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.

BACKGROUND:The VARIVAX® Pregnancy Registry was established in 1995 to monitor pregnancy outcomes of women who received varicella vaccine (ie, VARIVAX) inadvertently while pregnant.METHODS:Health care providers and consumers sent voluntary reports about women who received VARIVAX 3 months before or during pregnancy. Follow-up occurred to evaluate pregnancy outcomes for birth defects. Outcomes from prospectively reported pregnancy exposures (ie, reports received before the outcome of the pregnancy was known) among varicella-zoster virus (VZV)-seronegative women were used to calculate rates and 95% confidence intervals (CIs).RESULTS:From 17 March 1995 through 16 October 2013, 1601 women were enrolled-966 prospectively-among whom there were 819 live births. Among 164 infants born to women who were VZV seronegative at the time of vaccination, no cases of congenital varicella syndrome (CVS) were identified (rate, 0 per 100, 95% CI, 0.0-2.2) and the birth prevalence of major birth defects was 4.3 per 100 liveborn infants (95% CI 1.7-8.6) with no pattern suggestive of CVS. No defects consistent with CVS were identified in any registry reports.CONCLUSIONS:Data collected through the VARIVAX pregnancy registry do not support a relationship between the occurrence of CVS or major birth defects and varicella vaccine exposure during pregnancy, although the small numbers of exposures cannot rule out a low risk. VARIVAX remains contraindicated during pregnancy.

Abstract Background Varicella, a contagious infectious disease caused by varicella zoster virus (VZV), can result in hospitalization and, occasionally, death. Varicella virus vaccine live (VVVL [VARIVAX]) was introduced in the United States in 1995. Methods This comprehensive review of the VVVL safety profile is based on 22 years of postmarketing adverse event (AE) data received through spontaneous and noninterventional study reports submitted by health care providers and on a review of the published literature (cumulatively from March 17, 1995, through March 16, 2017, during which period >212 million doses were distributed globally). Results The VVVL safety profile was consistent with previous publications, with common AEs including varicella, rash, and pyrexia. AE reports have decreased over time, from ~500 per million doses in 1995 to ~40 per million doses in 2016; serious AEs comprise 0.8 reports per million doses. Secondary transmission was rare (8 confirmed cases); polymerase chain reaction analysis indicated that 38 of the 66 reported potential secondary transmission cases of varicella were attributable to wild-type VZV. The prevalence of major birth defects in the Pregnancy Registry was similar to that in the general US population. In total, 86 cases of death were reported after vaccination with VVVL; immunocompromised individuals appeared to be most at risk for a fatal varicella- or herpes zoster–related outcome. Conclusions This comprehensive 22-year review confirms the overall safety profile for VVVL, with no new safety concerns identified. Since VVVL’s introduction in 1995, notable declines in varicella cases and in varicella-related deaths have occurred compared with the prevaccination period.

Background: The Centers for Disease Control and Prevention (CDC) coordinates the Vaccines For Children (VFC) program, which provides free vaccines to qualified children in the US. In 2009, the CDC issued Vaccine Storage Requirements, which were later replaced (2012) with an interim guidance and toolkit for vaccine storage and handling. The guidance called for use of Digital Data Loggers (DDL) to monitor vaccine storage temperatures. We describe a change in frequency of Incorrect Product Storage Reports (IPSRs) following issuance of the 2009 CDC guidance. Methods: Merck & Co., Inc., Kenilworth, NJ, USA, systematically evaluates vaccine safety concerns for all products. The safety database was queried (01-Jan-2004 through 31-December-2016) to identify all IPSRs associated with 10 vaccines. We compared IPSRs received prior to and following the 2009 CDC guidance, comparing reports received from the US with those received from international sources during the same period. Results: Following the release of the DDL guidance, a progressive increase in IPSRs was identified in the US (1 report received in 2004, 12,993 reports in 2016). In contrast, non-US IPSRs - have not had a similar increase: no reports received in 2004, 216 reports received in 2016. US reports of IPSRs 2004 through 2016 account for 96% of reports worldwide. There were no serious reports found in the database in conjunction with IPSRs, nor were there any additional safety findings in any of the reports with additional events reported. Conclusion: VFC DDL guidance was followed by an increase in IPSRs. No similar trend was seen outside the US (where no broad change in DDL guidance occurred). Despite the increase in IPSRs, there have been few associated adverse events (AEs) reported; no new safety concerns were identified. These findings suggest that the increase in IPSRs was associated with the introduction of use of DDLs, and suggests the need for further impact assessment. (C) 2017 Elsevier Ltd. All rights reserved.

18-Year Summary of Pregnancy Outcomes English Willis, MD; Ann Marko, BSN, RN; Mona Marin, MD; Sonja Rasmussen, MD; Stephanie R. Bialek, MD, MPH; Ann Redfield, MSN, RN; Maureen Mcgee, BSN, RN; Adrian Dana, MD; Clinical Safety and Risk Management, Merck Research Laboratories, Merck and Co., Inc., North Wales, PA; Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA; Influenza Division, Centers for Disease Control and Prevention, Altanta, GA

Vaccines that contain live attenuated varicella-zoster virus (VZV) (Varivax, ProQuad, and Zostavax [all products of Merck & Co., Inc.]) are contraindicated during pregnancy. To monitor the pregnancy outcomes of women inadvertently vaccinated with VZV-containing vaccines immediately before or during pregnancy, Merck and CDC established the Merck/CDC Pregnancy Registry for VZV-Containing Vaccines in 1995. This report updates previously published summaries of registry data, provides the rationale for the closure of the registry, and describes plans for continued monitoring of the safety of these vaccines when inadvertently administered to pregnant women or immediately before pregnancy. From inception of the registry in 1995 through March 2012, no cases of congenital varicella syndrome and no increased prevalence of other birth defects have been detected among women vaccinated within 3 months before or during pregnancy. Although a small risk for congenital varicella syndrome cannot be ruled out, the number of exposures being registered each year (approximately two varicella-susceptible women exposed during the high-risk period for congenital varicella syndrome) is now too low to improve on the current estimate of the risk.