Positive pressure ventilation puts infants at risk of developing chronic lung disease (CLD). Chronic lung disease in turn has been linked many times over, as a risk for long term impacts on development. So if one could reduce the amount of positive pressure breaths administered to a neonate over the course of their hospital stay, that should reduce the risk of CLD and by extension developmental impairment. At least that is the theory. Around the start of my career in Neonatology one publication that carried a lot of weight in academic circles was the Randomized Trial of Permissive Hypercapnia in Preterm Infants which randomized 49 surfactant treated infants to either a low (35-45) or high (45-55) PCO2 target with the thought being that allowing for a higher pCO2 should mean that lower settings can be used. Lower settings on a ventilator would lead to less lung damage and therefore less CLD and in turn better outcomes. The study in question did show that the primary outcome was indeed different with almost a 75% reduction in days of ventilation and with that the era of permissive hypercapnia was born.
The Cochrane Weigh in
In 2001 a systematic review including this and another study concluded that there was insufficient evidence to support the strategy in terms of a benefit to death or chronic lung disease. Despite this lack of evidence and a recommendation from the Cochrane group that permissive hypercapnia be used only in the context of well designed trials the practice persisted and does so to this day in many places. A little lost in this discussion is that while the end point above was not different there may still be a benefit of shorter term ventilation.
A modern cohort
It would be unwise to ignore at this point that the babies of the late 90s are different that the ones in the current era. Surfactant and antenatal steroid use are much more prevalent now. Ventilation strategies have shifted to volume as opposed to pressure modes in many centres with a shift to early use of modalities such as high frequency ventilation to spare infants the potential harm of either baro or volutrauma. Back in 2015 the results of the PHELBI trial were reported Permissive hypercapnia in extremely low birthweight infants (PHELBI): a randomised controlled multicentre trial. This large trial of 359 patients randomized to a high or low target pCO2 again failed to show any difference in outcomes in terms of the big ones “death or BPD, mortality alone, ROP, or severe IVH”. What was interesting about this study was that they did not pick one unified target for pCO2 but rather set different targets as time went on reflecting that with time HCO3 rises so what matters more is maintaining a minimum pH rather than targeting a pCO2 alone which als0 reflects at least our own centre’s practice. There is a fly in the ointment here though and that is that the control group has a fault (at least in my eyes)
|Day of life
In the original studies of permissive hypercapnia the comparison was of a persistent attempt to keep normal pCO2 vs allowing the pCO2 to drift higher. Although I may get some argument on this point, what was done in this study was to compare two permissive hypercapnia ranges to each other. If it is generally accepted that a normal pCO2 is 35-45 mmHg then none of these ranges in the low target were that at all.
How did these babies do in the long run?
The two year follow-up for this study was published in the last month; Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO2 targets: the PHELBI follow-up study. At the risk of sounding repetitive the results of Bayley III developmental testing found no benefit to developmental outcome. So what can we say? There is no difference between two strategies of permissive hypercapnia with one using a higher and the other a lower threshold for pCO2. It doesn’t however address the issue well of whether targeting a normal pCO2 is better or worse although the authors conclude that it is the short term outcomes of shorter number of days on ventilation that may matter the most.
The Truth is Out There
I want to believe that permissive hypercapnia makes a difference. I have been using the strategy for 15 or so years already and I would like to think it wasn’t poor strategy. I continue to think it makes sense but have to admit that the impact for the average baby is likely not what it once was. Except for the smallest of infants many babies these days born at 27 or more weeks of gestation due to the benefits of antenatal steroids, surfactant and modern ventilation techniques spend few hours to days on the ventilator. Meanwhile the number of factors such chorioamniotitis, early and late onset sepsis and genetic predisposition affect the risks for CLD to a great degree in the modern era. Not that they weren’t at play before but their influence in a period of more gentle ventilation may have a greater impact now. That so many factors contribute to the development of CLD the actual effect of permissive hypercapnia may in fact not be what it once was.
What is not disputed though is that the amount of time on a ventilator when needed is less when the strategy is used. Let us not discount the impact of that benefit as ask any parent if that outcome is of importance to them and you will have your answer.
So has permissive hypercapnia failed to deliver? The answer in terms of the long term outcomes that hospitals use to benchmark against one and other may be yes. The answer from the perspective of the baby and family and at least this Neonatologist is no.
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.
I have probably received more requests for our glucose gel protocol than any other question since I started writing on this blog. Dextrose gel has been used more and more often for treatment of hypoglycemia such that it is now a key strategy in the management of low blood sugar in ours and many other institutions. If you are interested in the past analyses of the supporting trials they can be found in these posts; Glucose gel For Managing Hypoglycemia. Can We Afford Not To Use It? and Dextrose gel for hypoglycemia: Safe in the long run? As you can tell from these posts I am a fan of dextrose gel and eagerly await our own analysis of the impact of using gel on NICU admission rates for one!
But What If You Could Prevent Hypoglycemia Rather Than Treating It?
This is the question that the same group who has conducted the other trials sought to answer in their dose finding study entitled Prophylactic Oral Dextrose Gel for Newborn Babies at Risk of Neonatal Hypoglycaemia: A Randomised Controlled Dose-Finding Trial (the Pre-hPOD Study). I suppose it was only a matter of time that someone asked the question; “What if we prophylactically gave at risk babies dextrose gel? Could we prevent them from becoming hypoglycemic and reduce admissions and improve breastfeeding rates as has been seen with treatment of established hypoglycemia?” That is what they went out and did. The group selected at risk patients such as those born to mothers with any type of diabetes, late preterm infants, SGA and others typically classified as being at risk but who did not require NICU admission at 1 hour of age when treatment was provided. The primary outcome was hypoglcyemia (<2.6 mmol/L) in the first 48 hours. Secondary outcomes included NICU admissions, breastfeeding rates in hospital and after discharge as well as formula intake at various time points.
The study sought really to serve as a pilot whose goal was to determine when compared to placebo whether several different regimens could prevent development of hypoglycemia. The groups were (with the first dose in each case given at 1 hour of age):
- Single dose of 40% dextrose gel – 0.5 mL/kg
- Single dose of 40% dextrose gel – 1 ml/kg
- Four doses of 0.5 mL/kg given every three hours with breastfeeding
- A single dose of 1 mL/kg then 3 X 0.5 mL/kg given q3h before each breastfeed.
In total 412 patients were randomized into 8 different groups (4 treatment and 4 placebo).
As The Saying Goes, Less Is More
The only dose of dextrose that reduced the risk of hypoglycemia in the first 48 hours was 0.5 mL/kg which provides 200 mg/kg of dextrose which is the same as a bolus of IV dextrose when giving 2 mL/kg of D10W. Curiously using a higher dose or using multiple doses had no effect on reducing the risk. Based on a difference of 14% between placebo and this group you would need to treat roughly 7 patients with dextrose gel once to prevent one episode of hypoglycemia. Also worth noting is that admission to NICU was no different but if one restricted the reason for admission to hypoglycemia the difference was significant (13% vs 2% risk; p = 0.04). What was not seen here was a difference in rates of breastfeeding and much effect on use of formula.
Why Might These Results Have Occurred?
Insulin levels were not measured in this study but I truly wonder if the reason for hypoglycemia in the other groups may have been transient hyperinsulinemia from essentially receiving either a very large load of glucose (1 mL/kg groups) or effectively 4 boluses of glucose in the first 12 hours of feeding. Rebound hypoglycemia from IV boluses is a known phenomenon as insulin levels surge to deal with the large dextrose load and I can’t help but wonder if that is the reason that all but the single dose regimen had an effect. It is also worth commenting that with so many secondary outcomes in this study the p values needed to reach significance are likely much smaller than 0.05 so I would take the reduction in NICU admissions for hypoglycemia with a grain of salt although at least the trend is encouraging.
I wouldn’t change my practice yet and the authors do acknowledge in the article that a much larger study is now being done using the single dose of 0.5 mL/kg to look at outcomes and until that is published I don’t think a practice change is in order. What this study does reinforce though is that providing multiple doses of dextrose gel may yield diminishing returns. While the goal here was prophylaxis, I can’t help but think about the patients who are symptomatic and receive two or three gels and still wind up with an IV. Could it be the same rebound hypoglycemia at play?
We also have to acknowledge that even if this is an effective preventative strategy, is it in the best interests of the babies to all receive such treatment when at least in 6 babies they wouldn’t have needed any? Could such treatment simply be reserved as has been done for those who develop hypoglycemia? Those who question the safety of the ingredients such as dyes that are found in the product may want some long term safety data before this becomes routine in at risk babies but it won’t surprise me if such strategies become commonplace pending the results of the larger trial on the way.
In April of this year the ALPS trial results were published in the New England Journal of Medicine (Antenatal Betamethasone for Women at Risk for Late Preterm Delivery) and I took the time to review the paper at the time Antenatal Steroids After 34 weeks. Believe the hype? In the analysis I focused on an issue which was relevant at the time, being a shortage of betamethasone. In a situation when the drug of choice is in short supply I argued that while the benefits of giving steroid to women at risk of delivery between 34 0/7 to 36 6/7 weeks was there, if I had to choose (as I did at the time) I would save the doses for those at highest risk of adverse outcome. Since the blog post though a couple of things have come out in the literature that I believe are worth sharing as it could truly influence practice.
The American College of Obstetricians and Gynecologists, moved by the results of the ALPS trial issued the following recommendations (shortened in places).
- Betamethasone may be considered in women with a singleton pregnancy between 34 0/7 and 36 6/7 weeks gestation at imminent risk of preterm birth within 7 days.
- Monitoring of late preterms for hypoglycemia (already being done)
- Do not give in the setting of chorioamnionitis.
- Tocolysis or delayed delivery for maternal indications should not be done in order to to allow for administration of late preterm antenatal corticosteroids.
- Do not provide if the pregnancy was already exposed to antenatal corticosteroids.
The exclusions above such as twins and triplets, diabetic pregnancies and previous receipt of steroids were included since the study had not included these patients. As the ACOG states in the summary, they will be reviewing such indications in the future and providing recommendations. I would imagine that if I were in a US based practice then this post might seem like old news since many centres would have started doing this. Given that the readers of this blog are based in many different countries around the globe and at least in Canada this has not become commonplace I thought it would be worth the update!
I posted the abstract for this review on my Facebook page the other day and it certainly garnered a lot of interest. Some of my readers indicated the practice is already underway. I was curious what a systematic review would reveal about the topic since the ACOG was so moved by the ALPS study in particular. Perusing through the Society of Obstetricians and Gynecologists of Canada (SOGC) I can’t find any commentary on this topic and certainly there are no new clinical practice guidelines since the ALPS study landed on my desktop.
Here are the pooled results from 6 trials:
- Lower risk of RDS (relative risk 0.74, 95% confidence interval 0.61 to 0.91)
- Mild RDS (0.67, 0.46 to 0.96)
- Moderate RDS (0.39, 0.18 to 0.89)
- Severe RDS (0.55, 0.33 to 0.91)
- Transient tachypnea of the newborn (0.56, 0.37 to 0.86)
- Shorter stay on a neonatal intensive care unit (−7.64 days, −7.65 to −7.64)
So across the board patients who receive antenatal steroids after 34 weeks still continue to see a benefit but looked at a different way the real benefit of the intervention is easier to see and that is through looking at the number needed to treat (NNT). For those of you who are not familiar with this analysis, this looks at how many patients one would need to treat in order to avoid the outcome in 1 patient.
For the outcomes above as an example the NNT for RDS overall is about 59 while for TTN 31 patients. Severe RDS which is less common after 34 weeks you might expect to require more patients to treat to help 1 avoid the outcome and you would be correct. That number is 118 patients. It is interesting to look at the impact of steroids in pregnancies below 34 weeks (taken from the Cochrane review on the subject) as the NNT there is 23! If you were to break these benefits down from 23-27 weeks though where the risk of RDS is quite high the NNT would be even lower. Steroids help, no question to reduce neonatal complications but as you can see even when there is a reduction in risk for various outcomes, the number of women you need to treat to get one good outcome is quite different.
Some Discussion With Obstetrics Is Needed Here
As you read through this post you may find yourself saying “Who cares? if there is a benefit at all most moms would say give me the steroids!” The issue here has to do with long term outcome. To put it simply, we don’t know for this type of patient. We know clearly that for patients at high risk of adverse outcomes eg. 24 week infant, the reduction in risks of infection, NEC, PDA, BPD etc from receiving antenatal steroids translates into many long term benefits. What about the patient who say is 35 weeks and would have none of those risks? Yes we are avoiding some short term outcomes that let’s be honest can be scary for a new parent but what are we trading this benefit for. The concern comes from what we know about steroids impact on the developing brain. Steroids lead to a developmental arrest but in very preterm infants there is no doubt that the protective effect on all of these other outcomes more than offsets whatever impact there is there. Incidentally I wrote about this once before and the section of interest appears at the end of the relevant post Not just for preemies anymore? Antenatal steroids for elective c-sections at term. In the absence of these other conditions could there be a long term impact in babies 34 – 36 6/7? My suspicion is that the answer is no but discussion is needed here especially in the absence of an endorsement by our Canadian SOGC. Having said all that I expect the future will indeed see an expansion of the program but then I do hope that someone takes the time to follow such children up so we have the answer once and for all.
Campaign Closed October 13,2016! Thank you everyone for the $9359.00 raised!
Each day the number of people following these sites grows and at the time of this post, the largest following on Facebook has over 8200 people who receive the feed on a daily basis. That is nothing short of remarkable and I hope that each of you gets something out of my writings and postings. I recognise that each post may not “light it up” in your mind but if you get at least a few “a ha” moments along the way then I am very happy that you have found these sites!
What This Is Not!
As I begin hinting at money, many of you may be thinking “here we go”, he is finally asking for some payment for this site! To be clear I have no interest in personal financial gain from this hobby I have developed, but rather find my joy in sharing ideas, getting your feedback and helping to generate interest overall in topics pertaining to Neonatology. I have no intention of ever asking for such payment but that doesn’t mean that I might not want to help someone else. For those of you who make philanthropy a part of your lives you will know the joy that comes from helping others. Being able to help others need not take tremendous dollars per donor when you have many people banding together to help a cause. This is the power that I am hoping to harness through this initiative and make a difference in care to our babies in hospital.
For the past year and a half, I have put my fingers to the keyboard to hopefully share my knowledge and expertise with you about an industry I am so passionate about.
My Philanthropic Side
When I am not busy finding content for the sites or being a Neonatologist, I am quite dedicated to philanthropy. One thing people may not realise about our province/country is that the government helps out the best they can financially but with the heavy demands of our province, they can’t meet all the needs. That’s why I’m proud of my partnership with the Children’s Hospital Foundation of Manitoba. The Foundation’s donors have helped bridge the gap so our hospital doesn’t go without the specialised items they need. From ultrasounds, starting a breast milk depot, specialised pediatric equipment and funding a position to support Quality Improvement in our unit to a soon to be announced Family Support coordinator position and so much more. But now, I turn to you to help us make the next difference in our unit.
The other day as the Facebook page hit 8,000 followers a thought struck me. What if I asked everyone on the page to just give $1 towards the purchase of a piece of equipment for babies in our units?
Hold Their Hand
In the Neonatal Intensive Care Unit (NICU), they are watched closely to make sure they are getting the right balance of fluids and nutrition. Incubators or special warmers help babies maintain their body temperature. This reduces the energy the babies have to use to stay warm and allow them to use that energy elsewhere.
Premature babies need to receive good nutrition so they grow at a rate close to that of babies still inside the womb. Babies born under 38 weeks have different nutritional needs than babies born at full term (after 38 weeks). They often have problems feeding from a bottle or a breast. This is because they are not yet mature enough to coordinate sucking, breathing, and swallowing.
Many NICUs will give donor milk from a milk bank to high-risk babies who cannot get enough milk from their own mother. But because the baby must be kept at a certain temperature to stay warm, so does their milk.
Thanks to the generous support of donors to the Children’s Hospital Foundation of Manitoba, 12 milk warmers have been purchased. However, we need 24 more warmers to keep up with demand. Each one costs $2,000 and will make a huge impact. An impact to help our babies get the nutrition they need at the temperature they require to survive and thrive.
So let’s hold their hand and let’s do it together! Has this journey of learning been worth at least $1 to you? If it has, then please help make a difference by giving at least $1. Giving more will only increase the power of this campaign! If you aren’t able to donate $1 or more, I ask that you share this post and challenge your friends to help make a difference to the over 1,000 patients we see a year. Click the link below to donate and make your difference today.
It seems like a sensational title I know but it may not be as far fetched as you may think. The pendulum certainly has swung from the days of liberal post natal dexamethasone use in the 1990s to the near banishment of them from the clinical armamentarium after Keith Barrington published an article entitled The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs in BMC Pediatrics in 2011. This article heralded in the steroid free epoch of the first decade of the new millennium, as anyone caring for preterm infants became fearful of causing lifelong harm from steroid exposure. Like any scare though, with time fear subsides and people begin asking questions such as; was it the type of steroid, the dose, the duration or the type of patient that put the child at risk of adverse development? Moreover, when death from respiratory failure is the competing outcome it became difficult to look a parent in the eye when their child was dying and say “no there is nothing more we can do” when steroids were still out there.
Over the last decade or so, these questions in part have been studied in at least two important ways. The first was to ask whether we use a lower dose of dexamethasone for a shorter period to improve pulmonary outcomes without adverse neurodevelopment? The target population here were babies on their way to developing chronic lung disease as they were ventilated at a week of age. The main study to answer this question was the DART study. This study used a very low total dose of 8.9 mg/kg of dexamethasone given over ten days. While the study was stopped due to poor recruitment (it was surely difficult to recruit after the 2001 moratorium on steroids) they did show a benefit towards early extubation. This was followed up at 2 years with no difference in neurodevelopmental outcomes. Having said that the study was underpowered to detect any difference so while reassuring it did not prove lack of harm. Given the lack of evidence showing absolute safety practitioners have continued to use post natal steroids judiciously.
The second strategy was to determine whether one could take a prophylactic approach by providing hydrocortisone to preterm infants starting within the first 24 hours to prevent the development of CLD. The best study to examine this was by Kristi Watterberg in 2004 Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial. Strangely enough the same issue of early stoppage affected this study as an increased rate of spontaneous gastrointestinal perforation was noted leading to early closure. The most likely explanation is thought to be the combination of hydrocortisone and indomethacin prophylaxis which some centres were using at the same time. An interesting finding though was that in a subgroup analysis, infants with chorioamnionitis who received hydrocortisone had less incidence of chronic lung disease. (more on this later) Although this of course is subject to the possible bias of digging too deep with secondary analyses there is biologic plausibility here as hydrocortisone could indeed reduce the inflammatory cascade that would no doubt be present with such infants exposed to chorioamnionitis in utero.
Has the answer finally come?
The DART study at 360 patients was the largest study to date to look at prophylaxis as a strategy. That is until this past week. The results of the PREMILOC study have been published which is the long awaited trial examining a total dose of 8.5 mg/kg of hydrocortisone over 10 days. We can finally see the results of a trial without the complicating prophylactic indomethacin trials interfering with results. Surprisingly this study was also stopped early (a curse of such trials?!) due to financial reasons this time. Prior to stoppage though they managed to recruit 255 to hydrocortisone and 266 to control groups. All infants in this study were started on hydrocortisone within 24 hours of age and the primary outcome in this case was survival without BPD at 36 weeks of age.
All infants were less than 28 weeks at birth and therefore had a high risk of the combined outcome and despite the study being stopped early there was indeed a better outcome rate in the hydrocortisone group (60% vs 51%). Another way of looking at this is that to gain one more patient who survived without BPD you needed to treat 12 which is not bad at all. What is additionally interesting are some of the findings in the secondary analyses.
The lack of a difference in males may well reflect the biologic disadvantage that us males face overcoming any benefit from the hydrocortisone. In fact for the females studied the number needed to treat improves to 6 patients only! Short term outcomes of less ventilation are sure to please everyone especially parents. Lastly, a reduction in PDA ligation is most probably related to an antiprostaglandin effect of steroids and should be cause for joy all around. Lastly, a tip of the hat to Dr. Watterberg is in order as those infants who were exposed to chorioamnionitis once again show that this is where the real benefit may be.
But what about side effects?
The rate of NEC is quite high but is so for both groups but otherwise there is nothing much here to worry the reader. Once and for all we also see that by excluding concurrent treatment with indomethacin or ibuprofen the rate of GI perforation is no different this time around. Reassuring results indeed, but alas the big side effect, the one that would tip the scale towards us using or abandoning treatment has yet to be presented. Steroids no doubt can do great things but given the scare from 2001 we will need to see how this cohort of babies fares in the long run.
The follow-up is planned for these infants and the authors have done an incredible job of recruiting enough patients to make the results likely believable. I for one can’t wait to see what the future holds. If I was a betting man though I would say this ultra low dose of hydrocortisone may be just the thing to bring this therapy finally into the toolbox of neonatal units worldwide. We have been looking for the next big thing to help improve outcomes and good old hydrocortisone may be just what the doctor ordered.