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  • Blog Entries

    • By AllThingsNeonatal in All Things Neonatal
      Just about all of our preterm infants born at <29 weeks start life out the same in terms of neurological injury.  There are of course some infants who may have suffered ischemic injury in utero or an IVH but most are born with their story yet to be told.  I think intuitively we have known for some time that the way we resuscitate matters.  Establishing an FRC by inflating the lungs of these infants after delivery is a must but as the saying goes the devil is in the details.
      The Edmonton group led by Dr. Schmolzer has had several papers examined in these blogs and on this occasion I am reviewing an important paper that really is a follow-up study to a previous one looking at the impact of high tidal volume delivery after birth.  I have written on this previous paper before in It's possibile! Resuscitation with volume ventilation after delivery.  On this occasion the authors have published the following paper; Impact of delivered tidal volume on the occurrence of intraventricular haemorrhage in preterm infants during positive pressure ventilation in the delivery room.This observational study had a simple enough premise.  Will the use of Vt > 6 mL/kg in infants given PPV for at least two minutes lead to worse rates of IVH?  All infants were < 29 weeks and if they had chest compressions or epinephrine were excluded.  All infants were treated equally in terms of delayed cord clamping and antenatal steroid provision.  Ventilation was done with a t-piece resuscitator and Vt measured with an NM3 monitor connected to the face mask.  First ultrasounds were done for all at 3 days of age.
      What did the authors find?
      One hundred and sixty five infants comprised this cohort.  Overall, 124 (75%) infants were in the high volume group compared to 41 (25%) with a mean VT<6 mL/kg. Median Vt were 5.3 (4.6-5.7) ml/kg for the low group and 8.7(7.3-10.6) mL/kg which were significantly different.
      When looking at the rates of IVH and the severity of those affected the results are striking as shown in the table.  Hydrocephalus, following IVH developed in 7/49 (14%) and 2/16 (13%) in the >6 mL/kg and <6 mL/kg VT groups.  Looking at other factors that could affect the outcome of interest the authors noted the following physiologic findings. Oxygen saturations were lower in the low volume group at  6, 13 and 14 min after birth while tissue oxygenation as measured by NIRS was similarly lower at 7,8 and 25 min after birth (P<0.001). Conversely, heart rate was significantly lower in the VT>6 mL/kg group at 5, 20 and 25 min after birth (P<0.001). Fraction of inspired oxygen was similar in both groups within the first 30 min. Systolic, diastolic and mean blood pressure was similar between the groups.  What these results say to me is that despite having lower oxygen saturations and cerebral oxygen saturation at various time points in the first 25 minutes of life the infants seem to be better off given that HR was lower in those given higher volumes despite similar FiO2.  Rates of volume support after admission were slightly higher in the high volume group but inotrope usage appears to be not significantly different.  Prophylactic indomethacin was used equally in the two cohorts.
      Thoughts for the future
      Once a preterm infant is admitted to the NICU we start volume targeted ventilation from the start.  In the delivery room we may think that we do the same by putting such infants on a volume guarantee mode after intubation but the period prior to that is generally done with a bag and mask.  Whether you use a t-piece resuscitator or an anesthesia bag or even a self inflating bag, you are using a pressure and hoping not to overdistend the alveoli.  What I think this study demonstrates similar to the previous work by this group is that there is another way.  If we are so concerned about volutrauma in the NICU then why should we feel any differently about the first few minutes of life.  Impairment of venous return from the head is likely to account for a higher risk of IVH and while a larger study may be wished for, the results here are fairly dramatic.  Turning the question around, one could ask if there is harm in using a volume targeted strategy in the delivery room?  I think we would be hard pressed to say that keeping the volumes under 6 mL/kg is a bad idea.  The challenge as I see it now is whether we rig up devices to accomplish this or do the large medical equipment providers develop an all in one system to accomplish this?  I think the time has come to do so and will be first in line to try it out if there is a possibility to do a trial.
    • By Stefan Johansson in Department of Brilliant Ideas
      If you are to read one paper on neonatal ethics this year, I'd argue that this is the one.
      Late last year, John Lantos, pediatrician and a leading medical ethicist, published a review in NEJM on the ethics around decision-making in the NICU. The paper is not open-access... but you can surely get it from within your hospital intranet or your university/hospital library.
      We have a fantastic toolbox in the NICU. We can provide live-saving treatments and support. Most newborns in the NICU survive to good long-term health.
      However, we also operate in a high-risk environment where some infant may suffer, some infants will die, and some infants will survive with difficult sequele. Which raises the question, by staff and by parents, what is the "right" thing to do in complex situations. When withholding and withdrawing life-sustaining therapies becomes a option to decide upon.
      How could we navigate in this landscape? IMHO, the review by Lantos is a good starting point on how to form a local practise.
      Lantos shares his reasoning about we cannot "solve" these discussion with "information" as such. Despite how hard we try,  data alone does not lead the whole way. Outcomes is hard to measure, they change over time and we all percieve risks differently. Therefore, information is difficult to standardize. Furthermore, those of us sharing the information will filter our presentation through our subjective selves, coping with opinions, experiences and our expertise in different ways. 
      The better alternative around ethical questions is shared decision-making. Two central quotes of the review is that
      and that
      Certainly, the future of neonatal care will bring more ethical questions to us. Refined prenatal diagnostics, the down-shifting boundary of viability and new treatment technologies in the future (like the artificial placenta) will impact how we think about fetal life and postnatal life, what is the "periviable grey zone" and what our fantastic toolbox can do.
      While improving our skills, from a medical/technical viewpoint, we also need to improve how we cope with the ethics around decision-making processes.
      Besides reading the review by John Lantos, I can recommend you to see this lecture from theh #99nicuMeetup in Copenhagen 2019, by Eduard Verhagen.
      (Feature Photo : Cropped photo by Liane Metzler on Unsplash)
    • By AllThingsNeonatal in All Things Neonatal
      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.

      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!
    • By AllThingsNeonatal in All Things Neonatal
      The metabolic syndrome describes the development as an adult of centripetal obesity, high blood pressure, high triglycerides, elevated blood sugar and low HDL cholesterol. These constellation of problems significantly increase the risk of cardiovascular disease, stroke and diabetes.
      The origins of this syndrome may begin in the newborn period as previous research has noted an association with infants who are born SGA and development of insulin resistance later in life as in the paper Insulin resistance in young adults born small for gestational age (SGA). A relationship to the metabolic syndrome has been also noted in the paper Small for gestational age and obesity related comorbidities.
      The theory here is that conditions in utero in which the fetus is chronically deprived of blood flow and nutrition lead to a tendency towards insulin resistance. The body is essentially trying to use any energy it is receiving to stay alive in an environment in which resources are scarce. Given that situation, resisting the effects of insulin by preventing storage of this needed energy serves a useful purpose but in the long run may be detrimental as the body become programmed to resist the effects of this hormone.
      What if this programming could be overcome?
      Breast milk certainly has many incredible properties and as we learn more we discover only more applications.  My previous post on putting breast milk in the nasal cavity is just one such example (Can intranasal application of breastmilk cure severe IVH?).  In 2019 Dr. Hair and Abram's group looked at this with respect to insulin resistance and with potential extrapolation to the metabolic syndrome in their paper Premature small for gestational age infants fed an exclusive human milk-based diet achieve catch-up growth without metabolic consequences at 2 years of age. Texas Children's Hospital uses an exclusive human milk diet for premature infants with the following criteria GA of <37 weeks, BW of ≤1250 g, with the diet maintained until approximately 34 weeks PMA.  Exclusive human milk is provided through a combination of mother's own milk and Prolacta instead of a bovine based human milk fortifier.  In this study they were able to prospectively track 51 preterm infants of which 33 were AGA and 18 SGA.  The first visit (visit 1) was performed at 12–15 months CGA and the second visit (visit 2) was at 18–22 months CGA.  The question at hand was whether these children would experience catch up growth at 2 years of age and secondly what their levels of insulin might look like at these times.  Higher insulin levels might correlate with levels of insulin resistance with higher levels being needed to maintain euglycemia.  As a measure of insuline resistance the authors used the calculation of the Non-fasting homeostatic model of assessment-insulin resistance (HOMA-IR) =  (insulin × glucose)/22.5 which has been validated elsewhere. Protein intakes were equal for both groups at about 4 g/kg of human milk protein.
      The Results Please
      The SGA group had greater weight gain between visit 1 and 2 as evidenced by a significant difference in the change in BMI z-score, AGA −0.21±0.84  vs.SGA 0.25±1.10.  I suppose this isn't too shocking as we know that many babies born SGA experience catch up growth after discharge.  What is surprising and once again speaks to the power of breast milk  is the impact observed on insulin levels and resistance to the same as measured by the HOMA-IR (AGA babies are the left column and SGA the right).

      The adjusted p vlaues for glucose were 0.06 with insulin and HOMA-IR being 0.02.  What does this mean?  Well, these are not fasting insulin levels which would be ideal but what it does say is that at fairly comparable glucose levels the level of insulin is higher in former AGA babies and the level of insulin resistance lower in the SGA infants!  This result is quite the opposite of what previous studies have shown as referenced above.  Aren't these growth restricted infants supposed to have had insulin resistance in utero and been programmed for life to have insulin resistance and as adults develop the metabolic syndrome?  This study falls short of making any claims about the latter as these infants are only two years of age.  What this study provides though is certainly a raised eyebrow.  There will be those of course that look at the size of the study and dismiss it as being too small but at the very least this study will lead to further work in this area.  This paper though adds to the mystery around the potential impacts of breast milk and certainly provides strength to the thought that perhaps breastmilk should be the exclusive source of nutrition for preterm infants in the NICU.  While I understand that not all women are able to produce enough for their own infants or may choose not to for a variety of reasons, with access to donor milk supply this could become a reality.  The cost savings to the health care system by preventing insulin resistance would be many fold greater than the cost of donor milk in the newborn period.
      Another intriguing question will be whether use of an exclusive human milk diet with use of only mother's own milk will have similar effects or even greater impact on glucose homestasis later in life.  I think the authors are to be commended for their dedication to work in this field and I certainly look forward to the next publication from this group.
  • Upcoming Events

    • 18 June 2019 Until 21 June 2019
      The 30th Annual Meeting of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC 2019) is a unique multidisciplinary forum for colleagues from around the world to meet and discuss a variety of topics, generating stimulating debates and fruitful collaborations. Join doctors, nurses and other allied healthcare professionals for this outstanding opportunity to take part in cutting-edge workshops, educational sessions and networking opportunities.    Learn Morehttps://espnic2019.kenes.com/
    • 01 July 2019 06:00 AM Until 30 September 2019 05:00 AM
      It is an online course which lasts 3 months, starting in July, 2019. 28 topics avilable 24/24 and 7/7. 22 mexican professors and 8 international ones. 

    • 05 September 2019 06:00 AM Until 09:00 PM
      After (another) successful meeting with NAVA enthusiast from several countries, we are ready to announce the date of the next workshop!
      The goal of this event is to increase skills on the use of NAVA ventilation in the NICUs, which already have some experience with NAVA and they have a Servo-i or Servo-n ventilator.
      Date: 05-06.09.2019
      Location: Turku, Finland
      Registration fee: 600€ + taxes (incl. lunches and refreshments during the workshops) 
      How to register: contact Hanna Soukka (hanna.soukka@utu.fi or NAVA@tyks.fi before June 30, 2019)
      The preliminary program is attached below.  In case of any questions, don't hesitate to ask here or email!
      We've received approval from Ethical MedTech.
      On behalf of Hanna Soukka and Baby Friendly Ventilation Study Group,
      NAVA workshop September 2019 invitation letter and preliminary program.pdf
    • 11 September 2019 Until 13 September 2019
      Evidence and Excellence in Perinatal Care - BAPM and EBNEO Conference 2019
      Join the fifth EBNEO conference of, this time in collaboration with the British Association of Perinatal Medicine
      11-13 September 2019 at the Northumbria University, Newcastle UK
      Click here for more info and to register!

    • 17 September 2019 Until 21 September 2019
    • 18 September 2019 Until 22 September 2019
      the 3rd Congress of Joint European Neonatal Societies (jENS)
      18. Sep 2019 – 22. Sep 2019
      Maastricht, Netherlands
      URL will be posted later.
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