Risk Factors of Isolated Microtia: A Systematic Review and Meta-Analysis

Background: Isolated microtia is a congenital facial anomaly, and its cause is unclear. This study systematically investigated related suspicious factors. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Four databases were searched for eligible case-control and cohort studies. Odds ratios and 95% confidence intervals were calculated for each exposure variable if data from at least two eligible studies were provided. If not, narrative syntheses were performed. Results: Twenty-eight articles were included. Meta-analyses were conducted with 22 articles, and 25 factors were identified to have significant association with isolated microtia. Moderate evidence showed that parental low education level, low birth weight (<2500 g), parity greater than or equal to 2, and family history of malformation (especially microtia); maternal intake of antibiotics, benzodiazepines, nonsteroidal antiinflammatory drugs, progesterone, and traditional Chinese medicine; in addition to maternal nongestational diabetes, upper respiratory infection, and radiation exposure increased the risk of microtia in offspring. Limited evidence showed that maternal Hispanic race, pesticide exposure, threatened abortion, history of spontaneous abortion, pet contact, and male gender were associated with increased risk. Maternal race of black or non-Hispanic, and living in an urban area were two protective factors found with moderate and limited evidence, respectively. Conclusion: This study has provided an initial investigation of potential factors associated with isolated microtia and evidence-based conclusion supporting prevention of modifiable factors.