Results on exposure during pregnancy from a pregnancy registry for AS04-HPV-16/18 vaccine.

OBJECTIVE: To assess pregnancy outcomes after exposure to AS04-HPV-16/18 vaccine (Cervarix, GSK, Belgium) prior to, or during pregnancy, as reported to a pregnancy registry.

METHODS: A pregnancy exposure registry was established to collect data in the United Kingdom and the United States. Exposure was defined as vaccination with AS04-HPV-16/18 within 60days before the estimated conception date and delivery. Reporting was voluntary.

RESULTS: Between September 2007 and November 2015, 306 pregnancy exposure reports were received of which 181 were prospective, evaluable reports. From these 181 reports, 154 (85.1%) pregnancies resulted in a live birth, 14 (7.7%) in spontaneous abortion, one (0.5%) in stillbirth, and 12 (6.6%) were electively terminated. There was no clustering of outcomes with respect to the timing of exposure. There were 18 infants born with a congenital anomaly of which nine were minor structural defects, seven were major structural defects, one was a hereditary disorder and one was likely the result of a congenital infection. In three cases of structural defect (two minor and one major), there was a temporal association to vaccination during the critical developmental period of gestation. There was no cluster or constellation of congenital anomalies suggestive of possible teratogenesis.

CONCLUSION: The pharmacovigilance plan to investigate the effects of inadvertent exposure to AS04-HPV-16/18 vaccine during pregnancy included assessment of pregnancy outcomes among women enrolled in clinical trials, evaluation of pregnancy exposure reports from all countries as part of routine passive safety surveillance, a large, well conducted post-authorization observational study, and the pregnancy registry. These registry data complement other data from clinical trials and post-marketing surveillance showing no evidence that vaccination with AS04-HPV-16/18 during the defined exposure period (within 60days before conception until delivery) increases the risk of teratogenicity.