1. H1N1 vaccination is not linked with increased risk for overall congenital malformations.
2. Risk increases for specific malformations could not be ruled out.
Evidence Rating Level: 1 (Excellent)
Study Rundown: During the 2009 H1N1 influenza epidemic, approximately 200 million individuals worldwide were effected and several national vaccination campaigns initiated. Previous studies have investigated a relationship between the vaccination of pregnant women and subsequent congenital malformation in the offspring. While most demonstrated mixed evidence, several studies did not consider the potential role of confounding error that may occur due to genetic and shared environmental factors.
In this population-based prospective cohort study, registry data from seven Swedish health centers comprising approximately 60% of the country’s population were obtained. Approximately 40,983 of the offspring were prenatally exposed to the government-sponsored AS03-adjuvanted monovalent vaccine (Pandemrix), with 14,385 in the first trimester and 7,502 in the first 8 weeks when the risk of congenital malformations may be highest. Overall, no increased risk was found between the exposed and unexposed offspring. Further, no statistically significant risk differences were found in a separate sibling analysis. In a subgroup analysis, however, a significant relationship between the risk of oral cleft and vaccine exposure was present. The current study includes more Pandemrix-exposed offspring compared to previous studies, successfully eliminates recall bias related errors, and examines the potential effects of confounding.
Overall, the study suggests H1N1 vaccination is not associated with congenital malformations when intrafamilial factors are taken into consideration. Limitations include malformations occurring in prior pregnancies that may influence the decision to be vaccinated during the study period. The study was also based on live births and cannot dismiss miscarriage or stillbirths caused by congenital malformations. Future studies should consider H1N1 vaccination increasing the risk of specific malformations.
In-Depth [prospective cohort]: Registry data on influenza A(H1N1)pdm09 vaccinations administered between 2009 and 2010 were linked to pregnant women during the pandemic, pregnancy characteristics, and malformation data. Vaccination during the first trimester and in the first 8 weeks of pregnancy were examined. Controls comprised of pregnancies during the same period but without recorded influenza A(H1N1)pdm09 vaccination. Swedish Medical Birth Register was utilized to obtain most covariate and pregnancy data, and the Swedish Total Population Register was used to identify siblings of offspring that were prenatally exposed to the vaccine during pregnancy. Congenital malformation was the main outcome measure and these were examined in offspring born between 1 October 2009 to 1 October 2011, approximately the period between the start of the campaign and 9 months after the end of the campaign (n = 97,869; 40,983 exposed and 56,886 unexposed).
About 4.98% and 4.96% were the adjusted risks in the exposed and unexposed offspring. Only malformations during the first year of life were included. The sibling comparators were born between 2001 and 2011. All exposed offspring together with their siblings were used in the study (n = 5597; 2383 exposed and 3214 unexposed). Adjusted odds ratio for any malformation was 0.98 (CI 0.89 to 1.07) for a full pregnancy and 1.03 (CI 0.88 to 1.19) for the first trimester. A subanalysis measured the risk of congenital heart disease, oral cleft, and limb deficiency. In this analysis, risk differences during the first 8 weeks of pregnancy were 0.12% for CHD, 0.10% for oral cleft and 0.02% for limb deficiency.
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