The 1960s saw the emergence of newborn screening for phenylketonuria.  This was an important milestone in the field of newborn care as it allowed us to screen children for something that we could do something about. Dietary manipulation could for the first time prevent the repercussions of this condition and allow these children to avoid the severe neurological impairment that would follow the natural course of the condition.  Since that time, our ability to screen for and offer treatment to modify other disease courses has expanded many fold which no doubt in terms of population health is a wonderful thing.

Here in Manitoba we are now screening for over 40 conditions with a useful site for information being provided by Manitoba Health.

The expansion of these programs has been possible due to the use of Tandem Mass Spectrometry. This technique provides the ability to screen for many conditions without increasing the amount of blood required.

The downside to more screening is that as the number of tests being sampled increases the risk of false positive results due to the presence of dietary additives.  An example of this is carnitine supplementation.  In our centre we were providing this to low birth weight infants based on demonstrated low levels of carnitine facilitated lipid metabolism.  After failing to find a clinical benefit after the metabolic derangements were noted we identified a larger issue in that many of our premature infants receiving carnitine supplementation had elevated acylcarnitine profiles on their Newborn Metabolic Screening (NMS) samples.  These false positive results led to repeated sampling via bloodspot analysis leading to unnecessary blood sampling and pain from heel lances.

Another set of conditions that we are now able to screen for are the aminoacidopathies.  This group of disorders involve abnormalities of amino acid metabolism leading to toxic elevations of one or more amino acids that can have significant neurodevelopmental impairment as a consequence.  Clearly in all of these tests the purpose is to avoid long-term deleterious consequences but as with carnitine, false positive results are very concerning as they lead to repeated sampling, and potentially larger blood draws if confirmation of the screening results are needed.  Add to this, that this further analysis requires consultation with metabolics consultants, nursing time for repeated sampling, and laboratory costs and you can see why minimizing false positives is needed.  Lastly the greatest impact is on the family who in many cases experience unneeded anxiety as they await confirmatory testing which may take a week or more to come back if the sample needs to be sent offsite.

A few years back I attended the PAS meeting in Boston and heard about a study on this subject from California that they were presenting in abstract form.   Withholding TPN and using D10W for a three hour period prior to collection of the NMS could reduce false positive aminoacidopathy screens by about 70%.  The reaction of our local laboratory was one of disbelief as the consensus was that such a short time frame could not clear the TPN sufficiently from the circulation.  Since the reference ranges for normal amino acid profiles in infants are from patients who are not receiving TPN this could create false positive elevations, which would require either repeat blood spot sampling or as above, trigger a formal consult to metabolics if the subsequent test is also positive.

In following up on the original abstract presentation I noted that the findings were in fact published as Reduction in Newborn Screening Metabolic False- Positive Results Following a New Collection Protocol.

In this 2 year retrospective cohort study, in 2010 NMS was done for all infants between 24-48 hours with no withholding of TPN and in 2011 the protocol was changed to hold TPN for 3 hours and use D10W before collection of the NMS. The main results of the study are shown below and of note all the False Positive results post intervention were statistically different to a significant degree after the change in practice.  Examining the entire group there was a 74% reduction in false positive results post practice change.

Preintervention (N=274) Post Intervention (N=265)
Birth Weight Negative (%) False Positive (%) Negative (%) False Positive (%)
<1000g 13 (65) 7 (35) 14 (82.4) 3 (17.6)
1001-1500 g 23 (92) 2 (8) 24 (96) 1 (4)
>1500 g 222 (96.9) 7 (3.06) 223 (100) 0 (0)
Total 258 (94.2) 16 (5.83) 261 (98.5) 4 (1.50)

Furthermore an 81% savings in health care costs per patient were realized in the change as well.  This is outlined below:

Item Preintervention Postintervention
Confirmatory testing 4653 434
Supplies for testing 46 12
Supplies for new protocol 0 465
Total 4699 911

The results speak for themselves yet the practice I don’t believe has been widely adopted and certainly not in our centre.  This past week however the following study was released in abstract form and inspired me to write this post as I believe the evidence is overwhelmingly in support of this practice change Stopping Parenteral Nutrition for Three Hours Reduces False Positives In Newborn Screening.

12 567 consecutive births in 1 hospital between May 2010 and June 2013 were analyzed to determine the FP for AA levels in the NMS.  The FP rate in infants > 1500g was much lower overall than for those under 1500g which may have been explained by less TPN use in that cohort.  Similar to the first study TPN was changed to D10W for three hours prior to collection of the NMS and resulted in a FP rate of 3.1% in the D10W group vs 11.8% in the TPN group.  This represents again an overall 74% reduction.

So there you have it.  Two studies showing the same results. The concept is simple, saves hospitals money and more importantly avoids unnecessary parental anxiety, needless blood sampling and consumption of time by nursing staff and other consultants.  This is not a high tech strategy that takes a great deal of education to implement.  Rather this can be started tomorrow wherever you are and it is my hope that by reading this at least one hospital out there aside from our own may adopt this small change to make a big impact on our patients.