Objective: To estimate the maternal and fetal risks of smallpox vaccination during pregnancy. DATA SOURCES: MEDLINE, Web of Science, EMBASE, Global Health, ClinicalTrials.gov, and CINHAL from inception to September 2014. METHODS OF STUDY SELECTION: We included published articles containing primary data regarding smallpox vaccination during pregnancy that reported maternal or fetal outcomes (spontaneous abortion, congenital defect, stillbirth, preterm birth, or fetal vaccinia). TABULATIONS, INTEGRATION, AND Results: The primary search yielded 887 articles. After hand-searching, 37 articles were included: 18 articles with fetal outcome data and 19 case reports of fetal vaccinia. Outcomes of smallpox vaccination in 12,201 pregnant women were included. Smallpox vaccination was not associated with an increased risk of spontaneous abortion (pooled relative risk [RR] 1.03, confidence interval [CI] 0.76-1.41), stillbirth (pooled RR 1.03, CI 0.75-1.40), or preterm birth (pooled RR 0.84, CI 0.62-1.15). When vaccination in any trimester was considered, smallpox vaccination was not associated with an increased risk of congenital defects (pooled RR 1.25, CI 0.99-1.56); however, first-trimester exposure was associated with an increased risk of congenital defects (2.4% compared with 1.5%, pooled RR 1.34, CI 1.02-1.77). No cases of fetal vaccinia were reported in the studies examining fetal outcomes; 21 cases of fetal vaccinia were identified in the literature, of which three neonates survived. Conclusion: The overall risk associated with maternal smallpox vaccination appears low. No association between smallpox vaccination and spontaneous abortion, preterm birth, or stillbirth was identified. First-trimester vaccination was associated with a small increase in congenital defects, but the effect size was small and based on limited data. Fetal vaccinia appears to be a rare consequence of maternal smallpox vaccination but is associated with a high rate of fetal loss.

  • Pregnant women
  • Smallpox
  • Safety