**2. Materials and Methods**

While conducting an ICH-GCP phase 2 clinical trial using a VLP vaccine against pandemic influenza A at the Mexican Institute of Social Security (IMSS, Mexico City, Mexico), 4555 male and nonpregnant female (confirmed by a negative pregnancy test) volunteers were included. Despite the use of contraceptive methods—as stated by the participants—40 women reported pregnancy in the postvaccination period (Table 1). We reported these events to the IMSS Ethics Committee and Comisión Federal para la Prevención de Riesgos Sanitarios (COFEPRIS) (the Mexican equivalent of the US Food and Drug Administration), and they both recommended that the pregnant women and their infants should remain under medical surveillance and be closely monitored according to local regulations.

The design of this study was a nested cohort study that included the 40 women who became pregnant after the influenza A(H1N1)pdm09 virus vaccination and their infants (Figure 1).


**Table 1.** Characteristics of the study population (women).


**Table 1.** *Cont.*

\* Student's *t* test comparing placebo vs. VLP 15 μg; \*\* Fisher's exact test comparing placebo vs. VLP 15 μg. VLP—virus-like particle.

**Figure 1.** Flow and details of the subjects in the trial. A total of 820 women volunteers participated in the phase 2 clinical trial to evaluate the safety and immunogenicity (part A) and safety (part B) of the VLP vaccine against influenza A(H1N1)pdm09 [6]. After vaccination, 40 women became pregnant—16 from the placebo group, 23 from the 15 μg VLP vaccine dose, and 1 from the 45 μg VLP vaccine dose. All these volunteers were provided with medical surveillance and close monitoring; clinical outcomes and VLP vaccine specific antibody titers in both mothers and their infants were evaluated. Both the Mexican Institute of Social Security and the National Institute of Perinatology Ethic Committees approved the study (IMSS:R-2011-785-040, INPer:212250-06181).
