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>
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!
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 .”
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.
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, use 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.
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!