Association Between Maternal Human Papillomavirus Infection and Adverse Pregnancy Outcomes: Systematic Review and Meta-Analysis

Abstract Background Experimental studies provide evidence of the harmful effect of human papillomavirus (HPV) infection on pregnancy, but observational studies are inconclusive. We systematically assessed the association between HPV and adverse pregnancy outcomes. Methods We searched electronic databases up to December 1, 2019. We included observational studies on the association between HPV and adverse pregnancy outcomes. We conducted a random-effect meta-analysis for each outcome and assessed heterogeneity between studies. Results From 3034 citations, we included 38 studies and quantitatively synthesized 36 studies. Human papillomavirus was significantly associated with preterm birth (age-adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI], 1.19–1.88), preterm premature rupture of membranes (aOR, 1.96; 95% CI, 1.11–3.45), premature rupture of membranes (aOR, 1.42; 95% CI, 1.08–1.86), intrauterine growth restriction (aOR, 1.17; 95% CI, 1.01–1.37), low birth weight (aOR, 1.91; 95% CI, 1.33–2.76), and fetal death (aOR, 2.23; 95% CI, 1.14–4.37). No significant association was found for spontaneous abortion (aOR, 1.14; 95% CI, 0.40–3.22) and pregnancy-induced hypertensive disorders (aOR, 1.24; 95% CI, 0.80–1.92). Most of the studies were of moderate or low quality, and substantial between-studies heterogeneity remained unexplained. Conclusions We found a consistent and significant association between HPV and preterm birth and preterm premature rupture of membranes. Human papillomavirus may also be associated with intrauterine growth restriction, low birth weight, and fetal death, but findings are limited by suboptimal control of biases. This meta-analysis suggests that HPV is associated with preterm birth and preterm premature rupture of membranes. Associations are also possible for other adverse pregnancy outcomes, but the potential biases and the small number of studies do not allow definitive conclusions.