Table 1.

Potential statistical approaches to investigate modifications of humoral immune response to vaccinations in infants after vaccination during pregnancy.

Statistical approach	Advantages	Disadvantages
Immunological modifications
Levels of antigen-specific antibodies*	-Simple statistical approach.	- Clinical significance unclear as it is not assessed against correlate of protection.
Geometric mean ratio of antigen-specific antibodies*	-Possibility of adjustment for co-variates that could affect immune response.	- Needs well-trained statisticians. - Clinical significance unclear as it is not assessed against correlate of protection.
Fold-change in antigen-specific antibody levels post- vs. pre –vaccination*	- Could be used to determine seroconversion rates.	- Requires both pre and post -vaccination antibody levels. - Not a true fold change for primary vaccination since you measure the change from maternal to infant antibodies.- Needs to be carefully interpreted as higher fold changes are expected if baseline antibody levels are low (as in the case of infants born to unvaccinated women) . - Seroconversion rates definition varies and affected by baseline antibody levels. - Clinical significance unclear as it is not assessed against correlate of protection.
Seroprotection rates*	- Simple statistical approach. - Provides more insights into clinical relevance.	- No adjustment for co-variates that could affect immune responses. - Some pathogens don't have well-defined correlate of protection.
Clinical significance
Increase in disease incidence, severity or hospitalization rates*	-Most accurate indicator of immunological modifications.	- Needs large-scale surveillance data that spans for long years after implementation of maternal vaccination program. - Might be difficult to determine for relatively rare diseases and diseases for which less severe presentations could be under-diagnosed and under-reported.

^*In infants born to vaccinated compared with unvaccinated mothers.