Risk of adverse fetal outcomes following administration of a pandemic influenza A(H1N1) vaccine during pregnancy.
BACKGROUND
Assessment of the fetal safety of vaccination against influenza A(H1N1)pdm09 in pregnancy has been limited.


OBJECTIVE
To investigate whether exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was associated with increased risk of adverse fetal outcomes.


METHODS
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.


METHODS
Major birth defects, preterm birth, and small size for gestational age.


RESULTS
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).


CONCLUSIONS
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.
Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark. bjp@ssi.dk
Björn
B
Pasternak
Henrik
H
Svanström
Ditte
D
Mølgaard-Nielsen
Tyra G
TG
Krause
Hanne-Dorthe
HD
Emborg
Mads
M
Melbye
Anders
A
Hviid
D000276:Adjuvants, Immunologic; D000328:Adult; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000453:epidemiology*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005317:Fetal Growth Retardation / Q000453:epidemiology*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000009:adverse effects*; D007251:Influenza, Human / Q000517:prevention & control*; D016017:Odds Ratio; D011247:Pregnancy; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000453:epidemiology*; D057216:Propensity Score; D012042:Registries / Q000706:statistics & numerical data; D012306:Risk; D014611:Vaccination / Q000706:statistics & numerical data; D055815:Young Adult
D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines