*3.1. Medical Outcomes in Women Who Became Pregnant after Vaccination with VLP Vaccine against Influenza A(H1N1)pdm09 Virus and Their Infants*

Table 1 describes the characteristics of the women studied. All volunteers included in the study were residents of the metropolitan area of Mexico City and were rightful claimants of full cover medical attention provided by the public health system; all were homemakers, literate, and none reported a medical history of chronic diseases (Table 1). The mean age was 26.1 ± 5.4 years (see Table 1 for the differences in characteristics among the placebo and 15 μg VLP groups). The mean time to become

pregnant after vaccination was 130 ± 115 days; the details on the elapsed time from vaccination to pregnancy are described in Table 1.

The gestational age of the newborns and the frequency of the delivery type were similar between the placebo and 15 μg VLP vaccine groups (Table 2). A similar average birth weight of newborns was observed between the placebo group (2878 ± 554 g) and the 15 μg VLP vaccine group (3081 ± 398 g; *p* > 0.05). The woman from the 45 μg VLP vaccine group delivered via cesarean section at 38 weeks of gestational age, the newborn had a birth weight of 3000 g and an Apgar score typical for a healthy newborn (8/9, 1 min and 5 min).


**Table 2.** Gestational age and delivery type in the placebo and 15 mg VLP vaccine groups.

\* Fisher's test.

None of the pregnant women from the placebo group were diagnosed with preeclampsia, fetal death, premature rupture of membranes, oligohydramnios, or gestational hypertension (Table 3). Two of the women from the VLP 15 μg group received a second immunization (28 days after the first dose); no obstetric complications or adverse events developed in these two women. Six (26%) of the women in the 15 μg VLP group experienced adverse events. These events were preeclampsia (*n* = 2), fetal death (*n* = 1), premature rupture of membranes (*n* = 1), oligohydramnios (*n* = 1), and gestational hypertension (*n* = 1). Table 3 describes the obstetric complications for both the placebo and 15 μg VLP groups; the epidemiological reference of obstetric adverse events reported for the Mexican population is also provided [12]. In all cases, the frequency of the above-mentioned events was not significantly different among the placebo and 15 μg VLP groups (Table 3). The patient who received the 45 μg VLP vaccine did not have any pathology during her pregnancy. In the placebo group, one patient had a preterm birth delivered by cesarean section at 36 weeks, whereas 2 out of 23 (8.7%) women in the 15 μg VLP vaccine group had a cesarean preterm birth at 35 and 36 weeks of gestational age. The woman in the 45 μg VLP vaccine group delivered at term gestational age.



\* COMEGO: Clinic Gynecology and Obstetrics Guides in Mexico 2015, Mexico, Nieto Eds.; \*\* Fisher's test comparing the placebo and the 15 μg VLP groups.

We evaluated 32 infants during the first year of life. Seven abandoned the study during follow-up, and in one case, consent was withdrawn. One infant (6.2%) from the placebo group was diagnosed with pneumonia during the surveillance period. In the 15 μg VLP group, one infant (4.3%) was diagnosed with a hydrocele, one infant (4.3%) was diagnosed with an umbilical hernia, and one infant (4.3%) was diagnosed with gastroesophageal reflux and bacterial pneumonia during medical surveillance (Table 4). Low birth weight and fetal distress were not statistically different between the placebo and 15 μg VLP vaccine groups (Table 4). The infant exposed to the 45 μg VLP dose did not present any pathology.


**Table 4.** Neonatal and one-year surveillance adverse events in infants of women in the vaccinated and placebo groups.

\* Fisher's test.
