Drugs In Early Pregnancy Research Articles

The Thalidomide Syndrome: Risks of Exposure and Spectrum of Malformations

Echos of the 1959 to 1961 thalidomide disaster are still with us in the form of the continuing appearance, although more rarely, of similarly malformed children. A teratologic timetable could be fashioned retrospectively, supporting the concept that different body parts and systems have periods of vulnerability and of resistance to thalidomide, probably the most potent primate teratogen known. Something between one in every two to one in every ten fetuses exposed at the critical development period were affected. The clinical affects are described from the literature on approximately 2500 children, and from extensive personal experience, and a complex though finite pattern of malformations is described, indistinguishable from sporadic nonthalidomide cases of malformations that continue to occur.

Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy.

To clarify the association of Bendectin and other drugs used in early pregnancy with the occurrence of congenital heart disease, we interviewed 298 mothers of children with congenital heart disease and 738 mothers of healthy controls. Differential recall of drug use by mothers of affected children and mothers of controls was evaluated by comparison of information collected by interview with that recorded in the prenatal record. Data derived from maternal interviews were generally consistent with the record data. Reported Bendectin use was minimally associated with congenital heart disease (prevalence odds ratio, 1.1; 90 per cent confidence interval, 0.8 to 1.5). The data from this study were consistent with previously reported associations of other drugs with congenital heart disease. In particular, aspirin use in early pregnancy was associated with about a twofold increase in the frequency of defects in septation of the truncus arteriosus (prevalence odds ratio, 2.1; 90 per cent confidence interval, 1.1 to 3.9).

Lithium and Pregnancy. A Cohort Study on Manic-Depressive Women

By record linkage of a discharge diagnosis registry and a medical birth registry we identified 350 women with manic-depressive disease who had born a child. The total delivery outcome was poorer than expected with a high perinatal death rate and a high malformation rate. Further studies revealed a high rate of perinatal deaths and/or congenital malformations among infants born of women who had used drugs in early pregnancy, and this phenomenon was concentrated to women who had used lithium and to heart defects. The sample is small, however, and there is no statistically significant difference between delivery outcome in women on lithium and in women on other psychotropic drugs. Until better risk estimates are obtained, lithium should not be used in early pregnancy.

Lithium and pregnancy. A cohort study on manic-depressive women.

By record linkage of a discharge diagnosis registry and a medical birth registry we identified 350 women with manic-depressive disease who had born a child. The total delivery outcome was poorer than expected with a high perinatal death rate and a high malformation rate. Further studies revealed a high rate of perinatal deaths and/or congenital malformations among infants born of women who had used drugs in early pregnancy, and this phenomenon was concentrated to women who had used lithium and to heart defects. The sample is small, however, and there is no statistically significant difference between delivery outcome in women on lithium and in women on other psychotropic drugs. Until better risk estimates are obtained, lithium should not be used in early pregnancy.

CONGENITAL ANOMALIES IN RELATION TO THE USE OF DOXYLAMINE/DICYCLOMINE AND OTHER ANTENATAL FACTORS AN ONGOING PROSPECTIVE STUDY

Recent publicity regarding possible teratogenic effects of the doxylamine/dicyclomine/pyridoxine combination (Debendox) has led to a degree of apprehension in women for whom the drug is prescribed, and in doctors who prescribe it. This study, based on an ongoing epidemiological surveillance programme, reports an analysis of the records of 1817 women for whom the drug was prescribed compared with 5771 non-users. The object of the study was to evaluate the outcome of pregnancy against exposure to the drug, taking into account the coexistent influences of other factors. Thorough statistical analysis disclosed no evidence of teratogenicity of the doxylamine/dicyclomine/pyridoxine overall, nor in relation to the skeletal or cardiovascular systems in particular. Two unexpected findings were an apparent moderate increase in genital tract abnormalities in users of this drug, and the possibility of a synergistic relationship between tobacco and this drug in early pregnancy, both aspects warranting further investigation.

Congenital anomalies in the pig: Teratogenic effects of trypan blue

The laboratory production of congenital anomalies serves several purposes. First, it often gives insight into abnormal morphogenesis. This occurred with Louw and Barnard's studies on intestinal atresia, 1 following the work of Fraser on cleft palate in inbred murine strains, 2 and as a result of investigations on the embryology of transposition of the great vessels in rodents. 3 Secondly, physiologically important congenital defects can be studied in laboratory animals, as Jackson did with aortic coarctation in dogs. 4 Careful measurements of abnormal physiology, not possible in the human, can be made and the results of therapy can be appraised in the laboratory before clinical trial. For this second purpose, it is important to study an animal similar to the human in the area studied. In many ways, the pig's cardiovascular physiology bears close resemblance to that of the human. 5,6,7 The size of miniature pigs of various ages, the long fetal period and the hardiness of the newborn pig make this animal suitable for detailed physiologic study at various prenatal and postnatal ages. The reproductive cycle of the pig, with heat every three weeks, makes this species a desirable one for teratologic investigation. For these reasons we tried, in the miniature pig, to produce clinically significant congenital cardiac lesions by the administration of a teratogenic drug in early pregnancy. Since the demonstration that the disazo dye, trypan blue, was teratogenic in rats, 8 the effects of this drug have been studied in various mammals. 9 The types of anomalies produced by the dye have varied according to species and strain but cardiovascular defects are prominent among the abnormalities. After a long trial-and-error process, it was found that intravenous administration of 100 mg./Kg. of trypan blue on the 10th day of pregnancy gave an increased incidence of cardiovascular and hindgut anomalies among the offspring.