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: 16.38). 05/2012; 344:e2794. DOI: 10.1136/bmj.e2794
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Björn Pasternak, Aug 24, 2015
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    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.
    Vaccine 10/2014; 32(52). DOI:10.1016/j.vaccine.2014.09.052 · 3.49 Impact Factor
  • BMJ (online) 05/2012; 344:e3091. DOI:10.1136/bmj.e3091 · 16.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Assessment of the fetal safety of vaccination against influenza A(H1N1)pdm09 in pregnancy has been limited. To investigate whether exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was associated with increased risk of adverse fetal outcomes. Registry-based cohort study based on all liveborn singleton infants in Denmark, delivered between November 2, 2009, and September 30, 2010. In propensity score-matched analyses, we estimated prevalence odds ratios (PORs) of adverse fetal outcomes, comparing infants exposed and unexposed to an AS03-adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy. Major birth defects, preterm birth, and small size for gestational age. From a cohort of 53,432 infants (6989 [13.1%] exposed to the influenza A[H1N1]pdm09 vaccine during pregnancy [345 in the first trimester and 6644 in the second or third trimester]), 660 (330 exposed) were included in propensity score-matched analyses of adverse fetal outcomes associated with first-trimester exposure. For analysis of small size for gestational age after second- or third-trimester exposure, 13,284 (6642 exposed) were included; for analyses of preterm birth, 12,909 (6543 exposed) were included. A major birth defect was diagnosed in 18 of 330 infants (5.5%) exposed to the vaccine in the first trimester, compared with 15 of 330 unexposed infants (4.5%) (POR, 1.21; 95% CI, 0.60-2.45). Preterm birth occurred in 31 of 330 infants (9.4%) exposed in the first trimester, compared with 24 of 330 unexposed infants (7.3%) (POR, 1.32; 95% CI, 0.76-2.31), and in 302 of 6543 infants (4.6%) with second- or third-trimester exposure, compared with 295 of 6366 unexposed infants (4.6%) (POR, 1.00; 95% CI, 0.84-1.17). Small size for gestational age was observed in 25 of 330 infants (7.6%) with first-trimester exposure compared with 31 of 330 unexposed infants (9.4%) (POR, 0.79; 95% CI, 0.46-1.37), and in 641 of 6642 infants (9.7%) with second- or third-trimester exposure, compared with 657 of 6642 unexposed infants (9.9%) (POR, 0.97; 95% CI, 0.87-1.09). In this Danish cohort, exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was not associated with a significantly increased risk of major birth defects, preterm birth, or fetal growth restriction.
    JAMA The Journal of the American Medical Association 07/2012; 308(2):165-74. DOI:10.1001/jama.2012.6131 · 30.39 Impact Factor
Show more