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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