BACKGROUND The effects of maternal medications and disease on neonatal hearing screening have scarcely been investigated. OBJECTIVE To verify the effect of maternal medications and disease during gestation on the results of the first otoacoustic emissions (OAE) test. METHODS We recorded perinatal and hearing screening data, medications during pregnancy and Labor (119 kinds of medication), hypertension/pre-eclamptic toxemia (HTN/PET) and diabetes mellitus (DM). RESULTS Of the 2306 infants studied, 214 (9.3%) failed the first OAE test. Vaginal delivery (VD) and cesarean delivery (CD) infants were analyzed separately. Multivariate logistic regression analysis showed: Independently significant variables associated with failed first OAE in VD infants included: Birth weight (BW) >4000g [OR 2.2 (1.1-4.3) p=0.026]; decreasing age at first OAE [OR 0.31 (0.17-0.6) p<0.001] and maternal DM [OR 2.2 (1.0-4.84) p=0.049]. The findings for CD infants were: male gender [OR 1.91 (1.24-2.96) p=0.004); decreasing age at first OAE [OR 0.34 (0.21-0.55) p<0.001]; maternal HTN/PET [OR 2.3 (1.22-4.3) p=0.01 and small-for-gestational-age (SGA) status [OR 2.9 (1.1-7.56) p=0.03]. CONCLUSIONS Increased failure on first OAE occurs in VD infants with BW >4,000g, early first OAE and DM; and in CD infants with male gender, early first OAE, HTN/PET and SGA status. It is yet to be determined whether postponing of first OAE beyond 48 hours of age will allow the reduction of false positive results on first OAE.