Medline ® Abstracts for References 20,30,31
of 'Treatment and outcome of nausea and vomiting of pregnancy'
Bendectin: review of the medical literature of a comprehensively studied human nonteratogen and the most prevalent tortogen-litigen.
Reprod Toxicol. 1995;9(4):337.
OBJECTIVE: to review the extensive literature pertaining to the reproductive and teratogenic effects of Bendectin and the opinions of the scientific experts for the defense and plaintiff. These data were evaluated with regard to the reproductive risks of Bendectin providing a scientific framework for evaluating the views of the experts in the Bendectin litigation.
DESIGN: the Bendectin literature was primarily obtained from articles cited in Research Alert of the Institute for Science Information. Other articles were obtained from Medline, review articles, and colleagues. An attempt was made to be all-inclusive, citing and reviewing all articles related to each subject being discussed. The literature includes epidemiologic studies, animal studies, in vitro studies, and basic science articles related to the principles of teratology and reproductive toxicology. Review articles, meta analyses, editorials, commentaries, articles in the press, and case reports were also included.
METHODOLOGY: the methodology utilized for the evaluation of Bendectin teratogenicity was presented. It consists of a five-part analysis of epidemiologic studies, secular trend analysis, animal studies, dose-response relationships, and biologic plausibility.
CONCLUSION: the five-part analysis of Bendectin reproductive effects indicates that therapeutic use of Bendectin has no measurable teratogenic effects. Presentations by many of the plantiff's experts failed to meet the scientific standards that should be expected of knowledgeable scientists and contributed to the persistence of Bendectin litigation.
Jefferson Medical College, Alfred I duPont Institute, Wilmington, DE 19899, USA.
Measuring drug effectiveness by default: the case of Bendectin.
Neutel CI, Johansen HL
Can J Public Health. 1995;86(1):66.
In 1983, Bendectin was voluntarily removed from the market by Merrell Dow Pharmaceuticals Inc. because of the many product liability suits pending. Earlier, 10 to 25% of pregnancies were exposed to Bendectin and over the years the drug was used in as many as 33 million pregnancies. The scientific evidence available pointed to the safety of Bendectin. This article considers some of the effects of the withdrawal of the drug. In 1983, hospital admissions for excessive vomiting in pregnancy per thousand live births rose by 37% over 1980-82 ratios and by 50% in 1984. In the United States, hospitalization rose by similar amounts. A rough estimate of excess hospital costs over the years 1983-87 is $16 million for Canada and $73 million for the U.S. Such estimates do not take into consideration other costs, such as extra physician visits, increased absenteeism from work, and the effect on quality of life of the pregnant woman and her family. No decrease in rates of congenital malformations could be shown to offset this increased cost to society.
Centre for Canadian Health Statistics, Ottawa.
Bendectin and birth defects: I. A meta-analysis of the epidemiologic studies.
McKeigue PM, Lamm SH, Linn S, Kutcher JS
"Bendectin" (Doxylamine/Dicyclomine/Pyridoxine) was widely used for the treatment of nausea and vomiting of pregnancy until 1983, when production was discontinued in the face of lawsuits alleging that the drug caused congenital malformations. We have conducted a meta-analysis of the 16 cohort and 11 case-control studies that report birth defects from Bendectin-exposed pregnancies. This meta-analysis provides an estimate of the relative risk of malformation at birth in association with Bendectin exposure. The pooled estimate of the relative risk of any malformation at birth in association with exposure to Bendectin in the first trimester was 0.95 (95% Cl 0.88 to 1.04). Separate analyses were undertaken for cardiac defects, central nervous system defects, neural tube defects, limb reductions, oral clefts, and genital tract malformations. In these categories, the pooled estimates of relative risk ranged from 0.81 for oral clefts to 1.11 for limb reductions, with all 95% confidence intervals enclosing unity. With the exception of studies for oral clefts and for pyloric stenosis, tests for heterogeneity of association indicated for each table that all studies were estimating the same odds ratio. These studies, as a group, showed no difference in the risk of birth defects between those infants whose mothers had taken Bendectin during the first trimester of pregnancy and those infants whose mothers had not. It is unlikely that Bendectin exposure contributed to the prevalence of congenital malformations in the population.
Consultants in Epidemiology and Occupational Health, Inc., Washington, DC 20007.