Is skin to skin care truly good for the developing brain?

Is skin to skin care truly good for the developing brain?

Skin to skin care or kangaroo care is all the rage and I am the first one to offer my support for it.  Questions persist though as to whether from a physiological standpoint, babies are more stable in an isolette in a quiet environment or out in the open on their mother or father’s chests. Bornhorst et al expressed caution in their study Skin-to-skin (kangaroo) care, respiratory control, and thermoregulation.  In a surprising finding, babies with an average gestational age of 29 weeks were monitored for a number of physiological parameters and found to have more frequent apnea and higher heart rates than when in an isolette.  The study was small though and while there were statistical differences in these parameters they may not have had much clinical significance (1.5 to 2.8 per hour for apnea, bradycardia or desaturation events).  Furthermore, does an increase in such events translate into any changes in cerebral oxygenation that might in turn have implications for later development?  Tough to say based on a study of this magnitude but it certainly does raise some eyebrows.

What if we could look at cerebral oxygenation?

As you might have guessed, that is exactly what has been done by Lorenz L et al in their recent paper Cerebral oxygenation during skin-to-skin care in preterm infants not receiving respiratory support.The goal of this study was to look at 40 preterm infants without any respiratory distress and determine whether cerebral oxygenation (rStO2)was better in their isolette or in skin to skin care (SSC).  They allowed each infant to serve as their own control by have three 90 minute periods each including the first thirty minutes as a washout period.  Each infant started their monitoring in the isolette then went to SSC then back to the isolette.  The primary outcome the power calculation was based on was the difference in rStO2 between SSC and in the isolette.  Secondary measures looked at such outcomes as HR, O2 sat, active and quiet sleep percentages, bradycardic events as lastly periods of cerebral hypoxia or hyperoxia.  Normal cerebral oxygenation was defined as being between 55 to 85%.

Surprising results?

Perhaps its the start of a trend but again the results were a bit surprising showing a better rStO2 when in the isolette (−1.3 (−2.2 to −0.4)%, p<0.01).  Other results are summarized in the table below:

Mean difference in outcomes
Variable SSC Isolette Difference in mean p
rStO2 73.6 74.8 -1.3 <0.01
SpO2 (median) 97 97 -1.1 0.02
HR 161 156 5 <0.01
% time in quiet sleep 58.6 34.6 24 <0.01

No differences were seen in bradycardic events, apnea, cerebral hypoexmia or hyperoxemia.  The authors found that SSC periods in fact failed the “non-inferiority” testing indicating that from a rStO2 standpoint, babies were more stable when not doing SSC!  Taking a closer look though one could argue that even if this is true does it really matter?  What is the impact on a growing preterm infant if their cerebral oxygenation is 1.3 percentage points on average lower during SSC or if their HR is 5 beats per minute faster?  I can’t help but think that this is an example of statistical significance without clinical significance.  Nonetheless, if there isn’t a superiority of these parameters it does leave one asking “should we keep at it?”

Benefits of skin to skin care

Important outcomes such as reductions in mortality and improved breastfeeding rates cannot be ignored or the positive effects on family bonding that ensue. Some will argue though that the impacts on mortality certainly may be relevant in developing countries where resources are scarce but would we see the same benefits in developed nations.  The authors did find a difference though in this study that I think benefits developing preterm infants across the board no matter which country you are in.  That benefit is that of Quiet Sleep (QS).  As preterm infants develop they tend to spend more time in QS compared to active sleep  (AS).  From Doussard- Roossevelt J, “Quiet sleep consists of periods of quiescence with regular respiration and heart rate, and synchronous EEG patterns. Active sleep consists of periods of movement with irregular respiration and heart rate, and desynchronous EEG patterns.”  In the above table one sees that the percentage of time in QS was significantly increased compared to AS when in SSC.  This is important as neurodevelopment is thought to advance during periods of QS as preterm infants age.

There may be little difference favouring less oxygen extraction during isolette times but maybe that isn’t such a good thing?  Could it be that the small statistical difference in oxygen extraction is because the brain is more active in laying down tracks and making connections?  Totally speculative on my part but all that extra quiet sleep has got to be good for something.

To answer the question of this post in the title I think the answer is a resounding yes for the more stable infant.  What we don’t know at the moment except from anecdotal reports of babies doing better in SSC when really sick is whether on average critically ill babies will be better off in SSC.  I suspect the answer is that some will and some won’t.  While we like to keep things simple and have a one size fits all answer for most of our questions in the NICU, this one may not be so simple.  For now I think we keep promoting SSC for even our sick patients but need to be honest with ourselves and when a patient just isn’t ready for the handling admit it and try again when more stable.  For the more stable patient though I think giving more time for neurons to find other neurons and make new connections is a good thing to pursue!

If A Little Caffeine Is Good Is A Lot Better?

If A Little Caffeine Is Good Is A Lot Better?

Caffeine seems to be good for preterm infants.  We know that it reduces the frequency of apnea in the this population and moreover facilitates weaning off the ventilator in a shorter time frame than if one never received it at all.  The earlier you give it also seems to make a difference as shown in the Cochrane review on prophylactic caffeine. When given in such a fashion the chances of successful extubation increase. Less time on the ventilator not surprisingly leads to less chronic lung disease which is also a good thing.

I have written about caffeine more than once though so why is this post different?  The question now seems to be how much caffeine is enough to get the best outcomes for our infants.  Last month I wrote about the fact that as the half life of caffeine in the growing preterm infant shortens, our strategy in the NICU might be to change the dosing of caffeine as the patient ages.  Some time ago though I wrote about the use of higher doses of caffeine and in the study analyzed warned that there had been a finding of increased cerebellar hemorrhage in the group randomized to receive the higher dosing.  I don’t know about where you work but we are starting to see a trend towards using higher caffeine base dosing above 5 mg/kg/d.  Essentially, we are at times “titrating to effect” with dosing being as high as 8-10 mg/kg/d of caffeine base.

Does it work to improve meaningful outcomes?

This month Vliegenthart R et al published a systematic review of all RCTs that compared a high vs low dosing strategy for caffeine in infants under 32 weeks at birth; High versus standard dose caffeine for apnoea: a systematic review. All told there were 6 studies that met the criteria for inclusion.  Low dosing (all in caffeine base) was considered to be 5- 15 mg/kg with a maintenance dose of 2.5 mg/kg to 5 mg/kg.  High dosing was a load of 5 mg/kg to 40 mg/kg with a maintenance of 2.5 mg/kg to 15 mg/kg.  The variability in the dosing (some of which I would not consider high at all) makes the quality of the included studies questionable so a word of warning that the results may not truly be “high” vs “low” but rather “inconsistently high” vs. “inconsistently low”.

The results though may show some interesting findings that I think provide some reassurance that higher dosing can allow us to sleep at night.

On the positive front, while there was no benefit to BPD and mortality at 36 weeks PMA they did find if they looked only at those babies who were treated with caffeine greater than 14 days there was a statistically significant difference in both reduction of BPD and decreased risk of BPD and mortality.  This makes quite a bit of sense if you think about it for a moment.  If we know that caffeine improves the chances of successful extubation and we also know it reduces apnea, then who might be on caffeine for less than 2 weeks?  The most stable of babies I would expect!  These babies were all < 32 weeks at birth.  What the review suggests is that those babies who needed caffeine for longer durations benefit the most from the higher dose.  I think I can buy that.

On the adverse event side, I suppose it shouldn’t surprise many that the risk of tachycardia was statistically increased with an RR of 3.4.  Anyone who has explored higher dosing would certainly buy that as a side effect that we probably didn’t need an RCT to prove to us.  Never mind that, have you ever taken your own pulse after a couple strong coffees in the morning?

What did it not show?

It’s what the study didn’t show that is almost equally interesting.  The cerebellar hemorrhages seen in the study I previously wrote about were not seen at all in the other studies.  There could be a lesson in there about taking too much stock in secondary outcomes in small studies…

Also of note, looking at longer term outcome measures there appears to be no evidence of harm when the patients are all pooled together.  The total number of patients in all of these studies was 620 which for a neonatal systematic review is not bad.  A larger RCT may be needed to conclusively tell us what to do with a high and low dosing strategy that we can all agree on.  What do we do though in the here and now?  More specifically, if you are on call tomorrow and a baby is on 5 mg/kg/d of caffeine already, will you intubate them if they are having copious apneic events or give them a higher dose of caffeine when CPAP or NIPPV that they are already on isn’t cutting it?  That is where the truth about how you feel about the evidence really comes out.  These decisions are never easy but unfortunately you sometimes have to make a decision and the perfect study hasn’t been done yet.  I am not sure where you sit on this but I think this study while certainly flawed gives me some comfort that nothing is truly standing out especially given the fact that some of the “high dose” studies were truly high.  Will see what happens with my next patient!