Differential Associations of Maternal Factors With Anotia and Microtia Laterality in a North American Case-Control...

Congenital underdevelopment of one or both ears (microtia/anotia) is the most common component of craniofacial microsomia (CFM). Although the right side is more commonly affected, social determinants of laterality remain understudied.

Using a multicenter North American case-control study of CFM (1996-2002), we evaluated associations between maternal periconceptional cigarette smoking, pregnancy intention, timing of pregnancy recognition, education, and prepregnancy body mass index with microtia/anotia, overall and by laterality. Cases were 137 children < 36 months with microtia/anotia identified at craniofacial centers; up to 4 controls per case (n = 678) were matched on residence, age at ascertainment, and calendar time. Exposures were ascertained from maternal interviews. We performed conditional logistic regression adjusted for maternal age and education to estimate odds ratios (ORs) and 95% CIs.

Among 137 cases, 51 (37%) were left-sided, 61 (45%) right-sided, 11 (8%) bilateral, and 14 (10%) unknown. Point estimates for smoking, later pregnancy recognition, lower education, and obesity were elevated overall, though confidence intervals were wide. Left-sided ORs were smoking 2.16 (95% CI: 0.88-5.30); unplanned pregnancy 1.36 (95% CI: 0.67-2.78); pregnancy recognition > 9 weeks after last menstrual period (vs. < 5 weeks) 3.64 (95% CI: 0.95-14.03); < 12 years of education (vs. ≥ 16 years) 5.24 (95% CI: 1.47-18.68); and obesity (vs. normal weight) 1.65 (95% CI: 0.58-4.63). Corresponding right-sided ORs were 1.28, 1.00, 1.63, 2.11, and 1.24.

Several maternal factors were modestly associated with microtia/anotia, with consistently larger estimates for left- than right-sided anomalies. These findings provide limited evidence that the etiology of microtia/anotia may differ by laterality and warrant confirmation in larger studies.