What a hard topic to resist commenting on. This was all over twitter and the general media this week after the New England Journal published the following paper; Antenatal Betamethasone for Women at Risk for Late Preterm Delivery. The fact that it is the NEJM publishing such a paper in and of itself suggests this is a top notch study…or does it?
Is there a benefit to giving antenatal steroids from 34 0/7 – 36 5/7 weeks?
That is the central question the authors here sought to answer. Would women who had a high risk of delivering during this time period have less risk of a composite primary outcome of treatment in the first 72 hours (the use of continuous positive airway pressure or high-flow nasal cannula for at least 2 hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 hours, extracorporeal membrane oxygenation, or mechanical ventilation) or stillbirth or neonatal death within 72 hours after delivery.
On the surface this seems like a very worthwhile set of outcomes to look at and the authors found in the end some pretty remarkable findings in a total of 2827 women randomized to placebo or betamethasone.
Looking at the results one sees that the primary outcome showed a significant difference with 2.8% less infants experiencing these conditions. However, when one looks at the details the only contributor to this difference was the need for CPAP or HFNC for >= 2 hours. A need for over 30% FiO2 for > 4 hours was also not different. No differences were noted in mechanical ventilation, ECMO, deaths whether stillbirths or neonatal deaths. Curiously, significant differences for secondary outcomes were seen with incidence of severe respiratory distress, and need for CPAP for over 12 hours.
These results are not truly that surprising at least for the primary outcome as if you asked most people working in the field of Neonatology how likely death, need for ECMO or even mechanical ventilation are from 34 – 36 weeks they would tell you not very likely. The other thing to consider is that the only real significant difference was noted for infants needing CPAP or HFNC for at least 2 hours. While this would interrupt maternal infant bonding, it wouldn’t necessarily mean an admission but rather in some cases observation and then transfer to the mother’s room.
Is it worth it?
To answer this question you need to know the best and worst case scenarios I suppose. Based on the reduction of 2.8%, you would need to treat 35 women with betamethasone to avoid the primary outcome but of course there is a range based on the confidence intervals around this estimate. The true estimate lies somewhere between 18 – 259 to avoid the outcome. Having said that, the estimate to avoid severe distress is 25 patients with a range of 16 – 56 which is pretty good value. In a perfect world I would probably suggest to women that there seems to be a benefit especially if one notes that in this study only 60% of the women received 2 dose of betamethasone so if rates of administration were higher one might expect and even better outcome. Ah but the world is not perfect….
There is only so much betamethasone to go around.
I find it ironic but the same day that this article came across my newsfeed so did a warning that we were about to run out of betamethasone vials in a certain concentration and would need to resort to another manufacturer but that supply may also run out soon as well. The instructions were to conserve this supply in the hospital for pregnant women.
In Canada as reported by the Canadian Neonatal Network in 2010, 38.1% of babies admitted to NICUs were below 34 weeks. Given that all babies would be admitted to NICUs at this gestational age and below that likely represents the percentage of births in those ages. An additional 31.8% or almost an equal number of babies will be born between 34 0/7 to 37 0/7 weeks meaning that if we were to start treating women who were deemed to be at risk of preterm delivery in that age range we would have a lot of potential women to choose from as these are the exact women in this strata who actually delivered early in Canada.
If I am forced to choose whether to give betamethasone to the mothers under 34 weeks or above when the resource we need is in scarce supply I don’t think there is much choice at all. Yes, this article comes from a reputable journal and yes there are some differences some of which are highly significant to consider but at least at this time my suggestion is to save the supply we have the babies who will benefit the most.
It is hard to believe but All Things Neonatal is a year old. When I started this little concept I had no idea what was to come but am delighted with where it has gone. While the Blog site itself has about 200 followers, the Facebook page is home to nearly 4200 followers with twitter accounting for over 500 more. What began as a forum for me to get some thoughts off my chest about neonatal topics or articles of interest has morphed into a place to create change. As I look back over the last year I thought I would update the readers of this page and other social media platforms what the outcome has been for some of the ideas that I have brought forward. We have implemented some of these suggestions into our own unit practices, so without further ado here are the updates for some (but not all!) of the changes we have introduced.
Articles pertaining to use of Telehealth in all aspects of medicine are becoming commonplace. Locally we have seen expansion of rural sites that can connect with us and a strong desire by existing sites to connect via telehealth for a variety of reasons. While the thrust of the program was to deliver advice to rural practitioners and support our level I and II units we have found such support leading to possibilities we had not dreamed of. Initial discussions via telehealth and in person have occurred examining whether such treatments as CPAP stabilization and NG feedings could be done in these sites. Being able to provide such care will no doubt lead to more stable infants being transported to our site and moreover the possibility of moving the care for infants needing only gavage feeding back to their home communities. Who knows what the future will hold for us as we also look forward to the hiring of a telehealth coordinator for NICU!
This has been one of my favourite topics to write about. The ability to sample CO2 from an area near the carina has been demonstrated to be accurate and to save pokes in the long run. Since writing this piece we have tried it on several babies by using a double lumen tube and found the results to be as accurate as described in the Israeli papers. In practice though, secretions have proved difficult to handle for longer periods of use as they can travel up the sampling lines and damage the filters in the analyzers. A costly issue to deal with that we are currently trying to solve. Being able to continuously sample CO2 and adjust ventilation without drawing frequent blood gases is somewhat of a dream for me and we will continue to see how we can go about making this an established practice but there is work to be done!
I think most people in Winnipeg would say the answer is yes. On this front two major positive changes have occurred in the last year in this regard. The first is that through a generous donation and the blessing of our health region we have been able to expand the use of donor breast milk from < 1250g for a two week period to < 1500g for a one month period. This wonderful change came about after much effort and was celebrated in December as we not only expanded the eligibility criteria but partnered with the NorthernStar Mother’s Milk Bank to provide donor milk to Manitobans (Manitobans Now Able To Support Premature Infants Through Donor Milk Program!). The other change which the above post also spoke of was the potential to eliminate bovine milk altogether with the use of Prolacta (Human based human milk fortifier). While we don’t have the approval to use the product as traditionally indicated, we have used it as a “rescue” for those patients who demonstrate a clear intolerance of bovine fortifier. Such patients would traditionally receive inadequate nutrition with no other option available but now several have received such rescue and we look forward to analyzing the results of such a strategy shortly!
Without question the most talked about change was the change in threshold for recommending resuscitation from 24 to 23 weeks. The change took almost a year to roll out and could not have been done without a massive educational rollout that so many people (a special thank you to our nurse educators!) took part in. Looking back on the year we have now seen several infants at 23 weeks who survived with a small minority dying in the newborn period. It is too early to look at long term outcomes but I think many of us have been surprised with just how well many of these children have done. Moreover I believe we may be seeing a “creep effect” at work as the outcomes of infants under 29 weeks have also improved as we developed new guidelines to provide the best care possible to these vulnerable infants. Antenatal steroid use is up, IVH down and at least from January to September of last year no infants died at HSC under 29 weeks! I look forward to seeing our results in the future and cannot tell you how impressed I am with how our entire team came together to make this all happen!
I wanted to share some of the initiatives that came forward or were chronicled on these pages over the last year to show you that this forum is not just a place for my mind to aimlessly wander. It is a place that can create change; some good, some great and no doubt some that won’t take. It has also been a place where ideas are laid out that have come from afar. From readers anywhere in the world who ask a question on one of the social media sites that get me thinking! I have enjoyed the past year and expect I will continue to enjoy what may spring forth from these pages for some time to come. Thank you for your contributions and I hope you get a little something out of this as well!
Every now and then I come across an instance when I discover that something that I have known for some time truly is not as well appreciated as I might think.
Twice in my career I have come across the following situation which has been generalized to eliminate any specific details about a patient. In essence this is a fictional story but the conclusions are quite real.
Case of the Flat Baby
A mother arrives at the hospital with severe abdominal pain and in short order is diagnosed with a likely abruption at 26 weeks gestational age. Fetal monitors are attached and reveal a significant fetal bradycardia with a prolonged period of minutes below 100 and sometimes below 60 beats per minute. She is rushed to the OR where an emergency c-section is performed.
A live born infant is handed to the resuscitation team after cord clamping is stopped at 30 seconds due to significant cyanosis and no respirations. After placing the infant in a polyethylene wrap and performing the initial steps of ventilation there is no respiratory effort and the baby is given PPV. After no heart rate is noted chest compressions commence followed by intubation and then epinephrine when a heart rate while detected remains below 60. The team gives a bolus of saline followed by another round of epinephrine and by 10 minutes a pulse of 80 BPM is detected. While a pulse is present it remains borderline and the baby shows no sign of any respiratory efforts.
The care providers at this point have a decision to make about continuing resuscitative efforts or not. One of the team members performs a physical exam at this stage and notes that the pupils are unresponsive to light with a 3 mm pupillary diameter. The team questions whether based on this finding irreversible neurological damage has occurred.
Pupillary Reactions in Preterm Infants
It turns out that much like many organs in the body which have yet to fully mature the same applies to the eye or more specifically in this case the pupil. Robinson studied 50 preterm infants in 1990 and noted that none of the infants under 30 weeks gestational age demonstrated any reaction to light shone in the eye. After 30 weeks the infants gradually realized this function until by 35 weeks all infants had attained this pupillary reaction to light.
Isenberg in the same year when examining 30 preterm infants under 30 weeks noted that in addition to the lack of pupillary constriction to light, as the gestational age decreased the pupillary diameter enlarged. The youngest infants in this study at 26 weeks had a mean pupillary diameter of 4.7 mm while by 29 weeks this number decreased to 2.9 mm. This means that the smaller the infant the larger the pupillary size and given that these are also the highest risk infants one can see how the appearance of a “fixed and dilated pupil” could lead one down the wrong path.
Deciding when to stop a resuscitation is never an easy decision. Add to this as I recently wrote, even after 10 minutes of resuscitation outcomes may not be as bad as we have thought; Apgar score of 0 at 10 minutes: Why the new NRP recommendations missed the mark. What I can say and obviously was the main thrust of this piece is that at least when you are resuscitating an infant < 30 weeks gestational age, leave the eyes out of the decision. The eyes in this case “do not have it”.
The scenario is often the same. Faced with a child born to a mother with risk factors for sepsis you decide to start antibiotics. The time comes closer to 36 – 48 hours when you must decide whether or not to continue. Each time we examine our results and look at cultures and try to do what is right. Yet defining right is sometimes hard for so many. If we had 100% sensitivity and specificity for all our tests it would be easy but we don’t. So what can we do?
If I had to have one wish though it would be that we could improve upon our diagnostic accuracy when it comes to treating suspected infections in the newborn. As health care providers we have an extremely loud inner voice trying to tell us to minimize risk when it comes to missing a true bacterial infection. On the other hand so much evidence has come forth in the last few years demonstrating that prolonging antibiotics beyond 48 hours is not just unwise in the absence of true infection but can be dangerous. Increased rates of necrotizing enterocolitis is just one such example but other concerns due to interfering with the newborn microbiome have arisen in more recent years. What follows are some general thoughts on septic workups that may help you (and myself in my own practice) as we move ahead into the New Year and may we cause less harm if we consider these.
The Role of Paired Blood Cultures
Although not published by our centre yet, we adopted this strategy for late onset sepsis a couple years back and have seen a significant reduction in work-ups deemed as true infections since adoption. While the temptation to do only one blood culture is strong as we have a desire to minimize skin breaks consider how many more there will be if you do one culture and get a CONS organism back. There will be several IV starts, perhaps a central line, repeat cultures etc. If you had done two at the start and one was positive and the other negative you could avoid the whole mess as it was a contaminant from the start. On my list of do no harms I think this may have the greatest benefit.
The Chest X-Ray Can Be Your Friend
While I am not a fan of routine chest x-rays I do believe that if you are prepared to diagnose an opacification on a chest x-ray as being due to a pneumonia (VAP or in those non-ventilated) that you need to follow this up with a repeat x-ray 24 – 48 hours later. If the opacity is gone it was atelectasis as a true pneumonia will not clear that easily. Well worth the radiation exposure I say.
If You Are Going To Do a Work-up Make It A Complete One
We hear often in rounds the morning after a septic work-up that the baby was too sick to have an LP and that we can just check the CSF if the blood is positive. There are two significant problems to this approach. The first which is a significant concern is that in a recent study of patients with GBS meningitis, 20% of those who had GBS in the CSF had a negative blood culture. Think about that one clearly… relying on a positive culture to decide to continue antibiotics may lead to partially treated GBS meningitis when you discontinue the antibiotics prematurely. Not a good thing. The second issue is that infants with true meningitis can have relatively low CSF WBC counts and may drift lower with treatment. Garges et al in a review of 95 neonates with true meninigits found that CSF WBC counts >21 cells per mm3 had a sensitivity of 79% and specificity at 81%. This means that in those with true meningitis 19% of the time the WBC counts would be below 21 leading to the false impression that the CSF was “fine”. If antibiotics were effective it could well be by 48 hours that the negative CSF culture you find would incorrectly lead you to stop antibiotics. Message: Do the CSF sampling at the time of the septic work-up whenever possible.
If We Aren’t Prepared To Do a Supra Pubic Aspirate Should We Not Collect Urine At All?
This provocative question was asked by a colleague last week and is based on the results of a study which was the topic of the following post: Bladder Catherterizations for UTI: Causing more harm than good? The gist of it is that it would appear that in many cases the results of a catheter obtained urine cannot be trusted. If that is the case then are we ultimately treating infections that don’t actually exist when the only positive culture is from a urine. I believe using point of care ultrasound to obtain specimens from a SPA will be the way to go but in the meantime how do we address the question of whether a UTI is present or not? May need to rely on markers of inflammation such as a CRP or procalcitonin but that is not 100% sensitive or specific either but may be the best we have at the moment to determine how to interpret such situations.
Lastly, Slow Down And Practice Good Hand Hygiene
So much of what I said above is important when determining if an infection is present or not. The importance of preventing infection cannot be understated. Audits of hand hygiene practice more often than not demonstrate that physicians are a group with some of the lowest rates of compliance. Why is that? As a physician I think it has nothing to do with ignorance about how to properly perform the procedure but rather a tendency to rush from patient to patient in order to get all the things done that one needs to do well on service or call. If we all just slow down a little we may eventually have less need to run from patient to patient as the rate of infections may drop and with it demand for our time.
If slowing down is something that you too think is a good idea you may want to have a look at the book In Praise of Slowness by Carl Honore (TED Talk by Carl Below) which may offer some guidance how to do something that is more easily said than done. Here is hoping for a little slower pace in the new year. We could reap some fairly large benefits!
Another year has passed and another World Prematurity Day is upon us. I thought about what to write for this day that draws attention to premature infants worldwide and was hit with many ideas which no doubt will form the basis for many posts to come. There was one thought that struck me though as being so important to think about as we push forward, striving to improve survival across the globe for our smallest patients. There is no doubt that you will have heard the expression “just because we can do something, should we?” In 2015 I don’t think this applies more than at this very moment.
At a Tipping Point
You see we are at a tipping point as Malcolm Gladwell explained so brilliantly in his book by the same name. In April of 2015 Rysavy et al published the results of survival and morbidity data for infants born in 24 US hospitals between the ages of 22 – 26 weeks. The nearly 5000 infants included demonstrated two very important things. Firstly, survival is possible at 22 and 23 weeks and there is a chance, albeit less than 50% that these infants will survive without moderate or severe disability. Secondly, at these gestational ages 75% of hospitals included provided active resuscitation to these infants. Given that this is the largest study out there and shows that survival is possible and we can expect to see some good outcomes it would seem logical to move forward with universal resuscitation of these infants would it not?
You Are Going To Practice on What?!
As the saying goes though, “Perfect Practice Makes Perfect”. Not all hospitals have equal performance at these gestational ages which is demonstrated in the ranges of outcomes across hospitals as shown in the Rysavy paper. To even suggest that we need to practice on premature babies will no doubt leave many of you feeling queasy but in essence that is what is truly needed to improve our outcomes further. An infant born at 22 – 24 weeks is vastly different than one born at a later gestational age. Their skin is extremely fragile and prone to breakage with resultant risk of infection. Their lungs are in a stage of development that has yet to produce any real abundance of gas exchanging alveoli and their brains lacking the sulci and gyri that are to come many weeks later. They are in need of meticulous “best practice” care and without that their outcomes are certainly to be influenced. Depending on the centre though, you may see 5, 10, 15, 20 patients a year at these ages. How can a team possibly gain enough experience in treating these children appropriately if they see 1 or 2 every two months? Add to this that you may have 10 different Neonatologists so on average each of you may take care of one patient a year at birth. This is a recipe prone to poor outcomes if you ask me.
The Evolution of the Small Baby Unit
The answer no doubt will lie in creating smaller teams; so called “Small Baby Units”. Such units have small groups of health care providers dedicated to treating such infants thereby increasing the frequency of individuals exposure to these babies. There is some recent evidence published in Pediatrics that supports this notion. Small Baby Unit Improves Quality and Outcomes in Extremely Low Birth Weight Infants. In this study a period of two years before and four years after opening such a unit were compared across a number of measures. The findings were as follows “There was a reduction in chronic lung disease from 47.5% to 35.4% (P = .097). The rate of hospital-acquired infection decreased from 39.3% to 19.4% (P < .001). Infants being discharged with growth restriction (combined weight and head circumference <10th percentile) decreased from 62.3% to 37.3% (P = .001). Reduced resource utilization was demonstrated as the mean number per patient of laboratory tests decreased from 224 to 82 (P < .001) and radiographs decreased from 45 to 22 (P < .001).” I hope you would agree that achievements such as these are worth the effort to create such an environment. Future studies I believe will confirm these findings although having the gold standard RCT may be difficult to achieve as I suspect we will have lost equipoise.
This brings me to the final point though and that is whether we are ready as a health care system for the increase patient load that this change will bring about. Based on an expected stay of 4 months for a baby born at this age and knowing the average number of such babies delivered per year, we would be looking at about 600 patient days per year added to each hospital’s occupancy in our two centres. This represents about a 5% increase in patient bed days per year. Five percent may not seem like a large increase at first blush but when we like many hospitals have been trying to deal with staffing issues and many days in which we are at or near capacity, this is not an insignificant challenge. It is a challenge though that we must face head on. Resources must be found, and space provided to accommodate for these children. We live in a world now where it is not solely up to us but to the family as well who must be integral to any such decision to either pursue or withdraw care. News of such infants surviving has spread to the public and I have no doubt that many families will have heard stories of such survivors. The next phase of care for these infants must address the shortcomings in care at the moment.
How do we educate families about what to expect in the long run?
How do we support these families when they make such difficult decisions either way?
How do we support our front line staff who may hold quite discrepant viewpoints about what is “right” yet expect them to function as one team moving clearly in a direction that supports the family?
How do we ensure that our focus on our smallest infants does not distract us from the attention needed by those born at later gestational ages?
I could go on but these are just some of the questions that I hope the next year begins to tackle. We are in the midst of an evolutionary point in Neonatology and we owe it to ourselves and the families we care for to navigate this change as best we can.