Pasternak, B. et al. Vaccination against pandemic A/H1N1 2009 influenza in pregnancy and risk of fetal death: cohort study in Denmark. BMJ 344, e2794

Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark.
BMJ (online) (Impact Factor: 17.45). 05/2012; 344(may02 1):e2794. DOI: 10.1136/bmj.e2794
Source: PubMed


To investigate whether an adjuvanted pandemic A/H1N1 2009 influenza vaccine in pregnancy was associated with an increased risk of fetal death.
Nationwide register based cohort study.
All clinically recognised singleton pregnancies that ended between November 2009 and September 2010. Individual level data on exposure to an inactivated AS03 pandemic A/H1N1 2009 influenza vaccine (Pandemrix) and potential confounders were linked to the study cohort using a unique person identifier.
The primary outcome measure was risk of fetal death (spontaneous abortion and stillbirth combined) in H1N1 vaccinated compared with unvaccinated pregnancies, adjusting for propensity scores. Secondary outcome measures were spontaneous abortion (between seven and 22 weeks' gestation) and stillbirth (after 22 completed weeks' gestation).
The cohort comprised 54,585 pregnancies; 7062 (12.9%) women were vaccinated against pandemic A/H1N1 2009 influenza during pregnancy. Overall, 1818 fetal deaths occurred (1678 spontaneous abortions and 140 stillbirths). Exposure to the H1N1 vaccine was not associated with an increased risk of fetal death (adjusted hazard ratio 0.79, 95% confidence interval 0.53 to 1.16), or the secondary outcomes of spontaneous abortion (1.11, 0.71 to 1.73) and stillbirth (0.44, 0.20 to 0.94). Estimates for fetal death were similar in pregnant women with (0.82, 0.44 to 1.53) and without comorbidities (0.77, 0.47 to 1.25).
This large cohort study found no evidence of an increased risk of fetal death associated with exposure to an adjuvanted pandemic A/H1N1 2009 influenza vaccine during pregnancy.

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    • "These findings were similar to those in other countries including the United States [26]. Internationally, data from A[H1N1]pdm vaccine surveillance did not identify safety concerns among either pregnant women or their infants [26] [27] [28] [29] [30]. Given the nature of passive reporting systems, national A[H1N1]pdm ESAVI surveillance systems generally could not provide evidence of a causal association between vaccination and reported serious ESAVI. "
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    ABSTRACT: As part of the vaccination activities against influenza A[H1N1]pdm vaccine in 2009-2010, countries in Latin American and the Caribbean (LAC) implemented surveillance of events supposedly attributable to vaccines and immunization (ESAVI). We describe the serious ESAVI reported in LAC in order to further document the safety profile of this vaccine and highlight lessons learned. We reviewed data from serious H1N1 ESAVI cases from LAC countries reported to the Pan American Health Organization/World Health Organization. We estimated serious ESAVI rates by age and target group, as well as by clinical diagnosis, and completed descriptive analyses of final outcomes and classifications given in country. A total of 1000 serious ESAVI were reported by 18 of the 29 LAC countries that vaccinated against A[H1N1]pdm. The overall reporting rate in LAC was 6.91 serious ESAVI per million doses, with country reporting rates ranging from 0.77 to 64.68 per million doses. Rates were higher among pregnant women (16.25 per million doses) when compared to health care workers (13.54 per million doses) and individuals with chronic disease (4.03 per million doses). The top three most frequent diagnoses were febrile seizures (12.0%), Guillain-Barré Syndrome (10.5%) and acute pneumonia (8.0%). Almost half (49.1%) of the serious ESAVI were reported among children aged <18 years of age; within this group, the highest proportion of cases was reported among those aged <2 years (53.1%). Of all serious ESAVI reported, 37.8% were classified as coincidental, 35.3% as related to vaccine components, 26.4% as non-conclusive and 0.5% as a programmatic error. This regional overview of A[H1N1]pdm vaccine safety data in LAC estimated the rate of serious ESAVI at lower levels than other studies. However, the ESAVI diagnosis distribution is comparable to the published literature. Lessons learned can be applied in the response to future pandemics. Copyright © 2014. Published by Elsevier Ltd.
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    • "In a small study in the United Kingdom, 77 pregnant women received AS03 adjuvant end vaccine in the second or third trimester; three-quarters of the newborn infants were found to have passive immunity at hemagglutination inhibition titers of 1:40 or greater consistent with clinical protection, as a result of transplacental transfer [43]. A study of a Danish cohort of approximately 7000 vaccinated pregnant women found no association between exposure to AS03- adjuvanted H1N1 monovalent vaccine during pregnancy and fetal death, preterm birth, major birth defects and fetal growth restriction [44] [45]. The data also provided preliminary evidence that excluded a high risk of adverse pregnancy outcomes in 345 women vaccinated in the first trimester because of pre-existing chronic diseases [46]. "
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    ABSTRACT: Vaccine-preventable infectious diseases are responsible for significant maternal, neonatal, and young infant morbidity and mortality. While there is emerging scientific evidence, as well as theoretical considerations, indicating that certain vaccines are safe for pregnant women and fetuses, policy formulation is challenging because of perceived potential risks to the fetus. This report presents an overview of available evidence on pregnant women vaccination safety monitoring in pregnant women, from both published literature and ongoing surveillance programs. Safety data were reviewed for vaccines against diseases which increase morbidity in pregnant women, their fetus or infant as well as vaccines which are used in mass vaccination campaigns against diseases. They include inactivated seasonal and pandemic influenza, mono- and combined meningococcal polysaccharide and conjugated vaccines, tetanus toxoid and acellular pertussis combination vaccines, as well as monovalent or combined rubella, oral poliomyelitis virus and yellow fever vaccines. No evidence of adverse pregnancy outcomes has been identified from immunization of pregnant women with these vaccines.
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    • "In addition, studies have shown that influenza vaccine during pregnancy, even in the first trimester, poses no additional risk to the developing foetus. In a recent study of over 50,000 pregnant women in Denmark, of whom over 7,000 had received the 2009 A/H1N1 influenza vaccine, there was no excess risk of miscarriage or stillbirth among vaccinated women [31]. A smaller study of 323 vaccinated pregnant women and 1,329 matched control subjects also found no excess risk of spontaneous abortion or foetal malformations among participants receiving the 2009 A/H1N1 vaccine, irrespective of time of vaccination [32]. "
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    ABSTRACT: Pregnant women are the highest priority group for annual influenza vaccination. Studies have shown unacceptably low uptake of both seasonal and pandemic A/H1N1 influenza vaccination among pregnant women. This paper will describe the study protocol and methodology of a randomised controlled trial designed to assess the effectiveness of a brief educational intervention in improving the uptake of seasonal influenza vaccine among pregnant women in Hong Kong. A randomised controlled trial will be conducted with pregnant women in at least the second trimester of pregnancy from four publicly funded hospital antenatal clinics in Hong Kong. Participants will be randomly assigned to either one of the two treatment groups: standard care (control) or standard care plus brief education (intervention). Pregnant women in the standard care group will receive the usual antenatal care with an educational pamphlet developed by the Hong Kong Centre for Health Protection and those in the intervention group will be provided with usual care plus a brief ten-minute education intervention. Content of the education session will cover four core components recommended in the research literature. The primary study outcome will be the proportion of participants who have received influenza vaccine during their pregnancy. A total of 184 pregnant women (92 per group) will be required to give an 80% power to detect a treatment effect of 15%. Most intervention studies aimed at improving influenza vaccination rates in pregnant women have targeted obstetric-care providers and the results of the two patient-oriented RCT interventions are conflicting. The high priority for vaccination given to pregnant women and the low influenza vaccination rate among pregnant women worldwide strongly indicates a need for interventions to improve uptake.Trial registration: This trial is registered with the Clinical Trials Registry at (NCT01772901).
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