Part 2: Does prophylactic dextrose gel really work?

Part 2: Does prophylactic dextrose gel really work?

In the first part of this series of posts called Can prophylactic dextrose gel prevent babies from becoming hypoglycemic? the results appeared to be a little lackluster.  The study that this blog post was based on was not perfect and the lack of a randomized design left the study open to criticism and an unbalancing of risks for hypoglycemia.  Given these faults it is no doubt that you likely didn’t run anywhere to suggest we should start using this right away as a protocol in your unit.

Another Study Though May Raise Some Eyebrows

New Zealand researchers who have been at the forefront of publications on the use of dextrose gel recently published another article on the topic Prophylactic Oral Dextrose Gel for Newborn Babies at Risk of Neonatal Hypoglycaemia: A Randomised Controlled Dose-Finding Trial (the Pre-hPOD Study).  As the short study name suggests “Pre-hPOD” this was a preliminary study to determine which dosing of dextrose gel would provide the greatest benefit to prevent neonatal hypoglycemia.  The study is a little complex in design in that there were eight groups (4 dextrose gel vs 4 placebo) with the following breakdown.

Dosing was given either once at 1 h of age (0.5 ml/kg or 1 ml/kg) or three more times (0.5 ml/kg) before feeds in the first 12 h, but not more frequently than every 3 h. Each dose of gel was followed by a breastfeed. The groups given prophylaxis fell into the following risk categories;

IDM (any type of diabetes), late preterm (35 or 36 wk gestation), SGA (BW < 10th centile or < 2.5 kg), LBW (birthweight > 90th centile or > 4.5 kg), maternal use of β-blockers.

Blood glucose was measured at 2 h of age and then AC feeds every 2 to 4 h for at least the first 12 h.  This was continued until an infant had 3 consecutive blood glucose concentrations of 2.6 mmmol/L.  With a primary outcome of hypoglycemia in the first 48 hours their power calculation dictated that a total sample size of 415 babies (66 in each treatment arm, 33 in each placebo arm) was needed which thankfully they achieved which means we can believe the results if they found no difference!

What did they find?

One might think that multiple doses and/or higher doses of glucose gel would be better than one dose but curiously they found that the tried and true single dose of 0.5 mL/kg X 1 offered the best result.  “Babies randomised to any dose of dextrose gel were less likely to develop hypoglycaemia than those randomised to placebo (RR 0.79, 95% CI 0.64–0.98, p = 0.03; number needed to 10.”

Looking at the different cumulative doses, the only dosing with a 95% confidence interval that does not cross 1 was the single dosing.  Higher and longer dosing showed no statistical difference in the likelihood of becoming hypoglycemic in the first 48 hours.  As was found in the sugar babies study, admission to NICU was no different between groups and in this study as with the sugar baby study if one looked at hypoglycemia as a cause for admission there was a slight benefit.  Curiously, while the previous study suggested a benefit to the rate of breastfeeding after discharge this was not noted here.

How might we interpret these results?

The randomized nature of this study compared to the one reviewed in part I leads me to trust these findings a little more than the previous paper.  What this confirms in my mind is that giving glucose gel prophylaxis to at risk infants likely prevents hypoglycemia in some at risk infants and given that there were no significant adverse events (other than messiness of administration), this may be a strategy that some units wish to try out.  When a low blood glucose did occur it was later in the group randomized to glucose gel at a little over 3 hours instead of 2 hours.  The fact that higher or multiple dosing of glucose gel given prophylactically didn’t work leads me to speculate this may be due to a surge of insulin.  Giving multiple doses or higher doses may trigger a normal response of insulin in a baby not at risk of hypoglycemia but in others who might already have a high baseline production of insulin such as in IDMs this surge might lead to hypoglycemia.  This also reinforces the thought that multiple doses of glucose gel in babies with hypoglycemia should be avoided as one may just drive insulin production and the treatment may become counterproductive.

In the end, I think these two papers provide some food for thought.  Does it make sense to provide glucose gel before a problem occurs?  We already try and feed at risk babies before 2 hours so would the glucose gel provide an added kick or just delay the finding of hypoglycemia to a later point. One dose may do the trick though.

A reader of my Facebook page sent me a picture of the hPOD trial which is underway which I hope will definitively put this question to rest.  For more on the trial you can watch Dr. Harding speak about the trial here.

Can prophylactic dextrose gel prevent babies from becoming hypoglycemic?

Can prophylactic dextrose gel prevent babies from becoming hypoglycemic?

I have written a number of times already on the topic of dextrose gels. Previous posts have largely focused on the positive impacts of reduction in NICU admissions, better breastfeeding rates and comparable outcomes for development into childhood when these gels are used. The papers thus far have looked at the effectiveness of gel in patients who have become hypoglycemic and are in need of treatment. The question then remains as to whether it would be possible to provide dextrose gel to infants who are deemed to be at risk of hypoglycemia to see if we could reduce the number of patients who ultimately do become so and require admission.

Answering that question

Recently, Coors et al published Prophylactic Dextrose Gel Does Not Prevent Neonatal Hypoglycemia: A Quasi-Experimental Pilot Study. What they mean by Quasi-Experimental is that due to availability of researchers at off hours to obtain consent they were unable to produce a randomized controlled trial. What they were able to do was compare a group that had the following risk factors (late preterm, birth weight <2500 or >4000 g, and infants of mothers with diabetes) that they obtained consent for giving dextrose gel following a feed to a control group that had the same risk factors but no consent for participation. The protocol was that each infant would be offered a breastfeed or formula feed after birth followed by 40% dextrose gel (instaglucose) and then get a POC glucose measurement 30 minutes later. A protocol was then used based on different glucose results to determine whether the next step would be a repeat attempt with feeding and gel or if an IV was needed to resolve the issue.

To be sure, there was big hope in this study as imagine if you could prevent a patient from becoming hypoglycemic and requiring IV dextrose followed by admission to a unit.  Sadly though what they found was absolutely no impact of such a strategy.  Compared with the control group there was no difference in capillary glucose after provision of dextrose gel (52.1 ± 17.1 vs 50.5 ± 15.3 mg/dL, P = .69).  One might speculate that this is because there are differing driving forces for hypoglycemia and indeed that was the case here where there were more IDMs and earlier GA in the prophylactic group.  On the other hand there were more LGA infants in the control group which might put them at higher risk.  When these factors were analyzed though to determine whether they played a role in the lack of results they were found not to. Moreover, looking at rates of admission to the NICU for hypoglycemia there were also no benefits shown.  Some benefits were seen in breastfeeding duration and a reduction in formula volumes consistent with previous studies examining the effect of glucose gel on both which is a win I suppose.

It may also be that when you take a large group of babies with risks for hypoglycemia but many were never going to become hypoglycemic, those who would have had a normal sugar anyway dilute out any effect.  These infants have a retained ability to produce insulin in response to a rising blood glucose and to limit the upward movement of their glucose levels.  As such what if the following example is at work? Let’s say there are 200 babies who have risk factors for hypoglycemia and half get glucose gel.  Of the 100 about 20% will actually go on to have a low blood sugar after birth.  What if there is a 50% reduction in this group of low blood sugars so that only 10 develop low blood glucose instead of 20.  When you look at the results you would find in the prophylaxis group 10/100 babies have a low blood sugar vs 20/100.  This might not be enough of a sample size to demonstrate a difference as the babies who were destined not to have hypoglycemia dilute out the effect.  A crude example for sure but when the incidence of the problem is low, such effects may be lost.

A Tale of Two Papers

This post is actually part of a series with this being part 1.  Part 2 will look at a study that came up with a different conclusion.  How can two papers asking the same question come up with different answers?  That is the story of medicine but in the next part we will look at a paper that suggests this strategy does work and look at possible reasons why.

Using Social Media To Create A Global Village

Using Social Media To Create A Global Village

As I prepare for a talk at the Canadian Association of Neonatal Nurses conference in Calgary tomorrow I am finding my excitement growing.  The theme of the conference this year is “Neonatal Care: It Takes a Village” and I am lucky enough to be speaking twice to this audience.  Screen Shot 2018-04-19 at 10.24.54 PM.pngThe first talk is all about the utilization of social media to help create this village and the second about a journey our centre took as we made some changes to our management of hypoglycemia.

With respect to the first talk, I am becoming increasingly convinced that the role of social media in medicine is to help create awareness.  There are so many publications that come out every week, month and year.  The numbers are in the hundreds of thousands if not millions with so many journals both legitimate and predatory, publishing at this time.  If you aren’t sure what predatory journals are you can read about them here.

The reality is that there is so much to digest out there and as the saying goes, not enough time!  That’s where social media comes in.  Being in a leadership role has its challenges. No matter how strongly you believe in something, if you don’t have the support of nursing (yes I know this may sound like pandering but it’s true) it is not going to fly in the hospital.  Traditional methods for introducing change have been to review an article (typically doctors) and discuss the worthiness of the analysis at a teaching rounds.  While nursing is often invited to such rounds, attendance is tough to get to any great deal.  The docs though may think its a great idea and then the “memo” comes out.  There are many who will follow what the directive says but how much do they truly understand of the change and as a result is their heart really in it?

A New Way To Spread The Word

Let’s face it, we are on our phones a lot!  It’s really how we digest so much of the news out there these days.  Who has the time to read a newspaper when the first paragraph of an article on our phone tells us 90% of what we really need to know?  When nurses take their break in the lounge is that the latest New England Journal of Medicine article on their phone that they are reading?  Maybe some but many (and I include docs, dieticians, respiratory therapists and others) are checking social media sites whether they be twitter, Facebook or even this blog.  Want to get a message out?  Put it into a digestible form where the analysis has been done and the arguments for change presented in a 500 – 1000 word form.  This isn’t to say that the original articles in their entirety aren’t worth reading but if you want to disseminate the rationale for a change their is power in this medium to get the word out.  Want a change to succeed, then first help people to understand the reason behind it and the transformation of practice will follow.

Going Global!

As I have said in several talks on the use of social media, if you present in a classroom you may educate 20 people, grand rounds 150 but in the world of social media its in the 1000s!  Posting on Social Media gets the word out and far!

April 11th I re-released Automatic adjustments of FiO2. Ready for prime time? after seeing the technology that formed the basis of this post demonstrated for me firsthand. The map below demonstrates what I am speaking about when I say going global!  Screen Shot 2018-04-19 at 10.10.29 PM This post was read on every continent with the exception of Antarctica for a total of 1882 times that day!  Whether it is a good strategy for all places or not is not the point.  The point is that people are reading and talking about things that they may not have heard or thought of before.  My goal in all of this is education and generating discussions.  We need to learn and learning should be done together.  Whether it is through comments on Facebook or directly on the Blog, we all benefit when we read, talk, debate and find a common ground with the most important patient and family being in the centre of it all.

As I prepare to present these concepts tomorrow I sincerely hope that we continue to see discussion coming from these posts and provide forums for our medical teams across the country to think about topics they might not have covered yet.  Thank you to all who have read or will start reading these posts as I have as much to learn from you as you from me.  Glad to be a part of such a wonderful conference and look forward to meeting som many of you tomorrow!


Should all babies be screened for hypoglycemia?

Should all babies be screened for hypoglycemia?

Hypoglycemia has to be one of the most common conditions that we screen for or treat in the NICU and moreover in newborn care in general. The Canadian Pediatric Society identifies small for gestational age infants (weight <10th percentile), large for gestational age (LGA; weight > 90th percentile) infants, infants of diabetic mothers (IDMs) and preterm infants as being high risk for hypoglycemia. It is advised then to screen such babies in the absence of symptoms for hypoglycemia 2 hours after birth after a feed has been provided (whether by breast or bottle). I am sure though if you ask just about any practitioner out there, they will tell you a story about a baby with “no risk factors” who had hypoglycemia. These one-off cases have the effect though of making us want to test everyone for fear that we will miss one. If that is the case though should we be recommending that all babies get at least one check?

The Canadian Pediatric Surveillance Program (CPSP)

The CPSP is a branch of the Canadian Pediatric Society that “provides an innovative means to undertake active paediatric surveillance and increase awareness of childhood disorders that are high in disability, morbidity, mortality and economic cost to society, despite their low frequency. I submit my surveys each month as i hope other Canadian Pediatricians do and help to determine the impact of these rare conditions in our Canadian population.  Like with any survey we rely on people taking the time to submit but there is always the risk that what is being sent in under represents the true burden of illness as some cases may not be identified.  Having said that, it is the best we have!

Turning our attention to hypoglycemia in low risk newborns

From April 2014 to March 2016 the CPSP searched for these types of patients and just published the results of their findings in Hypoglycemia in unmonitored full-term newborns—a
surveillance study by Flavin MP et al.  What I like about the study is that they have been able to look at a group of babies that fall outside those identified as being at risk in the CPS statement Screening guidelines for newborns at risk for low blood glucose.  They were looking for severe hypoglycemia by using a threshold of < 2.0 mmol/L (36 mg/dl) and all infants must have received IV dextrose.  In the end after excluding ineligible cases they had 93 babies who met criteria.  Based on the Canadian birth rate this translates to an incidence of 1 in every 8378 births. These babies were all supposed to be low risk but there were in fact clues that while not strictly identified as risks in the CPS statement could have increased the likelihood of a low blood glucose.  Twenty three percent of mothers had maternal hypertension and another 23% were obese while 47% had excessive weight gain during pregnancy.  Furthermore, 8% of mothers were treated with a beta blocker (most likely labetalol I would think) during pregnancy which is a risk factor for hypoglycemia although not specifically cited in the current CPS statement.

A concerning finding as well was the likelihood of severe symptoms in this group on presentation. Twenty percent presented with major clinical signs (seizure, apnea or cyanosis). Median glucose levels at presentation were much lower than those without major signs (median = 0.8 mmol/L, interquartile range [IQR] = 0.5 versus 1.6 mmol/L, IQR = 0.7; P < 0.001).  Lastly, providers were asked about neurodevelopmental concerns at discharge approximately 20% were thought to have issues.

Are these patients really low risk though?

Twenty five percent of the patients submitted had a birth weight less than the 10%ile for GA.  These patients as per the CPS guideline recommendations are actually considered at risk and should have been screened.  The second issue to address has to do with the way we diagnose diabetes in pregnancy.  All women are provided with the oral glucose tolerance test around 28 weeks of pregnancy. No test is perfect but it is the best we have.  Women who have excessive weight gain in pregnancy (almost 50% of the cohort) are at higher risk of developing diabetes or some degree of insulin resistance as are those who are classified as obese.  I have long suspected and think it may be the case here that some babies who do not meet the criteria for screening as their mothers do not have a diagnosis of GDM actually are at risk due to some degree of insulin resistance or perhaps their mothers develop GDM later.  The evidence for this are the occasional LGA babies who are born to mothers without a GDM diagnosis but who clearly have been exposed to high insulin levels as they behave like such affected infants with poor feeding and low sugars in the newborn period.  The authors here comment on those that were SGA but how many in this cohort were LGA?

The effect of hypertension can also not be minimized which was present in about a quarter of patients.  These babies while not being officially SGA may have experienced a deceleration in weight gain in the last few weeks but remained above the 10%ile.  These infants would not have the glycogen stores to transition successfully but would not be targeted as being at risk by the current definitions.

Should we be screening everyone then?

If we acknowledge that about 25% were IUGR in this study (<10%ile) and should have been screened, the expected rate would be 1:1170 births alone.  In Manitoba with our 17000 births a year we would capture about two extra babies a year which translates into a low of pokes for a lot of healthy babies.  Given the further information that 1:5 babies who are identified may have neurodevelopmental concerns it would take about 2-3 years of testing to prevent one concern.  That pick up rate for me is far too low to subject so many babies to testing.  What this study though does highlight is the need to view risk factors a little less strictly.  Babies who are almost meeting the criteria for being LGA or those whose mother’s have taken lebetalol should have a low threshold for screening.  Should hypertension on medications, excessive maternal weight gain or obesity in the mother be considered a risk?  What I didn’t see in the end of this study were patients who truly were AGA, being born to healthy non overweight mothers presenting as high risk.

Maybe what is really needed based on this study is to re-evaluate what we consider at risk.  In the meantime, maybe we should be testing a few extra babies who fall into these “lesser” risk categories.  Better yet a study isolating such patients and looking at the frequency of hypoglycemia in these patients is warranted to get a better idea of whether they are indeed risks.

Screening for congenital heart disease; will early discharge be its ruin?

Screening for congenital heart disease; will early discharge be its ruin?

In 2017 the Canadian Pediatric Society published the practice point Pulse oximetry screening in newborns to enhance detection of critical congenital heart disease.  In this document we recommended universal screening for CCHDs but stressed the following:

“Recognizing that delivery and time of discharge practices vary across Canada, the timing of testing should be individualized for each centre and (ideally) occur after 24 hours postbirth to lower FP results. And because the intent is to screen newborns before they develop symptoms, the goal should be to perform screening before they reach 36 hours of age.”

This recommendation was put in place to minimize the number of false positive results and prevent Pediatricians and Cardiologists nationwide from being inundated with requests to rule out CCHD as earlier testing may pick up other causes for low oxygen saturation such as TTN.  The issue remains though that many patients are indeed discharged before 24 hours and in the case of midwife deliveries either in centres or in the home what do we do?

A Population Study From the Netherlands May Be of Help Here

Researchers in the Netherlands had a golden opportunity to answer this question as a significant proportion of births occur there in the home under the care of a midwife. Accuracy of Pulse Oximetry Screening for Critical Congenital Heart Defects after Home Birth and Early Postnatal Discharge by Ilona C. Narayen et al was published this month in J Peds. About 30% of births are cared for by a midwife with about 20% occurring in the home. The authors chose to study this population of infants who were all above 35 weeks gestation and not admitted to an intensive care nor had suspicion of CCHD prior to delivery. The timing of the screening was altered from the typical 24-48 hours to be two time points to be more reflective of midwives practice. All patients were recruited after birth with the use of information pamphlets. The prospective protocol was screening on 2 separate moments: on day 1, at least 1 hour after birth, and on day 2 or 3 of life. The criteria for passing or failing the test are the same as those outlined in the CPS practice point. As part of the study, patients with known CCHDs were also screened separately as a different group to determine the accuracy of the screening test in patients with known CCHD.


There were nearly 24000 patients born during this period. Only 49 cases of CCHD were identified by screening and of these 36 had been picked up antenatally giving a detection rate of 73%. Out of 10 patients without prenatal diagnosis who also had saturation results available the detection rate was 50%. Three of the misses were coarctation of the aorta (most likely diagnosis to be missed in other studies), pulmonary stenosis (this one surprises me) and TGA (really surprises me). The false-positive rate of pulse oximetry screening (no CCHD) was 0.92%. The specificity was over 99% meaning that if you didn’t have CCHD you were very likely to have a negative test. Not surprisingly, most false- positives occurred on day 1 (190 on day 1 vs 31 infants on day 2 or 3). There were five patients missed who were not detected either by antenatal ultrasound. These 5 negatives ultimately presented with symptoms at later time points and all but one survived (TGA) so out of 24000 births the system for detecting CCHD did reasonably well in enhancing detection as they picked up another 5 babies that had been missed antenatally narrowing the undetected from 10 down to 5.

Perhaps the most interesting thing about the study though is what they also found. As the authors state: “Importantly, 61% (134/221) of the infants with false-positive screenings proved to have significant noncardiac illnesses re- quiring intervention and medical follow-up, including infection/ sepsis (n = 31) and PPHN or transient tachypnea of the newborn (n = 88)”

There are certainly detractors of this screening approach but remember these infants were all thought to be asymptomatic. By implementing the screening program there was opportunity to potentially address infants care needs before they went on to develop more significant illness. Under appreciated TTN could lead to hypoxia and worsen and PPHN could become significantly worse as well. I think it is time to think of screening in this way as being more general and not just about finding CCHD. It is a means to identify children with CCHD OR RESPIRATORY illnesses earlier in their course and do something about it!