{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T11:32:51Z","timestamp":1789903971548,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,8,30]],"date-time":"2006-08-30T00:00:00Z","timestamp":1156896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2007,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Case\u2010control studies are often used to examine putative teratogenic drug effects during organogenesis but these studies are subject to confounding by indication, recall, and participation bias. The case\u2010time\u2010control approach is less susceptible to these sources of bias. We studied congenital abnormalities following exposure to phenytoin, phenobarbital, and diazepam in early pregnancy, i.e., second and third month, compared to mid\u2010pregnancy, i.e., fifth and sixth month of pregnancy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed data from the Hungarian Case\u2010Control Surveillance of Congenital Abnormalities (1980\u20131996) in a case\u2010time\u2010control study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study included 22\u2009843 children with congenital abnormalities (cases) and 38\u2009151 children with no abnormalities (controls). Overall, odds ratio (OR) for congenital abnormalities after exposure to one of the three drugs in early pregnancy was 1.2 (95% confidence interval (CI): 1.0\u20131.4). Among children exposed to phenytoin OR for congenital abnormalities was 3.7 (95%CI: 0.3\u201349.6), for children exposed to phenobarbital the OR was 1.1 (95%CI 0.7\u20131.7), and for diazepam, OR for congenital abnormalities was 1.2 (95%CI: 1.0\u20131.4).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The associations we found between the drugs examined and congenital abnormalities were either only borderline significant or not statistically significant. The case\u2010time\u2010control study provides an interesting way of using existing case\u2010control data to study rare side effect of drugs taken during pregnancy. Copyright \u00a9 2006 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.1288","type":"journal-article","created":{"date-parts":[[2006,8,30]],"date-time":"2006-08-30T10:20:07Z","timestamp":1156933207000},"page":"181-188","source":"Crossref","is-referenced-by-count":51,"title":["Use of phenytoin, phenobarbital, or diazepam during pregnancy and risk of congenital abnormalities: a case\u2010time\u2010control 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