A population-based case-control teratologic study of oral dipyrone treatment during pregnancy.

OBJECTIVE

To study the possible human teratogenic effect of oral dipyrone, an antipyretic and analgesic drug treatment during pregnancy.

DESIGN AND SETTING

The analysis of cases with different congenital abnormalities and their matched population controls without congenital abnormalities, in addition to a comparison between cases and malformation controls (Down's syndrome) in the population-based, large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996.

STUDY PARTICIPANTS

22 843 neonates or fetuses with congenital abnormalities (cases), 38 151 matched newborns without congenital abnormalities (population controls) and 834 neonates or fetuses with Down's syndrome (malformation controls).

MAIN OUTCOME MEASURES

25 congenital abnormality groups.

RESULTS

1382 (6%) cases, 1911 (5%) population controls and 74 (8.9%) malformation controls were born to mothers treated with dipyrone during pregnancy. The case-matched population control analysis showed a higher rate of diaphragmatic defect (adjusted prevalence odds ratio [POR] 2.7; 95% CI 1.0, 6.8), cardiovascular malformations (POR 1.3; 95% CI 1.0, 1.7) and other isolated congenital abnormalities (POR 1.8; 95% CI 1.1, 2.9) after oral dipyrone treatment during the second and third months of gestation, i.e. in the critical period for most major congenital abnormalities. However, the evaluation of only medically recorded dipyrone use did not confirm these possible associations. The comparison of dipyrone treatment between 25 congenital abnormalities groups and malformation controls as the referent group also did not show any difference in the dipyrone use during the second and third months of gestation.

CONCLUSIONS

The higher occurrence of dipyrone treatment in the case mothers compared with population control mothers can be explained by recall bias and/or chance. However, the higher rate of diaphragmatic congenital abnormalities can be considered as a signal and merits further investigation.