M McMillan1, K Porritt2, D Kralik3, L Costi4, H Marshall5. 1. School of Pediatrics and Reproductive Health, The University of Adelaide, Adelaide 5005, SA, Australia. Electronic address: mark.mcmillan@adelaide.edu.au. 2. Joanna Briggs Institute, Faculty of Health Sciences, The University of Adelaide, Adelaide 5005, SA, Australia. Electronic address: kylie.porritt@adelaide.edu.au. 3. Women's and Children's Hospital, 72 King William Road, North Adelaide 5006, SA, Australia. 4. Women's and Children's Hospital, 72 King William Road, North Adelaide 5006, SA, Australia. Electronic address: lynn.costi@adelaide.edu.au. 5. Vaccinology and Immunology Research Trials Unit (VIRTU), Women's and Children's Hospital and School of Pediatrics and Reproductive Health & Robinson Institute, The University of Adelaide, Adelaide 5005, SA, Australia. Electronic address: helen.marshall@adelaide.edu.au.
Abstract
BACKGROUND: Pregnant women are considered the most important risk group for influenza vaccination. Despite this, the potential risk of harm from the vaccine on the fetus is a key factor in low uptake of the vaccine. This systematic review aimed to synthesize the best available evidence on the safety of influenza vaccination during pregnancy on fetal development. METHODS AND FINDINGS: A search of the literature was undertaken from the inception of each database up to March 2014. Both observational and clinical trials were considered. Fetal outcomes were present in 19 observational studies, and 14 of those were primarily investigating the monovalent influenza A (H1N1) 2009 vaccine. There was significant methodological and clinical heterogeneity of the included studies and a narrative summary and tabling of results was performed. Fetal death outcomes for women in later pregnancy ranged from OR 0.34 to 2.95 with 95% confidence intervals crossing or below the null value. Spontaneous abortion less than 24 weeks ranged from HR 0.45 to OR 1.23, with 95% confidence intervals crossing or below the null value. Congenital malformations for women vaccinated during their first trimester ranged from OR 0.67 to 2.18 and imprecise confidence intervals crossed the null value. Included in this review were some high quality studies, although overall the studies have a high risk of selection and confounding bias. CONCLUSIONS: Results do not indicate that maternal influenza vaccination is associated with an increased risk of fetal death, spontaneous abortion, or congenital malformations. Statistical imprecision and clinical and methodological heterogeneity of the observational studies mean it is not possible to totally exclude adverse effects. Further studies investigating women vaccinated during their first trimester should be the highest priority to allow for more precise estimates, especially for spontaneous abortion, and congenital abnormality outcomes.
BACKGROUND: Pregnant women are considered the most important risk group for influenza vaccination. Despite this, the potential risk of harm from the vaccine on the fetus is a key factor in low uptake of the vaccine. This systematic review aimed to synthesize the best available evidence on the safety of influenza vaccination during pregnancy on fetal development. METHODS AND FINDINGS: A search of the literature was undertaken from the inception of each database up to March 2014. Both observational and clinical trials were considered. Fetal outcomes were present in 19 observational studies, and 14 of those were primarily investigating the monovalent influenza A (H1N1) 2009 vaccine. There was significant methodological and clinical heterogeneity of the included studies and a narrative summary and tabling of results was performed. Fetal death outcomes for women in later pregnancy ranged from OR 0.34 to 2.95 with 95% confidence intervals crossing or below the null value. Spontaneous abortion less than 24 weeks ranged from HR 0.45 to OR 1.23, with 95% confidence intervals crossing or below the null value. Congenital malformations for women vaccinated during their first trimester ranged from OR 0.67 to 2.18 and imprecise confidence intervals crossed the null value. Included in this review were some high quality studies, although overall the studies have a high risk of selection and confounding bias. CONCLUSIONS: Results do not indicate that maternal influenza vaccination is associated with an increased risk of fetal death, spontaneous abortion, or congenital malformations. Statistical imprecision and clinical and methodological heterogeneity of the observational studies mean it is not possible to totally exclude adverse effects. Further studies investigating women vaccinated during their first trimester should be the highest priority to allow for more precise estimates, especially for spontaneous abortion, and congenital abnormality outcomes.
Authors: Daniel B Hawcutt; Nicki-Jayne Russell; Hannah Maqsood; Koushan Kouranloo; Simon Gomberg; Catriona Waitt; Andrew Sharp; Andrew Riordan; Mark A Turner Journal: Br J Clin Pharmacol Date: 2016-09-12 Impact factor: 4.335