A grenade was thrown this week with the publication of the Australian experience comparing three epochs of 1991-92, 1997 and 2005 in terms of long term respiratory outcomes. The paper was published in the prestigious New England Journal of Medicine; Ventilation in Extremely Preterm Infants and Respiratory Function at 8 Years. This journal alone gives “street cred” to any publication and it didn’t take long for other news agencies to notice such as Med Page Today. The claim of the paper is that the modern cohort has fared worse in the long run. This has got to be alarming for anyone reading this! As the authors point out, over the years that are being compared rates of antenatal steroid use increased, surfactant was introduced and its use became more widespread and a trend to using non-invasive ventilation began. All of these things have been associated with better short term outcomes. Another trend was declining use of post-natal steroids after 2001 when alarms were raised about the potential harm of administering such treatments.
Where then does this leave us?
I suppose the first thing to do is to look at the study and see if they were on the mark. To evaluate lung function the study looked at markers of obstructive lung disease at 8 years of age in survivors from these time periods. All babies recruited were born between 22-27 completed weeks so were clearly at risk of long term injury. Measurements included FEV1, FVC, FVC:FEV1 and FEF 25-75%. Of the babies measured the only two significant findings were in the FEV1 and ratio of FEV1:FVC. The former showed a drop off comparing 1997 to 2005 while the latter was worse in 2005 than both epochs.
Variable | 1991-92 | 1997 | 2005 |
%predicted value | N=183 | N=112 | N=123 |
FEV1 | 87.9+/-13.4 | 92.0+/-15.7 | 85.4+/-14.4 |
FEV1:FVC | 98.3+/-10 | 96.8+/-10.1 | 93.4+/-9.2 |
This should indeed cause alarm. Babies born in a later period when we thought that we were doing the right things fared worse. The authors wonder if perhaps a strategy of using more CPAP may be a possible issue. Could the avoidance of intubation and dependence on CPAP for longer periods actually contribute to injury in some way? An alternative explanation might be that the use of continuous oximetry is to blame. Might the use of nasal cannulae with temporary rises in O2 expose the infant to oxygen toxicity?
There may be a problem here though
Despite everyone’s best efforts survival and/or BPD as an outcome has not changed much over the years. That might be due to a shift from more children dying to more children living with BPD. Certainly in our own centre we have seen changes in BPD at 36 weeks over time and I suspect other centres have as well. With concerted efforts many centres report better survival of the smallest infants and with that they may survive with BPD. The other significant factor here is after the extreme fear of the early 2000s, use of postnatal steroids fell off substantially. This study was no different in that comparing the epochs, postnatal glucocorticoid use fell from 40 and 46% to 23%. One can’t ignore the possibility that the sickest of the infants in the 2005 cohort would have spent much more time on the ventilator that their earlier counterparts and this could have an impact on the long term lung function.
Another question that I don’t think was answered in the paper is the distribution of babies at each gestational age. Although all babies were born between 22-27 weeks gestational age, do we know if there was a skewing of babies who survived to more of the earlier gestations as more survived? We know that in the survivors the GA was not different so that is reassuring but did the sickest possible die more frequently leaving healthier kids in the early cohorts?
This bigger issue interestingly is not mentioned in the paper. Looking at the original cohorts there were 438 in the first two year cohort of which 203 died yielding a survival of 54% while in 1997 survival increased to 70% and in 2005 it was 65%. I can’t help but wonder if the drop in survival may have reflected a few more babies at less than 24 weeks being born and in addition the holding of post natal steroids leading to a few more deaths. Either way, there are enough questions about the cohorts not really being the same that I think we have to take the conclusions of this paper with a grain of salt.
It is a sensational suggestion and one that I think may garner some press indeed. I for one believe strongly though as I see our rates of BPD falling with the strategies we are using that when my patients return at 8 years for a visit they will be better off due to the strategies we are using in the current era. Having said that we do have so much more to learn and I look forward to better outcomes with time!
It is true that mortality increases at a lower gestational age and I am sure that this data was reflected by the NBs between 22 and 24 weeks.
However, I am struck by the fact that those who received CPAP had more lung damage and alterations in pulmonary function, what parameters would they use? PEEP, FIO2 and the interface.
How can I quote or read the complete article?
I read this study with concern , but this may not be what has been practiced for many years . Back in the day therapy such ncpap was reserved for infants post intubation after being destroyed via our treatments, levels so low and equipment so inferior it’s sad. With only one place in the world Jen tang Wong unit who mastered ncpap therapy. Compare and contrast the period post 2005 where we learned how not destroy lungs, ncpap levels that are meaning ful. Add the extremes of premature infants routinely treated there is no comparison. As a resp person the question of airflow limitation , being solely blamed on treatment is mis placed. Their are many 8 yr old with severe airflow problems who were never premise. I think that we should use this as question for science not an answer. I was in the old days the infants did terrible and they were much more mature they were blinded etc. The question is what are we doing to the long term Heath of 22 23 24 week gestation infants we. Treat and who is going to fund there long term disabilities
so well said as always John. Thank you for teaching me as much as you have over the years!
My thoughts exactly. In the last few years we have gone away from regular surfactant and intubations, while aiming for early nCPAP to avoid invasive ventilation. I fear this may not include that information in the study. I too would like more info and to be able to read what was published and the methods of ventilation used on the ELBW’s.
The biggest problem is not recognising when non-invasive strategies fail. Prem’s are very succeptable to oxidative stress, and lung collapse evokes an inflammatory response which exacorbates this. Lung structure at 22-25 weeks is not sufficient to support ventilation and oxygenation using non-invasive strategies: less than 5% of this cohort will avoid an endotracheal tube and mechanical ventilation. It is likely less harmful to pursue a gentle/lung protective ventilation strategy such as oscillation or high frequency jet ventilation and extubating at the earliest appropriate time using appropriate levels of CPAP, i.e. starting at the MAP the baby was using whilst ventilated.
It was very interesting to me, to read your input on this article. Thank you for making me think twice, when reading the conclusions, specially since I am not a Neonatologist. I am a pediatric anesthesiologist, and I do neonates, but not all the time.
Here is the citation for the article:
Doyle, L. W., Carse, E., Adams, A., Ranganathan, S., Opie, G., & Cheong, J. L. (2017). Ventilation in Extremely Preterm Infants and Respiratory Function at 8 Years. New England Journal of Medicine, 377(4), 329-337. doi:10.1056/nejmoa1700827
I came into your blog to ask everyone about something else, and got caught on, reading the article!
I want to ask your opinion on the ideal site to place the temperature probe on neonates, in an incubator. There are studies that say, the axilla is better, there are many others that say the abdomen skin is better, and others that say it makes no difference, to give feedback to the incubator .
What do you usually do at your NICU? Does it really matter where you measure temperature?
In the neonate, does skin temperature really reflect core temperature?
If I am writing about something off topic, is there a better place than this where I should write? I could not find where, so I am sorry I wrote off topic, here.
Angela thank you for reading the post. We typically put the temperature probe on the abdomen. Skin temperature is the best measure we have other than using esophageal or rectal probes to measure core temperature during therapeutic hypothermia.
Thank you !
We utilize axilla or over the liver in our NICU.. the axilla works well with fat babies, but not well in the low weight infants. For them, the liver works closest to core with the good blood flow through it. It must have a reflective covering, and the infant should not lie on the probe. Dont tuck it into the diaper…. it will give falsely high readings and the baby will get cold stressed.
Thank you Denise!
Great discussion and as you all have pointed out, we should continue the debates and studies of short and long term mobilities in the population of babies born below 28 weeks gestation.
There are many co-founding variables in this study, among them,the gestational age and the parameters used to ventilated. One variable that often changes, is the “grouping” of infants less than 28 weeks gestation for analysis. The infants 21-22-23 weeks behave very differently than babies of 24-26 weeks and these differ from infants 27 and 28 weeks gestation.
In my opinion we also need to separate infants of mothers who received or did not receive prenatal steroids. The use of prenatal steroids should be more than 90% of infants born at or below 34 weeks gestation and maybe up to 36 weeks (this point is for another discussion). The dramatic differences between treated and untreated are so great that we should separate them in any study or discussion.
What about post-natal use of steroids, did any of those babies receive it? What about other co-morbilities? Were they corrected for?
We need other studies to investigate these results
Thank you Guillermo for bringing up many important variables that could greatly influence these outcomes.
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I didn!t read the original paper. But one thought came to my mind when I have seen times of these three periods. I would put the worsening of 2005 cohort to not enough implemented and experienced not invasive approach. It is not only about how but also how well is something done. We all need time to get experience and excelence to get ripes of our work