Player is loading...

Embed

Embed code

Transcriptions

Note: this content has been automatically generated.
00:00:00
actually i have to uh
00:00:03
okay good morning i yeah um it's really great pleasure
00:00:08
for me to e. i. you have you
00:00:13
um and i'm actually one of the persons who studied in the oven
00:00:17
and work for it uses you eat but never visit our own
00:00:21
oh i definitely will take advantage to see this lovely city often
00:00:27
oh so many thanks too much laughs especially you asked me to uh give
00:00:32
you an overview of this non invasive fit the native diagnoses are um
00:00:38
and he on this first slide you see actually the different things that are
00:00:43
currently use when you talk about non invasive could make hats thing
00:00:48
and that matters actually are asked me to give you
00:00:51
an overview on that non invasive prenatal screening
00:00:56
most common and i like the water so far where a chromosome abnormalities
00:01:02
and this is the screening k. which means it required config nation wide screen i
00:01:08
believe by invasive testing war from your native was off to the delivery
00:01:14
and that it has to be distinguish concerning in on
00:01:17
basically made diagnoses where they have like no
00:01:22
which does not require it creates sequent confirmation so i'm going to concentrate
00:01:27
on this creating maybe but i notice that all the time yeah and
00:01:31
you might get that goes it currently is we even more confined
00:01:38
since uh mainly for totally hate it i mean that in conditions
00:01:45
so this is the program i thought to start with some basics
00:01:49
oh for a an i. p. s. and then i will continue with if you um information about
00:01:55
the conventional screening test uh for the most common trying to me i also would like to
00:02:01
very few things about the expanded n. i. t. and uh and
00:02:05
all these challenges that are associated with an i. p. s.
00:02:10
so wonderful to wouldn't but there are many things uh at that a benefit
00:02:14
also way complex affable c. and that will finish with some conclusion
00:02:19
so the media that if i'm i've been an i. p. t. if the so called said if we
00:02:25
feet will d. n. a. image on the block but be careful this is actually
00:02:30
not quite true because what you are alive if plus i call
00:02:36
the anyway
00:02:39
because of this sheet of d. n. a. fragments originate from the
00:02:43
placenta and this is extremely important to keep in mind
00:02:49
just small fragments they're not self besides your neck fragments and that
00:02:53
you can protect them already from the fifty weeks of gestation
00:02:57
the concentrates it rises uh with the age of the pregnancy
00:03:02
and very important also if your allies these fragments you all with an allies
00:03:07
the maternal hand to defeat respect if the path and put your name
00:03:12
this is a well uh showing here this is the best uh from the mother to
00:03:15
green amount i defeated so called features that you see it originates from the thing
00:03:21
and so this means that each deviation that you will fee
00:03:26
actually can originate i go from the placenta or for that matter
00:03:33
to tell the proportion of these feet lower percentile d. n. a. is to
00:03:37
do forty percent the and uh and used to you should not
00:03:42
suggested before ten weeks because you need a quite an
00:03:46
uh a proportional futile d. n. a. e.
00:03:49
and usually after ten weeks you should be fine um because then you have at least ten percent
00:03:55
and the elegant thing about that is that after the delivery this uh f. e. t. d. n. a. is
00:04:01
disappearing very quickly so you don't have to risk of contamination of
00:04:06
former pregnancy which is always that problem when analysts else from defeats
00:04:13
so there are many different uh methods to penalise uh these uh
00:04:17
d. n. a. fragments and the most commonly use is
00:04:20
a quantitative analysis and again you analyse quantified
00:04:25
the feet will the maternal b. n. a. molecules for each comes on
00:04:31
which means actually that you need the validation for each chromosome anomalies
00:04:36
that you would like to give without in the past so you need
00:04:39
a normalised comments on the value for each comes on abnormality
00:04:44
so this is a show in here with this uh scheme ah so these are the d. n. a. fragments and
00:04:50
you see the blue argument all notes and why it should be defeat now and see for instance you have
00:04:56
case of twenty percent to feed that yeah right so you
00:04:59
have to have a validation for each chromosome separately
00:05:03
and he for instance you see when you are a confronted with the
00:05:07
tried to be twenty one when says then you have more
00:05:10
uh d. n. a. molecules of the chromosome twenty one and this has to be quantified
00:05:15
for each chromosome abnormality and it's given usually in the form of sets course
00:05:21
and he on the slide you see that uh for instance all these colours at different patients
00:05:26
and what is also very important to real life is that most lab
00:05:31
or two is although that can't it's only for twenty twenty one
00:05:35
eighteen and thirteen beefy that's that's course of all chromosomes usually
00:05:42
soho when she you know and that it's it's
00:05:45
so that's why sometimes maybe you have already had that experience that you bought all to do without that that
00:05:52
the lab says well we found that way to me sixteen or whatever because they see everything for most
00:05:57
platforms that i used easy for instance these are the chromosomes
00:06:01
here downstairs he other sets wasn't used to try
00:06:04
to be thirteen this is it twice in eighteen and this is uh trying to me twenty one
00:06:09
uh so we realised that the d. n. a. from
00:06:12
defeat orange inaudible effect will be fixed really important
00:06:16
and they have invaluable validation sway sake that you need at least four percent
00:06:22
and this should be marked on the report so this is always very important that you lock
00:06:28
hell is the d. n. a. a fraction from feed for the present
00:06:33
no that's like some life a little bit the big differences between the diagnostic comes all modalities and the n. i.
00:06:39
and this is very important especially for the new technologies because sometimes maybe you have a child from
00:06:45
had an i. p. s. and then use off question but is this if sufficient can i
00:06:51
be reliable understand what uh if you have a suspicion of ties between one nevertheless
00:06:57
would fit me so standard diagnostic coyote type gives you an ounce of wall
00:07:02
and appointees including people in the white board and to know that most
00:07:06
of the n. i. t. f. don't give a announced on that we played
00:07:09
you only want the panorama that maybe wouldn't know especially adult situations
00:07:15
a diagnostic standard cat that gives you whatever is out on the most
00:07:18
like that means that the on one without and twice i mean
00:07:22
partial tries to meet the rear but thinks it's in try to twenty one finds it's less than one percent
00:07:29
but it it it means that only part of the twice i mean that is that three times there
00:07:34
what i even tried to twenty one is two to three percent where that
00:07:39
makes it then that's that's got that gives you also and on
00:07:42
on all the tracks locations in versus either comes on sunday important here
00:07:47
each isn't duplications this means that the the little piece that is missing or toppled
00:07:54
and here see this that that kind of type gives you the without when they certain size only
00:08:00
and the size was defined as more than five megabyte bank wouldn't to keep in mind
00:08:07
because nowadays especially for the if michael deviations
00:08:12
no those are actually smaller than five michael basis and that's why actually now if you have
00:08:18
before comes on an abnormality actually this that that kind of type was
00:08:22
replaced by the so called microwaves which see the smaller deletions and
00:08:27
that's more than five make a basis like the michael division twenty q. one one
00:08:31
really unsuitable men many many many more with hundreds of them exist actually
00:08:37
not that i'd keep the convection no gives you a non
00:08:42
thing about as we twenty one eighteen thirty even pop
00:08:46
does not if you without about logan was like for instance if you have a child was
00:08:51
alone was like twenty percent within a p. s. have not even you these off
00:08:56
or the parser tried to me is we don't know your base not sufficient data here to say
00:09:01
how is the performance for parser tries to me think if you the convention i like yes
00:09:06
then the expanded and i guess that means that you also check out the chromosomes
00:09:11
yeah it's important to keep in mind concerning the deletions out my
00:09:15
could deletion panels where they test for the most common
00:09:19
he shuns this is fine if you do it genome wide
00:09:24
deletion test you see that the one that you
00:09:29
uh can i am may see our big once they are so that means that
00:09:35
an expanded and i please even if rather than the standard kind of time
00:09:41
see you more than seven megabytes isn't as bad as i thought it gives you more than five
00:09:46
it's very important to keep in mind so no oh and i. p.
00:09:49
s. approach replace the diagnostic comes on and that is no today
00:09:56
now let's talk about the conventional an i. p. s. since two thousand
00:10:00
twelve it's commercial license switzerland and it's two thousand fifteen it's reimbursed
00:10:06
according to the list of analysis i actually since two thousand eighteen it costs
00:10:10
five hundred intent with facts and it for twenty one eighteen and thirteen
00:10:15
and you see you that it has to be reported it if you could fraction
00:10:20
and would you also see is that it's windows if two weeks it's
00:10:23
one empowerment or higher for these three couples one on it
00:10:28
and the character performance for these we come with homeland it's really good and i show you
00:10:32
get cable a format big meant that analyses which was published in two thousand sixteen
00:10:38
at the group of patients and this the group actually compare yeah to do
00:10:42
without for cans it won't twice me eighteen it had to be thirteen
00:10:47
for the general up static populations so for high low with we mean
00:10:52
when i was population so women we have a high risk for one of these three and up ladies
00:10:59
so what is interesting is the positive predictive and this is actually the first thing to look at
00:11:04
i do see actually eat for the highways population for down
00:11:08
syndrome is ninety eight percent which is actually quite
00:11:11
good that means that ninety eight percent of the positive test results are we've tried me twenty one it
00:11:18
yes good for twenty eighteen and the also it's good for twice a month so t.
00:11:23
and what you see here actually for the channel of thirty population so for what we've been
00:11:28
specially for young women the positive predictive but it's still good for twenty twenty one
00:11:33
but actually not good for twelve and thirteen and eighteen so you have much more
00:11:38
false positives can we put it in the low population uh a pregnant woman
00:11:44
and this is due of course because that that reportedly predictive value correlate with the prevalence
00:11:49
of the disease which is of course less common in low with young women
00:11:54
now what about the probability of false negatives this is a pool of course important for union
00:11:59
anthologies because you have a child and you have a suspicion maybe of twenty twenty one
00:12:05
what can you say so you see it um the probability of a
00:12:09
false negative is again high in the highways population especially for
00:12:14
titan eighty one eleven thirty at very low negligible in the and
00:12:20
the general population of of women especially for the younger ones
00:12:24
and that this fact that i think it's really interesting and if he shows you
00:12:28
really nicely that to the positive predictive value varies with the maternal age
00:12:34
and as you can see in young women here on this access you have to meet women h. e. the positive but if you had a blue
00:12:39
what let me twenty one that's what i do see that it rises with
00:12:43
the age of the market so do with of a false positive
00:12:47
it's especially high for younger women so if we can say where they have uh with
00:12:50
with one in ten thousand to twenty five years but they want to do it
00:12:54
you have to be aware and to tell them especially don't situation that actually she takes a rather high risk
00:12:59
to have a false positive then to find anything and this is very important to keep in mind
00:13:04
so the performance if we pull all this without the sensitivity and specificity for this week
00:13:10
is absolutely great so there's no doubt about it i guess especially higher than
00:13:15
the normal traditional first as a timid screening way to have actually detection wait for twenty
00:13:20
twenty one for ninety percent and the false positive rate of five percent so clearly
00:13:25
uh these uh uh are the conclusions that are generally accepted for these to
00:13:30
weaken with normal abnormality definitely it uh it is uh the best test
00:13:36
especially for twenty twenty one a little bit less good for twenty meeting thirteen back up
00:13:41
it's not a hundred percent accurate so it should not be used as a final diagnosis for positive without never
00:13:48
so each an i. p. s. positive or negative it's a screening test and we'll put it does have to be confirmed
00:13:56
now what about the sex chromosome and operates
00:14:00
so within forty six six forty seven six six or climb effect so most
00:14:07
platforms than most providers they offer which routinely the six uh comes up with i think
00:14:12
but it at a good controversial because of cool with these thing
00:14:16
uh types don't we have fulfil the criteria for population screening
00:14:22
and we have to know that the accuracy is not as good as
00:14:27
to try to twenty one thirteen and eighteen which is shown here
00:14:32
uh uh i thought the that was published uh last year and where val wait i'm different
00:14:38
and that sex chromosome abnormalities uh one with us with one hundred
00:14:42
and thirty six and you see that the document it
00:14:46
confirm remote confirmation cabinet type is only in sixty four percent of the case because according
00:14:52
to the cancelling that the patients had maybe they said well we accept it
00:14:56
and they did not confirm that if they accepted to confer i'm
00:14:59
you see that positive predictive value is actually not that good
00:15:03
and it is really bad for the x. chromosome as you can
00:15:08
see here only twenty eight percent for forty six weeks
00:15:13
fifty percent for what republics and this has a reason
00:15:19
because you have to know that we wait and we lose out its comes in with that wage all of us
00:15:26
so you remember you pass the potential maternity and i so
00:15:31
many times actually you just have to to the market
00:15:35
so be careful especially if you do it in say old within and we have a tendency of have
00:15:42
more more or do we mean that that it older than thirty five so be careful about that
00:15:47
yeah you can have an on like knows but twelve sex chromosome abnormality
00:15:52
it's not the way that the the lady which hath yourself before
00:15:57
and it has the twelve and the bait yeah sure
00:16:00
and forty five x. it's a very common confined to saint louis up no matter
00:16:04
so that you just have it didn't placenta but it does not little affect the chart so you see
00:16:11
these are very complicated cases of course many people would like to know
00:16:14
the sex with people it fine but be careful because if
00:16:19
if you are confronted then in kind of sex chromosome abnormality that you found and
00:16:24
the officer this completely normal this is really a difficult on that point
00:16:31
so you see that many challenges of this in i. p. s. and so
00:16:35
i would like to summarise again the false positives the confined percent moderate
00:16:40
is found in wanting to be sent off when you do a korean as well as biopsy so you have to
00:16:46
be aware that you will find all so was i season because you test the placenta
00:16:51
d. n. a. and probably this rate is higher because you pass the hopeless that
00:16:58
banishing twain very important to know he caught the vanishing to it can be it and then i'll probably d.
00:17:06
so this was so the self this white and that you know it goes
00:17:10
into circulation of the month so you may have to the vanishing twine
00:17:14
we should not don't when there is a tension between story
00:17:18
also i want to know that our and nobody's can can then have a kind of a
00:17:25
a fact also on the validation to pointed to devalue shade of twenty twenty
00:17:29
one thirteen and eighteen so this can also give a false positive
00:17:33
private on the organ transplants very important to us before you do
00:17:37
it in i. t. s. because for instance if you have
00:17:40
i laid you had advanced that format may i don't know you would find why
00:17:47
chromosome in the d. n. a.
00:17:50
so then you will be standards because you have actually uh
00:17:54
if you have a female ultrasound advanced always start as you can imagine technical problems
00:18:01
of course always a reason for false positive and then is incidental findings maternal was like
00:18:08
i have each year three to four ladies who problem with the forty five takes without and they
00:18:14
are have to be fun because all of a sudden they are herself forty six weeks mostly
00:18:22
but on a copy number right it's it's not we add that we
00:18:24
have found my conclusion twenty two q. one one integrated one
00:18:31
because of the and actually if the child has nothing but the one that's
00:18:36
because it has the placenta handed them out
00:18:40
error in last but not least mail but john goodman latency can be discovered is that
00:18:46
because the south of the malignant tool it's also destroying go with the circulation of them out there
00:18:52
and so this is they typically if you have a profile with many many different and nobody's on one of them is
00:18:58
and this in say that actually you would have a mother with that you like and we had we think yet
00:19:03
it's a two year old lady who did the test much although she had with one in nineteen
00:19:09
thousand but will that her friend stuff that says you wanted to do with this one
00:19:15
and being all we found
00:19:17
okay the front and nobody's because you remember it the lab sees the result of or the common so
00:19:22
and this is really a strong indication to look for to mike and being goes you had that much good
00:19:29
everything went well and finally we can say well luckily that we found it
00:19:34
but this has to be discussed before because this is a of was very very challenging and false negatives
00:19:41
no twice what i it partially twice a means then that more site confined to
00:19:46
defeat that's very rare but it takes place that actually if it does
00:19:50
have the twice only twenty one hundred percent that has nothing you'd have the
00:19:54
fact that not if you remember that and finally insufficient feature faction
00:20:01
so this was about the sex chromosomes and now what about expanded in i. p.
00:20:06
f. so this is also a a lot of platforms instead of this
00:20:13
and mainly actually to identify the copy number creating so good uses and applications
00:20:19
it may be justified because as you can see here um significance
00:20:23
in v.'s p. in one point seven percent of pregnancies
00:20:28
it's a big figure actually but most of them are way up there anyway so
00:20:33
that we have again the problem of the positive predictive value you remember
00:20:37
so they are michael deletion which offered the testing off the most column
00:20:42
micro deletions you see the sensitivity if uh not that bad
00:20:47
now what about the whole genome and i please so he again i repeat myself
00:20:51
but keep in mind that actually you only see large c. n. b.'s
00:20:58
so um and make it if it's part of an i. p. s. especially for new methodology used
00:21:06
that's not the whole replace my could deletion a micro array analysis in no way today
00:21:14
and the positive predictive value is where it but it slows already so actually
00:21:20
here we are a little bit in a conflict because this kind of
00:21:23
stuff do without the may actually negate the benefit of convention yep yes which
00:21:28
is to be due with the fourth but the polls positive without
00:21:32
for comment resumes and to reduce the invasive testing so
00:21:38
now what about the target and nobody's tries to me sixteen fifteen k. tonight all
00:21:45
the others so these are sort of way of some of the things that
00:21:49
are not viable when they are quickly so if we see them and they're
00:21:54
good at the pagan c. is a productive it must be a mosaic
00:22:00
so could defeat moderate or a placenta mosaic
00:22:05
no you see that one side evaluate that they only eight percent
00:22:09
uh off the n. a. p. s. without for where noticeable tried to meet
00:22:13
well we have to save it with the two feet look more time
00:22:18
now you can argue that and this is argued that some confined
00:22:23
content model isn't it more that may be associated with into
00:22:26
two groups with today she pregnancy complications so it makes sense
00:22:29
to know the origin of this but this actually is
00:22:33
evaluated for tries to be fixed you there uh they thought that didn't you you can correlate it but remote
00:22:39
out there's the confined percent more than i actually don't really know what we can do with this without
00:22:47
then maybe a justification to look for a big hole so if you have a chromosome that is involved
00:22:53
where you have been printing possibilities like on some seven eleven fourteen or fifteen
00:22:59
this may prompt and look for uni planted by the mean
00:23:02
defeated okay bought in general is a lot of uncertainty
00:23:08
concerning the clinic the significance of this way of the someone tries to me and the optimal management is not yet
00:23:14
clear so that's why i actually minnows substitute and genetic professionals fight this apparently
00:23:20
we comments to do the n. i. p. s. for the current
00:23:23
uh for the conventional twenty twenty one thirteen and eighteen
00:23:28
in or populations actually not always only in that in
00:23:31
the highways bought without sex chromosome anomalies without where
00:23:36
out so much why the me and without this young between me and the reason actually if that
00:23:42
we would like to have a benefit for the patient and if it's not so far sufficient
00:23:47
evidence here that we really do days so as you can see the clinical utility of
00:23:53
except for the annotator thing to include panels of mike but the reason she nonwhite assessment
00:23:58
has yet to be demonstrated as such to clinical implementations so far of this testing to be
00:24:03
me too but this is quite a new this is just channel two thousand and ninety
00:24:09
so we also they this in switzerland we have here a an expert a commission
00:24:14
that we work together with the s. s. acted immediate meeting fit that
00:24:17
this with society of medical genetics and that this with society of china coaches
00:24:22
and you can find this one each bedside and also be it so
00:24:28
think conclusions that it's clear that the n. i. t. s. for the twenty
00:24:31
twenty one thirteen and eighteen is the most sensitive and specific screenings
00:24:37
so that social whether one has to be aware that the
00:24:41
positive predictive value is lower anything lower with population
00:24:46
all highways and ideas results require confirmation it can be that it only off to that it will be
00:24:52
because some patients say well we wanted to know the with for twenty twenty one but we
00:24:58
i don't want to have to with often invasive type things of the new right then have to confirm this after that we
00:25:05
now the routine screening for sex chromosome abnormalities deletions duplications and we end
00:25:10
up ladies is currently network not recommended by most professional societies
00:25:15
and especially for the neon nice um and negative even
00:25:19
expounded an i. p. s. that's currently by far
00:25:22
not excluded come with normal abnormality especially not the mike division mike duplications so
00:25:27
if you have a child don't burn unit what what you think
00:25:30
it may become with homo and that they can say well that would
00:25:33
they even that expounded in i. p. s. it's not sufficient
00:25:40
so it's it's complex and the it requires appropriate pretend that's that's a cost that counts
00:25:45
selling so with the tickets to ensure when the good in clinical setting but
00:25:51
um actually you read about bands that they're thank you very much for your attention

Share this talk: 


Conference program

Welcome words
Matthias ROTH-KLEINER and Philipp MEYER, resp. Lausanne and Aarau
22 Jan. 2019 · 9:34 a.m.
Welcome words
Markus Hodel, Lucerne
22 Jan. 2019 · 9:39 a.m.
Short report - Outcome of very preterm infants
Philip Thwaites, Zürich
22 Jan. 2019 · 9:42 a.m.
Short report - Bronchopulmonary dysplasia (BPD)
Ikbel El Faleh, Lausanne
22 Jan. 2019 · 9:50 a.m.
Non-invasive prenatal diagnosis
Siv Fokstuen, Geneva
22 Jan. 2019 · 10:36 a.m.
Fetal diagnosis and therapy (part 1)
David Baud, Lausanne
22 Jan. 2019 · 11:33 a.m.
Fetal diagnosis and therapy (part 2)
Nicole Ochsenbein-Kölble, Zurich
22 Jan. 2019 · 11:51 a.m.
Minimal invasive therapy of congenital malformations
S. Holland-Cunz, Basel
22 Jan. 2019 · 12:03 p.m.
Discussion
22 Jan. 2019 · 12:26 p.m.
Management of PPROM around 34 weeks (part 1)
R. Pfister, Geneva
22 Jan. 2019 · 2:48 p.m.
Management of PPROM around 34 weeks (part 2)
B. Martinez de Tejada, Geneva
22 Jan. 2019 · 3:06 p.m.
Late termination of pregnancy : legal, ethical and medical aspects
R. Favre, Strasbourg (France)
22 Jan. 2019 · 3:58 p.m.
The beginning of life
T. Berger, Lucerne
22 Jan. 2019 · 4:40 p.m.
Awards and Closing words
22 Jan. 2019 · 5:04 p.m.