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Developmental outcomes for extreme preemies after delivery room CPR.

AllThingsNeonatal

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Developmental outcomes for extreme preemies after delivery room CPR.

We have all been there.  After an uneventful pregnancy a mother presents to the labour floor in active labour.  The families world is turned upside down and she goes on to deliver an infant at 27 weeks.  If the infant is well and receives minimal resuscitation and is on CPAP we provide reassurance and have an optimistic tone.  If however their infant is born apneic and bradycardic and goes on to receive chest compressions +/- epinephrine what do we tell them?  This infant obviously is much sicker after delivery and when the family asks you “will my baby be ok?” what do you tell them?  It is a human tendency to want to reassure and support but if they ask you what the chances are of a good outcome it has always been hard to estimate.  What many of us would default to is making an assumption that the need for CPR at a time when the brain is so fragile may lead to bleeding or ischemia would lead to worse outcomes.  You would mostly be right. One study by Finer et al  entitled Intact survival in extremely low birth weight infants after delivery room resuscitation.demonstrated that survival for infants under 750g was better if they had a history of CPR after delivery.  The thought here is that more aggressive resusctiation might be responsible for the better outcome by I would presume establishing adequate circulation sooner even if the neonates did not appear to need it immediately.

The Canadian Neonatal Network

In Canada we are fortunate to have a wonderful network called the Canadian Neonatal Network.  So many questions have been answered by examining this rich database of NICUs across the county.  Using this database the following paper was just published by Dr. A. Lodha and others; Extensive cardiopulmonary resuscitation of preterm neonates at birth and mortality and developmental outcomes. The paper asked a very specific and answerable question from the database.  For infants born at <29 weeks gestational age who require extensive resuscitation (chest compressions, epinephrine or both) what is the likelihood of survival and/or neurodevelopmental impairment (NDI) at 18-24 months of age vs those that did not undergo such resuscitation?  For NDI, the authors used a fairly standard definition as “any cerebral palsy (GMFCS1), Bayley-III score <85 on one or more of the cognitive, motor or language composite scores, sensorineural or mixed hearing impairment or unilateral or bilateral visual impairment.”  Their secondary outcomes were significant neurodevelopmental impairment (sNDI), mortality, a Bayley-III score of <85 on any one of the components (cognitive, language, motor), sensorineural or mixed hearing loss,or visual impairment.sNDI was defined as the presence of one or more of the following: cerebral palsy with GMFCS 3, Bayley-III cognitive, language or motor composite score <70, hearing impairment requiring hearing aids or cochlear implant, or bilateral visual impairment”

What did they discover?

It is a fortunate thing that the database is so large as when you are looking at something like this the number of infants requiring extensive resuscitation is expected to be small.  The authors collected data from January 1, 2010 and September 30, 2011 and had a total number of infants born at less than 29 weeks of 2760.  After excluding those with congenital anomalies and those who were born moribund they were left with 2587.  From these 80% had follow-up data and when applying the final filter of extensive resuscitation they were left with 190 (9.2%) who received delivery room CPR (DR-CPR) vs 1545 who did not receive this.

Before delving into the actual outcomes it is important to note that neonates who did not receive DR-CPR were more likely to be born to mothers with hypertension and to have received antenatal steroids (89 vs 75%).  With these caveats it is pretty clear that as opposed to the earlier study showing better outcomes after DR-CPR this was not the case here.

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The results are interesting in that it is pretty clear that receiving DR-CPR is not without consequence (higher rate of seizures, severe neurological injury, BPD).  Looking at the longer term outcomes though is where things get a little more interesting.  Mortality and mortality or neurodevelopmental impairment are statistically significant with respect to increased risk.  When you take out NDI alone however the CI crosses one and is no longer significant.  Neither is CP for that matter with the only statistically significant difference being the Bayley-III Motor composite score <85.  The fact that only this one finding came out as significant at least to me raises the possibility that this could have been brought about by chance.  It would seem that while these infants are at risk of some serious issues their brains in the long run may be benefiting for the neurological plasticity that we know these infants have.

The study is remarkable to me in that an infant can have such a difficult start to life yet hope may remain even after dealing with some of the trials and tribulations of the NICU.  Parents may need to wade through the troubling times of seizures, long term ventilation and CPAP and then onto a diagosis of BPD but their brains may be ok after all.  This is one of the reasons I love what I do!

 
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I would object to the interpretation that the CIs crossing 1 for several secondary outcomes suggests that these results are likely due to chance.  On the contrary, the available evidence suggests that it is more likely these are real associations (though potentially with small effect sizes particularly for non-motor outcomes).  First, all of the presumably mechanistically related outcomes have the same qualitative effect (ie CPR has the worse outcome) whereas if these were truly random, we might see some outcomes favor the CPR group.  Second, for the outcomes where the CI does cross 1, most of the 'mass' of the CI still favors the no-CPR group.  Third, the one contrary study you cited aside, the prevalence of pre-existing evidence favored the no-CPR before this study was even done (ie the prior was not non-informative).

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