title: The possible association between the combination of vaginal metronidazole and miconazole treatment and poly-syndactyly Population-based case-control teratologic study.
abstract: The objective of the study was to investigate the human teratogenic potential of vaginal metronidazole+miconazole treatment during pregnancy, because these antimicrobial drugs separately did not indicate human teratogenic potential in our and other studies. The analysis of cases with 21 groups of congenital abnormalities and their all matched controls was carried out in the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996 including 38,151 pregnant women who had newborn infants without any congenital abnormalities (control group) and 22,843 pregnant women who had newborn infants or fetuses with congenital abnormalities. The prevalence of vaginal metronidazole+miconazole treatment during pregnancy was 2.5% (N=576) in the case group and 2.2% (N=846) in the control group [crude prevalence odds ratio (POR) with 95% confidence interval (CI): 1.2, 1.0-1.3]. The analysis of cases and their matched controls indicated an association between vaginal metronidazole+miconazole use and poly/syndactyly during the second through third months of gestation (adjusted POR 6.0, 95% CI 2.4-15.2). This finding may be connected with recall bias, although this bias was restricted by the evaluation of maternal drug use only during the critical period of poly/syndactyly and by evaluating only medically recorded metronidazole+miconazole treatment. The conclusion of the study is that this finding can be regarded as a signal for the possible association between vaginal treatment of metronidazole+miconazole during pregnancy and poly/syndactyly without any plausible biological hypothesis.
authors.affiliation: Foundation for the Community Control of Hereditary Diseases, Törökvész lejto 32, H-1026 Budapest, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kazy
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Puhó
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Czeizel
mesh_terms: D000282:Administration, Intravaginal; D000328:Adult; D000935:Antifungal Agents / Q000009:adverse effects*; D000981:Antiprotozoal Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D007231:Infant, Newborn; D016015:Logistic Models; D018811:Maternal Exposure / Q000009:adverse effects*; D008795:Metronidazole / Q000009:adverse effects*; D008825:Miconazole / Q000009:adverse effects*; D016017:Odds Ratio; D017689:Polydactyly / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D011247:Pregnancy; D012042:Registries; D013576:Syndactyly / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology
chemical_list: D000935:Antifungal Agents; D000981:Antiprotozoal Agents; D008795:Metronidazole; D008825:Miconazole