Risk factors of microtia: A systematic review and meta-analysis

Background: The pathogenesis of microtia is still unclear. Various risk factors have been studied but they remain inconclusive. We conducted the first ever systematic review and meta-analysis to look for the association between microtia and various environmental risk factors. Methods: Relevant case-control studies published between January 2000 to October 2014 were identified through a systematic search in PubMed and EMBASE. Reference lists from relevant review articles were also searched. Studies were included if they meet our selection criteria. Out of 1706 potential articles, 12 were included in the systematic review and 8 in the meta-analysis. Results: Risk factors which showed significant positive association with microtia were: cold-like syndrome during pregnancy (OR = 2.15; 95 % CI = 1.36, 3.41, P = 0.001); multiple gestation (OR = 1.55; 95 % CI = 1.05, 2.29, P = 0.03); and gestational diabetes (OR = 1.48; 95 % CI = 1.04, 2.10, P = 0.03). Risk factors which showed positive association but statistically insignificant were: threatened abortion (OR = 1.22; 95 % CI = 0.69, 2.15, P = 0.50); smoking during pregnancy (OR = 1.05; 95 % CI = 0.63, 1.77, P = 0.84); alcohol during pregnancy (OR = 1.08; 95 % CI = 0.65,1.80 P = 0.77); urinary tract infection (OR = 1.04; 95 % CI = 0.59, 1.84, P = 0.89); essential hypertension (OR = 1.04; 95 % CI = 0.74, 1.47, P = 0.82); maternal diabetes (OR = 3.98; 95 % CI = 0.72, 21.96, P = 0.11); respiratory tract infection (OR = 1.26,95 % CI = 0.84,1.88, P = 0.26); chronic disease during pregnancy (OR = 1.29,95 % CI = 0.99,1.69, P = 0.06); severe nausea/vomiting (OR = 1.16; 95 % CI = 0.66, 2.04, P = 0.61); NSAIDs during pregnancy (OR = 1.17, 95 % CI = 0.61,2.22, P = 0.64); antihypertensives during pregnancy (OR = 1.84,95 % CI = 0.94,3.62, P = 0.08); and illegal drugs during pregnancy (OR = 1.69; 95 % CI = 0.65, 4.39, P = 0.28). Reduced risk for microtia was found with these factors: folic acid (OR = 0.55; 95 % CI = 0.33, 0.92, P = 0.02); advanced maternal age (OR = 0.94; 95 % CI = 0.79, 1.11, P = 0.45); ampicillin during pregnancy (OR = 0.80,95 % CI = 0.50, 1.28, P = 0.35); and metronidazole during pregnancy (OR = 0.77,95 % CI = 0.40, 1.48 P = 0.44). Conclusions: Our study indicates cold-like syndrome, multiple gestation, and gestational diabetes as significant risk factors for microtia; whereas folic acid consumption during pregnancy is shown to be a protective factor. Studies on risk factors for microtia are still very limited to establish the definitive risk factors. Further large-scale and multicentre studies are needed to clarify the role of key risk factors for the development of microtia. Level of Evidence: Level II, risk / prognostic study. © 2016, Springer-Verlag Berlin Heidelberg.