OBJECTIVE: To determine the ability of Brucella abortus strain RB51 to induce placentitis and abortion in bison after SC vaccination. ANIMALS: 10 pregnant bison cows, 3 to 10 years old and at 3 to 8 months' gestation. PROCEDURE: Pregnant bison cows on a Montana ranch were vaccinated SC with 10(9) colony-forming units of B abortus strain RB51. Two cows, identified prior to the study, were euthanatized and examined 5 weeks after vaccination to obtain optimal histologic samples of placenta. Other cows were euthanatized and examined after abortion. After euthanasia, tissue specimens were collected for histologic and immunohistochemical evaluation. Tissue and fluid specimens for bacteriologic culture were also collected during necropsy. RESULTS: Of 8 cows, 2 aborted at 68 and 107 days after vaccination. Aborting cows had endometritis. Strain RB51 was isolated from reproductive tissues and supramammary lymph nodes. Fetal lesions were not seen; however, fetal bronchial lymph nodes and amniotic fluid contained strain RB51. Cows examined 5 weeks after vaccination had placentitis and endometritis, with numerous bacteria within trophoblastic epithelial cells that were immunoreactive for strain RB51 antigen. Strain RB51 was isolated from placentomes and numerous lymph nodes. Fetal lesions were not seen 5 weeks after vaccination; however, strain RB51 was isolated from numerous lymph nodes and lung, allantoic fluid, and rectal swab specimens. CONCLUSIONS: The vaccine candidate B abortus RB51 has tropism for the bison placenta, and can cause placentitis, which induces abortion in pregnant bison. The vaccine dose used was similar to that being tested in cattle, but may not be appropriate for pregnant bison.

INTRODUCTION:Inactivated influenza vaccine is recommended in any stage of pregnancy, but evidence of safety in early pregnancy is limited, including for vaccines containing A/H1N1pdm2009 (pH1N1) antigen. We sought to determine if receipt of vaccine containing pH1N1 was associated with spontaneous abortion (SAB).

METHODS:We conducted a case-control study over two influenza seasons (2010-11, 2011-12) in the Vaccine Safety Datalink. Cases had SAB and controls had live births or stillbirths and were matched on site, date of last menstrual period, and age. Of 919 potential cases identified using diagnosis codes, 485 were eligible and confirmed by medical record review. Exposure was defined as vaccination with inactivated influenza vaccine before the SAB date; the primary exposure window was the 1-28days before the SAB.

RESULTS:The overall adjusted odds ratio (aOR) was 2.0 (95% CI, 1.1-3.6) for vaccine receipt in the 28-day exposure window; there was no association in other exposure windows. In season-specific analyses, the aOR in the 1-28days was 3.7 (95% CI 1.4-9.4) in 2010-11 and 1.4 (95% CI 0.6-3.3) in 2011-12. The association was modified by influenza vaccination in the prior season (post hoc analysis). Among women who received pH1N1-containing vaccine in the previous influenza season, the aOR in the 1-28days was 7.7 (95% CI 2.2-27.3); the aOR was 1.3 (95% CI 0.7-2.7) among women not vaccinated in the previous season. This effect modification was observed in each season.

CONCLUSION:SAB was associated with influenza vaccination in the preceding 28days. The association was significant only among women vaccinated in the previous influenza season with pH1N1-containing vaccine. This study does not and cannot establish a causal relationship between repeated influenza vaccination and SAB, but further research is warranted.

OBJECTIVE:To evaluate the risk of spontaneous abortion after quadrivalent human papillomavirus (4vHPV) vaccination before and during pregnancy across seven integrated health systems within the Vaccine Safety Datalink.

METHODS:Within a retrospective observational cohort, we compared risks for spontaneous abortion after 4vHPV in three exposure windows: distal (16-22 weeks before the last menstrual period [LMP]), peripregnancy (within 6 weeks before the LMP), and during pregnancy (LMP through 19 weeks of gestation). Women 12-27 years of age with a pregnancy between 2008 and 2014, with continuous insurance enrollment 8 months before and through pregnancy end, and with a live birth, stillbirth, or spontaneous abortion were included. Pregnancies were identified through validated algorithms. Spontaneous abortions and stillbirths were verified by chart review with spontaneous abortions adjudicated by clinical experts. We excluded multiple gestations, spontaneous abortions before 6 weeks of gestation, and women using medications increasing risk of spontaneous abortion. Spontaneous abortion risk after 4vHPV during pregnancy was compared with distal vaccination using time-dependent covariate Cox models. Spontaneous abortion risk for peripregnancy compared with distal vaccination was evaluated with standard Cox models.

RESULTS:We identified 2,800 pregnancies with 4vHPV exposure in specified risk windows: 919 (33%) distal, 986 (35%) peripregnancy, and 895 (32%) during pregnancy. Mean age was 22.4 years in distal and peripregnancy groups compared with 21.4 years among women vaccinated during pregnancy. Among women with distal 4vHPV exposure, 96 (10.4%) experienced a spontaneous abortion. For peripregnancy and during pregnancy exposures, spontaneous abortions occurred in 110 (11.2%) and 77 (8.6%), respectively. The risk of spontaneous abortion was not increased among women who received 4vHPV during pregnancy (adjusted hazard ratio 1.10, 95% CI 0.81-1.51) or peripregnancy 1.07 (0.81-1.41).

CONCLUSION:Inadvertent 4vHPV exposure during or peripregnancy was not significantly associated with an increased risk of spontaneous abortion.

OBJECTIVE:To assess a possible association between Yellow fever (YF) vaccine (inadvertently) administered during early pregnancy and spontaneous abortion.

METHOD:A hospital-based case-control study conducted in a Brazilian town after a YF vaccine campaign that followed an epidemic of dengue. The study included 39 women who attended a university hospital with spontaneous abortion (cases) and 74 pregnant women attending the antenatal clinic of that hospital (controls).

RESULTS:The crude odds ratio (relative risk estimate) of this association was 2.49, which dropped to 2.29 (95% CI 0.65-8.03) when adjusted for several confounders by multiple logistic regression. Dengue and exposure to organophosphate insecticide fogging during pregnancy were not associated with spontaneous abortion.

CONCLUSION:This study, although small and with low power, provides some evidence that women vaccinated with YF vaccine during early pregnancy have an increased risk of having spontaneous abortion. Based on these findings a sensible recommendation should be to avoid YF vaccination of pregnant women unless their risk of acquiring YF outweighs the risk of vaccine-related abortion.