I'm going to ask associate Professor Michael Gold to come and give us a
speech and then will take the questions Michael is a pediatric allergist and
immunologist who holds the joint position in the discipline of pediatrics
at the University of Adelaide and is medical unit head of pediatric allergy
and immunology at the Women's and Children's Health Network
He has a clinical research interest in the prevention of childhood food allergy and
vaccine safety he has been appointed as an expert advisor to our national and
international commities which include the WHO global advisory committee for
vaccine safety the common border Department of Health and Ageing the TGA
the ASCIA anaphylaxis working party and the Centre for Research excellence in food allergy
that's enough? So I think if there's any question you can pass it on
thanks for the invitation I've enjoyed the talks immensely
It really does show that both for CMV and Zika how important the vaccine
and developing a vaccine will be and thanks again for covering pertussis
This talk is going to be a little bit different way because
I'm just gonna give you - I'm going to entertain you
I'm gonna give you a sort of very broad overview of immunization and
pregnancy so what I want to cover is a bit of the history and the rationale of
why we would bother delivering immunizations in pregnancy
I'll cover a little bit on influenza - pertussis has been covered - but I really
want to really emphasize the efficacy and the safety of delivering
these vaccines in pregnancy and i'm going to talk a little bit about safety
surveillance because that's a particular interest of mine so take-home message
I think has already been delivered I think we should all be promoting
immunization in pregnancy
obviously with these vaccines
Immunization as we all know starts with smallpox and smallpox
is a congenital infection and if you visit the hunter museum
at the royal college of surgeons in England you can actually see the
specimen which is from a foetus and it shows some congenital smallpox and it
was actually sent to Edward Jenner to demonstrate this and we
know this is where immunisation started that you really induce a
cowpox infection which is live and attenuated and that protects you against
smallpox and that is where it all started in 1796 so this depicts
Jenner immunizing i'm sure he got informed consent before hand
I'm an eight-year-old boy called Phipps and subsequent to that he
inoculated the a child with smallpox to really demonstrate the efficacy of this
Immunisation in pregnancy
I'm going to talk about two aspects the first is protecting the infant and
the other is protecting the mother and in fact it was it was in 1879
83 years after Jenner's experiment with vaccinations that it was
recognized that infants born to vaccinated mothers were protected against
small box so if we talk about immunization in pregnancy it really goes
back to the start of some of the immunisation and it's recognized
really from then onwards in terms of immunisation protecting infants
of course this has been done for decades and it's been done for decades
with protection - to obviously prevent neonatal tetanus
I've only seen two cases of tetanus in my career one in Adelaide
a three-year-old I think Celia knows the case as well a child who was
completely unimmunised because the parents were conscientious objectors and
that parent presented to the GP saying could my child have lock jaw and in fact
the childhood did have lock jaw that child was admitted to ICU
given tetanus immune globulin and parents still refused to immunise the child
So neonatal tetanus really has been a huge success in terms of
immunising mothers to prevent it so in this line here you can see the
immunization rates i guess for maternal immunization and here are the rates
falling for neonatal tetanus
So in 1998 WHA estimated there were close to 800,000 newborns who died from
neonatal tetanus - and 2010 60,000 In 2014 they're still obviously
in many countries around the world is neonatal - there is neonatal tetanus so it's
still an ongoing issue but not as severe
Protection of the mother - this is the second reason obviously why we should
immunize mothers and I just want to make one point but I've just chosen this
quite old study from 1986 to demonstrate this and this is a risk of acute
respiratory disease amongst pregnant women during influenza A epidemics and this is
the rate per thousand in women who are not pregnant and
this is the rate per thousand in those who are pregnant and these are the
different influenza serotypes and you can see that there is an excess rate
we've got here 22-23 this is per thousand for those who are pregnant
so the point I want to make is that pregnancy is really a state
of local and and systemic immunosuppression and the pregnant
mothers - and this is being demonstrated you know I mean obviously with the H1N1
pandemic but also with that seasonal influenza - pregnancy is a state
of immunosuppression because obviously in terms of actual of rejecting the fetus
there have to be huge physiological factors both locally and systemically to immunosuppress
so the mother obviously doesn't reject the fetus so the point
I'm trying to make is that should be a strong motivation because pregnant
mothers are obviously at risk - greater risk - of if they do acquire many infections
or infectious diseases - of being worse off
Influenza vaccination - we haven't touched on but that's really protecting
both the mother from what I've just said but also from the infant and as
you know we would recommend influenza vaccination for pregnant mothers
so this is data from Australia the top one and
this was during the H1N1 influenza A and this is data from
victoria australia and what I put up there here really is just
a count of maternal and fetal death from Victoria but this is a
systematic review and this covers each one of these lines represents a
study and this looks at fetal death after mothers who have acquired
influenza and if you're right of the line there in an excess in deaths and you
can see for most of the studies I'm looking at fetal outcomes after the
maternal influenza that there is an excess of fetal death
This is just one of the studies and this shows the
effectiveness of influenza vaccine and
this shows both controls and influenza and this is one of the few
randomized control trials you can see in terms of the immediate and
neonatal outcomes the differences in the infants in terms of those
who were vaccinated and those who weren't - that is the mothers who were vaccinated
This is very recent data from Western Australia so a lot of the data
that we get for influenza vaccination both from a safety point
of view but also from an efficacy comes from Western Australia because they've had a very
active and state-funded immunization program particularly for the infants
but this is their data - it's not a randomized control trial but it's
simply looking at basically infants hospitalized for respiratory
infection - so we're not even talking about influenza - this is just all
respiratory infections in newborns it's a cohort study and it's looking at
it's looking back at the rates for vaccinated and unvaccinated mothers and
you can see the difference between the two and for those who more statistically
inclined you can see the odds ratio here on being less than 1 which means its
protective and these being significant across the studies
We've already touched on pertussis and this has been mentioned by Lynn
but i really just want to emphasize the points that pertussis infection in
terms of mortality and morbidity in a developed country like
Australia really affects infants under four months of age so this is a 17
year retrospective study all our ACR and ICU admissions - 373 over that period
84% less than four months of age and 88%
less than six months of age so you can see the greatest burden for ICU admission
under four months of age 55% required respiratory support
23 deaths - but important 20 of the 23 were less than four months of age
so the point to make here is that those infants have not had the time
obviously to be immunized so this is why this cocooning comes into it and
also why maternal immunization is so important and it's just to
emphasize that I think cocooning is a really difficult and
less effective than the maternal immunization in terms of actually
does this work or not this is a case-control study from the UK
they're not a huge number of cases in this particular study
and this really takes a case of pertussis presenting in the
neonatal period and then looks back to see whether the mother has been
vaccinated or not and then it's looked at and then by doing that you
can actually calculate your vaccine effectiveness and in this particular
study they had very high rates of vaccine effectiveness - 91%
I want to move on to safety and just like i mentioned
that immunization of pregnant mothers was recognized very early on to
protect newborn babies
Safety of vaccines has been a concern since the onset of vaccination
so i don't know how many of you have seen this cartoon but it actually
came out for years after Jenner's experiment and it was published by the
anti-vaccine lobby at the time and what this depicts is Jenner vaccinating and
then cowpox lesions or cowlesions developing in the vaccinated subjects
a very very famous cartoon from the time I want to make this point that
when you ask pregnant mothers why they did not receive the
influenza vaccination and again this is from the MMWR is that safety comes
out as being more of a concern to mothers then efficacy so it's
really safety that we need to convince many mothers on
I'm going to just give you some brief snapshots of the safety data around
pertussis vaccination - so pertussis vaccination for pregnant mother's really
was taken up big time in 2014 and before in the UK and this is really their
safety data - it is observational data in other words this wasn't a
randomized control trial
this simply looked at vaccinated and unvaccinated mothers and looked
at many of the outcomes that you would be interested in as midwives and obviously
as Obstetricians and that is: stillbirth, neonatal death, placenta previa,
cecearian section, premature labor, postpartum hemorrhage
The numbers in each group are in the thousands or tens of thousands which is
always reassuring from a safety point of view to know that many people have been
immunized and the only one that I just highlight for interest is actually the
preeclampsia and actually a reduction of risk so you can see that when you
match that to controls are 0.674 for the vaccinated
which gives a risk of 0.52 which is significant so a curiosity and to say that
even immunization and may even protect you against some of the adverse outcomes
this is a much smaller study this was a randomized control trial and
this did use a placebo and the point I want to make here is that if you just look at fever
if you look at the immunised groups - so these were mothers who were immunised
during pregnancy so antepartum you've got a 3% rate of fever
whereas if you look at those who were immunised after pregnancy 26% had
fever or if they were non-pregnant 9.4% so I'm trying to make the point
that for many of those systemic effects that in fact the adverse - the side
what I would call side effects really - to vaccination may be less common and I
think that does tie in with pregnancy being a relative state of immunosuppression
this is what parents are going to - or that mothers are going to ask you
how do you know anything is safe?
and you cannot prove safety that is the issue
if you get on a flight I can't prove to you that that flight is going to be safe
what I can prove to you is that there are no adverse events or adverse
reactions that have been detected or found and that's what we're really
looking at adverse events and reactions now this is really what changed the
world in terms of pharmacovigilance and i'm sure many of you will recognize the
structure of that molecule
The actual structure that actually depends whether it's teratagenic or not
so this is obviously thalidomide and prior to the thalidomide
disaster there was no such thing as pharmacovigilance so thalidomide
was used and registered without any animal experiments or any real human
experience as to safety so pharmacovigilance and pregnancy really
go hand-in-hand that's where it all started there's an interesting
Australian connection and that is that this person is Dr McBride he is well he
was an obstetrician in Sydney and he wrote the simple letter to the
lancet I think I'm which is only one paragraph but changed the whole face of
pharmacovigilance because he again - like the Zika story - you know noticed this
phocomelia in a collection of children
So we know there are FDA pregnancy categories and i won't go through all of
them but the big issue in terms of safety and assessing
that in pregnancy is that pregnancy often precludes involvement in clinical
trials so often obviously for drug trials or vaccine trials pregnancy is
often an exclusion criteria
clinical trials maily occur for currently recommended vaccines in pregnancy
and really if we look at the post-licensure so once the vaccine or drug
is licensed how do we actually detect adverse events
largely by passive surveillance which is really reporting and that has it's own problems
So really there's a call internationally for greater I suppose
protocols of evaluating both drugs and vaccines in pregnant women and
this has been driven by the NIH but also by the WHO
and also if you're interested by this consortium so the global alignment of
immunization safety assessment in pregnancy so that I'm just trying to
make the point that there's a lot of work going on internationally
about trying to define better pregnancy outcomes from a drug and
vaccine and monitoring point of view so in summary as we know coverage is
really the most important factor and it's been well shown in many vaccine
studies that the knowledge and attitude of the health provider which is really you
determines how confident parents or mothers are in in taking up
that advice so you should be confident about the benefits and you should know
obviously the facts and knowledge around vaccination both efficacy and safety
I think it's very important to engage all stakeholders there should be
communication around adverse events and many of these such as stillbirth
preterm delivery, congenital abnormalities, may well of course be coincidental
events and this is the big challenge is really to really differentiate
a coincidental event from a drug or vaccine reaction and I think assessment on
safety there's a lot of work going on within pregnancy to try and do
clinical trials better in pregnant women in order to provide the
level one data that's required
thanks very much