Summary of final data from the 9-valent human papillomavirus vaccine pregnancy registry (2014-2021)

The 9-valent human papillomavirus (9vHPV) vaccine targets human papillomavirus (HPV) types 6/11/16/18/31/33/45/52/58. Although its use in pregnant women is not recommended, inadvertent exposures during early pregnancy could occur as the indicated age range includes the ages of child-bearing potential. A pregnancy registry was created as a post-marketing regulatory commitment using spontaneous reports of 9vHPV vaccine exposure during pregnancy that were received from the United States (from December 2014 through March 2021) and followed through the completion of pregnancy. Primary pregnancy outcomes included congenital anomalies, live births, fetal deaths, elective terminations, and miscarriages. Enrolled prospective reports were used for rate calculations. Of the 180 prospectively enrolled pregnancies, 70 had known outcomes. There were 66 live births that resulted in 67 live born infants (95.7%; one twin pregnancy), one elective termination, and three miscarriages (estimated rate, 4.3% [3/69] of known outcomes excluding elective terminations). All three miscarriages occurred in the first trimester in women who had been vaccinated prior to detection of pregnancy. There were three major birth defects among the prospective reports, with an estimated rate of 4.5% (3/67). Findings from this analysis of the US 9vHPV vaccine pregnancy registry do not suggest an increased risk of major birth defects and miscarriage in women who received the vaccine. There is no apparent pattern of congenital anomalies to suggest potential adverse effects of exposure to the 9vHPV vaccine during pregnancy. This analysis is consistent with prior clinical trial experience and post-licensure observational data with the quadrivalent HPV and 9vHPV vaccines.