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

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.