Seasonal Influenza Vaccination During Pregnancy and the Risk of Major Congenital Malformations in Live-Born Infants: A 2010-2016 Historical Cohort Study

Clin Infect Dis. 2020 Jun 23;ciaa845. doi: 10.1093/cid/ciaa845. Online ahead of print.


Background: Available evidence indicates that seasonal inactivated influenza vaccination during pregnancy protects both the mother and her newborn, and is safe. Nevertheless, ongoing safety assessments are important in sustaining vaccine uptake. Few studies have explored safety in relation to major congenital malformations, particularly in the first trimester when most organogenesis occurs.

Methods: Anonymised UK primary care data (the Clinical Practice Research Datalink), including a recently developed Pregnancy Register, were used to identify live-born singletons delivered between 2010 and 2016. Maternal influenza vaccination was determined using primary care records and stratified by trimester. Ascertainment of major malformations from infant primary care records was maximized by linkage to hospitalization data and death certificates. The relationship between vaccination and major malformations recorded in the year after delivery and in early childhood was then assessed using multivariable Cox regression.

Results: A total of 78,150 live-birth pregnancies were identified: 6,872 (8.8%) were vaccinated in the first trimester, 11,678 (14.9%) in the second and 12,931 (16.5%) in the third. Overall, 5,707 live-births resulted in an infant with a major malformation recorded in the year after delivery and the adjusted hazard ratio when comparing first-trimester vaccination to no vaccination was 1.06 (99%CI, 0.94-1.19; p=0.2). Results were similar for second and third-trimester vaccination and for analyses considering major malformations recorded beyond the first birthday.

Conclusions: In this large, population-based historical cohort study there was no evidence to suggest that seasonal influenza vaccine was associated with major malformations when given in the first trimester or subsequently in pregnancy.

Keywords: Congenital Malformations; Influenza Vaccine; Pregnancy; Safety.