Background: Infants < 3 months of age are at highest risk for developing severe complications after pertussis. The majority of pregnant women has low concentrations of pertussis-specific antibodies and thus newborns are insufficiently protected by maternally transferred antibodies. Acellular pertussis vaccination during pregnancy was recently implemented in various countries. Here, we assessed the evidence for safety and effectiveness of pertussis vaccination during pregnancy. Methods: We searched Medline, Embase, and ClinicalTrials.gov from January 1st 2010 to January 10th 2019. We assessed risk of bias (ROB) using the Cochrane ROB tool and ROBINS-I. We evaluated the quality of evidence using the GRADE approach. Results: We identified 1273 articles and included 22 studies (14 for safety; 8 for effectiveness), comprising 1.4 million pregnant women in safety studies and 855,546 mother-infant-pairs in effectiveness studies. No significant differences between vaccinated and unvaccinated women and their infants were observed for safety outcomes with the exception of fever and chorioamnionitis. Compared to no vaccination, three studies showed a significantly increased relative risk for the presence of the ICD-9 code for chorioamnionitis in electronic patient data after pertussis vaccination. However, no study reported an increased risk for clinical sequelae of chorioamnionitis after vaccination during pregnancy, such as preterm birth or neonatal intensive care unit admission. Vaccine effectiveness against pertussis in infants of immunized mothers ranged from 69 to 91% for pertussis prevention, from 91 to 94% for prevention of hospitalization and was 95% for prevention of death due to pertussis. Risk of bias was serious to critical for safety outcomes and moderate to serious for effectiveness outcomes. GRADE evidence quality was moderate to very low, depending on outcome. Conclusion: Although an increased risk for a diagnosis of fever and chorioamnionitis was detected in pregnant women after pertussis vaccination, there was no association with a higher frequency of clinically relevant sequelae. Vaccine effectiveness for prevention of infant pertussis, hospitalization and death is high. Pertussis vaccination during pregnancy has an overall positive benefit-risk ratio. In view of the overall quality of available evidence ongoing surveillance of chorioamnionitis and its potential sequelae is recommended when pertussis vaccination in pregnancy is implemented. Trial registration: PROSPERO CRD42018087814, CRD42018090357.

Electronic healthcare databases are of increasing importance in health research and mortality is one of the most relevant outcomes. However, data in these databases need to be validated, since they are often generated for reimbursement purposes. The aims of this study were to compare mortality figures from the German Pharmacoepidemiological Research Database (GePaRD) on an aggregated level with external data from the Federal Statistical Office of Germany (FSOG) and to assess consistency of records of death from core data and hospital data within GePaRD. The study population comprised insurants of four statutory health insurances providing data for GePaRD with either continuous insurance coverage from January 1st to December 31st 2006 or until death. The sex-specific mortality rate, stratified and standardized by age, and the percentage of hospital deaths among all deaths was compared with data from the FSOG. Furthermore, the agreement between the dates of death according to hospital data and core data was assessed within GePaRD. The study population comprised 12,033,622 insurants. Compared to FSOG data, the age-standardised mortality rate in GePaRD was 21 % and 29 % lower in women and men, respectively. Regional analyses also indicated lower mortality rates in all federal states except for Bremen, where the age-standardised mortality rate was similar to FSOG data for both sexes. The percentage of hospital deaths among all deaths corresponded well with external data. The proportion of inpatient deaths also recorded in the health insurance core data was 98.5 %. Furthermore, 94 % of dates of death documented in hospital agreed with the dates of death according to the health insurance core data. The lower mortality rates in almost all federal states might result from the higher socioeconomic status of the GePaRD study population compared to the overall population in Germany. In the federal state of Bremen, where socioeconomic representativeness is higher due to additional inclusion of two local health insurances, the mortality rates were in good accordance with external data. Agreement of the percentage of hospital deaths among all deaths between GePaRD and national statistics suggested completeness of outpatient mortality information.