presentation [1.72 Mo PDF]

Vaccination of Prégnant Women:
Benefit/Risk Assessment
Carol J. Baker, M.D.
Professor of Pediatrics, Molecular Virology and
Microbiology, Baylor College of Medicine,
Houston, Texas, USA
Fondation Mérieux, Veyrier-du-Lac
June 24, 2014
Financial Disclosure
In the past 12 months I have been a
consultant to Novartis Vaccines and an
advisory board member of Pfizer, Inc.
My Point of View as a Discussant
● Physician: “disease fighter”
● Decreasing mortality is quantifiable (good)
● Decreasing morbidity (hospitalization, disability) is good
● Public Health Advisor:
● Vaccines were the greatest medical advance in the 20th
century (exception = clean water)
● Efficacy (benefits) documented
● Risk (safety) is never zero and is a probability
● Benefit/Risk balance is a value judement
Maternal Vaccination
Is Not A New Concept

1879: Maternal immunisation with cowpox virus
conferred protection against smallpox in mothers & infants

1938: Maternal immunisation with whole cell pertussis
vaccine protected infants from complications of pertussis

1961: Maternal immunisation with tetanus toxoid
vaccine (New Guinea); millions of maternal and neonatal
deaths prevented worldwide since then

1964: Inactivated influenza vaccine recommended
Tetanus Immunisation During Pregnancy
Moccia P. The state of
the world's children
2009 maternal and
newborn health. New
York, NY: United
Nations Children's
Fund (UNICEF); 2008.
But It Is Complicated

From the outset, there was debate about benefit/risk
and vaccine uptake has been meagre

More important was the lack of data to assure safety
and efficacy

Thalidomide: the most important adverse event for
pregnant women in medical history changed everything
more than 60 years ago – birth of regulatory agencies

Anything during pregnancy could bring harm to the
unborn whether biologically plausible or not

Thus, potential risk trumped benefit – pregnant women
What Followed Thalidomide?

FDA regulations excluded pregnant women from
enrollment in clinical trials
 FDA still doesn’t have a licensing pathway for vaccines
 Vaccine manufacturers remain concerned about liability
 Obstetrical providers perceive unwillingness of women
to receive recommended vaccines during pregnancy
 Discussion of benefit/risk involving pregnant women all
but ceased until the 2009 influenza pandemic
Historical Note: Influenza Enhanced Disease Burden
during Pregnancy Assumed Risk Was Negligible
Burney LE. Public
Health Rep. 1964
Oct; 75(10):944.
First US influenza
vaccine
recommendation
Recommended But
Not Administered
WHO Prequalified TIV Vaccines:
Package Inserts 2012
Company/Vaccine
Pregnancy Comment
GSK (Flulval)
Animal reproduction ND
Limited data do not indicate
adverse foetal outcome
Animal and pregnant
women studies ND; should
only be given when
necessary
Pregnancy category C;
animal studies ND; not
known if it can cause harm
Green Cross (GCFLU)
Sanofi (FLUZONE)
Rationale for Vaccination of
Pregnant Women: Benefits
● Mother’s “gift” to fetus/newborn is her
immunoglobulin G (IgG) or her immunity
against infectious diseases for weeks/ months
● Placental transfer of maternal immunity
(antibodies) begins at 17 weeks (passive
transport)
● By 33 weeks, maternal = fetal levels
● By 40 weeks, total fetal IgG exceeds maternal
levels (active transport)
Vaccination During Pregnancy
“Nature’s Gift”
Decreasing severity of
early childhood infections
Maternal antibody
Before birth
Child’s own antibody
Birth
Infant immunization schedule starts
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Pediatrics
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Two Events That Shifted
The Discussion in the U.S.A.
● 2009 H1N1 Pandemic Influenza



Pregnant women were priority group 1
Accounted for 5% of deaths (1% of population)
Vaccine uptake rose from ~12% to 49%
● Pertussis Young Infant Deaths US, UK/Wales




Virtually all deaths in < 3 month old infants
Increased risk of hospitalization in infants <6 months
With WC pertussis vaccine, maternal immunisation
protected mothers and young infants
Infants require 3 doses of DTaP for protection
Maternal and Young Infant Influenza
Infections Worldwide

Burden of disease is substantial

Increased risk of complications and death in pregnant
women due to pulmonary compromise

If no maternal influenza-specific IgG, risk of
complicated influenza in baby (fever/sepsis)

No influenza vaccine available if <age 6 months
At age 6 months, 2 doses, 4-weeks apart, required for
protection (uptake in 2013 ~70% for 1 or 2 doses)

TIV uptake in 2013 only 48% in pregnant women
Finally Some Influenza Risk
(Safety) Data
Denmark registry
Outcomes:
birth defects
preterm birth
fetal growth
53,432 babies
6989 exposed
343 1st trimester
No difference in rate
of outcomes
maternal vaccinated
vs. non-vaccinated
women
Pregnancy Immunisation with
Influenza Vaccine: Benefits*
* Steinhoff, McDonald, Pfeifer, Muglia. Lancet 2014;383:1611
Pediat Infect Dis J 2013;32:1374
Worldwide Benefit
Two Events That Shifted
The Discussion in the U.S.A.
● 2009 H1N1 Pandemic Influenza



Pregnant women were priority group 1
Accounted for 5% of deaths (1% of population)
Vaccine uptake rose from ~12% to 49%
● Pertussis Young Infant Deaths US, UK/Wales




Virtually all deaths in < 3 month old infants
Increased risk of hospitalization in infants <6 months
With WC pertussis vaccine, maternal immunisation
protected mothers and young infants
Infants require 3 doses of DTaP for protection
USA Data
England/
Wales Data
Level 3
emergency
declared 4/12;
Tdap to
pregnant
women; 79%
reduction in
infants <3mo.
Pertussis in a 3-Week-Old:
Cough for 4 days, blue spell in AM, hospital admission,
ventilator at 6 hours, ECMO at 12 hours, death at 18 hours
Vaccination of Pregnant Women:
Conclusions
● Immune mechanisms during pregnancy differ, but do
allow for adequate responses to inactivated vaccines
● Maternally-derived specific IgG can prevent
maternal/fetal/neonatal/young infant mortality and
mortality (benefit)
● Inactivated vaccines (eg, influenza) are safe (risk)
● We must not continue to exclude pregnant women or
their offspring from vaccine-derived benefits (equity)
Thank You
Merci Beaucoups