Safety of yellow fever vaccination in pregnancy: findings from a cohort of active duty US military women

Background: Yellow fever (YF) is a rare viral disease that can be prevented through receipt of a live attenuated vaccine. In the US military, service members must receive the YF vaccine before assignment to endemic areas, putting active duty service women at heightened risk for inadvertent exposure during preconception or pregnancy. Few studies have investigated the safety of YF vaccination in pregnancy to date, and none in a military population.

Methods: Department of Defense Birth and Infant Health Research program data were used to identify pregnancies and infants among active duty US military women, 2003-2014. Multivariable regression models estimated associations with YF vaccine exposure during preconception/pregnancy and adverse outcomes (e.g. spontaneous abortion, birth defects). Sensitivity analyses were performed that excluded pregnancies exposed to other live vaccines. For analyses of birth defects only, a secondary sensitivity analysis was performed that excluded infants diagnosed with chromosomal anomalies.

Results: Of the 196 802 pregnancies and 160 706 singleton infants identified, 1347 (0.7%) and 1132 (0.7%), respectively, were exposed to the YF vaccine. No increased risks for adverse pregnancy or infant outcomes were observed in the main analysis. In sensitivity analyses that excluded pregnancies exposed to other live vaccines, preconception YF vaccine exposure was associated with birth defects [adjusted risk ratio (aRR) = 1.71, 95% confidence interval (CI) = 1.08-2.73]; this association was attenuated when further excluding infants with chromosomal anomalies (aRR = 1.59, 95% CI = 0.97-2.62).

Conclusions: Overall, YF vaccine exposure did not appear to be associated with most adverse outcomes among this population of pregnant military women. A tenuous association between preconception YF vaccine exposure and birth defects was observed in sensitivity analyses, which may warrant further investigation.