First-Trimester Influenza Infection Increases the Odds of Non-Chromosomal Birth Defects: A Systematic Review and Meta-Analysis

Viral infections during pregnancy raise several clinical challenges, including birth defects in the offspring. Thus, this systematic review and meta-analysis aims to prove and highlight the risk of birth defects after first-trimester maternal influenza infection. Our systematic search was performed on 21 November 2022. Studies that reported maternal influenza infection in the first trimester and non-chromosomal congenital abnormalities were considered eligible. We used odds ratios (OR) with 95% confidence intervals (CIs) to measure the effect size. Pooled ORs were calculated with a random effects model. Heterogeneity was measured with I² and Cochran’s Q tests. We found that first-trimester maternal influenza was associated with increased odds of developing any type of birth defects (OR: 1.5, CI: 1.30–1.70). Moreover, newborns were more than twice as likely to be diagnosed with neural tube defects (OR: 2.48, CI: 1.95–3.14) or cleft lip and palate (OR: 2.48, CI: 1.87–3.28). We also found increased odds of developing congenital heart defects (OR: 1.63, CI: 1.27–2.09). In conclusion, influenza increases the odds of non-chromosomal birth defects in the first trimester. The aim of the present study was to estimate the risk of CAs in the offspring of mothers affected by first-trimester influenza infection.