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Influenza Vaccination in
Pregnancy: Current evidence and
selected national policies
Lancet Infectious Disease
2008:8: 44-52
Summary By Dr Ng YY
Flu n pregnancy
Pregnant women are more vulnerable during pandemic
influenza
• 4 X higher risk of maternal death during severe season
as compared to regular season
• Hospitalized pregnant women with respiratory illness had
higher odds of
– Preterm delivery
– Fetal distress
– Cesarean section
(as compared to hospitalized pregnant females without respiratory illness)
Pregnancy n co-morbidities
• 3x more likely to have resp illness during
flu months as compared to healthy pregnant women
• Highest rate of hospital admission in
pregnant females with history of asthma
1918-1919 Pandemic
20 million deaths with pregnant women at high risk for
complications/death
Maryland
1350 pregnant female n flu:
• Overall case fatality: 27%
• Case fatality with pneumonia: 54%
Chicago
101 hospitalized pregnant female n flu
• Overall case fatality: 32%
• Case fatality with pneumonia: >50%
1957-1958 pandemic:
New York: 216 Influenza deaths
22 deaths in unvaccinated
pregnant women
(7 had rheumatic heart disease)
England and Wales: similar doubling risk
Minnesota, USA
11 deaths in unvaccinated pregnant women contributed to
50% of maternal mortality (all had fulminant,
haemorrhagic pulmonary oedema)
Risk to fetus
Transplacental transmission of flu virus:
RARE
No IgM anti-flu antibodies in cord sera of
138 infants whose mothers had positive
serology
Risk to neonate from maternal infection
Hospital admission rates:
• Lowest for < 5 months old
• Highest for > 6 - 23 months old
Flu vaccine
• Antibody response to flu vaccine similar in pregnant and
non-pregnant women
• 87-99% transplacental transfer of flu-specific maternal
antibodies
• Cord titers did not differ significantly if maternal
vaccination in 2nd or 3rd trimester
• Half life of antibodies in babies: 43-53 days
• Infants < 6 mths less likely to have resp illness when
born to immunized pregnant women
3rd trimester vaccination
Significant protection for mother and child
From febrile respiratory illnesses
( randomized effectiveness trial of maternal flu
immunization in 3rd trimester)
Vaccine safety
1959-1965 US Collaborative Perinatal Project
• First trimester influenza vaccination not associated with
minor or major malformations in 2 studies
(650 mother –child pairs and 50,897 pregnant women)
Followed up to age 7 years old for hearing impairment, learning disabilities
and malformations
• All trimester vaccination not associated with excess
childhood malignancies
( 2291 pregnant women and children followed up to 4 years old)
Vaccine safety
1998-2003 historical cohort database in Texas
• 2nd and 3rd trimester vaccination
• 252 pregnant women
• Followed up for 42 days post vaccination
No difference in outcomes
– of pregnancy
– infant hospital admission up to 6 months old
Compared to matched unvaccinated healthy controls
Adverse effects
•
No serious adverse effects of flu
vaccination in pregnancy
•
•
•
•
Mild fever 1.3%
Flu like symptoms
Headache
Dizziness
Thiomersal vaccine
• Flu vaccine containing thiomersal (an organic
mercury compound used since 1930s as a preservative in vaccines)
not contraindicated in pregnant women
• No association with neurodevelopmental
disorders or autism
Limited safety data in 1st trimester
• 1366 reports of adverse reactions to flu
vaccine
– 8 occurred in pregnancy
( 7 vaccinated in 1st trimester
• 1 stillbirth
• 3 spontaneous abortions
• 3 fetal growth retardation of which 2 delivered
prematurely)
Flu Immunization
Pregnancy associated with
higher morbidity and
mortality from influenza
infection
USA CANADA
AUSTRALIA:
Vaccinate all pregnant
women in any trimester
WHO recommendation:
ALL PREGNANT WOMEN
during flu season
UK:
Vaccinate pregnant women
with high risk co-morbidity
in any trimester
Singapore
No routine recommendation
Germany
Avoid 1st trimester
vaccination
Conclusion
Evidence to support flu vaccination
1. Healthy pregnant women in 2nd and 3rd
trimester
2. Pregnant women with co morbidities in
any trimester
As pregnant women are more vulnerable
Conclusion
• No serious adverse effect of flu vaccination - limited data on safety
in 1st trimester
• Significant protection during third trimester immunization
• Vaccines containing thiomersal not contraindicated in pregnant
women
• Preference for thiomersal free flu vaccine - precautionary measure
only