Pregnant women are the WHO priority group for influenza vaccination, but evidences of effectiveness and safety come from observational studies, prone to confounding by indication and healthy-vaccinee bias.

The healthy-vaccinee bias, probably occurring in pregnant women, can overestimate the effectiveness and safety of the vaccine. Indeed, better educated women with healthier behaviors, seeking better medical care, may be more adherent to vaccinations recommended by doctors, scientific societies, health authorities. US and European surveys confirm this hypothesis.

Therefore, it is fundamental to assess vaccine effectiveness and safety from randomized controlled trials (RCTs). Cochrane reviews have identified only one RCT at “low-risk of bias”: the reported maternal, perinatal, and infant deaths and hospitalization were not clearly reassuring, and showed a Number Needed to Vaccine of 55 for mothers, with an excess of local adverse effects. A Cochrane review concluded that pregnant women’s inactivated influenza vaccinations provide uncertain/very limited protection against influenza-like illnesses and influenza. Three other RCTs consistently showed a nonsignificant excess of deaths in the offspring of vaccinated pregnant women, with a significant excess of total serious adverse events in the larger one. Some observational studies suggested possible adverse effects of the inflammation following the vaccination. The inflammation following an influenza is much higher, but to avoid one flu are needed about 55 vaccinations.

Further independent trials with appropriate study designs and comparison groups are required before promoting this universal seasonal vaccination.

Meanwhile, vaccination in 2°-3° trimester could be offered, communicating the existing uncertainties, to promote informed choices. Moreover, also other useful behavioral and environmental measures can reduce infectious diseases.