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.


METHODS
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.


METHODS
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).


METHODS
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.
Bánhidy
Ferenc
F
Second Department of Obstetrics and Gynecology, School of Medicine, Semmelweis University, Budapest, Hungary.
Acs
Nándor
N
Puhó
Erzsébet
E
Czeizel
Andrew E
AE
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D001724:Birth Weight / Q000187:drug effects; D016022:Case-Control Studies; D019587:Dietary Supplements; D004177:Dipyrone / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004314:Down Syndrome / Q000209:etiology; D005260:Female; D006548:Hernia, Diaphragmatic / Q000209:etiology; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D006814:Hungary; D007231:Infant, Newborn; D008423:Maternal Age; D011247:Pregnancy
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004177:Dipyrone