Risk factors for trisomy 21: Maternal cigarette smoking and oral contraceptive use in a population based case control study

Purpose: We examined maternal smoking and oral contraceptive use as possibl e risk factors in the genesis of cases of trisomy 21 of maternal origin. Th is is the first epidemiological study to categorize cases of trisomy 21 by parent of origin and timing of the meiotic error before assessing possible risk factors. Methods: We used chromosome 21-specific DNA markers to assign origin to each case. Structured interviews were employed to determine mate rnal smoking and oral contraceptive use around conception. Results: The odd s ratio (OR) for maternal smoking was significantly increased among younger mothers (OR = 2.98; 95% CI = 1.01-8.87), but only in a particular subset o f meiotically-derived cases. The combined use of cigarettes and oral contra ceptives increased the risk further (OR = 7.62; 95% CI = 1.63-35.6); howeve r, oral contraceptive use alone was not a significant risk factor. Conclusi on: Our results indicate that categorizing cases of trisomy 21 by parent an d timing of the meiotic error allows more precision in identifying risk fac tors and may shed light on mechanisms of meiotic nondisjunction.