Epidemiological Analysis and the Nomogram for Possible Risk Factors for Severe Microtia

Abstract

Background: Microtia is a severe congenital malformation of the external ear. This study aimed to explore the epidemiologic characteristics and the possible risk factors in patients with severe microtia in China, and integrate significant variables into a predictive nomogram. Methods: A total of 965 patients with microtia were included. This retrospective case study was conducted from July 2014 to July 2019 at Plastic Surgery Hospital in China. The detailed questionnaires concerning potential risk factors were completed and data were gathered. Chi-Square and Fisher tests were used to analyze the variables, and a multivariate logistic regression model was used to select variables related to severe microtia, and then construct a nomogram. The nomogram model was evaluated by the concordance index (C-index), calibration plot, and receiver operating characteristics (ROCs) curve. Bootstraps with 1000 resamples were applied to these analyses. Results: Of the 965 microtia patients, 629 (65.2%) were male and 867 (89.8%) were sporadic. The cases were observed more commonly in unilateral (83.1%) and right-sided (52.0%). And multiple malformations were observed in 392 (40.6%) cases. Multivariate logistic regression analysis showed that maternal age, miscarriage frequency, virus infection, anemia, using progesterone, paternal alcohol intake, and topography of living areas were associated with a higher risk of severe microtia. All the significant variables were combined into a predictive nomogram (C-index = 0.755,95% CI = 0.703–0.807). Higher prediction accuracy (adjusted C-index = 0.749) was further verified via bootstrap validation. The calibration plot showed good performance, and the ROCs curve analysis demonstrated high sensitivity and specificity. Conclusions: Most microtia patients are male, sporadic, and accompanied by other malformations, which are similar to the phenotypic analysis results of other studies. A nomogram predicting severe microtia was constructed to provide scientific guidance for individualized prevention in clinical practice.

Factors associated with nonsyndromic anotia and microtia, Texas, 1999–2014

“…Like ours, most prior studies also found increased risk of A/M in children of older women (Hoyt et al, 2014). Both Guo et al (2021) and Stallings et al (2018) reported the greatest risk increase among women ≥40 years of age. We did not find a significant increase in prevalence for women aged ≥40 years.…”

“…Male sex and older maternal age have each been evaluated in relation to A/M. Previous epidemiologic assessments have reported a preponderance of males among cases with A/M (Guo et al, 2021; Ryan et al, 2019; Stallings et al, 2018), a pattern which is observed for many structural birth defects (Michalski et al, 2015). Like ours, most prior studies also found increased risk of A/M in children of older women (Hoyt et al, 2014).…”

“…A/M demonstrates a slight male preponderance (Cabrejo, Persing, & Alperovich, 2019; Michalski et al, 2015; van Nunen, Kolodzynski, van den Boogaard, Kon, & Breugem, 2014). While 80%–90% of cases are unilateral, the condition can occur bilaterally (Shaw, Carmichael, Kaidarova, & Harris, 2004; Stallings et al, 2018; Suutarla et al, 2007) and one‐quarter to one‐half of affected individuals have co‐occurring birth defects (Guo et al, 2021; Llano‐Rivas, González‐del Angel, del Castillo, Reyes, & Carnevale, 1999; Mastroiacovo et al, 1995; Rollnick, Kaye, Nagatoshi, Hauck, & Martin, 1987; Stoll, Alembik, Dott, & Roth, 2016; Suutarla et al, 2007). Bilateral presentation and co‐occurring birth defects are more common among the 10%–40% of affected individuals with A/M syndromes (Cabrejo et al, 2019; Llano‐Rivas et al, 1999), which include oculo‐auriculo‐vertebral spectrum (Tingaud‐Sequeira, Trimouille, Sagardoy, Lacombe, & Rooryck, 2022), CHARGE syndrome (Blake & Prasad, 2006), Treacher‐Collins syndrome (van Nunen et al, 2014), and trisomies 13, 18, and 21 (Stoll et al, 2016).…”

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

“…Recent studies on microtia have moved beyond these siloed single-factors hypotheses, testing approaches to combine these independent predictors. For instance, Guo and colleagues have established a multivariate logistic model and identified seven significant factors of severe microtia ( 16 ). Similarly, a case-control study focused on severe microtia/atresia has spotted several environmental exposure factors using the multivariate logistic model ( 17 ).…”

Epidemiological Study of Neonatal Congenital Microtia in Shandong Province, China, 2011–2020

“…3 Researchers believe that living environment and genes work together to cause microtia. 4 The study has reported that 8.3 to 434 of every 100,000 newborns in the world have congenital microtia. 5 Congenital microtia seriously affects the physical and mental health of children, and also increases the medical burden of society.…”