Vaccination during pregnancy Karin Batty 11 September 2013
Transplacental antibody transfer Transport of IgG across the placenta 1 Active, selective, intracellular process Increases with advancing gestational age 17 weeks process begins 33 weeks maternal and fetal IgG equalise* 40 weeks fetal IgG higher than maternal* *For some antibodies 2
Transplacental antibody transfer Fetal IgG influenced by 1 IgG concentration in maternal blood Type of vaccine Time between vaccination and delivery Gestational age at delivery Transplacental antibodies in the newborn Can reduce the risk of vaccine-preventable diseases in the early weeks-months of life 2-7
Which vaccines? All inactive and subunit vaccines BUT Disease risk vs. emotional risk Influenza Hepatitis B Pertussis Tetanus Focus on influenza and pertussis (Tdap) vaccines
Maternal influenza disease risks Higher risk of influenza complications 8, 9 Pneumonia Longer hospital stay Delivery complications 10 Preterm delivery (4x) Fetal distress (2.5x) Caesarean delivery (4x) Death Risk increases with advancing gestational age 8, 9
Neonate/infant influenza disease risks Neonate 10 Preterm delivery (4x) Small gestational age Infants <6 months 8 Highest risk influenza and complications in <23 months age group No licensed flu vaccine
Neonate/infant pertussis disease risks Infants <6 months11, 12 Highest risk of hospitalisation and death in <12 months age group Incomplete vaccine course until 5 months
Maternal benefits from influenza vaccination Limited data on immunogenicity and efficacy for pregnant women Seroresponse Slightly lower/similar, pregnant vs. non-pregnant woman of the same age3, 13-15 Acute/febrile respiratory illness Similar presentation rates, vaccinated pregnant vs. unvaccinated pregnant women of the same gestation 17 13, 16, Except a landmark RCT in Bangladesh 18 Febrile respiratory illness 36% reduction, vaccinated pregnant women vs. unvaccinated pregnant women
Fetal/infant benefits from maternal influenza vaccination Odds of prematurity and small for gestational age reduced 19 Significantly reduces the risk of disease in the infant for several months5, 18, 20, 21 Decreased MAARI* and AOM* events infants <12 months Course of PCV7 with maternal flu vaccination vs. PCV7 without maternal flu vaccination22, 23 *MAARI medically attended acute respiratory infection *AOM acute otitis media
Infant benefits from maternal pertussis vaccination Reduces the risk of severe disease for 4 6 weeks2, 11 Indirect newborn protection1, 24 Infants <6 months most likely to get pertussis from their mother 25
How is safety monitored? Population-based cohort studies Retrospective and database review studies Clinical trials Post-marketing surveillance and adverse event reporting systems, e.g. Vaccine Adverse Event Reporting System (VAERS)
Inactive vaccines are safe in pregnancy Pregnant women and inactive vaccines U.S. since 1957 (tetanus and IPV vaccines) Worldwide since the 1970s (tetanus vaccines) Clinical trials since 1988 (other inactive vaccines) No evidence of harm identified On the course of the pregnancy, fetus or newborn
Prospective influenza safety studies Heinonen et al., 1973 27 1959 through 1965 n=2,291 influenza vaccine (650 in first 4 months gestation) Children followed up for 7 years Eick et al., 2011 5 2002 through 2005 n=1,169 influenza vaccine
Retrospective influenza safety studies France et al., 1995 28 2002 through 2005 n=3,160 vaccinated vs. 37,969 not vaccinated Black et al., 2004 17 1997 through 2002 n= 3,719 vaccinated vs. 45,866 not vaccinated Pool & Iskander, 2006 29 VAERS review 2000 through 2003 Estimated 2 million doses 26 AEFI reports Moro et al., 2010 30 VAERS review 1990 through 2009 Estimated 11.8 million doses 148 AEFI reports
First trimester influenza safety Sheffield et al., 2012 31 n=10,225 (439 first trimester) No increase in major malformation rates Decrease in overall stillbirth rate
Retrospective Tdap safety Zheteyeva et al., 2012 32 VAERS review 2005 through June 2010 Tdap not routinely recommended pregnant women during this time 132 AEFI reports 55 reports were Tdap administration during pregnancy No unexpected pattern maternal, fetal, or infant AEFIs Injection site reactions most frequent non-pregnancy AEFI
Why vaccinate? Influenza vaccine Timing Tdap vaccine Maternal protection Pregnancy/fetal protection + Newborn protection Vaccinate anytime during pregnancy At the beginning of flu vaccination programme, or As soon as a woman identified as being pregnant during flu season Direct newborn protection + Indirect newborn protection Vaccinate between 28 38 weeks gestation Ideal timing 31 33 weeks, or Before 36 weeks
Barriers and motivators Vaccine accessibility Accessible at no/low cost to patients 33-35 Knowledge Accurate and consistent information dissemination33, 34, 36 Influenza disease risks 33-36 Safety and efficacy of the vaccines 34-36 Two-for-one benefit 34 Erroneous information from family and friends needs to be countered by the provider 34 Providers may be knowledgeable but fail to convey the facts to women 34
Barriers and motivators Influence of health professionals Most women accept the vaccine If providers explain the threat of influenza and recommend maternal vaccination 33-36 Women perceive an indifferent provider as a barrier to vaccination 34 Wiley et al., 2013, n=815 30 Women who received a recommendation were 20x more likely to have been vaccinated 68% of unvaccinated women would have had the vaccine if it had been recommended
Messages Maternal, fetal and infant benefits Influenza and Tdap vaccines are safe during pregnancy Timing of vaccination Accurate and consistent information Clear health professional recommendation
Questions?
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