Reports of cell-based influenza vaccine administered during pregnancy in the Vaccine Adverse Event Reporting System (VAERS), 2013-2020

Abstract Background In November 2012, the first cell cultured influenza vaccine, a trivalent subunit inactivated influenza vaccine (Flucelvax(®), ccIIV3), was approved in the United States for adults aged ≥18 years. A quadrivalent version (ccIIV4) was later approved in 2016 and replaced ccIIV3. The safety of ccIIV3 or ccIIV4 (ccIIV) was not assessed for pregnant women or their infants during pre-licensure studies. Objective To assess the safety of ccIIV administered during pregnancy in pregnant women and their infants whose reports were submitted to VAERS during 2013–2020. Material and methods We searched VAERS for United States reports of adverse events (AEs) in pregnant women who received ccIIV from 1 July 2013 through 31 May 2020. Clinicians reviewed reports and available medical records and assigned a primary clinical category for each report. Reports were coded as serious based on the Code of Federal Regulations definition. Results VAERS received 391 reports following ccIIV administered to pregnant women. Twenty-four (6.1%) were serious. Two neonatal deaths were reported. No maternal deaths occurred. Among reports with trimester information (n = 340), ccIIV was administered during the second trimester in 170 (50%). The most frequent pregnancy-specific AE was premature delivery in 85 (21.7%) reports, followed by dysmature placenta in 13 (3.3%) and pre-eclampsia/eclampsia in ten (2.3%). The most common non-pregnancy specific conditions were infectious conditions in 32 (8.2%). Among infant conditions, low birth weight was reported in 62 (15.9%) reports. Fifteen birth defects were reported; in 12 with gestational age information, administration of the vaccine occurred late in the second trimester or later. Conclusions Review of maternal ccIIV reports in VAERS was not unexpectedly different from other maternal influenza vaccine safety VAERS reviews.