Influenza vaccination during early pregnancy and risk of major birth defects, US Birth Defects Study To Evaluate Pregnancy exposureS, 2014-2019.

Purpose: Studies of influenza vaccination during pregnancy and major birth defects generally provide reassuring findings. To maintain public confidence, it is important to continue evaluating the safety of maternal vaccination using well characterized, population-based data. This study extended previous research to examine associations between maternal influenza vaccination and selected birth defects using data from the Birth Defects Study To Evaluate Pregnancy exposureS, a US, multisite case-control study.

Methods: Mothers of case children (diagnosed with a birth defect) and control children (without a birth defect diagnosis) were identified from population-based birth defect surveillance programs and recruited to complete a telephone interview. Data from 2675 case and 1575 control mothers (participants) with deliveries during 2014-2019 were analyzed. Influenza vaccination exposure during the critical exposure period (one month before pregnancy through the first pregnancy month [B1P1] for spina bifida or through the third pregnancy month [B1P3] for other selected birth defects) was assessed controlling for several participant covariates. Logistic regression with propensity score adjustment was used to estimate adjusted odds ratios (aORs) and 95 % confidence intervals (CIs). Several secondary analyses were conducted. A probabilistic bias analysis examined the effect of exposure misclassification.

Results: The aOR observed between B1P1 influenza vaccination exposure and spina bifida was 0.9 (95 % CI: 0.4-2.0). The aORs for B1P3 exposure and other selected birth defects examined ranged from 0.4 to 1.3, with 95 % CIs including the null except those for cleft lip ± cleft palate (aOR: 0.6; 95 % CI: 0.4-0.9) and gastroschisis (aOR: 0.4; 95 % CI: 0.2-0.7). Results from secondary analyses were similar to the primary analyses, and those from probabilistic bias analysis were similar to respective primary and secondary analyses.

Conclusion: Findings showed no statistically significant positive associations between influenza vaccination and the selected birth defects, supporting public health efforts to promote optimal vaccination coverage among pregnant women.