The analysis of the Gardasil pregnancy registry data has provided "reassuring" results regarding the potential risks of exposure to the vaccine during pregnancy, Dr. Fabio Lievano reported at a meetingof the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
Based on more than 2,500 pregnancies reported to Merck and enrolled in the registry over a 6-year period, the overall rates of spontaneous abortion, fetal deaths, and congenital anomalies were "at or below background rates," and no pattern in the type of birth defects has been identified, said Dr. Lievano, executive director of clinical risk management at Merck Research Laboratories. Merck is the manufacturer of the quadrivalent HPV vaccine, which provides coverage against HPV types 6, 11, 16, and 18. The vaccine was approved in the United States in 2006, is marketed as Gardasil, and is administered in a three-dose series.
Gardasil is not recommended for use in pregnancy, and as part of the company’s postmarketing safety commitments for the Food and Drug Administration and European and Canadian regulatory authorities, Merck established a pregnancy registry to monitor outcomes associated with inadvertent pregnancy exposures. Women were enrolled in the pregnancy registry if they were living in the United States, Canada, or France and had received a dose of Gardasil within 1 month of their last menstrual period or at any time during pregnancy.
Between June 1, 2006, and May 31, 2012, 2,802 pregnancies exposed to the vaccine were enrolled in the registry, reported from health care providers and vaccinees. (Enrollment closed on Dec. 31, 2012.) The main outcomes the company monitored were infant outcomes (congenital anomalies) and pregnancy outcomes, which included elective abortions, spontaneous abortions (before 20 weeks’ gestation), fetal deaths (at 20 weeks or later), and live births.
Of the 2,440 prospective pregnancy reports (received before the pregnancy outcome was known), about 91% indicated exposure to the vaccine occurred before the end of the first trimester. Of the total exposed pregnancies, there were 102 (3.6%) elective abortions (including 1 associated with anencephaly and hypoplastic heart) and 105 (3.7%) spontaneous abortions (including 1 triplet pregnancy and 1 with a chromosomal anomaly).
Among the 1,460 newborns, 1,381 (95%) had normal outcomes. Of the remainder, 34 had major congenital anomalies and 45 had minor congenital anomalies.
The rate of spontaneous abortions was 6.7/100 outcomes, Dr. Lievano said, noting that the background rate among clinically recognized pregnancies is 15%. The rate of fetal deaths was 0.8/100 outcomes (live births plus fetal deaths) compared with the background rate of 0.62-1/100.
The overall rate of major congenital anomalies was 2.5/100 live born infants, compared with the background rate of 2.67/100 live born infants. The rate of congenital anomalies appears to be similar to the background rates, and the anomalies reported in the registry have varied in type and etiology, Dr. Lievano said, concluding that the analysis "does not support a causal relationship" between exposure to the vaccine in pregnancy and the birth defects reported in the registry,
Of the 362 retrospective reports of pregnancy exposures in the registry (those with outcomes that were known at the time of enrollment), there were 319 known pregnancy outcomes, which included 61 spontaneous abortions and 8 fetal deaths. Among the retrospective reports, 25 infants had major congenital anomalies, including 13 with an isolated anomaly, 4 with two anomalies each, 3 with multiple anomalies, and 2 with multiple anomalies as part of a chromosomal abnormality, he said.
As of April, the FDA, as well as the European Medicines Agency and Health Canada, consider that the company has met the postmarketing pregnancy registry commitment. The results will be published and will be added to the drug’s label. Merck will continue to update the registry with reports of exposures and will provide periodic safety updates to the regulatory agencies, Dr. Lievano said.
The updated ACIP statement on HPV vaccine, which is being planned, will advise that pregnancy exposures continue to be reported to Merck and to the FDA and CDC’s Vaccine Adverse Event Reporting System (VAERS).
The updated Gardasil pregnancy registry website says that cases of exposure to Gardasil during pregnancy should be reported to Merck at 877-888-4231.