-III Motor composite score <85.  The fact that only this one finding came out as significant at least to me raises the possibility that this could have been brought about by chance.  It would seem that while these infants are at risk of some serious issues their brains in the long run may be benefiting for the neurological plasticity that we know these infants have.

The study is remarkable to me in that an infant can have such a difficult start to life yet hope may remain even after dealing with some of the trials and tribulations of the NICU.  Parents may need to wade through the troubling times of seizures, long term ventilation and CPAP and then onto a diagosis of BPD but their brains may be ok after all.  This is one of the reasons I love what I do!

Using the printed word to treat apnea of prematurity

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.

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

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 dietitians 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!

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

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…

Is skin to skin care truly good for the developing brain?

Is skin to skin care truly good for the developing brain?

Skin to skin care or kangaroo care is all the rage and I am the first one to offer my support for it.  Questions persist though as to whether from a physiological standpoint, babies are more stable in an isolette in a quiet environment or out in the open on their mother or father’s chests. Bornhorst et al expressed caution in their study Skin-to-skin (kangaroo) care, respiratory control, and thermoregulation.  In a surprising finding, babies with an average gestational age of 29 weeks were monitored for a number of physiological parameters and found to have more frequent apnea and higher heart rates than when in an isolette.  The study was small though and while there were statistical differences in these parameters they may not have had much clinical significance (1.5 to 2.8 per hour for apnea, bradycardia or desaturation events).  Furthermore, does an increase in such events translate into any changes in cerebral oxygenation that might in turn have implications for later development?  Tough to say based on a study of this magnitude but it certainly does raise some eyebrows.

What if we could look at cerebral oxygenation?

As you might have guessed, that is exactly what has been done by Lorenz L et al in their recent paper Cerebral oxygenation during skin-to-skin care in preterm infants not receiving respiratory support.The goal of this study was to look at 40 preterm infants without any respiratory distress and determine whether cerebral oxygenation (rStO2)was better in their isolette or in skin to skin care (SSC).  They allowed each infant to serve as their own control by have three 90 minute periods each including the first thirty minutes as a washout period.  Each infant started their monitoring in the isolette then went to SSC then back to the isolette.  The primary outcome the power calculation was based on was the difference in rStO2 between SSC and in the isolette.  Secondary measures looked at such outcomes as HR, O2 sat, active and quiet sleep percentages, bradycardic events as lastly periods of cerebral hypoxia or hyperoxia.  Normal cerebral oxygenation was defined as being between 55 to 85%.

Surprising results?

Perhaps its the start of a trend but again the results were a bit surprising showing a better rStO2 when in the isolette (−1.3 (−2.2 to −0.4)%, p<0.01).  Other results are summarized in the table below:

Mean difference in outcomes
Variable SSC Isolette Difference in mean p
rStO2 73.6 74.8 -1.3 <0.01
SpO2 (median) 97 97 -1.1 0.02
HR 161 156 5 <0.01
% time in quiet sleep 58.6 34.6 24 <0.01

No differences were seen in bradycardic events, apnea, cerebral hypoexmia or hyperoxemia.  The authors found that SSC periods in fact failed the “non-inferiority” testing indicating that from a rStO2 standpoint, babies were more stable when not doing SSC!  Taking a closer look though one could argue that even if this is true does it really matter?  What is the impact on a growing preterm infant if their cerebral oxygenation is 1.3 percentage points on average lower during SSC or if their HR is 5 beats per minute faster?  I can’t help but think that this is an example of statistical significance without clinical significance.  Nonetheless, if there isn’t a superiority of these parameters it does leave one asking “should we keep at it?”

Benefits of skin to skin care

Important outcomes such as reductions in mortality and improved breastfeeding rates cannot be ignored or the positive effects on family bonding that ensue. Some will argue though that the impacts on mortality certainly may be relevant in developing countries where resources are scarce but would we see the same benefits in developed nations.  The authors did find a difference though in this study that I think benefits developing preterm infants across the board no matter which country you are in.  That benefit is that of Quiet Sleep (QS).  As preterm infants develop they tend to spend more time in QS compared to active sleep  (AS).  From Doussard- Roossevelt J, “Quiet sleep consists of periods of quiescence with regular respiration and heart rate, and synchronous EEG patterns. Active sleep consists of periods of movement with irregular respiration and heart rate, and desynchronous EEG patterns.”  In the above table one sees that the percentage of time in QS was significantly increased compared to AS when in SSC.  This is important as neurodevelopment is thought to advance during periods of QS as preterm infants age.

There may be little difference favouring less oxygen extraction during isolette times but maybe that isn’t such a good thing?  Could it be that the small statistical difference in oxygen extraction is because the brain is more active in laying down tracks and making connections?  Totally speculative on my part but all that extra quiet sleep has got to be good for something.

To answer the question of this post in the title I think the answer is a resounding yes for the more stable infant.  What we don’t know at the moment except from anecdotal reports of babies doing better in SSC when really sick is whether on average critically ill babies will be better off in SSC.  I suspect the answer is that some will and some won’t.  While we like to keep things simple and have a one size fits all answer for most of our questions in the NICU, this one may not be so simple.  For now I think we keep promoting SSC for even our sick patients but need to be honest with ourselves and when a patient just isn’t ready for the handling admit it and try again when more stable.  For the more stable patient though I think giving more time for neurons to find other neurons and make new connections is a good thing to pursue!