Objective: We have previously found an association between the combination of topical and vaginal clotrimazole treatment during pregnancy and a decreased prevalence of preterm births in the populationbased data set of the Hungarian CaseControl Surveillance of Congenital Abnormalities. Thus the objective of this secondary analysis in the expanded data set was to evaluate potential confounders and to examine the possible interaction of clotrimazole with other drugs. Study design: Medically recorded birth weight/gestational age, in addition the prevalence of preterm birth and low birthweight infants of newborn infants without birth defects born to mothers with or without clotrimazole treatment during pregnancy were compared in the expanded control data set of the Hungarian CaseControl Surveillance of Congenital Abnormalities, 1980-1996. Results: The 17-year data set included 38,151 newborn infants and 8.1%were born to mothers who received clotrimazole treatment during pregnancy. There was an increase in mean gestational age among the exposed relative to the unexposed, resulting in a significant (34-64%) reduction in the prevalence of preterm births. This finding could not be explained by confounders and/or interaction with other drugs. Conclusion: The protective effect of clotrimazole for preterm birth was confirmed. We conclude that the protective effect of topical clotrimazole during pregnancy may be attributable to the beneficial effect of clotrimazole in the restoration of the abnormal colonization of the female genital organs and its known antibacterial and/or antiprotozoal effect. Objective: We have previously found an association between the combination of topical and vaginal clotrimazole treatment during pregnancy and a decreased tendency of preterm births in the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities. Thus the objective of this secondary analysis in the expanded data set was to evaluate potential confounders and to examine the possible interaction of clotrimazole with other drugs. Study design: Medically recorded birth weight / gestational age, in addition the prevalence of preterm birth and low birthweight infants of newborn infants without birth defects born to mothers with or without clotrimazole treatment during pregnancy were compared in the expanded control data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Results: The 17-year data set included 38,151 newborn infants and 8.1% were born to mothers who received clotrimazole treatment during pregnancy. There was an increase in mean gestational age among the exposed relative to the unexposed, resulting in a significant (34-64%) reduction in the prevalence of preterm births. This finding could not be explained by confounders and / or interaction with other drugs. Conclusion: The protective effect of clotrimazole for preterm birth was confirmed. We conclude that the protective effect of topical clotrimazole during pregnancy may be attributable to the beneficial effect of clotrimazole in the restoration of the abnormal colonization of the female genital organs and its known antibacterial and / or antiprotozoal effect.