Biophysical Assessment by ravenms

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									Biophysical Assessment of the High-Risk Fetus

                Michael Emerson, M.D.




                                                1
I.   Background of Biophysical Assessment                                   The heart rate test was more likely to be abnormal first, decreased breathing
                                                                            activity next, decreased movement next and tone last. This exactly reflects
     A.   Definition: multiple biophysical parameters are evaluated at a
                                                                            the model that I gave you at the beginning so that our clinical observation
          single setting                                                    of what goes wrong mirrors perfectly what was hypothesized in the model
                                                                            to be the way in which things disappear. It tells you that if your NST is your
          1.   Dynamic                                                      only abnormal component, and everything else is still pretty much intact,
               a.   Fetal heart rate (FHR): nonstress test (NST)            that the likelihood of significant hypoxia is small. If your NST and your
                                                                            fetal breathing activity are both either diminished or absent, your likelihood
               b.   Fetal breathing movements (FBM)                         of hypoxia goes up substantially and if you add a third element, you might
                    (1) Incidence                                           as well stop at the point because you have enough information to consider
                                                                            intervening on that baby.
                    (2) Rate
               c.   Fetal body movements (FM): incidence                    Let's go on to the issue of the fact that you could probably get away from
                                                                            having to do all of these variables and really you can eliminate movement,
               d.   Fetal blood flow: Doppler velocimetry                   because once you get anything past breathing and NST your prognosis
          2.   Static                                                       doesn't change whether you add movement or whether you add tone in
                                                                            terms of the likelihood of a compromised outcome.
               a.   Amniotic fluid volume (AFV)
                                                                            I am going to come back to tone because tone is our best window of
                    (1) Pockets
                                                                            anything that we look at into things occurring above the brainstem.
                    (2) Quadrants                                           Remember one of the things I mentioned in my previous talk that was a
                                                                            concern is that you can have a brain injury, unrecognized, the fetus recovers,
               b.   Neurologic tone: flexion-extension
                                                                            survives and goes on and produces an apparently okay NST and may
               c.   Placental grade                                         produce an okay AFV. How are you going to know that? The fact of the
                                                                            matter is that you may only know that by looking at fine motor activity of
     B.   Significance of biophysical parameters                            the fetus. You may only know that by watching the pattern of activity and
          1.   FHR: interrelationship of autonomic nervous system           the fact of making an observation that the fetus doesn't change state. So
                                                                            these are things that become more subtle. We are still a long way away
               (ANS), acid-base balance, oxygenation, conduction,           from being able to reach this holy grail of predicting antenatal brain damage
               contract                                                     at the time that it occurs so that when they baby comes out and looks
                                                                            terrible and becomes a casualty that we are not consistently taken to task for
               a.   Clinical significance: standard tool assessing fetal-   doing something wrong during the process of labor and delivery.
                    placental respiration, caloric reserves
                                                                            Again, if we take a look at management schemes, if we do testing, most of
               b.   Baseline data                                           our testing is done on babies near term and if we have a normal test, this is
                    (1) Rate                                                a very robust statement of fetal condition, because we have the chronic
                                                                            component which is the amniotic fluid and we have the activity components.
                    (2) Variability                                         Together, that test can be robust enough to keep you in good stead for up
                    (3) Response to stimuli                                 to a week as opposed to the NST which is generally a two to three time a
                                                                            week exercise. If you did a perfectly normal biophysical profile and a
                    (4) Periodic changes                                    patient's clinical status didn't change, then that could be good and be robust
                                                                            for you up to a week.
          2.   FBMs
               a.   Examples                                                If you have one abnormal parameter, it really depends on what it is. But in
                                                                            general, you want to look at the baby a little more closely and probably
                    (1) Central respiratory regulation
                                                                            repeat that test to see whether you are dealing with a process in becoming,
                    (2) Acid-base balance                                   if that is a nonreactive NST, or if that is oligohydramnios. Again, amniotic
                                                                            fluid is not an absolute. You are allowed about a 10-20% variation in your
                    (3) Oxygenation                                         AFI between the examination of sessions. The fetus urinates, the fetus
                    (4) Neuromuscular integrity.                            swallows and so forth but you do want to look at the baby within 24 hours.
                                                                            Then, if you are still not satisfied, that is when you invoke your CST. That
                    (5) Maturity                                            is when we most commonly invoke our CSTs.
               b.   Clinical significance
                                                                            If you have two or more abnormal parameters, we look at that in a mature
                    (1) Episodic                                            baby as being an indication to go ahead and deliver. In an immature baby,
                    (2) Related to time of day                              we would probably back that up with a CST. We want to be sure because
                                                                            we are looking at events that bear some relationship to fetal behavior that
                    (3) Electrocortical state                               we are not looking at the possible influence of maternal medication. The
                    (4) Maternal fed state                                  maternal medications that are notorious for reducing the biophysical scores
                                                                            are medications that interfere with CNS function. Mag sulfate certainly is
               c.   Baseline data                                           a classic. When you have babies on mag they just lie there because their
                    (1) Incidence (percent time spent breathing)            mag levels get to the same level as their mother's. So if you want to know
                                                                            what the baby is doing, look at the mom. If she is lying back there, she can't
                    (2) Rate                                                watch her soap operas because she's got diplopia, she is groggy, sleepy, not
                                                                            moving around, the baby is doing the same thing. So when you are trying
                    (3) Variability
                                                                            to evaluate babies whose mothers are receiving magnesium for preterm
                    (4) Fetal body movements                                labor, for example, if you are doing biophysical assessment, that becomes
                                                                            a issue. It is a problem because you have blunted the things that you are
               a.   Examples

                                                                                                                                                             2
               (1) Neuromuscular integrity                              looking for most carefully so then you are reduced to looking for issues that
                                                                        get very basic like are there late decelerations associated with contractions
               (2) Oxygenation
                                                                        in this mother that you are tocolyzing?
               (3) Caloric reserves
                                                                        The standard score, as I mentioned to you, has five components in it. The
         b.    Clinical significance: rough measure of caloric homeo-   thresholds for scoring these components are really, quite frankly, arbitrary.
               stasis                                                   Generally, fetal breathing of more than 60 seconds would be reassuring
                                                                        under most circumstances. Movements, tone, AFV, or AFI and your NST.
         c.    Baseline data                                            We use a modified scoring system that works out to 10 and 10 is a nice
               (1) Incidence (percent time spent moving)                number. Eight and 10 are not necessarily equivalent because as I mentioned
                                                                        to you it depends on what you've lost points for. What happens when your
               (2) Numeric counts                                       score goes down is that you start this exponential increment in bad
    4.   AFV                                                            outcomes, whether it is antepartal death… you can see here, there is no
                                                                        linear relationship at all. It just shoots right up there and your incidence of
         a.    Examples                                                 fetal distress and your incidence of neonatal depression are all elevated and
               (1) Aggregate of fetal urination                         you can make the same statement about babies that end up with abnormal
                                                                        neurologic outcome as a result of asphyxial injury. So there is a very, very
               (2) Gastrointestinal motility                            sharp demarcation once you get to scores that are less than 6 and that
                                                                        should be regarded as being, again, a signal to intervene.
               (3) Tracheal flow
               (4) Membrane exchange                                    Now let's get to the evidence. The evidence unfortunately is very limited.
                                                                        There really have only been a couple of trials that have compared the
         b.    Clinical significance
                                                                        biophysical profile, the comprehensive profile, to the NST. The NST at that
               (1) Peaks at 34-36 weeks                                 time was the gold standard. These are trials that are 10 years old. The
                                                                        numbers are not very large but what you see here, and this is actually not
               (2) Reflects visceral shunting in high-risk adaptions    what the, I think, authors really wanted to show, but it is what in fact they
               (3) Anomalies                                            have shown is that compared to the NST, the biophysical profile in these
                                                                        two studies doesn't appear to make a difference in your outcomes. Your
               (4) Growth disturbances                                  perinatal deaths, your low Apgars, your intrapartal fetal distress cases were
         c.    Baseline data: quantitative assessment                   similar. I can say this because your confidence intervals include the number
                                                                        1.
               (1) Pockets
               (2) Quadrants                                            Why is that? Why do you suppose that is the case? The reason that is the
                                                                        case is what you have done is you have taken a test which is part your
    5.   Neurologic tone: reflex activity which may be elicited with    biophysical profile, you set that off as your gold standard, and now you are
         sound or it may be spontaneous                                 comparing the rest of your biophysical profile to that test. Remember, in
                                                                        these centers the NST was done separately from the rest of the biophysical
         a.    Clinical significance                                    profiles so you could have tests in which the NST, had they been done
               (1) Oxygenation                                          together, would have been different than when they were done separately.
                                                                        But I would say that the overwhelming issue here is the numbers are far too
               (2) Central nervous system integrity                     small to make you feel comfortable that this is a definitive statement about
                                                                        how good the biophysical profile really is.
               (3) Motor function
         b.    Baseline data                                            I think the other issue here is that we probably won't get better control data
                                                                        than what I have shown here. There just isn't money to do the studies. The
               (1) Flexion-extension
                                                                        NICHD isn't interested funding that kind of work anymore and so we are
               (2) Attitude                                             going to have to take it on faith that what I have told you physiologically
                                                                        makes a lot of sense. If you understand the components and what they are
               (3) Startle reflex                                       trying to tell you and interpret the differences between the chronic and acute
               (4) Sucking                                              components and remember that the test is not perfect, it gives you more
                                                                        information than does any single component. I think at that point what we
    6.   Placental grade                                                are seeing here is the fact that this is the best case scenario we are going to
         a.    Morphologic description of placental maturity (senes-    have. This doesn't stop me from doing biophysical profiles but it makes me
                                                                        very careful in terms of interpreting the biophysical profile as a single stand
               cence)                                                   alone test.
         b.    Clinical significance
                                                                        Let's talk about umbilical flow velocimetry and let's put this into a location
               (1) Crude estimate of placental aging                    where you can take something away that might be helpful for your practice.
               (2) May be more advanced in disease states               The story of Doppler really goes back now a decade and a half so it is not
                                                                        really news but I think if we take a look at the cord.
C. Concept of fetal states
    1.   Biophysical behavior is related at term to organized           Let's look at the circulation that we are dealing with and why this is a very
                                                                        interesting part of the fetal circulatory system. Again, I promised I would
         clusters called "states"                                       give you a little bit of physiology here because I think it makes you better
                                                                        consumers to understand what the label means rather than just going ahead
         a.    State 1: quiet sleep
                                                                        and buying the product. Here, actually, is the part of the circulation that we
         b.    State 2: rapid eye movement sleep                        are interested in and it is way, way downstream but here are the umbilical
                                                                        arteries. As you know, the umbilical arteries course along either side of the
         c.    State 3: intermediate

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              d.   State 4: "wakefulness" (active)                        bladder and eventually join the central circulation and are tributaries off the
                                                                          iliac, the aorta and receive a fairly downstream blood flow from the main
         2.   State influences
                                                                          pump up here. Here you see the umbilical vein going back up and getting
              a.   Time of day: circadian rhythms                         admixed with the enterohepatic circulation. Eventually that oxygenated
                                                                          blood enters the right atrium where it encounters a current coming from the
              b.   Maternal diet status, oxygenation                      superior vena cava.
              c.   Maternal drugs
                                                                          So what the arterial circulation of the umbilical cord really is doing is it is
              d.   Gestational age                                        the last tributary to bring blood back to the placenta for processing. So it
III. Technique of Biophysical assessment                                  has an obviously very important physiologic role because the placenta is a
                                                                          surrogate lung, it is a surrogate GI system, it is a surrogate kidney and it
    A.   Instrumentation                                                  acts as a way of dealing with the acquiring of essential nutrients, substrates,
         1.   Electronic FHR monitor                                      oxygen and the detoxification of the blood by getting rid of CO2 and
                                                                          hydrogen ions and broken down metabolites from substrates that have
              a.   Doppler                                                already been processed.
              b.   Air encephalogram (AECG)
                                                                          Now, if we take a look at the developmental basis for velocimetry, we
         2.   Realtime ultrasound (US)                                    know that after the mid trimester, placental adaptation generally is fixed in
                                                                          terms of the number of cotyledons, the number of central vessels that exist
    B.   Test conditions
                                                                          on the chorionic plate. The main change that occurs in the placental
         1.   Standardized for                                            circulation of the fetus is a large increase in terminal villus units or the so-
                                                                          called microvasculature of the placenta.
              a.   Time of day
              b.   Maternal status                                        Physiologically, this is a system that is adapted to give you a low resistance
                                                                          to flow in its terminal end. Abnormal resistance to umbilical blood flow then
              c. Length of observation                                    is a process that suggests that something is going wrong, either by
         2.   Concurrent acquisition of biophysical                       infarction of this vascular tree or by perhaps initially a hypoplastic situation
                                                                          where you don't get this great proliferation of vessels to great quantities.
IV.Test Interpretation
    A. "Standard" biophysical profile:                                    Experimentally, abnormal systolic/diastolic patterns, which I will show you
                                                                          shortly, can be created with placental infarction and this has been done
         1.   Sequential NST and US                                       successfully in laboratory animals through embolization. So you can
         2.   NST: two or more accelerations >15 beats per minute         recreate this by destroying selectively parts of your placenta. You can
                                                                          recreate this increased resistance to flow that you get in a compromised
         (bpm) in 20 minutes                                              baby. In addition, pathologic examination of the placenta has shown a very
         3.   Realtime scan                                               good correlation between terminal villus capillary counts and the waveform
                                                                          patterns that are seen, again, in disturbed pregnancies.
              a.   FBM: >30 seconds of continuous breathing
              b.   FM: >3 movements                                       The nice thing about looking at the umbilical vessels is that it is easy and
                                                                          96% of the time you've got two shots at getting one. They are easy to
              c.   Fetal tone: >1 flexion-extension episode               identify. They are easy to see. They have long courses and this is just
                                                                          recapitulation of what I have already told you, but the fact of the matter is
              d.   AFV: one pocket of 10 mm x 10 mm
                                                                          why pick a target that is hard to find? Part of the appeal also is the fact that
              e.   Placement grade <3                                     this is a circulation that is very stable. Under situations where there is
                                                                          chronic hypoxemia, we have preservation and actually an increase in blood
         4.   Overall test requires 25-70 minutes
                                                                          flow to the placenta which is your umbilical arterial circulation, the brain
         5.   Scoring system                                              and the heart and you can see under a chronic hypoxemia - the white boxes
                                                                          - that everything else is diminished. This tells you how well adapted the
              a.   Each parameter ranges from 0 (abnormal) to 2           fetal circulatory system is to environmental stress resulting in chronic
                   (normal)                                               hypoxemia.
              b.   Total score >8 is normal; <4 is abnormal               If we take a look at the Doppler examination itself, again it is a very simple
    B.   Alternative approach                                             technique and that has really been part of the appeal because you can do it
                                                                          in an office. The technology now for operating the Doppler equipment is
         1.   Concurrent recording of all parameters under standardized   really very simple and it has been made even simpler because it has onboard
              conditions                                                  computers. It is the same technology that we have used for years to just
                                                                          capture fetal heart rate. It is just specially adapted to both an auditory and
         2.   Data relaxed to institutional normal values                 visual display that captures the waveform that is unique to the umbilical
         3.   Value >two standard deviations from normal: abnormal        arterial circulation. I can take anybody from scratch who has never done it
                                                                          before and make them experts in about 20 minutes. The probes here are
         4.   Test performed for 60 minutes                               standardized, generally operating at about 3.5 MHz, and we get a nice
         5.   Normal test: all parameters normal                          display screen. When we use the continuous wave, which are the cheaper,
                                                                          more mobile machines, we generally take a look at the cord with a real time
         6.   Abnormal test equals two or more of the parameters          ultrasound before so we pick a part of the cord that is neither near the
                                                                          beginning, near the egress of the cord from the abdomen, nor near the end
              abnormal PR decline >50%
                                                                          where it is implanted into the chorionic plate. Because in that intervening
                                                                          space it makes relatively little difference where you intersect the artery
                                                                          when you are doing repetitive examinations.


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V.   Summary of Previous Clinical Experience                                     If we are going to be more sophisticated and use a continuous viewing
                                                                                 system, the so-called duplex Doppler system that you have in most of your
     A.   Benefits
                                                                                 mainframe ultrasound machines, then there are a couple of issues that
          1.   Improved detection of anomalies, intrauterine growth              become critical. One is your scanning angle or angle of insonation. The
                                                                                 advantage of this, of course, is that you can see your waveform unequivo-
               retardation (IUGR) cord problems                                  cally as you are scanning your vessels so you know that you are not looking
          2.   Diagnosis of neuromuscular, neurologic problems                   at something else. But I can tell you as well that the data that you get from
                                                                                 this approach are very, very similar to those that you get from a good
          3.   Two or more abnormal parameters appear to increase                continuous wave machine that is well aimed.
               sensitivity
                                                                                 I throw this in here. We have color and I am sure many of you have color
          4.   Corroboration of abnormal fetal acid-base.                        also. Is there an advantage in using color in terms of insonating the umbilical
     B.   Drawbacks                                                              arteries? I would submit to you that it unequivocally tells you that you are
                                                                                 looking at arteries… well, maybe that is going to be an issue… it certainly
          1.   Placental grade: not useful                                       is helpful when you are dealing with babies that are oligohydramniotic. So
          2.   Fetal breathing affected by                                       it helps you visualize the cord and aim your Doppler probe better. It is not
                                                                                 absolutely necessary and you can effectively do this kind of insonation
               a.    Diet                                                        without having color.
               b.    Labor
                                                                                 Again, what you are doing with either approach is you are sending a beam
               c.    Time of day                                                 into a moving stream of red cells. These red cells will send you back a
                                                                                 reflection that is at a slightly different frequency. There is a shift. You hear
          3.   Tone: questionable benefit
                                                                                 it. It is the "whoosh-whoosh" that you hear. That is the difference in
          4.   AFV: no standards                                                 Doppler signal going in and reflective signal coming back. It is processed
                                                                                 by your machine and then it is displayed on the screen. The display on the
          5.   Time-consuming, labor intensive, expensive                        screen, the so-called waveform, is really a Fourier transformation of zillions
          6.   Not proven superior to FHR testing with or without AFV            of data points that are all reflected by these populations of red cells that are
                                                                                 moving in different directions at different speeds. You could never deal with
               assessment                                                        this on a three-dimensional plot. It would look like a mountain range so it
VII. Doppler Velocimetry                                                         is reduced to two dimensions by Fourier transformation.

     A.   Fetal-placental circulation                                            There are different ways of dealing with the waveform. Most of the
          1.   The fetal umbilical-placental circulation                         schemes use a peak. Either a peak to trough, the so-called S/D ratio or a
                                                                                 peak to mean velocity. A peak to mean velocity is the so-called pulsatility
               a.    Anatomy                                                     index. There are advantages and disadvantages to both approaches. They
                     (1) The fetal cardiovascular system is characterized        convey similar information. The only advantage of using the pulsatility index
                                                                                 is when you have either an absent or a reverse end diastolic velocity, you
                            by a relatively high output, low pressure/low        can still get a number. Not that it is necessarily important if you ever have
                            resistance network which oxygen delivery is          an absent or a reverse end diastolic velocity.

                            regulated                                            We generally take a number of cycles. We sample them. We average them
                                                                                 and this reduces the likelihood that the fluctuation you see from session to
                     (2) Blood flow is phasic and influenced by
                                                                                 session is going to be just due to an observational technique issue. We do
                            (a) Cardiac cycle: systole and diastole, which       at least three repetitions. We take about 15 cycles and then we pool them,
                                                                                 average them and come up with our results. Our onboard computer, of
                                provide two surges; the direction of flow is
                                                                                 course, gives you the PI. It gives you also, I should mention, the resistance
                                rate-dependent                                   index because you will see this in some publications. It is the peak less
                                                                                 trough over the peak. Again, PI and S/D and RI all convey similar types of
                            (b) Afterload: increases with peak systolic flow     information. They are not really apples and oranges.
                                and decreases with peak diastolic flow
                                                                                 If we take a look then at clinical interpretation, which is really sort of the
                            (c) Breathing: increased tracheal pressure in-       big payoff here, what is the clinical interpretation? What do we get from
                                creases venous forward flow and umbilical        that? You are going to get a number. Obstetricians are enamored of
                                                                                 numbers. We have Apgar scores, we have Bishop's score, we have the
                                vein pulsations                                  breech score, we have various pelvic scores. I mean, we really love numbers
               b.    Umbilical vessels                                           and this is a number so we should love it. But we have to understand how
                                                                                 to use it and what it really means. What it really means is nothing unless you
                     (1) Two arteries                                            have a scale of reference in which to apply the number that you get. If you
                            (a) One     to   two   millimeters   in   diameter   don't have that then all that you have is a number. There are times when that
                                                                                 is not necessary and there are times where you have abnormalities of your
                            anastomosing at chorionic plate                      end diastolic flow. Remember that it should always be a positive waveform
                            (b) The number of cotyledons and three orders        in diastole and the only time that the positive waveform disappears are
                                                                                 under circumstances of extremely increased downstream resistance.
                                of branches are constant after 14-16 weeks       Depending on degree, it may disappear or it may appear on the other side
                                                                                 of the x-axis.
                            (c) Growth results from proliferation of terminal
                                syncytial budding stemming form capillary        In addition, we look at this clinically in sequence over time because this is
                                                                                 not a static observation. It is a moving target. If we take a look at here at
                                plexus which protect villi from blood pressure

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                       (BP) changes                                   what is known for normal pregnancy, and we now have a lot of data on
                                                                      normal pregnancy, basically over time there is a decline in the overall trend
              (2) Intervillous pressure: 10-15 mm Hg
                                                                      of the S/D ratio or pulsatility index as the fetus becomes more mature. The
              (3) Umbilical arterial pressure equals fetal systemic   reason for that is really very simple. Over time as the placenta increases in
                                                                      size, your downstream vasculature continues to grow and you continue to
                  pressure                                            reduce your downstream resistance.
              (4) Umbilical blood flow
                                                                      If you take a look at a waveform, and this is just one graph. There is an S/D
                  (a) Peaks at midgestation                           ratio that however old the fetus is going to be distinctly abnormal and that
                  (b) Resistance falls by 3% per day                  is an S/D ratio over 4. From that point forward, an abnormal S/D ratio is
                                                                      really going to depend on where you are in gestation and that is an important
                  (c) Blood flow decreases in proportion to fetal     point. Because as you get closer to term, at 40 weeks, if you have an S/D
                       weight                                         ratio that is over 3, that is an abnormal ratio. It would not be an abnormal
                                                                      S/D ratio, say, at 30 weeks. You can see here there is a pretty broad spread
         c.   Control of umbilical flow                               between… these are the 5th and 95th percentiles so that again gestational
              (1) No feedback system for pressure or resistance,      age trends and there are few absolutes unless you are greater than 4 or at
                                                                      term, if you are greater than 3.
              not directly affected by hypoxia
                                                                      Now let's look at what happens as we start losing the integrity of the fetal-
              (2) Not innervated beyond first 2 cm proximal
                                                                      placental circulation. You start getting a gradual widening between peak and
              (3) Constricted by vasoactive agents                    trough until we get down towards the bottom here. You can see that the
                                                                      trough almost has disappeared and then at the bottom we see the trough
                  (a) Prostanoids
                                                                      appears on the other side of the x-axis. So this is a progression from normal
                  (b) Angiotensin-II                                  to absent end diastolic and finally to reverse end diastolic velocity. You very
                                                                      rarely see this evolve over single pregnancy because the absent or reverse
                  (c) Bradykinins                                     end diastolic velocity in and of itself is a very uncommon finding.
                  (d) Vasoconstriction leads to increased O2
                                                                      If we take a look, even without numbers, if you take a look at two
                  extraction                                          waveforms on the same scale, you don't have to have numbers to tell you
              (4) Flow rate                                           that this looks a lot different from this. This baby has a normal S/D ratio of
                                                                      about 2.5 and this baby has an S/D ratio that is about 5. How did we do
                  (a) Determined by systemic perfusion pressure       that? We took the peak, we took the trough and we did a ratio. Simple. This
                  difference (A-V)                                    is actually done for you. You might be able to see on the machine here, you
                                                                      actually have these computers for you on board so there is no processing
                  (b) Responds to changes in                          you have to do yourself. Here is an absent end diastolic velocity and here
                       i.    FHR                                      is one in which the end diastolic velocity appears on the other side of the x-
                                                                      axis.
                       ii.   Stroke volume
                       iii. Cardiac contractility                     Where is the payoff for this particular technology? The payoff is really
                                                                      limited but there is an area in which I think it makes sense to consider
         d.   Responses to stress                                     adding Doppler to your armamentarium. That is in the situation where you
                                                                      have a pregnancy that is either thought to be growth restricted or has a very
              (1) Acute hypoxia: redistribution or cardiac output
                                                                      high probability based on maternal disease or past history or lifestyle of
                  leads to decreased umbilical blood flow to de-      being a growth restricted pregnancy. The reason that we pick this is the
                                                                      clinical studies that have been done so far suggest that the yield is very high
                  crease in cardiac output which leads to venous
                                                                      in this particular subgroup. Further, there is a collection of pathologic
                  return                                              observations that have looked at the placentas of these babies and have
                                                                      correlated placental morphology with Doppler velocimetry.
              (2) Chronic hypoxemia: restricted placental growth
                  leads to decreased capillary bed size; terminal
                                                                      Remember, IUGR is not a pure population. It is a spectrum and you may
                  resistance does not fall or may increase            have IUGR in which the baby is asymmetrically poorly grown in which the
C. Clinical manifestations of vascular flow                           head generally is relatively spared, the body is not and then you have the
                                                                      symmetrically IUGR baby where everything is small. This is generally… the
    1.   Determinants of volume flow                                  asymmetrics are the ones that appear later in pregnancy, the symmetrics
         a.   Vessel diameter and wall thickness                      earlier and remember that the symmetrics are the ones that are more likely
                                                                      to have other very serious problems - chromosomal problems, infections
         b.   Vessel linearity and uniformity (distensibility)        and other malformations.
         c.   Turbulence: transmission and reflection
                                                                      The interesting thing here is because you are looking at a developmental
         d.   Blood volume properties                                 process in the placenta, what you are observing here is that the waveforms
              (1) Density                                             on sequential Doppler velocimetry of the umbilical vasculature may start
                                                                      appearing to be abnormal before you have any other evidence to support
              (2) Viscosity                                           that this baby is having trouble growing or adapting to an intrauterine
                                                                      environment. The general lead time can be as much as several weeks so that
              (3) Cell morphology
                                                                      if had a situation, if you had a pregnancy in which you thought that here is
         e.   Applied pressure                                        a high-risk for IUGR, mom is hypertensive or has advanced diabetes,
                                                                      wouldn't it be nice to get a heads up on things that are going to be going
              (1) Pulsatility

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              (2) Amplitude                                               wrong downstream so that you can start looking at the baby more closely?
                                                                          That is certainly something that has been observed by a number of authors
         f.   Peripheral resistance
                                                                          that have looked at the application of Doppler to this population.
    2.   Characteristics of fetal-placental vasculature
                                                                          The other area in which there has been some value in the use of Doppler
         a.   Small diameters, thin walls                                 have been twins. I am not going to belabor that point. You had a very nice
         b.   Short length, nonlinear, easily distended                   talk on twin pregnancy before. But the fact of the matter is that twins are
                                                                          more prone to having growth disturbances. They are more prone to having
         c.   Numerous branch points: angle turbulence                    abnormalities of placental circulation to begin with and discordance between
         d.   Differences in maternal and fetal blood                     twins and discrepant fetal growth are the hallmarks of twin gestations. We
                                                                          have altered the distribution of twins in our population by assisted reproduc-
         e.   Pulsatile flow related to rate and systemic pressure        tive technologies so we are seeing more of them and certainly of the areas
         f.   Low resistance systems                                      where one could apply Doppler, this area makes sense.

    3.   Semiquantitative measurements of circulation                     Again, this is sort of an extreme example. I know these babies are the same
         a.   Empirical indices of flow velocity                          age because I saw them when they born although they don't look like they
                                                                          are at all related. Here you have this nice robust twin over here and then
              (1) A:B (S/D) ratio: f(max): systolic peak/f(min):          you've got his little brother over here who really doesn't look quite so
                                                                          healthy. Here is another parable of Doppler done in twin pregnancy. This
                      diastolic peak
                                                                          is the parable of the good girl and the bad boy. Over here you see twin 1.
              (2) Pulsatility index (PI): f(max) - f(min)/f(mean)         Nice normal Doppler velocimetry, nice heart rate tracing. On the right,
                                                                          you've got twin 2. Absent end diastolic velocity, sort of a nonreactive trace
              (3) Pourcelot's ratio (resistance index): f(max) -
                                                                          here. Here you can see the graph of twin 2. The bad boy who never has
                      f(min)/f(max)                                       normal Dopplers in the third trimester and the good girl's whose Dopplers
                                                                          are always within the normal range and so you go ahead and deliver these
              (4) Frequency index profile: median of peak/mean            babies. You sort of split the difference and deliver them at about 34 weeks
                      during cycle                                        and the good girl weighs 2,000 grams and the bad boy weighs 1,000 grams.
                                                                          The point here is as an adjunct to measure to supporting your hypothesis
D. Doppler studies of normal and complicated pregnancies                  that the placenta is not functioning well in a discordant growth that again
    1.   Normal pregnancies                                               Doppler has a role in twin gestation.

         a.   Waveforms are characterized by high flows with low          As a sole screening modality for fetal well being in the third trimester,
              resistance                                                  Doppler is very limited. Again, I show you this slide for the NSTs. Here is
                                                                          the same basic slide for Doppler. The big four. Postdates, diabetes, IUGR
         b.   Curves generated across pregnancy are similar for           and hypertension. Not surprisingly, the only populations in which Doppler
              systolic/diastolic (S/D) ratio, pulsatility index           appears to have potentially assisted detection of compromise have been the
                                                                          IUGR and the hypertensive group and you can see that is really below 50%
              (1) Slope changes at 28 and 36 weeks                        sensitivity here. In the diabetic group and in the postdates group it is
              (2) Variation inversely proportional to gestational         relatively useless. The only exception in the diabetic group are those who
                                                                          have advanced diabetes with vascular complications. So we don't do it all
              length                                                      in our postdate pregnancies. We long ago abandoned using Doppler in that
                                                                          group and we focus on the hypertensive, IUGR and multi-fetal gestations.
         c.   No significant effect with changes in viscosity either at
              high shear (RBC aggregates broken up) or low shear          In closing the session on Doppler, I have to tell you the reason that I spent
                                                                          time on this subject is that Doppler is the best studied from the standpoint
              (RBCs clumped)
                                                                          of evidence and outcomes based of all of the modalities that I have shared
         d.   No significant relationship to umbilical venous flow        with you this morning. There have been about a dozen trials in the past
                                                                          decade that have been reported in Europe looking at umbilical Doppler.
    2.   Intrauterine growth retardation                                  Nine included only high risk patients which I think really is the province of
         a.   High sensitivity and consistent finding of elevated flow    this particular investigation. If we take a look again of this table of
                                                                          outcomes here, if you look at all of the outcomes and this is all of the trials
              resistance indices                                          pooled together, what you see here for the most part is that if you look at
         b.   Worst prognosis associated with absent or reversed          general populations, there appear to be no advantages in using Doppler. If
                                                                          we focus on perinatal death, this is now getting into the general population,
              end-diastolic flows                                         perinatal death as an endpoint, what you see here in the area of most
         c.   Highly predictive or placental pathology                    importance is stillbirth because that is something we can do something
                                                                          about potentially by antepartal surveillance, you can see that we are starting
         d.   Histology: obliterated or reduced terminal arterioles in    to make a dent. In fact, the application of Doppler as part of the surveillance
              villi                                                       in the high risk populations resulted in a 38% decrease in stillbirth and this
                                                                          contributed to about a 33% fall in overall perinatal death and this was
         e.   Separate population of IUGR fetuses with anomalies          significant. You see this confidence interval falls below 1. If we focus only
              had normal S/D ratios, indicating nonplacental source       on high risk pregnancies, which is the true province, it is even more
                                                                          dramatic. You can see here that perinatal mortality falls by 50% or greater
              of problem                                                  for stillbirths in the population in which Doppler was used as part of the
                                                                          screening modality.
         f.   Waveform indices may be elevated weeks to months
              prior to clinical diagnosis of IUGR. This sign is typi-     If we take this to heart, what we can we really take away from this? First
                                                                          of all, these were not trials done in the United States so you could attribute
              cally, the first abnormal sign in testing schemes

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     3.   Multiple gestation (twins)                                     this to different forms of antenatal care. They were trials that are done very
                                                                         close to our particular era of practice. That in addition, we could either say
          a.   Clinical concerns
                                                                         that we refuse to believe this because it wasn't done in a U.S. center or we
               (1) Relative IUGR after 28-29 weeks                       can say that perhaps there is something to the addition of Doppler to
                                                                         selected high risk populations. That, in fact, that if we are to really call it
               (2) Twin-twin transfusion syndrome                        like it is, let's now put our collective thoughts together and perhaps retrace
          b.   Methodology                                               where we have gone this morning before I open this up to general questions
                                                                         once again.
               (1) Realtime scan to locate individual cords
               (2) Values are similar to singletons except when IUGR     What are we really trying to accomplish with antepartal testing? We are
                                                                         really trying to prevent stillbirth, but preventing stillbirth due to possible
               is present                                                preventable causes and what is the major preventable cause is preventable
               (3) Twin-twin transfusion syndrome characterized by       perinatal asphyxia. So I am backing this up because really if we had a good
                                                                         way of reliably reproducibly measuring health so that we could confidently
                   size disparity with equivalent S/D ratios             say that asphyxia is either present, the risk of asphyxia is either highly
          c.   Study results: S/D ratio differences of >0.4 associated   present or highly absent, that would be a giant step forward. A relatively
                                                                         accessible testing scheme which uses clinical features that we can get our
               with IUGR                                                 hands around to identify fetuses at such high risk that labor should be
                                                                         avoided and perhaps early intervention should be encouraged. Translating
     4.   Diabetes mellitus
                                                                         that possibly into model systems to even improve our ability to forecast
          a.   Few data reported indicates that, regardless of           intrapartum outcomes before the onset of active labor. Because you know
                                                                         that the intrapartum area is where a number of unforeseen problems might
               size-for-dates classification, elevated S/D ratio sug-
                                                                         occur.
               gests an arrest of fetal growth over time
                                                                         Now, if we take a look at antepartal testing, if accelerations are present, the
          b.   Elevated S/D ratios are also associated with higher       likelihood of not having an asphyxiated baby is pretty high. If accelerations
               incidence of perinatal complications                      are absent and persistently absent, the likelihood of having a baby that is
                                                                         affected by hypoxemia or acidemia is almost as high but not quite as high.
     5.   Normal labor                                                   If we look at heart rate variability, as measured objectively by computer, not
          a.   Fleischer et al in 1987 studied twelve normal             by the eyeball, normal variability, again, very low likelihood of asphyxia.
                                                                         Certainly not zero and if variability is abnormal or absent, again, very high.
               parturients                                               Decelerations the same story. So what you see here with antepartal heart
               (1) No significant differences in S/D ratios during any   rate testing is that, again, normal or abnormal antepartal heart rate testing
                                                                         alone approaches the target but you can see that you have to be willing to
                   phase of uterine contraction                          accept a significant error. I would call an error of 15-20% in calling a baby
               (2) No differences noted between latent phase, active     well and an error of 30-40% in calling a baby ill a significant error. Because
                                                                         it means that you are going to intervene much more likely on a baby that is
                   phase, after rupture of membranes, or with            going to be well on the one hand and you are going to miss babies that you
                   administration of oxytocin                            should have delivered.

          b.   Smart et al in 1981 studied ten normal patients with      Now let's look at biophysical profile testing. If you look at biophysical
                                                                         profile testing, if you have a score of less than 8, there was a 90%
               similar findings
                                                                         sensitivity in positive predictive value for asphyxia. This was a selected
     6.   Postdatism                                                     population delivered without labor. If you look at Manning's study, looking
                                                                         at the correlation of biophysical profile with cordocentesis for blood gases
          a.   Recent ,data suggest that S/D ratio may be a good
                                                                         done at the same time, there is a stepwise linear relationship between
               predictor of perinatal morbidity in this population       biophysical score and umbilical venous pH. If you look at a computerized
                                                                         biophysical profile that we do in cord blood gases, there is a linear
          b.   S/D ratio is not reflective of oligohydramnios            relationship between score and ultimate umbilical artery pH at delivery. So
     7.   Establish relationship of velocity parameters to clinical      again, it suggests that biophysical profile testing by multiple components
                                                                         moves you a step closer to making a good assessment for the absence or
          conditions                                                     presence of asphyxia without either over or undercalling the situation.
E.   Conclusions
                                                                         If we look at Doppler velocimetry, again, as a sole predictor, this varies a
     1.   Doppler waveform analysis is a relatively new application      lot from study to study but the bottom line here is that as a sole predictor,
          which can be performed with moderately priced equipment        that again, is no better than any of the other isolated tests that we do. Again,
                                                                         these are based principally on high risk populations. You might ask
     2.   The semiquantitative measurement of velocity waveforms         yourself, "Gee. What does a 40% likelihood of hypoxia do for me?" I can
          are now generated by current hardware, and are relatively      assure you if somebody told me that this baby has a 40% likelihood of
                                                                         getting hypoxia, that would get my attention. We intervene for likelihood
          reproducible throughout gestation                              of compromise far, far lower than that in our obstetric practice. That would
     3.   Doppler information can be obtained rapidly by easily          get my attention.

          trained personnel
     4.   The usefulness of Doppler measurements of fetal umbilical
          vessels remains to be established but shows promise in
          the evaluation of fetuses at risk for IUGR

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The markers for perinatal asphyxia, conventional testing, trying to use what we currently have to predict it consistently or
sufficiently early really have problems. I am being very honest with you because part of my career has really been in this area. I
am saying that we have to understand that there are limitations in trying to go after this target. When we look at studies, remember
that we are looking at studies that are all population based and the populations, even though I have melded them together to give
you these meta-analyses, the populations may tend to be somewhat different from each other. My population, I know, is different
from yours. They don't talk the same way. Their lifestyles are different and therefore the findings from one state might not be
generalizable to another. In reality, there should be a lot more work done in this area. Even though it has been around for two
decades or more, some of the real seminal basic work that should have been done has not been done and that is a pity.

But I think that also gives us an opportunity here to look at where we should go. These are areas that we are working at and other
centers are working at to give us a better handle on how to best assess babies. I happen to be an advocate of the computer approach
because I think that deals with a lot of number crunching that is very hard to do with pencil and paper. But also there is context.
We should really approach this issue of perinatal assessment trying to uncover the risk in these babies and we should do it really
with the knowledge that we already know a lot about each pregnancy, or we should. We should know a lot about the antecedent
risk factors. We should know a lot about that patient's prior history. We should know a lot about her current state of health and
the things that are really putting this baby at risk. Those invariably should reflect on how we interpret the data and how we use it.
That again means that you do have to do some individualization.

There is, again, little question that if you get your hands on a high risk pregnancy early, then you are able to establish early the
baseline age of this pregnancy through good ultrasound, rule out anomalies through good ultrasound. Make an assessment of where
you are starting from, again, with good ultrasound, and using that as your backbone, you will end up with a better scheme for
prospectively following this baby. I am not dismissing the possibility that as we get further into the information age, that some of
this assessment could be translated into a home environment. So in other words, we could take patients that we don't want to have
doing a lot of running around, we can bring technology to their homes through home visits, through telemetry, bring it back to us
and make it actually more convenient for our patients. I know that is probably more difficult to do in Chicago where you have
weather. We don't have that problem. We just have a fairly difficult road structure to deal with. But that is again something that
I am sure is going to happen progressively more and more in the future.




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