TY - JOUR

T1 - Risk of adverse fetal outcomes following administration of a pandemic influenza A(H1N1) vaccine during pregnancy

AU - Pasternak, Björn

AU - Svanstrom̈, Henrik

AU - Mølgaard-Nielsen, Ditte

AU - Krause, Tyra G.

AU - Emborg, Hanne Dorthe

AU - Melbye, Mads

AU - Hviid, Anders

PY - 2012/7/11

Y1 - 2012/7/11

N2 - Context: Assessment of the fetal safety of vaccination against influenza A(H1N1) pdm09 in pregnancy has been limited. Objective: Toinvestigate whether exposure toanadjuvanted influenzaA(H1N1)pdm09 vaccine during pregnancy was associated with increased risk of adverse fetal outcomes. Design, Setting, and Participants: Registry-based cohort study based on all live-born 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. Main Outcome Measures: 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.

AB - Context: Assessment of the fetal safety of vaccination against influenza A(H1N1) pdm09 in pregnancy has been limited. Objective: Toinvestigate whether exposure toanadjuvanted influenzaA(H1N1)pdm09 vaccine during pregnancy was associated with increased risk of adverse fetal outcomes. Design, Setting, and Participants: Registry-based cohort study based on all live-born 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. Main Outcome Measures: 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.

UR - http://www.scopus.com/inward/record.url?scp=84863707296&partnerID=8YFLogxK

U2 - 10.1001/jama.2012.6131

DO - 10.1001/jama.2012.6131

M3 - Journal article

C2 - 22782418

AN - SCOPUS:84863707296

VL - 308

SP - 165

EP - 174

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0098-7484

IS - 2

ER -