stirrhs (fr) - Inflammation, electrocortical and vagal activity with acute and chronic hypoxia in near term fetal sheep - Commentaires

Thanks Jo. Is it done at

frasch — Thu, 08 Oct 2009 18:40:59 -0400

Thanks Jo. Is it done at Sunnybrook?
Martin

Jo Watson RN, MScN,

jowatson — Thu, 08 Oct 2009 17:39:43 -0400

Jo Watson RN, MScN, ACNP
Director, Obstetrics and Gynaecology
Sunnybrook Health Sciences Centre
Hi Martin
Fetal scalp sampling during labour is a technique used during labour to inform decision making regarding timing of delivery when the fetal heart tracing is not normal.
Jo

Hi Martin, Thanks for your

mcintyre — Thu, 08 Oct 2009 12:04:12 -0400

Hi Martin,

Thanks for your responses and for the statistics you provided. The 70% vs. 10-15% split is an interesting one to think about. As you say, the cognitive deficits are often subtle and do not emerge until much later so I can imagine that it is difficult to go back and pin-point the exact cause of the neurological difficulties.

All the best with your research,
Alex.

Hi Heather, thank you for

frasch — Wed, 07 Oct 2009 23:52:04 -0400

Hi Heather,

thank you for your feedback.

1. A very valid question. Of course, in nature, the variance is higher as to frequency, duration and the degree of UCO. However, in science we model things while keeping them reproducible and well quantifiable, hence the chosen paradigm. It is well conceivable as mimicking human labour process. In fact, base excess deterioration rates due to FHR decelerations found in fetal sheep near-term are very similar to those found in humans.
2. HRV = heart rate variability.
3. We allowed three days of recovery after each surgery and measured baseline control levels of arterial blood gases, lactate, base excess and cardiovascular measures as well as recorded baseline ECOG activity finding physiological amounts of sleep state like activity prior to commencing UCO. So I am confident that fetal sheep were in good shape at baseline.

I hope my answers were useful.
Please feel free to ask more!

Best,
Martin

Hi Alex, thank you for your

frasch — Wed, 07 Oct 2009 23:40:38 -0400

Hi Alex,
thank you for your feedback!
1. This site gives an idea about the numbers on cerebral palsy, one of the most dreaded and immediately severe complications due to brain injury intrapartum: http://www.ofcp.on.ca/guide.html
Briefly, 'It is estimated that one out of every 500 babies, and up to one in three premature babies is affected to some extent. There are over 50,000 Canadian with CP.'
Don't forget that CP is just one of the conditions. There more subtle alterations, rather functional in nature, that often get revealed during school age as cognitive difficulties for example. You may check out the recent Lancet review by Saigal and Doyle:
Saigal, S. and Doyle, L.W. (2008) An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet 371, 261-269.
I have to get more precise: in fact, about 70% of brain injuries diagnosed after birth are believed to have their origin in processes occurring antenatally, not during labour.
Intrapartum brain injury accounts for around 10-15%. I mention some reasons for antenatal processes playing the major role in my reply to Jo.
Of course, some brain injuries are genetic in origin. This can be tested for. But this certainly does not constitute the major portion of the spectrum.
2. ECOG is something done in animals only, not in humans (see Thaler for example who studied EEG). ECOG is done by making burr holes as you described and placing electrodes on top of the dura.
Human EEG is placed on the skin while minimizing the impedance to improve the conductivity. There is no fundamental difference between ECOG and EEG, as both are measuring cerebral electrical activity (field potential activity).
3. Kingston meeting is the Eastern Perinatal Investigator Annual Meeting (PIM) on November 11-13, 2009 at the Holiday Inn Kingston-Waterfront Hotel in Kingston, ON. It is a very interdisciplinary and transdisciplinary meeting.
4. Yes. My PI is a clinician and a scientist, so I have the clinical advice and expertise there at all times. I also work on this with engineers and patent experts.

Thank you Alex,
Martin

Thank you Jo. This is a good

frasch — Wed, 07 Oct 2009 23:16:22 -0400

Thank you Jo.
This is a good suggestion!
We are now at a very early stage where we first need to ensure the idea works in humans per se. When, hopefully!, we get to the point of designing a first prospective human study, we should definitely involve all players involved in the care.
We are thinking about this now already in the way that we are seeking to make the use of the technology as user-friendly as possible. This includes minimizing subjectivity factor.
Best,
Martin

Hi Jo, thank you for your

frasch — Wed, 07 Oct 2009 23:12:22 -0400

Hi Jo,
thank you for your question.
Our sheep work does suggest that there is a specific pattern in ECOG related to UCO-induced FHR decels that appears well in advance of severe acidemia. You have a point suggesting that fetal pHa scalp sampling should be as helpful. I cannot tell why at this very moment, but I know that this procedure is hardly done anymore, at least not in North America. The problem with scalp blood sampling seems to me to be that you don't know if you sample an OK pHa when it is going to deteriorate (this is a very individual feature depending not only on intrapartum process, but also (most likely to an overwhelming degree in fact!) on the antepartum processes such as intermittent and recurrent hypoxia or infections). If you do sample a pHa < 7.00, then you have to deliver anyway.
Martin

Jo Watson RN(EC)

jowatson — Wed, 07 Oct 2009 22:04:19 -0400

Jo Watson RN(EC) PhD(cand)
Director, Obstetrics and Gynaecology
Sunnybrook Health Sciences Centre

Hi Martin
Thinking about your question related to transdisciplinarity, is it reasonable to include health care professionals who provide care to women in labour in your work as they are the potential end users in your efforts at knowledge translation?
Jo

Jo Watson RN(EC) PhD

jowatson — Wed, 07 Oct 2009 21:57:18 -0400

Jo Watson RN(EC) PhD cand
Director, Obstetrics and Gynaecology
Sunnybrook Health Sciences Centre

Hi Martin
Thanks for sharing your work.

I am wondering if there is a specific pattern of fetal heart rate and ECOG spectral edge frequency onsetting at moderate pH and base excess levels in the course of the UCO well in advance of the threshold for severe acidemia and increased risk for asphyxia-mediated brain injury, could you simply use intrapartum fetal scalp sampling and intervene at an earlier stage when the pH falls below a newly established level?
Jo

Hi Martin, Your presentation

Allaway — Wed, 07 Oct 2009 14:14:28 -0400

Hi Martin,

Your presentation was very interesting. Thank you.

I have know knowledge of fetal monitoring past the first trimester. I am a researcher working in ovarian function and have experience in the infertility clinic performing early pregnancy ultrasounds.

I have a few questions

1. How do you know the induced repetitive UCO are having the same effect as natural UCO? What I mean by this is the acidemia that develops developing faster or slower, to a similar, smaller, or larger degree, is the hypoxia developing faster or slower, etc.

2. What does HRV mean? I tried to search but found many things that didn't make sense in this context.

3. I am not sure that I am following exactly how your methods worked. Wouldn't performing the surgery negatively influence the information you were trying to get and understand.

Thanks,
Heather

Hi Martin, Your research is

mcintyre — Wed, 07 Oct 2009 10:30:04 -0400

Hi Martin,

Your research is very interesting and seems to hold considerable promise for providing better ways of detecting potential fetal brain injury. This is an area of interest for me as I am a psychology student and often see patients with neurological difficulties as adults.

I, like Eric, am trying to wrap my head around your research. I just have some basic questions.

1) What is the prevalence rate of brain injury / neurological conditions resulting from fetal compromise during delivery? How do we know that the brain injury / neuro problems are due to the delivery itself and are not genetic or something that occurred in utero.

2) Forgive me for this basic question, but how does ECOG work with fetal sheep or human fetuses (a la Thaler et al in Ped Research) if the electrodes go directly on the dura via skull burr holes? I am picturing a few different scenarios here...

3) What is the meeting in Kingston that you are referring to when you talk about knowledge transfer?

4) Have you consulted or worked with researchers from other disciplines or clinician on this project? I am curious to hear what front-line people would think about potentially using EEG/ECOG in clinical practice.

Thank you,
Alex.

Hi Eric, thank you very much

frasch — Mon, 05 Oct 2009 18:12:14 -0400

Hi Eric,
thank you very much for your input. Your suggestion regarding my second question was most unexpected and neat. Thank you for that! I have to think about it. GC effects on lung maturation are quite acute, 24hours time window prior to labour is sufficient to induce the effect on pneumocytes type II if I remember correctly. I do not know if the same were true for CAP stimulation, but this would be fairly easy to test! I will get back to you if I find a way to do it.
As for your questions:
1. ECOG = electrocorticogram, brain electrical activity (field potentials) acquired from the electrodes placed directly onto the dura through skull burr holes.
EEG = electroenkephalogram, the more commonly used term in neonatal and adult human applications, because here the electrical activity is acquired through the skin using variations of suction, subdermal or other electrodes all geared towards minimizing impedance to improve signal to noise ratio. The latter is considerably better in ECOG which is why it is not be taken for granted that what we can measure with ECOG, we can also measure with EEG. Hence the need to test for this. Another source of lower signal to noise ratio in EEG are muscle and movement artifacts in the fetus. (The respiration is less relevant prior to birth as a source of artifacts for EEG, because it occurs only intermittently).
2. You are right that ECOG and FHR as we found are prognostic of impending acidemia. Clinically, only FHR is used, but here is the rub: FHR has a low positive predictive value for acidemia and a high negative predictive value for hypoxia. That is, if FHR patterns are normal, an obstetrician can be sure that fetus is experiencing no hypoxia. If they are NOT normal, it is like in about a 50/50 chance. On top of this, just knowing that a fetus is having hypoxia is not enough to warrant labour induction, since every fetus will tolerate it differently (in terms of susceptibility to develop a brain injury and the time he or she takes to become vulnerable).
ECOG is not used clinically as a routine method. However, there is at least one recent study by Thaler et al in Ped Research showing that it can be done. The problem with their study is the electrode design: it is hardly something, one would be willing to adopt clinically.
Hope these thoughts were useful and thank you again for sharing yours Eric!
Best,
Martin

Hi Martin, Thank you for

boucher — Mon, 05 Oct 2009 17:06:38 -0400

Hi Martin,

Thank you for your presentation, it was very interesting and looks very promessing.

I have next to no knowledge in fetal monitoring, so I would like to ask you a couple of basic questions in order to better understand your work.
-1- What is the difference between ECOG and EEG?
-2- From what I understood, ECOG and FHR are suffisant to mesure early signs of acidemia. Is ECOG used in clinical stetings? Could you clarify the reasons why you need to compare ECOG to EEG, as it relates to clinical implication of your work.

As for your secound question:''Can you suggest explanations for the mediation of cerebral neuroprotection via efferent vagus nerve?''

As you pointed out :'' increased vagal activity inhibits the release of pro-inflammatory cytokines such as IL-1β''.
A quick pubmed shearch wielded a interesting paper: Increased rat serum corticosterone suggests immunomodulation by stimulation of the vagal nerve by De Herdt et al.. As the title suggest, they show that stimulation of the vagus nerve results in an increase in serum corticosterone levels.

So part of the answer may lie in vagus-mediated increase in serum cortisol levels. If this holds true, activating CAP in pre-terms could have the additional benefit of accelerated lung development, without the need of exogenous synthetic glucorticoids. What do you think?

Thank you

Eric

Inflammation, electrocortical and vagal activity with acute and chronic hypoxia in near term fetal sheep

frasch — Fri, 02 Oct 2009 01:09:17 -0400

Resumé of the project

Study 1. Electrocortical activity during repetitive umbilical cord occlusions with worsening acidemia in the ovine fetus near term.