I work in an NICU that is no different in at least one way than yours. We have been seeing a growing volume of Neonatal Abstinence Syndrome (NAS) in our units for the last number of years. In fact I recall one week on service last year where 10/24 patients in our unit or roughly 42% were suffering from this condition. When I use the word suffering I should also mention that the staff experience this too. These infants are resource intensive in that they cannot be left alone for too long and as part of their management demand or require frequent feeding to keep their scores down.
Coincident with a talk I will go to at the PAS this afternoon on NAS, the NEJM released an article today showing the trends in the US over the period 2004 – 2013.
As the saying goes misery loves company and the following graph tells the story of NAS in North America very well. There has been a dramatic rise in admissions with a progressive increase in length of stay.
The use of opioid analgesic use in pregnancy has risen to an extremely high level and in large part is contributory in the US to such high rates of admission. The answer may also lie in a change to the approach of treatment that occurred in the middle of this epoch and is shown in the next figure indicating what type of medication was utilized for treatment. In 2010 the Cochrane Database for Systematic Reviews published a comparison of the evidence supporting either opiates or phenobarbital for the primary treatment of NAS.
The conclusions of this paper changed the practice in our own and from the data presented here other centres as around 2009 – 2010, the use of phenobarbital decreased while morphine rose consistent with the recommendations from this group. Morphine was selected as it appeared to reduce the incidence of seizures although I have to mention I have never seen a case myself, so I remain curious as to how common they really are. In the review they also commented however that the use of opiates for treatment was associated with a prolongation of hospital stay. The reasons for this are in part explained by practitioner reluctance to discharge an infant home on an opiate. Doing so on low dose phenobarbital would have a much greater comfort level due to the common use for seizure control over the years in a home setting. This may be reflected in the findings as well in this paper that the practice of discharging on medications for NAS control decreased during the period studied from 4% down to 1-2%. Given the large number of babies being seen, this would represent a lot more infants in hospital and therefore a longer stay.
It is also tempting to blame the drugs that the mothers were exposed to but it would appear that there really is no basis for this based on this graph from the supplementary appendix The percentage of infants exposed to methadone remained the same, so higher use can not be blamed (which has been associated with higher rates of NAS).
Compounding the problem of NAS is that there are competing demands in many areas of the country where higher birth rates demand more NICU beds which are quite often occupied with NAS babies. There is clearly work that is needed in the field to turn the tide and reduce NAS admissions and certainly length of stay. As for how to do this there are a few ideas.
1. Might Burprenophine rather than methadone be a better option for maternal treatment? There may be something there
2. Treat the approach to NAS the same as that for headaches. Get on top of it quickly! Although not published, our own centre’s experience was that when we switched to predominantly using morphine we found that many of the infants required not only morphine but phenobarbital and often clonidine to control their symptoms and had the mean length of stay increase dramatically to 3-4 weeks per patient. What we discovered thanks to a very dedicated nurse with a passion for NAS management was that we were not doing what we said we would. Specifically, once the infant qualified for treatment we were not giving loads of 0.1 mg/kg of morphine q2h until controlled but rather in many instances waiting a little longer and then using 0.05 mg/kg as loads. Since reinforcing that we need to get on top of the issue right away (like with a headache before it becomes entrenched) the use of morphine monotherapy has increased dramatically.
3. Never admit these children in the first place. We have an agreement with the postpartum ward that the initial monitoring for NAS can occur in the room with the parents. The lack of separation encourages breastfeeding which in and of itself has led to some infants being successfully managed without ever coming to the NICU. We still see infants coming but those that do have had 2 -5 days less time in the NICU decreasing the usage of NICU beds for this purpose with the added benefit of increasing maternal/infant bonding. Better yet there are models out there of mother-infant homes that these dyads can be discharged from hospital to. Having them out of the hospital environment may be the best thing for them altogether and avoid treatment with medications at all.
4. Consider discharging infants on morphine or other opiate. There is no question that during the acute phase these children need to be in hospital as there are significant side effects from morphine not the least of which is respiratory depression. Once a patient in weaning from the morphine and has successfully decreased the dosing or interval by 30 – 50% it is exceedingly unlikely that on the lower daily dosage they will start having symptoms. In the presence of a reliable family with good supports that has been screened by a social worker such treatment can be completed outside the hospital. Some may be worried about what could happen if the medication is taken by an older child or parent but as you know the amount of drug that would be sent home when dosed at 0.05 mg/kg or less for a few doses would not impact such larger individuals.
I am grateful to NEJM for publishing this article as it shows we are not alone. Your suspicions that NAS is on the rise are accurate. NAS is here and it’s not going anywhere. The question is what are you going to do about it?!
I was inspired to write this post after sharing a review of an article from 2013 on my Facebook page. The article pertained to the use of a 40% dextrose gel to treat neonatal hypoglycemia
We have been using this glucose gel in our population for nearly two years and have noted great success in avoiding admissions for hypoglycemia, however this remains unpublished. I was surprised to hear how many places have yet to adopt such treatment and based on the comments on the page it would appear that adoption of such gels are on their way in some locations. The popularity of this post though inspired me to write this piece, which summarizes the evidence for the use of gels in the neonate.
What is the Evidence For Using Glucose Gels
Surprisingly there is actually very little in the way of publications on the topic. In 1992, there was a small randomized trial which failed to show a benefit in terms of variability of one serum glucose to the next but it did not look at other functional outcomes such as impact on maternal infant separation or success in breast-feeding.
The next study is in fact the one mentioned in the article that was posted on Facebook called the Sugar Babies study. Dr. Harris in this case studied 118 infants who received 40% dextrose gel vs 119 who received a placebo gel. All of the infants in this study were selected based on risk factors for hypoglycemia (IDM, IUGR, LBW, LGA, near term) and were all 35 weeks or greater. Each infant had to be less than 48 hours of age when enrolled. Infants received 0.5 mL/kg 40% dextrose gel (200 mg/kg). This was designed to deliver the same amount of sugar as would be given with a D10W bolus of 2 mL/kg. In order to receive the treatment the blood glucose had to be < 2.6 mmol/L so equivalent to our own standards in Canada and the US. Treatment failure, which was the primary outcome was defined as a blood glucose < 2.6 mmol/L despite two treatments with gel. The significant findings were quite interesting and are shown in the table below.
|Admission to NICU
|# formula feeds (median)
|Formula fed at 2 weeks
What was not found to be significant and in and of itself is a very important finding is a higher incidence of rebound hypoglycemia in the dextrose gel group. This was a potential concern as provision of dextrose in theory could cause a spike in insulin secretion thereby dramatically lowering the blood glucose but thankfully this was not observed.
Dextrose Gel Improves Breastfeeding Rates
These results I believe speak for themselves but it is extremely important to highlight the benefit here. The use of the dextrose gel was also able to enhance success at breastfeeding rates. This was accomplished in all likelihood by a reduction in admission to NICU and less reliance on formula to achieve satisfactory blood glucose. As these infants were all less than 48 hours old it is safe to assume that in many cases the mother’s milk had not yet come in so if the glucose measured was low, health care providers were more likely to intervene with an offering of formula. It is worth noting that while this is the only significant study in the field there is a letter to the editor in which another author describes the use of a sublingual sugar powder for treating the same, which was met with similar success. There is no actual peer-reviewed study to examine however so we will leave it as simply an interesting point.
New Study on The Way
If these results leave you still being skeptical you may be pleased to hear there is a very large study (2129 babies needed) beginning enrolment in New Zealand with the primary outcome of admission to the NICU. This prospective RCT will hopefully put to rest any questions about this treatment that have delayed implementation in many units.
As a final thought regarding the Sugar Babies study, one of the differences that came close to reaching statistical significance was the rate of IV insertions for dextrose. In the dextrose gel group the rate was 7% vs 14% in the placebo. With a p value of 0.09 it suggests that with a larger study size a difference may have been reached. The idea that we have the option of using a therapy that can decrease formula use, improve breastfeeding rates including those found post discharge and lastly decrease the poking of infants for IV dextrose is a goal well worth pursuing. Is this enough evidence for you? I would encourage all who read this piece to ask their NICU the question of whether a trial of dextrose gel is worthwhile. It could make a big difference far beyond treating a number.
If you are from North America and watched Tom Cruise in his heyday then you have seen Jerry Maguire and recognized instantly the second part of the title of this post. If you haven’t seen the film it is worth watching. Even if you have you can see a short clip from the film that inspired the title of this post here and it is really worth watching!
Why such a title for a post? I am always intrigued when I see a spike in viewership from a particular country which today happened to be France and yesterday Argentina. For previous posts it has been such countries as Oman, Great Britain and yesterday Brazil. This leads me to wonder what is it about some posts that light a fire and others that only generate a little smoke? There is a world of Neonatology to talk about and as the writer of this blog I do my best to find topics that I believe will be of broad interest to many.
As I have seen such spikes come and go I have come to the realization that perhaps there are topics that are of immense interest to the people of one country and others that quite simply fall flat. Are they not pertinent as the technology being discussed for example is simply not available there or simply an uninteresting topic.
My goal has been and will continue to be to try and stimulate discussion or at least provoke some thought on a global basis and thereby create a global community for cross pollination of ideas. With that being said, my question to the readers of this blog is what would you like to hear about? I ask not because I am running out of ideas; on the contrary with each week of news stories and articles pertaining to Neonatology it seems like the topics are endless. Rather my question stems from the realization that as I sit in my North American city my scope of what is important or relevant to Neonatal practice is somewhat limited.
I welcome your comments and thoughts for future posts! Although my goal was to provide some education to people who took the time out of their day to read these posts I now realize that I can ask the same of my readership. Please educate me as to what is important or relevant to you! I can not promise to write about every topic I receive but I will certainly try and pick ones over time that I feel I can write about.
Look forward to hearing from you!
I am not trying to scare my readership off with this title but this is a real question that is gaining traction in the scientific community and beyond. In fact as the picture for this article demonstrates, mainstream media has grabbed hold of the topic as well.
The concept here involves “Epigenetics”. This is a blossoming field and in basic terms means that our DNA carries certain coding to produce an effect but only if there is an external stimulation that kick-start the process. Alberta Health Services has published a wonderful video explaining in lay terminology the concept which can be found here http://www.albertafamilywellness.org/resources/video/science-seconds-epigenetics
Take for example maternal smoking in pregnancy. I could ask anyone on the street including smokers whether smoking is a good thing for a pregnant woman to do and in every case other than satisfying their nicotine addiction the answer would be no. Smoking in fact has been linked to neonatal outcomes including reduced newborn weight, altered neurodevelopment amongst other things. What is now known though is that something is happening at the DNA level in those kids who are born to these mothers. In the case of smoking the DNA experiences increased methylation and the expression of microRNA becomes dysregulated. As a medical student I simply thought that the effect was all related to poor placental blood flow from the nicotine and other toxins in the smoke but what is happening clearly in addition to such effects are actual changes at a microscopic level. For a complete discussion of the effect of smoking click on the following link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581096/
Another example of this phenomenon is in allergic disease. It is well-known that a major risk factor for asthma, eczema, food allergy and allergic rhinitis is a family history of one of these such conditions. Curiously though if you have a grandparent or parent that lived on a farm that association is weakened. Think about that for a moment. You didn’t live on the farm, your mother or your grandmother did. Something about the farm affected their DNA and because of it even though your father had bad eczema as a child you don’t. For a thorough review of this topic click here.
What about the title of this article? Are mother’s really to blame for the widespread epidemic of childhood obesity? There is no doubt that dietary choices by the children themselves and access to sugary drinks and soft drinks must take some of the responsibility but a paper from the Mayo clinic has ignited a bonfire of controversy on the internet by claiming that maternal obesity leads to in utero programming that condemns your children to obesity in adolescence. The controversial paper can be found here: http://www.ncbi.nlm.nih.gov/pubmed/?term=25440888 and a discussion in the Globe and Mail here http://www.theglobeandmail.com/life/health-and-fitness/health/studying-obesity-through-maternal-health-before-and-during-pregnancy/article21834086/
In essence one of the most common expressions of my childhood was wrong. It really isn’t “you are what you eat” but rather ” You are what your mother or your grandmother ate”! Beyond that, it is turning on its head the concept that many people have before they start a family. How many times when you were a young person did you smoke, consume excessive alcohol, eat too much fatty food, experiment with illicit drugs or travel to destinations with poor sanitation and perhaps even acquire a tropical infection. In each of these instances you thought, it’s my life and no one is at risk except for myself. It turns out we may have been very wrong! These decisions might not have caused you any serious harm but they may have implications for your children or grandchildren or great-grandchildren who happen to acquired a gene that is sensitive to these past exposures!
I am not an expert in the field by any stretch of the imagination but I wanted to publish this more as a resource for people to become aware of this exploding field of science. It is turning traditional genetics on its head and unravelling such things as why two people with the same genetic mutation have such different manifestations of a condition.
If you are interested further in this topic I would refer you to some incredible videos that explain this extremely well by the BBC program Horizon. You can find this program on YouTube at the following URL and there you will find the rest of the videos in this 5 part series. Get ready to have your world turned upside down!