Predicting the Risk of Microtia From Prenatal Factors: A Hospital-Based Case-Control Study

Background: Although a wide range of risk factors for microtia were identified, the limitation of these studies, however, is that risk factors were not estimated in comparison with one another or from different domains. Our study aimed to uncover which factors should be prioritized for the prevention and intervention of non-syndromic microtia via tranditonal and meachine-learning statistical methods. Methods: 293 pairs of 1:1 matched non-syndromic microtia cases and controls who visited Shanghai Ninth People's Hospital were enrolled in the current study during 2017-2019. Thirty-nine risk factors across four domains were measured (i.e., parental sociodemographic characteristics, maternal pregnancy history, parental health conditions and lifestyles, and parental environmental and occupational exposures). Lasso regression model and multivariate conditional logistic regression model were performed to identify the leading predictors of microtia across the four domains. The area under the curve (AUC) was used to calculate the predictive probabilities. Results: Eight predictors were identified by the lasso regression, including abnormal pregnancy history, genital system infection, teratogenic drugs usage, folic acid supplementation, paternal chronic conditions history, parental exposure to indoor decoration, paternal occupational exposure to noise and maternal acute respiratory infection. The additional predictors identified by the multivariate conditional logistic regression model were maternal age and maternal occupational exposure to heavy metal. Predictors selected from the conditional logistic regression and lasso regression both yielded AUCs (95% CIs) of 0.83 (0.79-0.86). Conclusion: The findings from this study suggest some factors across multiple domains are key drivers of non-syndromic microtia regardless of the applied statistical methods. These factors could be used to generate hypotheses for further observational and clinical studies on microtia and guide the prevention and intervention strategies for microtia.