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

BACKGROUND: Isolated microtia is a congenital facial anomaly and its etiology 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: 28 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 (<2500g), parity≥2, family history of malformation (especially microtia), maternal intake of antibiotics, benzodiazepines, NSAIs, progesterone and traditional Chinese medicine, as well as maternal non-gestational diabetes, upper respiratory infection and radiation exposure increased the risk of microtia in offspring. Limited evidence showed that maternal Hispanic race, pesticides exposure, threaten abortion, history of spontaneous abortion, pet contact and male infant were associated with increased risk. Maternal race of Black, non-Hispanic and living in urban area were two protective factors found with moderate and limited evidence, respectively. CONCLUSIONS: This study has provided an initial investigation of potential factors associated with isolated microtia and evidence-based conclusion supporting prevention over modifiable factors.