Smoking and the risk of oral clefts: exploring the impact of study designs

BACKGROUND: Maternal cigarette smoking is a suspected cause of oral clefts, although this association has not been firmly established. We used case-crossover, case-time-control, and bidirectional case-crossover designs to supplement findings from a case-control study of maternal smoking and oral clefts among offspring in a large birth registry. METHODS: Data are from the Swedish Medical Birth Registry. From 1983 through 1997 there were 678 recorded cases of cleft palate and 1175 cases of cleft lip with or without palate. Maternal smoking status was ascertained in early pregnancy. Controls for the case-control study were a random sample of infants born without a cleft; controls for the case-crossover designs were nonmalformed infants born to case mothers. RESULTS: Cleft palate was positively associated with maternal smoking in all study designs, whereas cleft lip with or without cleft palate was associated with smoking only in the case-control design. In the case-control design, the odds ratios for cleft palate were 1.2 (95% confidence interval = 1.0-1.5) for women who smoked 1 to 9 cigarettes per day and 1.4 (1.1-1.8) for women who smoked 10+ cigarettes per day. In the case-time-control analysis, the odds ratio for cleft palate with maternal smoking was 3.2 (1.3-7.4) and in the bidirectional case-crossover design, the odds ratio was 2.2 (1.1-4.1). CONCLUSIONS: An association between smoking and cleft palate was supported by all designs, whereas that between smoking and cleft lip with or without cleft palate was not. Case-only designs are a viable option in birth registries and may yield more information than a case-control design alone.