The rise of donor milk banks and depots in recent years has been a welcome addition to the care of preterm infants. We have known for many years that “breast is best” and advocate for mother’s own milk whenever possible. When this is not possible we previously turned to formula but with the availability of pooled pasteurized donor milk many hospitals have focused on expanding the indications for use. Through personal communications in Canada we are a bit all over the map in terms of indications with some centres restricting use based on birth weight while others taking into account, gestational age as the main criteria. With respect to duration some centres use 2 weeks, others 4 and then others until a gestational age is reached which may mean up to 10 weeks of use for a baby born in that centre at 24 weeks. While variation exists it is hard to find anyone who would suggest this is a bad thing to provide.
The main reason for pushing expansion of programs is the strong evidence that avoidance of bovine milk is associated with a reduction in the risk of NEC. Many studies have been done in this regard and the Cochrane systematic review concluded that formula increased the risk of necrotising enterocolitis: typical risk ratio 2.77 (95% CI 1.40 to 5.46); risk difference 0.04 (95% CI 0.02 to 0.07).
While donor milk is a wonderful nutritional product for sure it does have one issue which is a lower protein content than mother’s own milk and as such dieticians will commonly increase the protein content from 0.9 g/dL to 1.2 g/dL by adding powder or more recently liquid protein supplements. One might expect then that doing so would provide a reduction is NEC, and an optimal source of nutrition for the growing preterm brain. Avoidance of NEC should reduce the risk of adverse neurodevelopmental outcome as the two have been linked before.
Enter the DOMINO Study
This Ontario, Canada based study utilized four NICUs to provide in a randomized fashion either donor human milk or formula with matching protein and caloric densities to 363 infants (181 donor milk, 182 formula). All infants were preferentially fed mother’s own milk but supplemented with donor or formula if unavailable and planned to use one or the other for up to 90 days or discharge whichever came first. The exposure to donor milk was quite long in comparison to our own units practice (1 month duration if born at < 1500g) . The median number of days for donor milk was 65 (IQR, 41-90). A significant risk to the results would be if there was a difference in amounts of mother’s own milk provided between the two groups but there was none. Exclusive feeding of mother’s own milk occurred in the Donor milk group (28.2%) and formula group (26.9%) respectively. Among infants requiring a supplement, there was no statistically significant difference between the donor milk and formula groups in the proportion of total enteral feeds for each infant consumed as mother’s milk (58.4% [IQR, 13.6%-96.0%] vs 63.3% [IQR, 9.6%-97.2%], respectively, P = .96).
Short term but not long term gains
Curiously (at least to me) I would have expected differences in some of the morbidities other than NEC but such was not the case.
The strength of using human milk though can not be understated as any reduction in NEC is an extremely important outcome regardless of whether long term neurodevelopment is affected positively or not.
in terms of the latter outcome no difference was observed between the two groups. The Bayley III findings were quite similar at 18 months which on the surface may cause everyone’s shoulders to sag as the benefit everyone hoped for did not transpire. Additionally, linear growth, head circumference and weight gain were not different between groups. This may simply reflect that protein and caloric intakes were indeed matched between groups whereas in the past, the lack of protein fortification led to delays in growth in the donor milk groups.
At the risk of sounding like the end of a Cochrane review I am not sure this is the final word on donor milk and outcome. Larger studies may be needed to get at the real truth. This was not a pure sample of donor milk vs formula as a significant percentage (over 20% in both groups) received purely mother’s own milk. Furthermore, in those that received supplements there was still a significant percentage that received some of mother’s own milk. The authors suggest that a larger sample size would unlikely have detected a difference and that may be the case but is it so due to where the study was done. What if the study were done in a centre with a very low rate of breastfeeding? I am concerned that the lack of response in outcome may reflect a dilution of the impact of the strategy by having such a successful rate of providing mother’s own milk.
All Is Not Lost
Using a glass is half full view, I think it is worth pointing out that this study should also provide some comfort for those centres that use formula as a supplement. Clearly the higher rate of NEC is not comforting to anyone but for those who survive to discharge the neurodevelopmental outcome is promising. Formula in some circles has taken on a view as almost a toxic substance but I often remind residents and fellows that while we prefer breast milk, formula has been used in NICUs for decades and not every patient who receives it will develop NEC. Yes it is a risk factor for NEC and when you don’t have an alternative it is an acceptable form of nutrition to use. What I think may be lost in the DOMINO study is that if you are a centre that uses formula as there is no access to DBM this should help provide reassurance to the families you care for. All is not lost after the DOMINO study. Every cloud has a silver lining and fear not this will not be the last study to test this hypothesis. At the moment it is just the best we have and this is not the last we will hear on this topic.
As a Neonatologist I doubt there are many topics discussed over coffee more than BPD. It is our metric by which we tend to judge our performance as a team and centre possibly more than any other. This shouldn’t be that surprising. The dawn of Neonatology was exemplified by the development of ventilators capable of allowing those with RDS to have a chance at survival. As John F Kennedy discovered when his son Patrick was born at 34 weeks, without such technology available there just wasn’t much that one could do. As premature survival became more and more common and the gestational age at which this was possible younger and younger survivors began to emerge. These survivors had a condition with Northway described in 1967 as classical BPD. This fibrocystic disease which would cripple infants gave way with modern ventilation to the “new bpd”.
The disease has changed to one where many factors such as oxygen and chorioamnionitis combine to cause arrest of alveolar development along with abnormal branching and thickening of the pulmonary vasculature to create insufficient air/blood interfaces +/- pulmonary hypertension. This new form is prevalent in units across the world and generally appears as hazy lungs minus the cystic change for the most part seen previously. Defining when to diagnose BPD has been a challenge. Is it oxygen at 28 days, 36 weeks PMA, x-ray compatible change or something else? The 2000 NIH workshop on this topic created a new approach to defining BPD which underwent validation towards predicting downstream pulmonary morbidity in follow-up in 2005. That was over a decade ago and the question is whether this remains relevant today.
I don’t wish to make light of the need to track our rates of BPD but at times I have found myself asking “is this really important?” There are a number of reasons for saying this. A baby who comes off oxygen at 36 weeks and 1 day is classified as having BPD while the baby who comes off at 35 6/7 does not. Are they really that different? Is it BPD that is keeping our smallest babies in hospital these days? For the most part no. Even after they come off oxygen and other supports it is often the need to establish feeding or adequate weight prior to discharge that delays things these days. Given that many of our smallest infants also have apnea long past 36 weeks PMA we have all seen babies who are free of oxygen at 38 weeks who continue to have events that keep them in hospital. In short while we need to be careful to minimize lung injury and the consequences that may follow the same, does it matter if a baby comes off O2 at 36, 37 or 38 weeks if they aren’t being discharged due to apnea or feeding issues? It does matter for benchmarking purposes as one unit will use this marker to compare themselves against another in terms of performance. Is there something more though that we can hope to obtain?
When does BPD matter?
The real goal in preventing BPD or at least minimizing respiratory morbidity of any kind is to ensure that after discharge from the NICU we are sending out the healthiest babies we can into the community. Does a baby at 36 weeks and one day free of O2 and other support have a high risk of coming back to the hospital after discharge or might it be that those that are even older when they free of such treatments may be worse off after discharge. The longer it takes to come off support one would think, the more fragile you might be. This was the goal of an important study just published entitled Revisiting the Definition of Bronchopulmonary Dysplasia: Effect of Changing Panoply of Respiratory Support for Preterm Neonates. This work is yet another contribution to the pool of knowledge from the Canadian Neonatal Network. In short this was a retrospective cohort study of 1503 babies born at <29 weeks GA who were assessed at 18-21 months of age. The outcomes were serious respiratory morbidity defined as one of:
(1) 3 or more rehospitalizations after NICU discharge owing to respiratory problems (infectious or noninfectious);
(2) having a tracheostomy
(3) using respiratory monitoring or support devices at home such as an apnea monitor
or pulse oximeter
(4) being on home oxygen or continuous positive airway pressure at the time of assessment
While neurosensory impairment being one of:
(1) moderate to severe cerebral palsy (Gross Motor Function Classification System ≥3)
(2) severe developmental delay (Bayley Scales of Infant and Toddler
Development Third Edition [Bayley III] composite score <70 in either cognitive, language, or motor domains)
3) hearing aid or cochlear implant use
(4) bilateral severe visual impairment
What did they find?
The authors looked at 6 definitions of BPD and applied examined how predictive they were of these two outcomes. The combination of oxygen and/or respiratory support at 36 weeks PMA had the greatest capacity to predict this composite outcome. It was the secondary analysis though that peaked my interest. Once the authors identified the best predictor of adverse outcome they sought to examine the same combination of respiratory support and/oxygen at gestational ages from 34 -44 weeks PMA. The question here was whether the use of an arbitrary time point of 36 weeks is actually the best number to use when looking at these longer term outcomes. Great for benchmarking but is it great for predicting outcome?
It turns out the point in time with the greatest likelihood of predicting occurrence of serious respiratory morbidity is 40 weeks and not 36 weeks. Curiously, beyond 40 weeks it becomes less predictive. With respect to neurosensory impairment there is no real difference at any gestational age from 34-44 weeks PMA.
From the perspective of what we tell parents these results have some significance. If they are to be believed (and this is a very large sample) then the infant who remains on O2 at 37 weeks but is off by 38 or 39 weeks will likely fair better than the baby who remains on O2 or support at 40 weeks. It also means that the risk of neurosensory impairment is largely set in place if the infant born at < 29 weeks remains on O2 or support beyond 33 weeks. Should this surprise us? Maybe not. A baby who is on such support for over 5 weeks is sick and as a result the damage to the developing brain from O2 free radical damage and/or exposure to chorioamnionitis or sepsis is done.
It will be interesting to see how this study shapes the way we think about BPD. From a neurosensory standpoint striving to remove the need for support by 34 weeks may be a goal worth striving for. Failure to do so though may mean that we at least have some time to reduce the risk of serious respiratory morbidity after discharge.
Thank you to the CNN for putting out what I am sure will be a much discussed paper in the months to come.
I am fortunate to work with a group of inter-professionals who strive for perfection. When you connect such people with those with skills in multimedia you create the opportunity for education. I can’t say enough about the power of education and moreover the ability to improve patient outcomes when it is done well.
With this post I am going to be starting to share a collection of videos that I will release from time to time. The hope with any release like this is that you the reader wherever you are may find some use from these short clips. My thanks to the team that put these together as the quality is beyond compare and the HD quality is great for viewing on any device.
Placing A Chest Tube Can Be A Difficult Thing
As I said to a colleague in training the other day, a chest tube may seem daunting but once you see how it is done it loses some of its intimidation. Having said that, once you see it placed it can be a long time between opportunities for you to view another. That is where having a repository of videos comes in that you can watch prior to the next opportunity. These very short clips are easy to access when needed and may calm the nerves the next time you are called to place a chest tube.
A Word About Chest Tubes
The videos in question demonstrate how to place a Thal quick chest tube. In case this looks foreign to you it may be because you are using the older generation style of chest tubes that come equipped with a trocar. Even without the use of the trocar, these rigid tubes carry a significant risk of lung laceration or other tissue injury. For a review of such complications related to chest tube insertion see Thoracostomy tubes: A comprehensive review of complications and related topics.
The jury as they say is still out with respect to the use of these softer chest tube sets. There is no question that they are easier to place than the traditional thoracostomy tube. Their pliability though does carry a significant risk of kinking or blockage as we have seen in some patients when the Thal chest tube set is used to drain fluid in particular. Less of an issue with air leaks.
Start of a series
This post I suppose marks a slightly new direction for the blog. While I thoroughly enjoy educating you with the posts about topics of interest I see an opportunity to help those who are more visual in their learning. The videos will be posted over the next while with accompanying written posts such as this. They can be accessed on my Youtube channel at
This is becoming “all the rage” as they say. I first heard about the strategy of feeding while on CPAP from colleagues in Calgary. They had created the SINC * (Safe Individualized Feeding Competence) program to provide an approach to safely introducing feeding to those who were still requiring CPAP. As news of this approach spread a great deal of excitement ensued as one can only imagine that in these days when attainment of oral feeding is a common reason for delaying discharge, could getting an early start shorten hospital stay? I could describe what they found with the implementation of this strategy but I couldn’t do it the same justice as the presenter of the data did at a recent conference in Winnipeg. For the slide set you can find them here. As you can imagine, in this experience out of Calgary though they did indeed find that wonderful accomplishment of shorter hospital stays in the SINC group. We have been so impressed with the results and the sensibility of it all that we in fact have embraced the concept and introduced it here in both of our units. The protocol for providing this approach is the following.
I have to admit, while I have only experienced this approach for a short time the results do seem to be impressive. Although anecdotal a parent even commented the other day that she felt that SINC was instrumental in getting her baby’s feeding going! With all this excitement around this technique I was thrown a little off kilter when a paper came out suggesting we should put a full stop to feeding on CPAP!
What caused my spirits to dampen? This study enrolled preterm infants who were still on CPAP at ≥ 34 weeks PMA and were taking over 50% of required feeding volumes by NG feeding. The goal was to look at 15 patients who were being fed on CPAP +5 and with a mean FiO2 of 25% (21-37%) using video fluoroscopic swallowing studies to determine whether such patients aspirate when being fed. The researchers became concerned when each of the first seven patients demonstrated abnormalities of swallowing function indicating varying degrees of aspiration. As such they took each patient off CPAP in the radiology suite and replaced it with 1 l/min NP to achieve acceptable oxygen saturations and repeated the study again. The results of the two swallow studies showed remarkable differences in risk to the patient and as such the recruitment of further patients was stopped due to concerns of safety and a firm recommendation of avoiding feeding while on CPAP was made.
Table 2. Percentage of all swallows identified with swallowing dysfunction
Variable Mean ± s.d.
Mean ± s.d.
Mean ± s.d.
Mild pen. %
Deep pen. %
Nasopharyngeal reflux %
Taking these results at face value it would seem that we should put an abrupt halt to feeding while on CPAP but as the saying goes the devil is in the details…
CPAP Using Ram Cannulae
Let me start off by saying that I don’t have any particular fight to pick with the RAM cannulae. They serve a purpose and that is they allow CPAP to be delivered with a very simple set of prongs and avoid the hats, straps and such of more traditional CPAP devices. We have used them as temporary CPAP delivery when moving a patient from one area to another. As the authors state the prongs are sized in order to ensure the presence of a leak. This has to do with the need to provide a way for the patient to exhale when nasal breathing. Prongs that are too loose have a large leak and may not deliver adequate pressure while those that are too tight may inadvertently deliver high pressure and therefore impose significant work of breathing on the patient. Even with appropriate sizing these prongs do not allow one to exhale against a low pressure or flow as is seen with the “fluidic flip” employed with the infant flow interface. With the fluidic flip, exhalation occurs against very little resistance thereby reducing work of breathing which is not present with the use of the RAM cannula.
Trying to feed an infant who is working against a constant flow as delivered by the RAM cannulae is bound to cause problems. I don’t think it should be a surprise to find that trying to feed while struggling to breathe increases the risk of aspiration. Similarly, under treating a patient by placing them on nasal prongs would lead to increased work of breathing as while you may provide the needed O2 it is at lower lung volumes. Increasing work of breathing places infants at increased risk of aspiration. That is what I would take from this study. Interestingly, looking at the slide set from Calgary they did in fact use CPAP with the fluidic flip. Smart people they are. It would be too easy to embrace the results of this study and turn your nose to the SINC approach to feeding on CPAP. Perhaps somewhere out there someone will read this and think twice about abandoning the SINC approach and a baby will be better for it.
* SINC algorithm and picture of the fluidic flip courtesy of Stacey Dalgleish and the continued work of Alberta Health Services
Producing milk for your newborn and perhaps even more so when you have had a very preterm infant with all the added stress is not easy. The benefits of human milk have been documented many times over for preterm infants. In a cochrane review from 2014 use of donor human milk instead of formula was associated with a reduction in necrotizing enterocolitis. More recently similar reductions have been seen in retinopathy of prematurity. Interestingly with respect to the latter it would appear that any amount of breast milk leads to a reduction in ROP. Knowing this finding we should celebrate every millilitre of milk that a mother brings to the bedside and support them when it does not flow as easily as they wish. While it would be wonderful for all mothers to supply enough for their infant and even more so that excess could be donated for those who can’t themselves we know this not to be the case. What we can do is minimize stress around the issue by informing parents that every drop counts and to celebrate it as such!
Why Is Breast Milk So Protective
Whether the outcome is necrotizing enterocolitis or ROP the common pathway is one of inflammation. Mother’s own milk contains many anti-inflammatory properties and has been demonstrated to be superior to formula in that regard by Friel and no difference exists between preterm and term versions. Aside from the anti-inflammatory protection there may be other factors at work such as constituents of milk like lactoferrin that may have a protective effect as well although a recent trial would not be supportive of this claim.
Could Mother’s Own Milk Have a Dose Response Effect in Reducing The Risk of BPD?
This is what is being proposed by a study published in early November entitled Influence of own mother’s milk on bronchopulmonary dysplasia and costs. What is special about this study and is the reason I chose to write this post is that the study is unusual in that it didn’t look at the effect of an exclusive human milk diet but rather attempted to isolate the role of mother’s own milk as it pertains to BPD. Patients in this trial were enrolled prospectively in a non randomized fashion with the key difference being the quantity of mothers own milk consumed in terms of a percentage of oral intake. Although donor breast milk existed in this unit, the patients included in this particular cohort only received mother’s own milk versus formula. All told, 254 infants were enrolled in the study. As with many studies looking at risks for BPD the usual culprits were found with male sex being a risk along with smaller and less mature babies and receipt of more fluid in the first 7 days of age. What also came up and turned out after adjusting for other risk factors to be significant as well in terms of contribution was the percentage of mother’s own milk received in the diet.
Every ↑ of 10% = reduction in risk of BPD at 36 weeks PMA by 9.5%
That is a really big effect! Now what about a reduction in costs due to milk? That was difficult to show an independent difference but consider this. Each case of BPD had an additional cost in the US health care system of $41929!
What Lesson Can be Learned Here?
Donor breast milk programs are a very important addition to the toolkit in the NICU. Minimizing the reliance on formula for our infants particularly those below 1500g has reaped many benefits as mentioned above. The availability of such sources though should not deter us from supporting the mothers of these infants in the NICU from striving to produce as much as they can for their infants. Every drop counts! A mother for example who produces only 20% of the needed volume of milk from birth to 36 weeks corrected age may reduce the risk of her baby developing BPD by almost 20%. That number is astounding in terms of effect size. What it also means is that every drop should be celebrated and every mother congratulated for producing what they can. We should encourage more production but rejoice in every 10% milestone.
What it also means in terms of cost is that the provision of lactation consultants in the NICU may be worth their weight in gold. I don’t know what someone performing such services earns in different institutions but if you could avoid two cases of BPD a year in the US I would suspect that nearly $84000 in cost savings would go a long way towards paying for such extra support.
Lastly, it is worth noting that with the NICU environment being as busy as it is sometimes the question “are you planning on breastfeeding?” may be missed. As teams we should not assume that the question was discussed on admission. We need to ask with intention whether a mother is planning on breastfeeding and take the time if the answer is “no” to discuss why it may be worth reconsidering. Results like these are worth the extra effort!
Throughout my career one thing has been consistently true. That is that wherever I was working and regardless of the role I have been an educator. I imagine the blog to a great extent is related to my interest in this aspect of my work. In the last few years much has been said about care by parents whether it be a general approach for family centred care or in formalized approaches such as FiCare which has also been formally studied in the research setting. When we speak of family centred care, one thing that I am constantly reminded of is that the focus of all of our efforts must be on the family and the patient. As I said recently to a colleague when discussing what was presented as a difficult discussion with another colleague due to a disagreement about the direction of management, when you put the patient first the discussion really isn’t difficult at all. It’s not about you or a colleagues ego but about the patient and if the management is not up to par then change direction and worry about managing egos later.
What We Know And What They Know
Another aspect that needs to be addressed is the difference in power that we have through knowledge. I am not talking about us exerting authority over families but from the perspective of us having the knowledge from years of experience in the field as to what is significant and what is not in terms of events in the NICU. The evidence for example with respect to neurodevelopmental outcome from apnea and bradycardia should give us reason to be optimistic the majority of the time. While in Edmonton I learned a great deal from one of my colleagues who was the lead author in a paper entitled Early childhood neurodevelopment in very low birth weight infants with predischarge apnea. While frequent apnea may be associated with mild motor impairments in their paper, the predictive value of these predischarge recordings is very limited when you take away those kids without severe IVH. I think about all of the parents we see who have their eyes glued to the monitors while they attend at the bedside and what they must be thinking. To us it is just a matter of time but I wonder for them how agonizing a time it really is! It isn’t just those infants who are nearing discharge and having apnea either as the CAP study at 5 years of age showed no difference in survival without disability in those infants who received caffeine vs those who did not. More frequent events may not be that detrimental after all. I am not suggesting we not treat patients as one never knows where the threshold lies to cause injury but these preemies are certainly made of some tough stuff.
Identifying Stress and Preparing Parents For it
The first step in dealing with this issue is to know it is there. Recognizing this, Melnyk and others performed an educational intervention targeting behaviour of families in their study Reducing premature infants’ length of stay and improving parents’ mental health outcomes with the Creating Opportunities for Parent Empowerment (COPE) neonatal intensive care unit program: a randomized, controlled trial. The group of parents who went through the program had better mental health outcomes compared to the control groups. The issue here and really is at the crux of the goal in writing all of this is that the stress that parents feel may not be overtly present. The squeaky wheel as the saying goes gets the grease and the parents that are demonstrating signs of poor coping are the first to draw the referrals to social work or engage in a deeper conversation with nursing at the bedside. All parents experience stress at least to a certain degree and it is all of our jobs to tease it out. On the other hand employing standardized approaches such as the COPE program for all parents might be another way of helping those who are in need but not clearly wearing a sign on their foreheads that say “help me”.
Don’t Underestimate the Power of Reassurance
So we know that much of what we see on the monitors will not lead to long term harm, transient central cyanosis during feeds will not damage the brain and apnea of prematurity is a distinct entity from SIDS. The parents on the other hand commonly make these links and additionally in case no one has mentioned it to you, those babies with TTN may one day develop asthma and those with hypoglycemia may have diabetes (we know both not to be true but I have been asked about this many times). This is why I believe it is our duty to explain why we are not worried about things that come up in the unit. Saying “don’t worry” or “that is normal preterm behaviour” may not be enough. Ask a parent what it is they are worried about and you may be surprised to find out the links that they have made in their heads, some of which may be valid but some completely false. I am not meaning to trivialize their concerns but rather validate them as real worries. If we have the knowledge and it is power as I said before then shouldn’t we use that power to help reduce their stress?
Engaging Families Can Reap Huge Dividends
The movement towards family centred care and more specifically care by parent will have a dramatic impact on this issue. As more and more centres move to engaging families to be part of rounds and not just listen and then ask questions but to take some degree of control and provide some of the reporting stress will be reduced. It is only logical. The more a family comes to understand what is significant and what is not in terms of reporting concerns the more confident they will be. Moreover, spending more time at the bedside leads to more skin to skin care and with that shorter hospital stays due to better cardiorespiratory stability. We aren’t there yet but we are headed in the right direction. In the meantime, take the time to ask a simple question “what are you worried about” to parents no matter how confident and strong they appear and you may find yourself with an opportunity to harness the power of education you have a make a real difference to a family in need.