To systematically summarize the literature on maternal influenza vaccination and the risk for congenital malformations using the methodology of meta-analysis.
PubMed, Scopus, and Embase databases (up to December 2014) as well as ClinicalTrials.gov (May 2015) and references of relevant articles were searched. The search strategy included combinations of the terms “influenza,” “vaccin*,” “pregnan*,” “safe*,” “adverse,” “congenital,” “malformation,” “defect,” and “anomal*.”
Eligible studies examined the association between antepartum or preconceptional maternal immunization with inactivated influenza vaccines (seasonal trivalent or monovalent H1N1) and the risk for congenital malformations. Studies with no or inappropriate control group (comparison with population background rates or other vaccine types) were excluded.
The risk for congenital anomalies after influenza vaccination was examined in 15 studies: 14 cohorts (events per vaccinated compared with unvaccinated: 859/32,774 [2.6%] compared with 7,644/245,314 [3.1%]) and one case–control study (vaccinated per cases compared with controls: 1,351/3,618 [37.3%] compared with 511/1,225 [41.7%]). Eight studies reported on first-trimester immunization (events per vaccinated compared with unvaccinated: 258/4,733 [5.4%] compared with 6,470/196,054 [3.3%]). No association was found between congenital defects and influenza vaccination at any trimester of pregnancy (odds ratio [OR] 0.96, 95% confidence interval 0.86–1.07; 15 studies; I2=36) or at the first trimester (OR 1.03, 0.91–1.18; eight studies; I2=0). When assessing only major malformations, no increased risk was detected after immunization at any trimester (OR 0.99, 0.88–1.11; 12 studies; I2=31.5) or at the first trimester (OR 0.98, 0.83–1.16; seven studies; I2=0). Neither adjuvanted (OR 1.06, 0.95–1.20; five studies; I2=18.8) nor unadjuvanted vaccines (OR 0.89, 0.75–1.04; seven studies; I2=22.6) were associated with an increased risk for congenital defects.
This systematic review did not indicate an increased risk for congenital anomalies after maternal influenza immunization adding to the evidence base on the safety of influenza vaccination in pregnancy.
Maternal immunization with inactivated influenza vaccines at any trimester of pregnancy, including the first, is not associated with an increased risk for congenital malformations.
Alfa Institute of Biomedical Sciences and the Department of Medicine−Infectious Diseases, Iaso General Hospital, Athens, Greece; the Department of Medicine, Karolinska Institutet and University Hospital, Stockholm, and the Department of Pediatrics, Central Hospital, Karlstad, Sweden; and the Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts.
Corresponding author: Matthew Ε. Falagas, MD, MSc, Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos Street, 151 23 Marousi, Athens, Greece; e-mail: firstname.lastname@example.org.
Konstantinos A. Polyzos was supported by the Alexander Onassis Public Benefit Foundation.
Financial Disclosure Dr. Falagas has participated in the advisory boards of Achaogen, Astellas, AstraZeneca, Bayer, and Pfizer; has received lecture honoraria from Angelini, Astellas, AstraZeneca, Glenmark, Merck, and Novartis; and has received research support from Angelini, Astellas, and Rokitan. The other authors did not report any potential conflicts of interest.
The authors thank Dr. Källén and Dr. Schaefer for providing additional information on their studies.